[Necroses in the granular cell layer of the cerebellum due to methylchloride intoxication in guinea pigs (author's transl)]. Neurotoxic action of methylchloride was reported by various authors. As this solvent is widely used in chemical industry the morphological changes in the CNS of guinea pigs due to methylchloride intoxication were comparatively studied by light- and electron-microscopy. 19 guinea pigs of both sexes (body weight 300-600 g) were individually exposed to inhalation of methylchloride mixed to normal breathed air in a 2 Vol.-% amount in a pressurised vessel of 20,000 cm3 volume (details on the experimental arrangement see VOLK 1973) for each 10 min 6 times a week. 3 control animals were fed like the experimental animals and exposed to normal breathing air for the same time in the pressurised vessel. The experimental period varied between 7 and 70 days, the number of inhalations was between 6 and 61. At the end of the experiment the animals were sacrificed by perfusion with 3% buffered glutaraldehyde under Thiogenal anesthesia. For light microscopy paraffin sections were prepared from tissue samples of the cerebrum, cerebellum, brain stem, mesencephalon, spinal medulla and spinal ganglia (stainings: HE; Turnbull's blue; Nissl; Klüver-Barrera; Mallory; Bodian and Kossa). For electron microscopy tissue blocks of the cortex, corpus callosum, striatum, mesencephalon and cerebellum as well as of spinal medulla and spinal ganglia were postfixed in 1% OsO4 and embedded in Araldit in the common way. Clinical observations--9 animals showed normal behaviour after 32 inhalations in 37 days.--6 animals displayed staggering, atactic moving of the head, retardation in spontaneous reactions and mobility. Ataxia and paresis of the hind legs occurred earliest after 17 inhalations. 4 animals showed all these symptoms only after 25 days. Morphological findings: Macroscopy: Occurrence of necroses in the cerebellar cortex was mainly observed in the lower part of the vermis; pressings of tissue in the occipital foramen, tissue swellings around the aqueduct and consecutive enlargement of the lateral ventricles occurred. Light microscopy: Changes in the Stratum granulosum in the lower part of the vermis as pyknosis of the cell nuclei and hydropic swelling of the cytoplasm (fig. 1a) were seen after 10 days. Focal necroses of the granular layer as well as "Status spongiosus" and edema occurred after 21 days (fig. 1b). In later phases these alterations were also present in other regions of the vermis and of the cerebellum, too. Furthermore, edema of the Lamina dissecans, hydropic swelling of the Bergmann's glia and marked edematous transformation of the molecular layer were observed. In this phase the hitherto intact Purkinje cells responded to the intoxication by homogenization of the cytoplasm and cell necroses. Electron microscopy: Initially an increase in density of the nuclear chromatin of the granular cells was observed associated with formation of homogeneous electron dense chromatin fragments which were finally released to the perikaryon (figs. 2a, 2b)...


The use of flurorescein investigations with concanavalin A, Lens culinaris lectin and Ricinus communis lectin. Investigations on methods for the utilization of fluorescein-isothiocyanate-labelled Concanavalin A, Lens culinaris lectin and Ricinus communis lectin for immunohistological demonstration as simple sugar moieties are reported. The stainings were carried out on rabbit erythrocytes. Ehrlich ascitee tumor cells and various mammalian tissues. Optimum results were obtained in living cells and native cryostate tissue sections. The influence of different fixing agents and conditions of fixation on the degree of tissue flurorescence were studied. Generally the fluorescense decreased by aldehyde fixation. Similar effect was observed following fixation by heat. Furthermore, changes in the pattern of fluorescence depending on the type of tissue and utilized lectin were observed after aldehyde fixation. The degree of tissue fluorescence was fairly independent of the pH value. The specificity of the particular reactions for saccharide demonstration was shown; glycerol is capable of a differently strong "hapten-like" action.


The proliferative activity of the adrenal cortex as influenced by carcinogenic and noncarcinogenic substances. A single oral toxic dose of carcinogens (N-nitrosomorpholine, aflatoxin B1, N--methyl-N-nitrosourea, urethan) causes a significant increase of the mitotic rate in the adrenal cortex 48 hours after application. Both, the control animals (water via stomach tube) and the animals treated with acetylsalicylic acid, arsenic, phenol and actinomycin D do not produce this effect. These findings confirm our previous results obtained by administration of acetylaminofluorene, diethylnitrosamine, dimethylnitrosamine and trinitroso-trimethylen-triamine. It is possible that the increased mitotic activity of the adrenal cortex is correlated with the substances applied.


Effects of the liver homogenate obtained following partial hepatectomy on cirrhosis of the liver. The authors studied the influence of liver homogenates as a whole and collected at various intervals after partial hepatectomy on cirrhosis of the liver. The lyophilized homogenates were administered over a period of 6 weeks to various groups of albino rats pretreated with CCl4 for a period of 6 months. The normal liver homogenate did not influence the histological and biochemical picture of the hepatocirrhosis. The material collected 48 hours after partial hepatectomy causes a moderate stimulation of the mechanisms of parenchymatous regeneration. 7 days after partial hepatectomy (in the postmitotic period) the hepatic regenerate shows a biological effect with lysis of collagen fibres and protection of parenchymatous cells.


The chemical structure of capreomycin.

The chemical structure of capreomycin. The chemical structure of capreomycin, antituberculous peptide antibiotic, was revised from the results of NMR-analysis in comparison with tuberactinomycins. Capreomycin IA and IB were concluded to possess the similar amino acid sequences in their cyclic peptide moieties to those of tuberactinomycins.


A simple staining technique to demonstrate chromosomal DNA replication. With the BrdU technique here described, Giemsa stained metaphases with either early or late replicational patterns can be obtained within 1 day after cell harvesting, showing a better resolution than 3H-thymidine autoradiography.


Investigation of group-specific antigen during the culture of MC-29 hepatoma. The short-time culture established from MC-29 chicken hepatoma was used for the analysis of cell morphology and expression of avian gs antigen. The content of gs antigen was not changed during the period of cultivation. Two morphologically different types of cells were present in tested tumour cells. Fluorescent antibody test showed the presence of gs antigen in both types of cells.


[Rhinosporidiosis: clinical aspects, epidemiology and ultrastructural studies on Rhinosporidium seeberi]. The author revises the main clinical aspect of the disease as well as its dignosis and its treatment. Rhinosporidium seeberi, first described by J.R. Seeber in 1900, then exhaustively investigated by J.H. Ashworth in 1923, has been accepted up to now as a phycomycete. Inside of the sporangial bodies, part of the polyp characteristic of the disease, are found spores, and in the spores, spherules, considered by Ashworth as food material. In 1955 the author did challenge the view of Ashworth because he had been able with the Feulgen stain to demonstrate the presence of DNA attached to the spherules. The results obtained by Vanbreuseghem were confirmed in 1964 by W.A.E Karunaratne and R. Cameron and Dorothy Russel. They were later confirmed in India by Lakshmanan. In an effort to understand better the real nature of Rhinosporidium seeberi which so far has never been successfully cultivated or inoculated in any animal, a study with the ultramicroscope has been done. Although it is difficult from the results obtained so far to decide of the real nature of R. seeberi, no proof has been found to confirm the theory of Ashworth. Quite evidently much has to be done to decide of the real nature of this interesting parasite.


Fibrinolysis and diabetic retinopathy.

Fibrinolysis and diabetic retinopathy. The spontaneous fibrinolytic activity of the blood is abnormally low significantly more often in persons with diabetes mellitus than in nondiabetic controls. The fibrinolytic response stimulated by venous occlusion is poor six times more frequently in diabetics than in controls, and the fibrinolytic activity of the endothelial cells is abnoramlly low in one-fourth of the diabetics tested. These changes are not related to the duration of diabetes. However, if patients with long-standing diabetes (greater than 10 years) are separated into those with retinopathy and those without, it is found that those who remain free from opthalmoscopically visible retinopathy have an almost normal fibrinolytic response on stimulation, while the others have a significantly lower response. This difference seems to be caused by a faulty plasminogen activator release mechanism. Compared with the other diabetics, those with retinopathy also have a significantly increased level of fibrinogen and of alpha2-macroglobulin, a protein that acts as an inhibitor of fibrinolysis. These findings imply a poor defense mechanism against fibrin deposits in the vessel walls in diabetes, which might contribute to the development of diabetic microangiopathy.


Direct effects of glucagon on protein and amino acid metabolism in the isolated perfused rat liver. Interactions with insulin and dexamethasone in net synthesis of albumin and acute-phase proteins. The isolated rat liver perfused for 12 hours at pH 7.10 with a suspension of bovine erythrocytes in Krebs-Ringer bicarbonate buffer containing 3 per cent bovine serum albumin has been used as a test system to study effects of glucagon and of dexamethasone in the presence and absence of insulin on net biosynthesis of rat serum albumin, fibrinogen, alpah1-acid glycoprotein, alpha2-(acute phase) globulin, and haptoglobin. Quantitative measurement of perfusate glucose, amino acid nitrogen, and urea affords a basis for determining net glucose and nitrogen balance in the perfusion system. Although the dose of dexamethasone (total 1.0 mug.) used was insufficient to induce synthesis of alpha2-acute phase globulin, net syntheses of albumin, fibrogen, alpha1-acid glycoprotein, and haptoglobin were increased. Glucagon given with dexamethasone depressed albumin and haptoglobin synthesis markedly, but not that of fibrinogen and alpha1-acid glycoprotein. Glucagon with dexamethasone markedly enhanced ureogenesis and glycogenolysis and elicited an exaggerated negative nitrogen balance. The unfavorable effects of glucagon on albumin and haptoglobin synthesis and on nitrogen balance were reversed by giving insulin simultaneously. It is emphasized that insulin is essential for positive nitrogen balance.


Modulation by alpha-2 macroglobulin of human lymphocyte proliferation in response to mitogens and antigen. The effect was studied of purified alpha-2 macroglobulin (a potent and polyvalent protease inhibitor) on normal human lymphocytes stimulated by phytohaemagglutinin, pokeweed mitogen, or by purified protein derivative as an antigen. At physiological concentration alpha 2 M has been found to inhibit mitogenic as well as antigenic stimulation. However at lower dilutions alpha 2 M acts in synergy either with the mitogen or with the antigen. At these dilutions thymidine incorporation is enhanced. alpha 2 M has no toxic or mitogenic effect on normal human lymphocytes. These data might indicate that two proteases may play a role in the proliferation of normal human lymphocytes.


Extinction, retention and induction of serum protein secretion in hepatoma-fibroblast hybrids. The production of four serum proteins has been analysed in several hepatoma-fibroblast hybrids. Extinction of albumin and alpha-foetoprotein production occurs systematically in intra and interspecific (rat X mouse) hybrids derived from mouse hepatoma cells (BW). Similar hybrids derived from two related clones of rat hepatoma cells either do not produce albumin (Fa32-derived hybrids), as the BW-derived hybrids, or retain the capacity to produce it, but at a reduced rate (Fu5-derived hybrids); some differences in the control of albumin production thus seem to exist between clonal hepatoma cell lines. The mouse hepatoma cell hybrids retain the capacity to secrete transferrin at a reduced rate, and C3 (the third component of complement) at a high rate. Further analysis of C3 production in interspecific hybrids showed that both parental genomes actively contribute to C3 production: induction of C3 secretion is thus observed in these hybrids.


Combined use of bleomycin in radiotherapy of a mouse mammary carcinoma. Experiments were carried out to determine TCD50 (50% tumor control dose) of 3rd generation isotransplants of a C3H mouse mammary carcinoma treated or not treated with Bleomycin. If the antibiotic was injected 30 min before a single X-ray dose, TCD50 was reduced. This reduction in TCD50 was independent of Bleomycin dose of more than 15 mg/kg, because of the upward-concave nature of Bleomycin dose-cell survival curve. The combined effect, when tested by TCD50 assays, appeared less than additive. This effect was further examined by a series of TD50 assays which revealed that these tumor cells were capable of repairing the potentially lethal damage induced by X-rays and that induced by Bleomycin. It was also found that the potentially lethal damage after combined X-ray and Bleomycin treatments was repaired. These findings indicated that the combined X-ray and Bleomycin treatment resulted in additive effect if the repair of potentially lethal damage in tumor cells were taken into account.


Immunohistological studies on alpha1-fetoprotein and alpha1-acid glycoprotein during azo dye hepatocarcinogenesis in rats. The relationship between morphological changes in the liver during azo dye hepatocarcinogenesis in rats and cell proteins, especially alpha1-fetoprotein and alpha1-acid glycoprotein, was investigated by the immunofluorescence method. The isoelectric focusing fractionation was made to isolate alpha1-acid glycoprotein from normal rat plasma and to obtain a crude antigen containing alpha1-fetoprotein from rat amnionic fluid. The specific fluorescence of alpha1-fetoprotein was detected in the cytoplasm of the transitional cell and the cancer cell with rather a small ratio of cytoplasm/nucleus. The immunohistological study of alpha1-acid glycoprotein suggests that the intracellular concentration of the protein may decrease in the cytoplasm of hepatocytes in hyperplastic nocules, but may increase in the cytoplasm of bile duct cells, oval cells, transitional cells, and cancer cells. Based on these findings, a rational doubt is cast on the general assumption that the cancer cell originates from the hepatocyte in the hyperplastic nodule.


Increased alpha1-fetoprotein production in rat liver injuries induced by various hepatotoxins. Serum alpha1-fetoprotein (AFP) concentration in 5-week-old rats was measured by the radioimmunoassay technique after a single administration of various hepatotoxins. Marked elevation of serum AFP concentrations occurred in rats treated with carbon tetrachloride, thioacetamide, D-galactosamine, allyl alcohol, allyl formate, and ethionine in 4 days of these treatments. The increased production of AFP appeared to be correlated with the induction of liver glucose-6-phosphate dehydrogenase (G-6-PD) among biochemical parameters studied for hepatocellular injuries. However, the difference in time courses of the increase in liver G-6-PD activity and serum AFP level following CC14 treatment suggested that the increased production of serum AFP and the induction of G-6-PD in injured liver were caused by closely related but different mechanisms. Pretreatment of CC14-injured rats with N,N'-diphenyl-p-phenylenediamine or aminoacetonitrile was effective not only in lowering the increased level of serum AFP and liver G-6-PD but also in preventing liver cell necrosis and steatosis induced by CC14. Treatment with a lower dose of thioacetamide resulted in littel elevation of serum AFP and liver G-6-PD with a markedly increased incorporation of 3H-thymidine into liver DNA without any evidence of liver injury. On the other hand, the administration of ethionine, which caused little necrosis of liver cells, produced increase in both serum AFP and liver G-6-PD levels with an only small increase of hepatic DNA synthesis compared to those following thioacetamide as well as CC14. These results suggest that the elevation of serum AFP is not directly related to the stimulation of hepatic DNA synthesis. Some additional mechanisms of specific gene amplification for AFP, which is geared to hepatic injury per se, appear to play a major role in the increased AFP production in injured liver.


Detection of e antigen and antibody: correlations with hapatitis B surface and hepatitis B core antigens, liver disease, and outcome in hepatitis B infections. Testing for e antigen and antibody (anti-e) was performed by immunodiffusion and counterelectrophoresis in patients with polyarteritis nodosa fulminant hepatitis, and chronic active hepatitis (CAH), in 59 asymptomatic carriers of hepatitis B surface antigen (HBsAg) who underwent liver biopsy, and in 150 carriers followed with sequential SGPT determinations. Counterelectrophoresis was more sensitive that immunodiffusion. Neither e antigen nor anti-e was found in the absence of HBsAg. Among HCsAg-positive patients with polyarteritis nodosa and CAH, e antigen was found in 16 of 18 and 13 of 22, respectively. It was not found in any of 43 patients with fulminant hepatitis, of whom 24 were HBsAg-positive. The e antigen was detected in none of 13 biopsied carriers with normal histology, 4 of 28 with nonspecific changes of 11 of 18 with CAH or chronic persistent hepatitis. Conversely, anti-e was present in 9 of 13 with normal biopsy, 7 of 28 with nonspecific changes, and none of 18 with CAH or chronic persistent hepatitis. The e antigen was found more commonly in nonbiopsied carriers with elevated SGPT, and anti-e in those with normal SGPT. Six carriers whose antigenemia terminated spontaneously had anti-e. The presence of e antigen correlated with a high titer of HBsAg, and with immunofluorescent detection of hepatitis B core antigen in the nuclei of hepatocytes. Conversely, anti-e was associated with significantly lower titers of serum HBsAg (P less than 0.001) and lack of detectable hepatitis B core antigen in the liver.


[Significance of serum digoxin concentration and its influencing factors]. In recent years it has become possible by means of a radioimmunoassay to measure Digoxin concentration in the serum of digitalized patients. With this method it could be shown that the resorption of Digoxin is decreased by partial resection of the samll intestines, by malabsorption syndromes, after ingestion of Neomycin, Colestyramine and antacids. In renal insufficiency, however, the elimination half-life period of Digoxin is increased conspiciously (from about 35 hours up to about 120 hours). This results in a raised serum concentration of cardiac glycosides unless the dosage is decreased considerably. The incidence of Digitalis intoxication in Digitalis treated patients has been reported to rank as high as 20%. There is, however, no strict correlation between the serum glycoside level and the clinical symptoms, because the glykoside concentration in the serum does not represent the pharmacologically active concentration at the receptor. Experimental investigations of cardiac glycoside binding to the receptor for cardiac glycosides in human heart cell membranes revealed, that receptor bound Digoxin for instance is diminished in serious renal insufficiency and it depends on the serum concentration of potassium, calcium and magnesium. In hypoxia, after myocardial infarction and in myxedema the sensitivity for cardiac glycosides is increased. The opposite is true in hyperthyreoidism, fever and in children. All of these factors have to be kept in mind and paid attention to in the clinical evaluation of the measured Digoxin concentration in the serum.


[Significance of serum alpha-fetoprotein determination. Experiences with our own radioimmunoassay]. Alpha-fetoprotein (AFP) was determined by a new radioimmunoassay in the sera of patients with different liver diseases. Compared to a normal group (n = 140, AFP levels below 15 ng/ml), most elevated AFP concentrations were found in 18 patients with primary liver cancer (PLC), 7 of whom showed Ouchterlony-positive levels (above 10,000 ng/ml). In 3 cases with liver cirrhosis, PLC was first suggested by high AFP levels between 1000 and 3600 ng/ml and later confirmed by histology. On the other hand, only 6 from 15 patients with other primary tumors and liver metastasis had AFP concentrations between 20 and 111 ng/ml. In 90% of 102 patients with liver cirrhosis AFP levels below 20 ng/ml were determined, while 13 cases showed elevated values up to 134 ng/ml. A transitory AFP increase between 20 and 238 ng/ml was seen in 32% of 63 cases in the early stage of acute hepatitis but 65% of 31 these cases in follow-up studies. 3 of 7 cases of chronic hepatitis gave similar results. The maximal AFP levels developed following the maximal transaminase activities by 5-18 days and coincided with a decrease of cholinesterase activity. The radioimmunological determination of AFP is recommended for earlier detection of the development of PLC in liver cirrhosis patients.


[New aspects and methods in gastroenterological diagnosis]. Advances in the diagnosis of gastrointestinal diseases are achieved by development of new methods and by an improved analysis of the obtained data. New aspects of screening examinations for gastrointestinal cancer in high risk groups concern endoscopic-bioptic methods, the endoscopic retrograde cholangio-pancreaticography, the ultrasonically-guided percutaneous fine-needle biopsy and immunological procedures. An increasing number of gastrointestinal peptides can be determined by radioimmunoassay. Breath tests may improve diagnosis in malassimilation.


[Persistent diarrhea in rheumatic disease]. The case history of a 52-year-old male with weight loss, steatorrhea and arthritis is presented. During clinical pathological conference, Whipple's disease was strongly suggested. The diagnosis could be proved morphologically. Antibiotic therapy with tetracycline 1 g daily for three months caused a prompt improvement. Small bowel biopsy showed disappearance of PAS-containing macrophages.


Interactions of glycosaminoglycans with DNA and RNA synthesizing enzymes in vitro. The sulfated glycosaminoglycans chondroitin 4-sulfate, chondroitin 6-sulfate, keratan sulfate, dermatan sulfate, heparin, and glycosaminoglycan polysulfate are competitive inhibitors of the DNA-dependent RNA polymerase, the DNA-dependent RNA polymerase and the RNA-dependent DNA polymerase (reverse transcriptase). The unsulfated glycosaminoglycans chondroitin and hyaluronate are without any influence on the synthesis of DNA and RNA. The strongest inhibitor is a glycosaminoglycan polysulfate with four sulfate groups per disaccharide unit. It has the following inhibitor constants: DNA polymerase, Ki = 1.5 X 10(-6) M; RNA polymerase, Ki = 0.9 X 10(-6) M; reverse transcriptase, Ki = 1.1 X 10(-6) M. The inhibition is closely correlated to the degree of sulfation of the glycosaminoglycans. There is a relationship between the sulfate/hexosamine ratio and the degree of inhibition. The inhibition of the DNA and RNA synthesizing enzymes by sulfated glycosaminoglycans depends on the nature of the template. With double-stranded DNA as template, inhibition occurs only when sulfated glycosaminoglycans are added before or shortly after (30 s) initiation of the synthesis. There is no inhibition if the inhibitors are added after the onset of the synthesis. On the other hand, with a single-stranded template synthesis was blocked completely at each phase of reaction.


Sunshine and the geographical distribution of the alleles of the Gc system of plasma proteins. Following the discovery by Daiger et al. (1975) that the Gc proteins of human plasma act as the carriers of vitamin D, the authors have plotted on a world map all available data on the frequency of the allele Gc2, and compared the distribution with that of sunlight. With some exceptions high frequencies of Gc2 correspond to low levels of sunlight and vice versa. Similar comparisons within Ireland show no such relation. The results are discussed in relation to natural selection and the incidence of rickets, due to vitamin D deficiency.


Late-replicating ring X-chromosomes identified by R-banding after BrdU pulse. Three new examples of mosaicism 45, XO/46, Xr(X). A detailed chromosome analysis was carried out in 3 patients presenting the mosaicism, 45, XO/46,Xr(X). In 2 patients, the r(X) chromosome was found to be late-replicating using R-banding techniques after a BrdU pulse administered 6 h before harvesting the leukocyte culture. The clinical symptomatology presents the great variability already observed in association with this karyotype. Only a short stature was common to the 3 patients. Case 1 is a 6-year-old girl with moderate mental retardation; case 2 is a 16-year-old girl with primary amenorrhea and absence of secondary sexual characteristics; case 3 is a 24-year-old woman whose puberty and normal sexual development occurred at age 17.


[Mesangiocapillary glomerulonephritis and rheumatoid arthritis. A case with diagnostic and therapeutic questions (author's transl)]. A 34 years old white male patient suffering from a seropositive "probable" rheumatoid arthritis developed a severe hypocomplementemic mesangiocapillary glomerulnophritis. Rheumatoid factor-Latextest and Waaler-Rose-Titers and IgM have been found highly elevated in the serum. The third component of complement (C3) was markedly depressed, while the fourth component (C4) was within the normal range. The rapid progression of both diseases forced us to start an immunosuppressive drug therapy using azathioprine and steroids, 18 months after the beginning of the treatment the patient is well, has only slight proteinuria, normal levels of complement and no joint pain. The possible connections between rheumatoid arthritis and mesangiocapillary glomerulonephritis in this case as well as the therapeutic approaches are discussed.


[Beta2-microglobulin: structure and function of an immunoglobulin-homologue (author's transl)]. The low molecular weight protein beta2-microglobulin can be isolated from urine and other biological fluids. There is structural homology of beta2-microglobulin with the immunoglobulins, in particular to the CH3 domaine of the IgG molecule. Beta2-microglobulin can be detected on the cell membrane of most cell types and is associated with the histocompatibility antigens in a non-covalent binding. The immunological function of beta2-microglobulin is unclear. Antibody against beta2-microglobulin inhibits the mitogen- and antigen induced lymphocyte proliferation as well as responder and stimulator cell function in the mixed lymphocyte culture. The lack of structural polymorphism of beta2-microglobulin argues against a direct receptor function. It is more likely that beta2-microglobulin exerts a receptor-coordinating effect on the various receptor systems.


Fc receptors and Ia antigens.

Fc receptors and Ia antigens. Antibody against Ia antigens inhibits the ability of B lymphocytes to bind aggregated immunoglobulin and to form EA rosettes. The explanation suggested for this phenomenon has been that Ia antigens are identical to or closely associated with Fc receptors. But a variety of observations preclude acceptance of this explanation since inhibition is also demonstrable with antibody against a wide variety of B cell surface components, including H-2K, H-2D, beta2 microglobulin, immunoglobulin, Ly 4.2. Furthermore, Fc receptor function can be separated from Ia antigens by capping or by isolation of membrane components. It seems likely that the mechanism of inhibition of Fc receptors by antibody against Ia antigens is part of a broader spectrum of effects induced when antibody binds to cell membrane antigens.


Immunology of the acetylcholine receptor. Myasthenia gravis is a spontaneously occurring autoimmune disease in which antibodies and lymphocytes are specifically reactive with nicotinic ACh receptors of skeletal muscle. Antibodies reactive with junctional receptors of human muscle are found in 90% of patients with myasthenia gravis and not at all in other diseases. Their capacity to cross the placenta suggests their involvement in the pathogenesis of neonatal myasthenia. The role of the thymus in myasthenia gravis remains a mystery, but it has a recently been established that the thymus contains nicotinic ACh receptors and that anti-receptor antibodies are present in myasthenic thymuses. Antibodies of myasthenic patients detect only partial cross reactivity between ACh receptors of different species. However, greater antibody binding is observed with receptors isolated from denervated rat muscle than with receptors from normal rat muscle. This suggests that extrajunctional and junctional ACh receptors might express different antigenic determinants. Although human antibodies bind minimally to ACh receptors of the electric organs of eels and marine rays, lymphocyte reactivity to electric eel receptors is found in high incidence in myasthenic patients. This suggests that electric organ and mammalian muscle ACh receptors may share more lymphocyte-defined than serologically-defined antigenic determinants. Both cellular and humoral immune responses to ACh receptors can be induced experimentally. Sufficient antigenic homology exists between receptors of different species that electric organ receptors are capable of inducing in mammals experimental autoimmune myasthenia gravis. Syngeneic muscle receptor also is immunogenic in rats. Induction of both myasthenia and antibodies to ACh receptor requires participation of thymus-derived lymphocytes. The majority of ACh receptors in myasthenic rat muscle exist complexed with antibody, but antibody is not bound directly to the receptor's ACh-binding site. Anti-receptor antibodies in vitro are capable of impairing the electrophysiological function of ACh receptors with minimal blocking of the ACh-binding site and in the absence of complement. Thus, myasthenia gravis and its experimental model provide unique biological tools for studying the structure, function and pathology of cell membrane receptors.


Immunology of the thyrotropin receptor.

Immunology of the thyrotropin receptor. Antibodies to the thyrotropin receptor appear to be responsible for hyperthyroidism in Graves' disease. The antibodies, described as thyroid-stimulating antibodies (TSAb) mimic the effects of thyrotropin (TSH) by binding to the TSH receptor and activating adenylate cyclase. TSAb consist of an electrophoretically heterogeneous population of IgG and the thyroid-stimulating site is formed by combination of heavy and light chains in the Fab part of the molecule. Binding studies indicate that the TSAb molecule interacts monovalently with membrane bound TSH receptors and that TSAb consists of an antibody population which shows a restricted heterogeneity with regard to TSH receptor affinity. Studies in patients with Graves' disease and hyperthyroidism indicate that the levels of TSAb correlate well with thyroidal iodine uptake and the absence of pituitary control of thyroid function. However in some patients with ophthalmic Graves' disease or autoimmune thyroiditis there is evidence of serum antibodies which interact with the TSH receptor but are unable to stimulate thyroid function.


Immunological aspects of sperm receptors on the zona pellucida of mammalian eggs. Sperm receptor sites on the surface of the zona pellucida are believed to be necessary for fertilization on the mammalian egg. Ovary specific antibodies are known to precipitate the zona pellucida and are also responsible for inhibition of sperm binding and subsequent fertilization. The nature of the proposed receptor sites which are blocked by antibodies are discussed relative to comparable studies in which phytoagglutinins and other agents are used to determine the chemical nature of sperm receptor sites.


Rapid quantitation of interferon with chronically oncornavirus-producing cells. The capacity of interferon to inhibit virus production in cells chronically infected with oncornavirus enabled us to develop a simple system for interferon quantitation that was independent of exogenous viral infection. The release of the virus to the culture medium was determined by its reverse transcriptase activity. The inhibitory effect of interferon in this system was linearly proportional to the log of its dilution over a range between 5 and 80% inhibiton. The sensitivity of the system was comparable to that of the vexicular stomatitis virus plaque reduction assay, whereas its reproducibility was found to be even better. This method is very rapid and can be completed within less than 24 h.


Complement-mediated killing of Acholeplasma laidlawii by antibodies to various membrane components. Mycoplasmas are useful models for biochemical studies of the mechanism of complement-mediated killing by antibodies to various membrane components. The purpose of this study was to determine the membrane antigens involved in immune killing of Acholeplasma laidlawii. Antibodies to A. laidlawii membrane total lipids, glycolipids, and phospholipids could be induced in rabbits after injection of reaggregates of the purified lipids with Mycoplasma hominis protein as the carrier. Killing of A. laidlawii membrane lipids were less effective than anti-membrane protein antisera in killing the organisms. Of the antisera to lipid components of A. laidlawii membranes, antiserum to phospholipids showed a more pronounced killing effect than antiserum to glycolipids. The antibodies to A. laidlawii in the rabbit antisera belong predominantly to the immunoglobulin G class of immunoglobulins. Double-diffusion tests in agar indicated that two immunologically reactive proteins are located on the membrane surface.


Reverse plaque formation by hog cholera virus of the GPE-strain inducing heterologous interference. A simple and rapid plaque procedure was developed for the assay of hog cholera virus (HCV) of a particular strain, GPE-, based on its intrinsic interference with vesicular stomatitis virus (VSV) on the primary swine testicle cells and on an established swine kidney cell line; the procedure is called the reverse plaque formation (RPF) method. The plaques were produced as colonies of HCV-infected cells which were VSV-sensitive, disintegrated cell sheet. These plaques became visible after 15 to 20 h of superinfection with VSV done 2 days after an initial inoculation of the GPE- strain. The plaque formation was inhibited by a specific antiserum against HCV. All cells within the plaque had HCV antigen detectable by fluorescent-antibody staining. The variations of reverse plaque count were low enough to permit virus titration. The relationship between virus concentration and the number of plaques was essentially linear. The titer measured by the RPF method was a little higher than that of the tube culture interference method.


Peroxidase staining in elicited and nonelicited mononuclear peritoneal cells from BCG-sensitized and nonsensitized mice. The peroxidase (PO) activity in nonelicited macrophages and in casein-elicited monocytes, obtained from peritoneal cavities of nonsensitized and BCG-sensitized mice and cultivated on glass for 1 or 2 h, was studied by light and electron microscopy, using the 3,3'-diaminobenzidine technique. These two types of glass-adherent peritoneal cells differed in PO activity. In macrophages, PO activity was predominantly in the nuclear envelope, rough endoplasmic reticulum, and occasionally in vesicles of the Golgi apparatus. In monocytes, PO activity was confined to cytoplasmic dense bodies resembling lysosomes, and was greater at 10 and 24 h after elicitation than at 96 h. The BCG sensitization did not significantly alter the proportion of cells with PO-positive granules in macrophages or monocytes from that observed in nonsensitized mice. From its lysosomal site, the PO in monocytes could come into contact with those microorganisms whose ingestion by these cells was followed by phagolysosome formation.


Specificity of inhibition of epithelial cell adhesion of Neisseria gonorrhoeae. Inhibition of epithelial cell adhesion (attachment) for individual strains of Neisseria gonorrhoeae is antigenically distinct.


The effect of new technologies in the training and utilization of dental auxiliaries in the US armed forces--Navy. The dental health care requirements of Navy and Marine Corps personnel exceed the treatment capabilities of the Navy Dental Corps. Through the effective training and efficient utilization of the various categories of auxiliaries, members of the naval service have all essential care completed. The staff of the Dental Technicians School has developed a task-based/self-paced curriculum for the basic dental assisting course. In the task-based curriculum instruction is limited to the psychomotor domain. Background knowledge from the cognitive domain is included only to the extent that the information is needed to perform designated tasks. There are 229 tasks in the inventory of the 12 week basic dental assisting course. These are organized into 17 instructional modules covering all aspects of chairside dental assisting. Student evaluation is based on demonstrated performance of the tasks and is graded on a pass/fail standard. The new curriculum is believed to be unique in dental auxiliary education. Because of the highly successful results in improving the quality of graduates, the positive student enthusiasm and acceptance of task-based instruction and the overall revitalization of every dimension of the basic dental assistant training program, development teams have begun to convert the other three courses of instruction conducted at the Dental Technicians School to the task-based curriculum format.


The histamine release process and concomitant structural changes in rat peritoneal mast cells. In vitro study on effects of compound 48/80 and the dependence of the process on cell preparation, temperature and calcium. Two morphologically different populations of rat peritoneal mast cells were observed in response to incubation with compound 48/80. Type 2 mast cells: cells with distinct contours exhibiting intracellular vacuoles containing altered granules and without signs of granule liberation; Type 3 mast cells: cells with indistinct countours and with varying number of granules liberated. The absence of calcium in the medium, high temperature (37 degrees C) in the presence as well as in the absence of calcium favoured type 2 versus the type 3 cells. The isolated mast cell population was less morphologically heterogeneous than the mixed cell population in response to the addition of compound 48/80. It is concluded that mast cells might release a great part of their histamine content without a concomitant liberation of the granule matrixes. The varying morphological pictures observed after incubating of mast cells with compound 48/80 is due to variable factors inherent to the experimental procedures.


The reconstruction of a fragment of primordial genetic information from modern proteins: PGI-FI (AHAP). In a continuation of earlier studies the connection between a reconstructed ancestral histone IV peptide and various sequences from non-histone proteins was investigated. This peptide, AHAP, was found to be related to partial peptides from the human encephalitogenic protein, immunoglobulin L-chains, fibrinopeptide A, glyceraldehyde-3-phosphate-dehydrogenase, TMV coat protein and several other proteins and protein families; for comparison, nodal sequences were employed wherever possible. The widespread occurrence of genetic information expressed in AHAP caused us to rename the peptide PGI-FI (primordial genetic information-fragment 1) since this peptide is apparently part of a very primitive and ancient genetic information, and may be called "protogene".


Correlations between clinical findings and urinary flow rate in benign prostatic hypertrophy. Measurement of urinary flow rate was carried out on 39 male patients with bladder outlet obstruction due to benign prostatic hypertrophy. All patients were over 50 years of age. Ten subjects, by clinical evaluation, had doubtful bladder outlet obstruction, nine had mild obstruction and 20 patients had moderate or severe obstruction. Four criteria were used for clinical diagnosis: obstructive symptoms, size of prostate by rectal digital exploration, volume of postmicturition residual urine and degree of bladder trabeculation seen on cystourethroscopy. Considerable inaccuracy results from basing the degree of impairment of urinary flow on the patient's obstructive symptoms, degree of prostatic enlargement, postmicturition residual urine or degree of bladder trabeculation. Severe obstruction symptoms generally indicate impaired urinary flow but the absence of obstructive symptoms does not exclude impaired flow.


The effect of a 6FG urethral catheter on urinary flow in benign prostatic hypertrophy. Free voiding and micturition alongside a fine indwelling urethral catheter of similar voided volumes of urine were recorded for 43 men over 50 years of age. All had benign prostatic hypertrophy. Ten men had no bladder outlet obstruction, seven had clinically questionable obstruction, nine had slight obstruction and 17 had moderate or severe bladder outlet obstruction. I found no statistically significant lowering of peak flow rate when voiding was carried out alongside an indwelling 6FG catheter in subjects with no obstruction and with various degrees of bladder outlet obstruction due to benign prostatic hypertrophy. My findings demonstrate that the lower urinary tract is not a simple hydrodynamic system but a biologically functioning organ. The bladder outflow tract possesses considerable elasticity and accommodation. The present findings justify the use of the fine perurethral catheter technic for urodynamic studies, particularly in subjects with clinically questionable bladder outlet obstruction due to benign prostatic hypertrophy.


Patterns of urinary flow in benign prostatic hypertrophy. Multiple urinary flow recordings were carried out on 51 men and without bladder outlet obstruction due to benign prostatic hypertrophy. All patients were over 50 years of age. Six urinary flow patterns (types 0-5) were defined. Types 0-3 were found in patients without obstruction, while all six patients were observed in those with clinical obstruction. Following prostatic surgery, only types 1, 2 and 3 were found. Only type 5 flow pattern can be determined by flow rate alone because it is by definition on the curve obtained when peak flow rate is below 4 ml per second. In this study, no type of flow pattern was characteristic of bladder outlet obstruction due to benign prostatic hypertrophy. The supposedly characteristic type of flow pattern in this clinical condition reported by earlier workers is mainly a result of a difference in the age distribution between their control and test groups.


Physical and chemical determinations of prostatic secretion in benign hyperplasia, prostatitis, and adenocarcinoma. With a view to detecting early biochemical changes in diseased prostate glands, polyamines, zinc, cholesterol, and physical measurements of pH and specific gravity were determined in expressed prostatic secretion. The pH of prostatic secretion from normal men was found to be higher than previously reported in the literature. The other measured substances and specific gravity were found to be decreased in prostatitis whereas the specific gravity was markedly elevated in those patients with adenocarcinoma. Clarification of physicochemical studies on prostate secretion may lead to a system of better monitoring the course of prostate disease.


Glycosaminoglycan staining in diseasesed dog skin. Diseased skin of dogs was stained using the critical electrolyte concentration-Alcian Blue method, PAS methods, and the high iron diamine technique. Digestion with testicular hyaluronidase and chondroitinase was also used to evaluate the staining results. Diseased skin exhibits a tendency for the glycosaminoglycans to revert to the condition seen in juvenile normal skin: epidermal glycoprotein content falls, total glycosaminoglycan content and the proportion undigested by hyaluronidase rises, and sulphation falls. In collagen, both hyaluronidase-stable material and sulphation increase, but follicle basement membrane does not show this trend towards the juvenile state.


Cellular patterns of post-mortem glycogenolysis in longissimus dorsi muscles of pigs at different live weights. Serial frozen sections of longissimus dorsi muscles from twelve Canadian Yorkshire breed pigs at different live weights (13-86 kg) were stained for glycogen by the periodic acid-Schiff (PAS) reaction and reacted for NAD tetrazolium reductase to determine the mitochondrial content of muscle fibres. Sections from muscles taken immediately post mortem and at 5 hr post mortem were compared and the patterns of glycogenolysis in high, intermediate and low mitochondrial content fibres were assessed on the basis of the percentage of initially PAS-positive fibres which became PAS-negative 5 hr post mortem. This form of assessment was necessary because not all fibres were PAS-positive immediately post mortem. In smaller pigs, only a few muscle fibres depleted their stainable glycogen by 5 hr and most of these fibres had a high mitochondrial content. In larger pigs, most or all initially PAS-positive fibres became PAS-negative 5 hr post mortem. Fibres with a low mitochondrial content accounted for most of the glycogenolysis detected histochemically in larger animals. The overall percentage of PAS-positive fibres was related to glycogen concentration (mg/g), r = 0.52, P less than 0.025, when samples with all PAS-positive fibres were excluded.


The effect of EDTA and metal cations on the 5-bromoindoxyl acetate esterase activity in the thyroid of the guinea pig. Miscellaneous metal cations and EDTA have been used as activators and inhibitors of esterase activity in the thyroid of the guinea-pig. The results indicate that the 5-bromoiondoxyl acetate esterase in the epithelial cells probably consists of two different A-esterase isoenzymes, one present in group I cells (the para-, intra-, and inter-follicular cells) and the other in group II cells (the follicular cells proper). The first isoenzyme seems to be calcium-dependent whereas the other is activated by various metal ions. Ca2+ + Mn2+ and Ca2+ + Co2+ were found to activate the esterase activity in group I cells. EDTA and Mn2+, on the other hand, activated the esterase activity in group II cells.


Vesicular stomatitis virus (measles) pseudotypes: tool for demonstrating defective measles infections. Mixed infection of Vero cells with measles and vesicular stomatitis viruses gives rise to phenotypically mixed infections virus particles possessing the properties of pseudotypes. Similar results were obtained when vesicular stomatitis virus was used to superinfect a defective measles system.


[Light microscopic findings of cryosurgically treated tonsils following chronic tonsillitis (author's transl)]. The light microscopic findings of tonsillar tissues from nineteen patients (aged 13-51) with the clinical diagnosis of chronic tonsillitis are described at sequential intervals following cryosurgical treatment. The Cooper instrument was used, containing liquid nitrogen and capacity limited cryoprobes as well as probes of a flow system. Two consecutive freeze-thaw cycles were used during a single session in each patient, with freezing time varied from 30 seconds to three minutes. In addition to primary cryosurgical tissue changes such as hyperemia, edema, inflammation, necrosis, fibroplasia with capillary increase, collagenous fibrosis and reepithelialisation, the following could be found: 1. A different cryosensibility of the cells and fibers within the cryolesion: The tonsillar septae are much more resistant to cold than the lymphoid tissue. Of this latter tissue, the reticulin cells and the lymphoblasts are more sensitive to the cold changes than are the matured lymphocytes. In the epithelium the stratum basale is as sensitive to cold as the lymphoreticulum. The outer epithelial cells are more resistant to cold than the basal cells. 2. A quick proliferation in the periphery of the cryolesion is seen in the form of an acanthosis and papillomatosis which begins before slough of necrotic debris occurs. 3. Sharp demarcation and protracted sloughing of necrotic epithelium from the free tonsillar surface or crypts and lymphoid tissue can be seen. 4. Reepithelialization can first be seen following slough of the cryonecrosis twenty days following cryosurgery, after which total reepithelialization occurs.


[Five-years synchronized radiotherapy in treatment of carcinoma of the head and neck: clinical results, 1970--1974 (author's transl)]. Increased tumor radiosensitivity can be achieved by the technique of synchronisation, although as yet this relationship has only been partial. Our clinical experiences from 1970-1974 with this technique lead to the following considerations: 1. Synchronized radiotherapy (Telecobalt) is administered twice weekly, independent of adjunctive medications (such as fluoro-uracil, vincristin or bleomycin). 2. Synchronized radiotherapy does not change previous indications for operative intervention. 3. The described technique permits successful treatment of advanced tumors as well as postoperative tumor recurrences of recurrences in previously-irradiated tisssues. 4. The radiosensitivity of poorly oxygenated tumor tissues may be increased. 5. Radiation dosage must not be reduced. 6. Distant tumor metastases can also be treated with additional chemotherapy (as synchronized chemotherapy).


Detection of O,O-diethyl-O-(2,5-dichlorophenyl) phosphorothioate and O,O-diethyl-O-(3,6-dichloro-2-pyridyl) phosphorothioate in meat fat. Two previously unreported organophosphorus residues have been detected in meat fat. The first, O,O-diethyl-O-(2,5-dichlorophenyl) phosphorothioate, apparently results from the debromination of bromophos-ethyl, while the other, O,O-diethy-O-(3,6-dichloro-2-pyridyl) phosphorothioate, presumably arises by the monodechlorination of chlorpyriphos. Mass spectral evidence is presented in support of the assigned structures and gas-liquid chromatographic retention data for the residues and their oxygen analogs are provided.


The appraisal of mediated materials for use in a modular curriculum. The faculty of the Nurse-Midwifery Education Program at the Medical University of South Carolina utilized a specially designed appraisal process to select mediated materials for use in the modules of their student-centered, self-paced curriculum. This appraisal process was successful and may serve as a model for other programs.


Metabolic requirements for interactions between nuclear and cytoplasmic membranes in the repair of damaged Amoeba nuclei. Amoeba nuclear envelopes were damaged using microsurgery, and metabolic requirements for the steps in their repair were studied, and my placing the cells in a solution containing one of several metabolic inhibitors. The first step in repair, the association of pieces of endoplasmic reticulum with holes in the nuclear membranes, appears to be a passive process since it was not affected by inhibitors of energy production, RNA synthesis, or protein synthesis. In contrast, fusion of pieces of endoplasmic reticulum with the nuclear membranes at the margins of the holes was blocked by KCN and dinitrophenol, indicating that membrane fusion requires energy derived from respiration, but RNA and protein synthesis inhibitors did not prevent fusion of pieces of endoplasmic reticulum with the nuclear membranes. The subsequent completion of repair and restoration of intact nuclear membranes was almost completely blocked by inhibitors of respiration, and it was reduced in the presence of actinomycin and emetine, suggesting that in addition to a requirement for energy, some later steps in the repair of the nuclear membranes require RNA and protein synthesis.


The analysis of Romanowsky blood stains by high-performance liquid chromatography. A high-performance liquid chromatographic procedure has been developed for separating and quantitating the components of thiazine dyes and compound blood stains. In terms of speed, quantitation, and component resolution, the assay reported here is superior to other reported chromatographic methods of cationic dye separation. The components present in commercial samples of thiazine dyes and LARCTM stain, a modified Wright-Giemsa stain, have been resolved in 25-40 min on a 5-mum microparticulate silica column using a methanol-water-glycine/acetic acid mobile phase. The mechanism of separation is demonstrated to be based predominantly upon the weak ion-exchange properties of silica.


Evaluation of a dual-staining method for acid-fast bacilli. A dual-staining procedure for acid-fast bacilli was found to have poor correlation with the Ziehl-Neelsen and auramine-rhodamine staining techniques.


Evaluation of the acid-fast smear.

Evaluation of the acid-fast smear. A retrospective analysis of the data involving all specimens submitted to the mycobacteriology laboratory over the past 20 months supports the continued use of the acid-fast smear as an aid in the detection of tuberculosis.


Acute effects of antiglomerular basement membrane antibody on the process of glomerular filtration in the rat. Nehron filtration rate (sngfr) and the factors controlling filtration were examined before and with 60 min of the intravenous infusion of 225-450 mug of antiglomerular basement membrane antibody (AGBM Ab) (greater than 50% antigenic saturation) in plasma-expanded (2.5% body wt) Munich-Wistar rats. Pressures in glomerular capillaries (PG) and bowman's space (Pt) were measured with a servo-nulling device, systemic (piA) and efferent arteriolar oncotic pressures (piE) were measured by microprotein methods, and nephron plasma flow (rpf) and sngfr were measured by micropuncture techniques in both control and post-AGBM Ab conditions in each rat. The sngfr fell from 52.7+/-2.9 to 24.1+/-1.9 nl/min per g kidney wt (n = 7, P less than 0.001). Both afferent and efferent arteriolar resistances increased and rpf fell from 221+/-25 to 90+/-9 nl/min per g kidney wt (P less than 0.001) but the hydrostatic pressure gradient across the glomerular membrane deltaP = PG - Pt) increased from 37+/- 1 to 50+/-2 mm Hg (P less than 0.001). The increase in deltaP and a numerical decrease in piA both acted to maintain sngfr after AGBM Ab and effectively nullified the influence of decreased rpf upon sngfr. The mean effective filtration pressure (EFP = deltaP - pi) increased from 14+/-2 to 30+/-3 mm Hg (P less than 0.001) while sngfr decreased. The major and critical reason for this reduction in sngfr was a decrease in the glomerular permeability coefficient from 0.077+/-0.017 to 0.014+/-0.001 nl/s per g kidney wt per mm Hg P less than 0.001) where sngfr=EFP-LpA.


Plasticity in the developing visual system: the effects of retinal lesions made in young rats. The central visual pathways of the rat have been used as a model for investigating the significance of axonal interactions in mammalian neural development. Attention is restricted largely to the aberrant distribution of optic axons to the ipsilateral side of the brain and their distribution in the superior colliculus after early unilateral eye damage. The normal ipsilateral retinotectal pathway in pigmented rats appears as a series of patches located anteriorly and laterally in the stratum opticum, whereas in albino animals it is a small area lying anteromedially. In both, a few axons are often found at the extreme posterior border of the superior colliculus. After unilateral eye enucleation at birth, an aberrant ipsilateral pathway from the remaining eye arises at the optic chiasm. It originates from all parts of the retina and terminates in the ipsilateral superior colliculus in a topographic fashion such that the upper retina projects laterally and the lower retina, medially. The pathway is heaviest anteromedially (from lower temporal retina) and lightest posterolaterally (from upper nasal retina). There is always a heavy projection to the extreme posterior border of the superior colliculus. In only two animals of a large series was direct intertectal sprouting found. After partial retinal lesions, there is again an ipsilateral pathway from the unlesioned eye which fills the projection area of the lesion. As after total enucleation, the pathway arises from most of the ipsilateral retina, not just that region homotypic to the lesion site, being heaviest from the lower temporal and lightest (or deficient) from the upper retina. There is suggestion of ordering of the projection into the deafferented region in that the ipsilateral degeneration after lesions in the intact eye is compact but does not fill the gap in the crossed projection completely. There is also indication that some intact parts of the retina lesioned at birth may also project in an inappropriate retinotopic fashion to the deafferented region. The corticotectal pathway shows a normal map. Study of the ipsilateral retinotectal pathway indicates that the axons terminating at the extreme posterior border of the superior colliculus arise from the lower temporal retina. The results are interpreted as indicating that the aberrant uncrossed pathways after complete or local retinal lesions, compare very closely in most features. Both distribute to the deafferented area of the superior colliculus -- in one, this is the whole surface, while in the other it is a small area. The fact that in the latter case axons are ending in quite inappropriate parts of the tectal map, may be explained more simply in terms of interactions between adjacent axons in the optic pathway rather than by an hypothesis involving a change in the cell labels across the tectal map.


The olivocerebellar projection in the cat studied with the method of retrograde axonal transport of horseradish peroxidase. III. The projection to the vermal visual area. Horseradish peroxidase (HRP) was injected separately in one of the cerebellar lobules VI, VIIA, VIIB, VIIIA or VIIIB (together corresponding to the vermal visual area) in 17 cats. After 1-3 days the distribution of labeled cells in the inferior olive was mapped. In spite of some overlapping it is clear that the various lobules of the vermal visual area receive fibers from separate parts of a horseshoeshaped region in the caudal half of the contralateral medial accessory olive (fig. 5C). The projection area of lobule VIIA is found caudomedially and overlapping with the area supplying lobule VIIB. This in addition receives a few fibers from the nucleus beta. Fibers terminating in lobule VIIIA arise caudolaterally as do fibers destined for lobule VIIIB. A central part of the total projection area projects to lobule VI. Following injections leading to a similar extent of cortical staining in lobules VI, VII or VIII the projection of labeled cells in the corresponding projection areas differ markedly. In the area of lobule VII apparently all cells are labeled, in the area of lobule VI the density of labeled cells is considerably less, and in that of lobule VIII there are rather few labeled cells. In a few cases with widespread staining of the cerebellar visual area there was spreading of HRP to the nucleus fastigii. The projection to this form the olive was therefore investigated to avoid erroneous conclusions. In the discussion it is pointed out that on most points our findings agree fairly well with the results of studies of the olivocerebellar projection undertaken with other methods (studies of retrograde cellular changes, electrophysiological methods). No support for a longitudinal subdivision of lobules VI-VIII was found. Studies of the available literature indicate that the areas in the medial accessory olive projecting onto lobules VI-VIII probably do not receive direct afferents from regions which are known to be concerned in the transmission of visually evoked impulses. Fibers to the olive from the superior colliculus appear to pass to the nucleus beta only. This projects mainly to the uvula, to a little extent only to lobule VII. However, it may be imagined that visual impulses may reach the vermal visual area via the inferior olive by way of intercalated neurons, for example in the mesencephalic RF. Major contingents of afferents to the olivary regions projecting onto the vermal area come from the spinal cord, the motor cortex and the periaqueductal gray.


Efferents from medial basal forebrain and hypothalamus in the rat. I. An autoradiographic study of the medial preoptic area. Efferent projections from the medial and periventricular preoptic area, bed nucleus of the stria terminalis and nuclei of the diagonal band were traced using tritiated amino acid autoradiography in albino rats. Medial and periventricular preoptic area efferents were not restricted to short-axon projections. Ascending projections from the medial preoptic area (mPOA) were traced through the diagonal band into the septum. Descending mPOA axons coursed in the medial parts of the medial forebrain bundle. Projections to most hypothalamic nuclei, including the arcuate nucleus and median eminence, were observed. In the midbrain, mPOA efferents were distributed in the central grey, raphe nuclei, ventral tegmental area and reticular formation. Projections from the mPOA were also observed to the amygdala through the stria terminalis, to the lateral habenula through the stria medullaris, and to the periventricular thalamus. Axons of the most medial and periventricular preoptic area (pvPOA) neurons had a distribution similar to more lateral mPOA neurons but their longest-axoned projections were weaker. The pvPOA did not send axons through the stria medullaris but did project more heavily than the more lateral mPOA to the arcuate nucleus and median eminence. Projections from the bed nucleus of the stria terminalis (nST) were in most respects similar to those from the medial preoptic area, with the major addition of a projection to the accessory olfactory bulb. The nuclei of the diagonal band of Broca (nDBB) gave a different pattern of projections than mPOA or nST, projecting, for instance, to the medial septum and hippocampus. Descending nDBB efferents ran in the ventral portion of the medial forebrain bundle. Among hypothalamic cell groups, only the medial mammillary nuclei received nDBB projections. nDBB efferents also distributed in the medial and lateral habenular nuclei and the mediodorsal thalamic nucleus.


Efferents from medial basal forebrain and hypothalamus in the rat. II. An autoradiographic study of the anterior hypothalamus. Using tritiated amino acid autoradiography, the efferent projections of the anterior hypothalamic area (AHA) were studied in albino rats. Axons from AHA neurons were not confined to local projections in the hypothalamus. Ascending AHA axons ran through the preoptic region, joined the diagonal band and distributed in the lateral septum. Descending AHA efferents within the hypothalamus coursed in a bundle ventromedial to the fornix. Projections were observed to the dorsomedial, ventromedial, arcuate and dorsal premammillary nuclei, and to the median eminence. Sweeping dorsomedially in the posterior hypothalamus, some AHA axons distributed in the central grey. AHA axons staying ventral projected to the supramammillary region, ventral tegmental area, raphe nuclei and midbrain reticular formation. Other AHA efferents distributed to the periventricular thalamus, to the medial amygdala via the stria terminalis or supraoptic commissure, and to the lateral habenula through the stria medullaris. For comparison with the AHA, efferent projections from the paraventricular nucleus (PVN) and from the ventromedial nucleus and adjacent basal hypothalamus (VMR) were studied. Projections from PVN neurons were not restricted to the median eminence and neurohypophysis. PVN efferents also distributed to many of the same regions as did those of the AHA but had somewhat different fiber trajectories and longer descending projections. VMR efferents were more widespread than those of the AHA, with projections extending into the lateral zona incerta and pontine reticular formation. Projections from the AHA were distinct from those of the medial preoptic area (mPOA). For example, while AHA axons descended in a bundle ventromedial to the fornix, mPOA axons ran in the medial forebrain bundle. Such anatomical differences may underlie experimentally demonstrated functional differences between the mPOA and AHA, for instance, in mediation of male and female sex behaviors.


Four-phase study of computer-assisted and slide-tape methods of stimulating clinical endodontic problems. 1. Computer-assisted instruction of stimulated clinical endodontic problems is superior to a slide-tape presentation for test selection but not for diagnosis and treatment planning. 2. The lack of a difference in diagnosis is likely due to the already superior performance of students in diagnosis at the University of Kentucky without computer assistance. A study with students of less background might reveal a difference in presentation methods. 3. Students with high GPSs score higher on a written test of endodontic clinical judgment. 4. Reliable results on the effects of a human tutor's supplementing machine instruction were not obtained. 5. Students felt that the problems presented in this study were useful in preparing for clinical treatment of patients. 6. After some exposure to machine methods of instruction, students divided into three sizable groups, one preferring a human teacher, another preferring a machine, and the third having no preference. The decision to use only machine or human instruction cannot then be made from student attitudes. 7. Students liked the active participation and immediate responses of the computer but not the time necessary to complete the problems. 8. Students liked the self-pacing, speed, and convenience of the slide-tape method but not the incompleteness of the problems presented by this method. 9. It appears that there is some justification from this study for offering both slide-tape and computer-assisted presentations to students.


Mandibular condylectomy in the guinea pig: quantitative triple fluorochrome study. Different-colored fluorochromes were administered sequentially to guinea pigs and the rate of bone formation measured in their condylectomized control contralateral hemimandibles. The values for labeled bone for condylectomized hemimandibles were lower than for the control contralateral hemimandibles of the same guinea pig. The differences in values of condylectomized and control contralateral sides for DCTC- and total surface area-labeled bone were statistically significant, but were not statistically significant for DCAF- and hematoporphyrin-labeled bone. There was partial regeneration of the condylar process. Although the condylectomized area was nearly normal in shape, its size and proportions were different from those of the contralateral hemimandibles that were not operated on. The greatest differences were noted in the length, height, and the distances measured between the inferior alveolar foramen and the mental foramen and the posterior border of the condyle.


The cracked tooth syndrome: additional findings. The results of this study add to the previous findings on the cracked tooth syndrome. Treatment to prevent further cracking is a must. Dentists should be aware of the syndrome and, after making the diagnosis, initiate necessary treatment.


High spontaneous release of histamine in vitro from leukocytes of persons hypersensitive to food. In vitro studies of antigenic release of histamine from peripheral leukocytes (basophils) have been done in more than 600 allergic children. Ordinarily only about 5% to 10% of the histamine content of leukocytes will leak out or be released "spontaneously" during incubation of suspensions in vitro, without the addition of antigen. A small percentage of children were found to have leukocytes that released 25% to 100% of the histamine content spontaneously during incubation. The significance of this was not apparent until recently, when studies were concentrated on children suspected of hypersensitivity reactions to foods, among whom a much greater prevalence of spontaneous histamine release from leukocytes was encountered. Of children proved by a double-blind food challenge to react with manifestations of immediate hypersensitivity, 100% had leukocytes that consistently released over 25% (usually between 50% and 100%) of the histamine content spontaneously without the addition of antigen. Such high spontaneous histamine release appears to be characteristic of persons with clinical evidence of hypersensitivity to food.


Objective clinical and laboratory studies of immediate hypersensitivity reactions to foods in asthmatic children. Clinical and laboratory observations were made with 38 children afflicted with chronic severe asthma (reversible obstructive airway disease) in which hypersensitivity to food was incriminated in the histories. Symptoms were evoked in double-blind food challenges in only 11/38 children and 14/70 challenges, and were characteristic of immediate-type hypersensitivity and were chiefly gastrointestinal, even though asthma was the common presenting complaint. There were no delayed reactions. Peanut was responsible for 8 reactions, egg for 5, and cow's milk for 1. The feature that most successfully identified those having positive reactions in challenges was a significant wheal reaction in a skin test by puncture technique using a verified extract of 1:20 W/V concentration. No subject with clinically significant, symptomatic hypersensitivity to food had a negative puncture test, and puncture tests were positive in only 10/56 instances of negative reactions in food challenges. Laboratory observations included release of histamine and enzymes from leukocytes and the levels of neutrophil enzymes in serum before and after food provocation tests. While these determinations were of interest with respect to the immunochemical basis of reactions to foods, they did not prove useful for practical clinical diagnosis. The outstanding laboratory findings was the occurrence of "spontaneous" release of 25% to 100% of the histamine from leukocytes in all cases proved clinically hypersensitive by food challenges, which suggests that this may be an indicator of immediate-type hypersensitivity to food. From the findings in the study, a general approach to food hypersensitivity was developed in which the immunologic components coupled with quantitative concentration-response relationships serve to render comprehensible the distinction between asymptomatic (immunologic) hypersensitivity and symptomatic (clinical) hypersensitivity.


Tolmetin sodium, a new anti-arthritis drug: double-blind and long-term studies. The effectiveness of tolmetin sodium in the treatment of rheumatoid arthritis was evaluated by: 1) a 12-week, double-blind study with a dosage range of 800-1600 mg daily; and 2) an open 2-year study with a dosage range of 400-2400 mg daily. The double-blind study involved 14 patients (7 tolmetin sodium, 7 placebo), and the long-term study involved 24 patients. At frequent intervals, evaluations were made of joint pain, swelling, stiffness and inflammation; grip strength; walking time; and subjective well-being. Various laboratory tests were also performed. In the double-blind study, tolmetin sodium proved superior to placebo and produced moderate improvement. In the long-term study, 5 patients improved markedly, 14 moderately, and 3 minimally. Severe side effefts were notably absent. Some mild side effects occurred but they were transient and did not interfere with therapy. Tolmetin sodium seems effective and safe in the management of rheumatoid arthritis.


Tissue fixation with diimidoesters as an alternative to aldehydes. II. Cytochemical and biochemical studies of rat liver fixed with dimethylsuberimidate. Rat liver fixed with dimethylsuberimidate (DMS) was studied to investigate the use of diimidoesters as dixatives for light and electron microscopic cytochemistry. Paraffin sections of liver fixed with DMS at pH 9.5 were weakly stained with the ninhydrin-Schiff procedure, indicating extensive reaction of NH3+ groups with the fixative. Nuclei were strongly strained by the Feulgen procedure, with no background [corrected] reaction. In contrast, glutaraldehyde fixation resulted in a significant background reaction in the cytoplasm and nuclei in controls for the Schiff-based stains. DMS-fixed liver stained intensely for glycogen with the Periodic acid-Schiff procedure, and biochemical analysis of glycogen retention and extractability indicated that DMS retained considerably more glycogen in sections than glutaraldehyde. DMS-fixed liver incubated for thiamine pyrophosphatase activity revealed reaction product in ER cisternae, Goli saccules and bile canaliculi. Peroxisomes were strongly reactive for catalase activity after incubation in diaminobenzidine medium, and reaction product of glucose-6-phosphatase activity was considerably greater following DMS fixation than after glutaraldehyde. Biochemical studies revealed up to twice as musch residual activity of glucose-6-phosphatase after DMS fixation. These results suggest that DMS may be useful as a primary fixative for certain cytochemical procedures.


Comparative immunoenzymatic localization of prolactin and growth hormone in human and rat pituitaries. Twelve human and twelve rat pituitaries were stained by an immunohistochemical method using a rabbit anti-ovine prolactin serum, a rabbit anti-human growth hormone serum and a sheep anti-rabbit immunoglobulin serum conjugated with horseradish peroxidase. On the same pituitary section, growth hormone cells were stained brown by using 3-3'-diaminobenzidine as peroxidase substrate, and prolactin cells were stained purplish blue by using 4-chloro-1-naphtol. Growth hormone cells outnumbered prolactin cells, especially in human pituitaries where the proportion is at least 10:1. No cells containing both brown granules stained for growth hormone and blue granules stained for prolactin were found in any of the sections examined. In the fetal pituitaries, there was no apparent hypertrophy of the prolactin cells, although the circulating levels of the hromone are known to be as high in the fetus at term as in the mother and much higher than in nonpregnant women.


Cytochemical reactions of human hematopoietic cells in liquid culture. Growth of human bone marrow in liquid suspension cultures has been used to study normal hematopoietic cell differentiation and abnormalities in blood diseases. A variety of cytochemical stains were applied to human marrow cells cultured in vitro for up to 14 days. AS-D- CHLOROACETATE ESTERASE AND ALPHA-NAPHYHYL BUTYrate esterase were most useful in distinguishing different cell lines in culture. Peroxidase activity disappeared with mononuclear phagocyte morphogenesis and diminished with culture in intermediate and mature granulocytes. Acid phosphatase activity and methyl greed pyronin staining intensity increased with macrophage maturation.


Platinum-pyrimidine complexes for electron microscopic cytochemistry of deoxyribonucleic acid. Platinum-pyrimidine complexes that are amorphous and highly soluble in water when used as sole electron-dense stains show high selectivity for nucleic acid-rich areas like chromatin, nucleolus and ribosomes. A method is presented for the selective staining of deoxyribonucleic acid. Glutaraldehyde-fixed tissue are exposed to 3 N HCL hydrolysis for an optimum time of 1 hr at room temperature before being embedded in Epon. Thin sections are then exposed to Schiff's reagent for 30 min and treated with 1% platinum-pyrimidine complex. The results inselective staining of structures containing deoxyribonucleic acid.


Results of virological and serological studies of three influenza A Hong-Kong epidemics in Leningrad. An analysis of morbidity of the population in the course of 3 influenza A/Hong-Kong epidemics showed a pronounced decrease in influenza affection of adult population in the last epidemic in 1971--1972. Comparative studies of the diagnostic value of CFR and HIT demonstrated identical sensitivity of CFR as a method of influenza diagnostics in both the epidemic and interepidemic periods. HIT was suitable for the detection of influenza only in the epidemic period. In the interepidemic period, the percentage of influenza infection diagnosed by means of HIT amounted to only 23--24 of all serologically confirmed cases of influenza. The highest percentage of virus isolation was observed when material from patients with serologically confirmed influenza was used. All strains of influenza A virus isolated in 1969 and 1970 were similar in their sensitivity to inhibitors of animal sera. Suring the last influenza epidemic, 2 of the 136 isolated strains were found to be resistant to gamma inhibitors and highly sensitive to the inhibitors showed their close relationship to gamma inhibitors. Antigenic analysis of the influenza A strains isolated during the 3 influenza epidemics revealed changes in the antigenic structure of the agents of the influenza epidemic in Leningrad in comparison with the standard strain A/Hong-Kong/I/68 (H3N2).


The major histocompatibility complex of the guinea-pig. II. Relationship between mixed leucocyte reactivity and serologically-defined phenotypes of the GPLA B locus and I region. The relationship between the mixed leucocyte reaction (MLR) and the serologically-defined antigens controlled by genes in the guinea-pig B locus (equivalent to the murine D or K region) and I region was investigated in various inbred and partially inbred strains and in guinea-pig families homozygous for their GPLA alleles. No MLR reactions could be detected among guinea-pig families of a closed colony which had been bred to homozygosity for their GPLA antigens. By contrast, animals which differed in their I region showed strong MLR reactivity. Animals with identical I regions as judged by four serologically-defined specificities only, but differ with respect to B locus determinants, yield appreciably lower MLR responses. It appears that in the guinea-pig, as in other mammalian species, the antigenic systems responsible for MLR reactivity are controlled primarily by genes identical with or closely linked to the I region of the major histocompatibility complex.


The diversity of mast cell-derived mediators: implications for acute, subacute, and chronic cutaneous inflammatory disorders. The mast cell in tissues represents an effector cell capable of elaboration of all the essential mediators of inflammation. The effects of uncontrolled activation may be divided into pharmacologic and inflammatory phases with attendant implications for the initiation of both acute and subacute pathologic processes. The elaboration of chemical mediators by the mast cell makes it possible to recruit blood cells and proteins essential to host defense by a controlled physiologic process that can proceed without significant local tissue damage. When uncontrolled, the same potentiality can be injurious, with the nature of the clinical problem depending upon the location of the cells, the intensity of activation, and the ratio of newly generated and preformed mediators released. The evidence that the mast cell can participate in each form of immunologic reaction--immediate, immune complex, and delayed- as a primary or secondary effector cell and the diversity of its products foretell an evolving recognition of its role in host defense and tissue injury. It is pertinent to develop further methods and criteria to define the nature and extent of mast cell participation in disease processes.


Effect of cyproterone acetate on androgen-dependent synthesis of alpha2u globulin in rats. Cyproterone acetate (CA, 2-5 mg/100 g body wt) inhibited androgenic induction of alpha2u globulin in spayed rats. In mature male rats, which normally produce alpha2u globulin, ten daily injections of CA did not inhibit synthesis of this protein. Long-term treatment of mature male rats (two injections every week for 12 weeks) showed only slight inhibition of alpha2u synthesis after 10 weeks of CA treatment. CA also failed to compete with 5alpha-dihydrotestosterone for the cytosol androgen-binding protein of male rat liver. The inhibitory effect of CA on the primary induction of alpha2u globulin in the spayed rat and its lack of effect on continued synthesis of this protein in maximally induced mature male rats are consistent with the hypothesis of a two-step mechanism for androgenic regulation of alpha2u synthesis, an initial CA-sensitive step followed later by a CA-insensitive step.


Cell-free translation of foot-and-mouth disease virus RNA into identifiable non-capsid and capsid proteins. Foot-and-mouth disease virus (a member of the picornavirus group) RNA could be translated effectively in an S-30 extract from Ehrlich ascites tumour cells. This translation was inhibited by aurintricarboxylic acid, cycloheximide, puromycin and RNase. Cell-free products of translation were identified by disc gel electrophoresis and immunoprecipitation with specific antisera. Gel electrophoresis of the products without prior immunoprecipitation suggested the synthesis of some of the non-capsid proteins and capsid proteins VP1, VP2 and VP3 of the virus. Immunoprecipitations with antisera against whole virus and VP3 indicated the synthesis of VP3 and of at least two additional peptides of 100 000 and 56 000 daltons containing antigenic sites of VP3. Gel electrophoresis after immunoprecipitation with antiserum against virus infection-associated antigen indicated the synthesis of a different 56 000-dalton protein appearing to resemble non-capsid protein NCVP5. The amount of foot-and-mouth disease virus and VP3-specific peptides in the virus RNA-directed products were measured by immunoprecipitation.


Hypotheses and recent findings concerning aetiology and pathogenesis of the muscular dystrophies. The survey reports recent findings and current hypotheses on the aetiology and pathogenesis of the muscular dystrophies. Briefly presented are (1) biochemical anomalies of structure and metabolism, (2) membrane defects, (3) the neural hypothesis, (4) the vascular hypothesis, and (5) the connective tissue hypothesis. At present, research interest is focused primarily on membrane structure and biochemistry, on neural muscle trophism, and on the genetic aspects of abnormalities in molecular biology. Whether the progressive muscular dystrophies are primary disorders of voluntary muscle or whether the primary alteration is located outside of the muscle still remains unknown.


[Cerebral embolism and psychosis with special reference to cardiac surgery (author's transl)]. Cerebral embolism can manifest itself in certain cases as pure psychosis. In the absence of neurological symptoms it might be mistaken for schizophrenia or manic-depressive psychosis. Cardiac disease and cardiac surgery involve a high risk of embolism. Microembolism plays a special role with extracorporal circulation. There is a significant increase of postoperative psychosis in cases with E.C.C. in comparison to closed heart surgery. Immediately post-operatively there occurs what has been described as the "catastrophic reaction" or "immobilization syndrome". This reaction is in fact an akinetic, parkinsonian-like state for which there is good evidence that it is due to transient microembolism of the basal ganglia ("striatum apoplexy"). After its disappearance around the 3rd--5th day "cardiac psychoses" (cardiac delirium) may manifest themselves. Patients who develop these "late" psychoses have a significantly higher correlation with endogenous psychoses in their family histories. On the psychopathological level--in the absence of disturbances of consciousness and orientation--it is not possible to differentiate between "exogenous" and "endogenous" psychosis. A special type of psychopathological reaction is dependent, as in neurological disease, on the severity of brain damage, its localization and on hereditary factors.


Papova virus-like particles in a nigral type of Creutzfeldt-Jakob disease. In this case of Cruetzfeldt-Jakob disease cortical biopsy demonstrated a large number of papova virus-like particles in the axons, dendrites, astroyctic processes and blood-vessel walls, while necropsy findings disclosed a striking status spongiosus and neuronal degeneration in the substantia nigra. The patient also suffered from a testicular feminization syndrome and was treated with immunosuppressive drugs for pemphigus vulgaris. The ready demonstration of viral particles, the rapid course of the disease and the unusual necropsy findings are discussed and related to the pre-existing diseases of the patient.


Recovery curves of the blink reflex during wakefulness and sleep. The paired shock technique was used to study the effect of sleep on the excitability of the short latency R1 and long latency R2 components of the electrically elicited blink reflex. During wakefulness, R1 returned, after transient potentiation, to its original level in about 150 ms following the conditioning stimulus. Contrastingly, R2 remained profoundly suppressed up to 800 ms, suggesting sustained reduction of excitability of the polysynpatic reflex pathways after the passage of a preceeding impulse. During non-REM and REM sleep, the recovery curve of R1 was similar in character, although different in time course to the one obtained during wakefulness. However, R2 was potentiated rather than suppressed by the conditioning stimulus during both phases of sleep. These findings indicate that, during sleep, the polysynpatic reflex pathways are not inhibited by a preceeding impulse to the same degree as in wakefulness.


[Pseudodystrophic muscle glycogenosis in adults. (Acid maltase deficiency syndrome) (author's transl)]. A 40-year-old man suffered for 5 years from a progressive proximal myopathy mimicking an atypical limb-girdle dystrophy. A "myopathic" pattern with myotonic and pseudomyotonic discharges was determined by electromyography. Enzyme histochemical and ultrastructural investigations of muscle and liver biopsies pointed to a glycogenosis. Biochemical investigations of muscle and liver samples confirmed this diagnosis, disclosing an acid maltase deficiency. Glycogen filled lysosomes were also revealed electron optically in skin fibroblasts but not in white blood cells. The literature concerning the late onset forms of acid maltase deficiency (type II glycogenosis) has been reviewed, and the clinical course has been compared with that of the infantile form (Pompe's disease). In early infancy the disease has a short and fatal course, with involvement of many organs. primarily skeletal muscules, liver and heart. In the late infantile and juvenile forms the course of the disease is slower, the organ involvement beeing not as severe; muscular symptoms begin to prevail. In adults, type II glycogenosis mimics muscular dystrophy with its prolonged course and the almost exclusive clinical involvement of proximal muscles. Biochemical and ultrastructural investigations have nevertheless demonstrated that other organs and tissues are also involved. The reasons for the variability of organ involvements in different ages are as yet unknown.


[Electric-sensoric examination and EEG to localize the focus of symptomatic epilepsy (author's transl)]. Somatosensory cortical evoked potentials (SRAP) have been studied in normal subjects and in epileptic patients. The value of this method with regard to intracerebral localization was compared with the results obtained by EEG, scintigraphy, arteriography and surgical exploration. Contralateral evoked potentials were recorded after electrical stimulation of the dorsum of the foot (spinal segment L5) and the ulnar side of the hand (spinal segment C7 or C8). Details of the methods are published elsewhere (Baust et al., 1972). In cases of symptomatic epilepsy the evoked potentials were abnormal, pathological or absent over the specific cortical area independent of whether there was an EEG focus or not. In cases with a normal EEG the changes in the evoked potentials were seen over that hemisphere which was localized by scintigramm, arteriography or surgery as being the side of the lesions (Fig. 1). The patients investigated here suffered from jacksonian epilepsy or grand mal with focal origin; pathologically the angiomas are to be mentioned in particular where the SRAP alterations, and not the EEG, demonstrate the damaged hemisphere (Fig.2). It can be concluded that the study of somatosensory evoked potentials can give more detailed information than the conventional EEG in cases of symptomatic epilepsy with a normal EEG.


[Unilateral blindness as a complication of carotid angiography (author's transl)]. In a patient with stenosis of the left internal carotid artery acute amaurosis of the left eye was observed after carotid arteriography. The macular branches of the central retinal artery and of the cilioretinal artery were obliterated by embolic material. Two further patients with carotid occlusion and stenosis, in whom spontaneous loss of vision occured, are presented. In such cases the diagnosis may be made with comparable accuracy by other methods, such as ophthalmodynamometry or angioscintigraphy, which entail risk to the patient.


Spastic paraplegia associated with Addison's disease: adult variant of adreno-leukodystrophy. Clinical and pathological features of an adult variant of adreno-leukodystrophy (ALD) are presented. A male with clinical and laboratory signs of Addison's disease (AD) developed at age 22 a slowly progressing paraplegia with slight sensory deficits in both legs and bladder and sphincter dysfunctions; he died at age 24 in an AD crisis. Autopsy revealed hyperplasia of lymphatic tissues, lymphocytic infiltrates in various organs including the CNS and adrenocortical atrophy with prominence of large ballooned, sometimes bizarre and occassionally striated cortical cells. CNS lesions consisted in incomplete demyelination of long tracts of brain stem and spinal cord with accentuation in the pyramical tracts; in these areas, perivascular cuffs of "epitheloid" histiocytic cells contained a strongly PAS-positive non-sudanophilic material. Electron microscopy demonstrated massive stroge of leaflet structures in perivascular histiocytes identical to the lamellar profiles previously described as specific for ALD. Some leaflets were found in close contact with compact lamellar arrays and with an electron-dense fingerprint material within astrocytes. In our case, the spastic paraplegia-AD syndrome which has been described previously in several clinical observations could be neuropathologically classified as an adult variant of ALD. Several differences to "classical" ALD occurring in young boys are stressed: the predominance of the endocrine disorder probably accounting for some of the perivascular lymphocyte infiltrates within the CNS; the absence of both clinical and pathological signs of diffuse cerebral involvement and the peculiar topistic pattern of CNS lesions and the very slow evolution of neurological signs paralleled by the absence of active sudanophilic demyelinating lesions. The possible mechanism of demyelination and the nature of the suggested metabolic defect in ALD are discussed. The ultrastructurally prominent leaflet structures may originate from myelin remnants, thus relating ALD to pathological storage of a myelin degradation product.


A radioimmunoassay for bovine parathyroid hormone. A radioimmunoassay for bovine parathyroid hormone (bPTH) has been developed. An antibody was raised in a goat against 1-84 b PTH which was directed against the carboxy-terminal part of the molecule (no cross-reactivity with synthetic 1-34 b PTH fragment). 1-84 b PTH was labelled with 125I using the chloramine-T method. The tubes were incubated at 4 degrees C for 6 days in an equilibrium system with 25% protein concentration. Separation was performed using plasma-coated charcoal. Jugular venous plasma PTH levels were shown to be increased in hypocalcemic parturient cows.


Effect of fixation on demonstration of phosphatases of Eimeria tenella grown in chick kidney cell cultures. The effects of fixation with various concentrations of glutaraldehyde or formaldehyde, acetone or ethanol, and freeze-drying on 5 phosphatases of Eimeria tenella and chick kidney cell cultures were demonstrated in situ. Gultaraldehyde inactivated the phosphatases more than did the formaldehyde, but the effect of the combination of the 2 (Karnovsky's fixative) was greater than that of either glutaraldehyde or formaldehyde alone. The higher the concentration of aldehyde and the longer the duration of exposure, the greater the inactivation. The order of sensitivity to aldehyde fixation of the enzymes tested was glucose-6-phosphatase greater than thiamine pyrophosphatase greater than 5'-nucleotidase greater than adenosine triphosphatase greater than acid phosphatase. Cytologic detail was preserved more efficiently with glutaraldehyde than with formaldehyde. Optimal preservation of enzyme activity for cytochemistry was with 2% glutaraldehyde for 30 min or 2% formaldehyde for 1 hr for G-6-Pase, TPPase, and 5'-nucleotidase, and with 2% glutaraldehyde or 2% formaldehyde for 2 hr with ATPase and AcPase. Quenching with subsequent fixation in cold acetone or ethanol resulted in complete inactivation of G-6-Pase, TPPase, and 5'-nucleotidase; although cells fixed in this manner yielded large amounts of reaction product for ATPase and AcPase, the distribution was diffuse, and some of it appeared to be artifactual. Quenching with subsequent freeze-drying was unsatisfactory because nearly all of the cell layers rolled off the cover glasses.


Rat alpha-fetoprotein: isolation, radioimmunoassay and fetal-maternal distribution during pregnancy. A method is described for the isolation of mg quantities of two forms of rat alpha-fetoprotein (AFP) from amniotic fluid by preparative disc-gel column electrophoresis using a continuous elution system. AFP isolated by this method is suitable for use as an antigen, can be labelled for use in a radioimmunoassay and serves as a reference standard. The characteristics of a new antiserum to AFP are also described. The protocol for a radioimmunoassay is outlined which permits the measurement of AFP in several fetal-maternal physiological compartments throughout gestation. Levels of AFP in fetal liver and fetal plasma suggest that secretion of AFP from liver occurs soon after synthesis with minimal hepatic storage. The pattern for AFP in maternal serum parallels that observed in amniotic fluid and fluctuations in maternal serum levels of AFP appear to be buffered by AFP accumulation in amniotic fluid. Fetal clearance of AFP under normal conditions may be relatively constant from Days 11-20 of gestation since an amniotic fluid: maternal serum AFP ratio of 30:1 is maintained during this period.


Equine infectious anemia virus: evidence favoring classification as a retravirus. Equine infectious anemia virus (EIAV) has a density of 1.154 g/cm3 in sucrose a high-molecular-weight RNA similar in size to Rauscher murine leukemia virus, and an internal virion reverse transcriptase that utilizes the synthetic RNA template poly(rA) but not the synthetic DNA template poly(dA), both with (dT)12 as primer. Although capable of utilizing manganese at low concentrations (approximately 0.1 mM), EIAV reverse transcriptase showed highest activity in the presence of 9 mM magnesium. The major protein of EIAV has a slightly lower molecular weight than the comparable protein of type C viruses and co-electrophoresed with 125I-labeled p25 of Mason-Pfizer monkey virus. A reference horse serum with antibodies to the major EIAV protein reacted only with EIAV and not with other type C or non-type C retraviruses. Reciprocally, a broadly reactive serum to type C virus p30s and specific sera to a variety of non-type C retraviruses did not react with EIAV. We recommend the inclusion of EIAV in the family Retraviridae.


Assay for type C virus in mouse sera based on particulate reverse transcriptase activity. Assay of particulate reverse transcriptase activity in the sera from feral mice naturally infected with type C virus provides a sensitive and rapid procedure for the determination of in vivo virus infection. The results compare well with assays for infectious virus and with complement fixation or competitive radio-immunoassays for the p30 internal antigen of the virus.


Interactions of vesicular stomatitis virus with murine cell surface antigens. The process of maturation of vesicular stomatitis virus (VSV) results in the loss of 70% of the H-2k antigenic activity from L-cell plasma membranes. This phenomenon is also demonstrated during VSV infection of cells of the H-2d haplotype. Using the method of inhibition of immune cytolysis, VSV-infected L5178Y tissue culture cells and VSV-infected METH A fibrosarcoma cells grown in vivo show a loss of H-2d activity of 73 and 76%, respectively. Using monospecific antisera, it is seen that VSV infection results in a significant loss of antigenic activity of the gene products of both the H-2D and H-2K regions in cells of the H-2d and H-2k haplotypes. In hybrid cells expressing H-2k as well as H-2b, VSV infection results in the decrease of both H-2 antigenic activities to the same extent. VSV purified from L cells shows considerable H-2k activity, but the reaction of this virus with anti-H-2k serum does not prevent a normal subsequent infection with this virus. VSV may associate with H-2 antigen in the culture medium, but the results of mixing VSV with uninfected H-2-containing homogenates suggest that this association occurs only when the host cell and the cell homogenate share the same H-2 haplotype. Velocity sedimentation of VSV, which would remove contaminating cellular membrane fragments, does not separate H-2 activity from VSV. H-2 activity is also stably associated with VSV throughout sequential sucrose gradient centrifugation steps. It is possible that H-2 antigen is a structural component of VSV grown in murine cells.