Immunochemical studies of lipids. IV. Chemical modification of Forssman globoside and immunological activities. N-deacylated and N-deacetylated Forssman globoside obtained from Forssman globoside by partial alkaline hydrolysis had no Forssman activity. After re-N-acetylation of the N-deacylated and N-deacetylated Forssman globoside, the N-acetylsphingosyl Forssman oligosaccharide thus obtained recoverd its activity. Moreover, after ozonolysis and reduction of the N-acetylsphingosyl Forssman oligosaccharide, the 2-N-acetoamido-1,3,4-trihydroxybutanoyl Forssman oligosaccharide thus obtained still had a haptenic activity, but couldn't show a precipitin reaction with Forssman antibody. On the other hand, the Forssman globoside and the N-acetylsphingosyl Forssman oligosaccharide gave rise to precipitin line on agar gel double diffusion, it was thus concluded that the aqueous solution of these substances formed spherical micelles to behave like a fairly macromolecular multivalent antigen.


Mechanism of histamine release by alpha-chymotrypsin from isolated rat mast cells. Alpha-chymotrypsin (CT) was modified chemically and physically by the treatments with diisopropyl fluorophosphate, L-(1-tosylamide-2-phenyl) ethylchloromethylketone, hydrogen peroxide and heat. After these treatments, CT lost or decreased both the enzymic activity and ability of releasing histamine from rat mast cells. Ca++ was essential for histamine release by CT, while it enhanced only slightly the enzymic activity. Process of histamine release by CT could be separated into two stages: CT-dependent but not Ca++-dependent, and Ca++-dependent but not CT-dependent. The activated state of mast cells produced by CT decayed rapidly at 37 degrees C in the absence of Ca++, but these cells responded to Ca++ by adding CT once again, suggesting reconstitution of cell membrane structure affected by CT. Isoproterenol, epinephrine, prostaglandin E1, and dibutyryl-cyclic AMP (0.01-0.1 mM) did not inhibit release of histamine induced by CT. Neither theophylline (0.01-0.1 mM) alone nor the combinations of these cyclic AMP-active agents with theophylline inhibited the release of histamine. But, in the presence of papaverine (0.01-0.1 mM) a marked, dose-dependent inhibition was observed. These data suggest that 1) release of histamine by CT from rat mast cells is causally related to its hydrolytic activity, 2) this activity causes a reversible change on mast cell membrane which probably facilitates Ca++-influx through the cell membrane, and 3) there are subtle differences among CT, compound 48/80 and antigens concerning the effect of cyclic AMP-active agents in histamine-releasing mechanisms in mast cells.


[Study of atrio-ventricular conductivity in patients with ischemic heart disease by recording electric potentials of the bundle of His]. Data concerning the recording of the depolarizing complex of the atrioventricular bundle during cardiac catheterization in patients with the ischaemic heart disease are presented. The elements of the His's bundle electrogram and the intervals characterizing the atrioventricular conductivity are analysed. In 12 patients, among the total 16 examined ones, selective coronary angiography revealed certain changes in the proximal portions of the coronary arteries. In the presence of distinct changes in the coronaries with a subtotal or total stenosis of the major coronary arteries the changes in the atrioventricular conductivity may be lacking. In 2 of the 12 patients conductivity disorders were revealed in the His-Purkinje section. The recording of the His's bundle electrogram permitted to precise the localization of the ectopic rhythms in some cases.


Hypercalcemia and neoplasia. Biologic, biochemical, and ultrastructural studies of a hypercalcemia-producing Leydig cell tumor of the rat. A localized, transplantable testicular tumor of the Fischer rat regularly produces hypercalcemia and increased phosphorus clearance in host animals. Light and electron microscopic examinations of the tumor indicate that it is of Leydig origin. There is no evidence that the tumor secretes any biologically active sex steroids, judges by weights of target tissues, when the tumor is grown in castrated or spayed rats. No radioactive steroid hormone formation in vitro was detected using 1-14C-acetate as a precursor although 14C was incorporated into the "C27" sterol fraction. Mass (micrograms) amounts of sex steroids were not detected after purifying large amounts of tumor extracts. The phytosterols, beta-sitosterol, stigmasterol, campesterol, were tentatively identified in tumor extracts but were also found in other tissues and in tumors not associated with hypercalcemia. Administered in vivo, human chorionic gonadotropin caused an acute rise in serum calcium in 3 to 5 hours in tumor-bearing hypercalcemic rats. Only trophic hormones with luteinizing hormone activity were found to compete with 125I-human chorionic gonadotropin for binding to the tumor homogenate in vitro indicating the tumor possessed luteinizing hormone receptors. When the tumor was transplanted intrasplenically, hypercalcemia did not occur unless adhesions formed, suggesting that the tumor hormone was rapidly metabolized by the liver and was probably of small molecular weight. Secretory granules, usually thought to be associated with peptide hormone secretion, were not detected at the ultrastructure level. Cortisol, conjugated estrogen, and an inhibitor of sterol biosynthesis (AY-9944) were effective in lowering the elevated serum calcium. Definitive identification of the agent causing lethal hypercalcemia has not been accomplished. The available data suggest it is not parathyroid hormone or vitamin D. The Leydig cell origin of the tumor, its response to human chorionic gonadotropin in vivo, the lack of secretory granules at the ultrastructural level, and biologic characteristics, all lead to the speculation that the secretory product of the tumor is a new hormonal substance, possibly a steroid precursor or related substance not previously described or is a known substance of small molecular weight whose calcium-mobilizing properties have not been fully characterized. This transplantable tumor may represent a model for one form of neoplastic hypercalcemia occurring in man and may have important implications in the general area of calcium and phosphorus homeostasis.


Focal and segmental glomerular hyalinosis and sclerosis in the rat. A glomerular disease spontaneously developing in Wistar rats was studied by light and electron microscopy and by immunofluorescence techniques. The disease is characterized by the local subendothelial deposition of hyaline material leading to increase of mesangial matrix and the development of adhesions. Immunofluorescence shows deposition of complement and IgM and to a lesser degree also of IgG in these lesions. There is a constant relationship of these early changes with the vascular pole of the glomerulus. It is confirmed that female rats are resistent to the disease as are male rats fed a sodium-deficient diet. A higher protein excretion was found in normally fed male rats as compared to female rats and to rats on a sodium-deficient diet. These differences already existed before the normally fed male rats developed glomerular disease. From these studies it is suggested that an appropriate name for this disease would be focal and segmental glomerular hyalinosis and sclerosis and that hemodynamic factors could be an important etiologic mechanism. The histopathology of the disease bears a striking resemblance to focal sclerosing glomerulopathy with segmental hyalinosis sometimes found in kidneys of patients with an idiopathic nephrotic syndrome.


Substernal gastric bypass of the excluded thoracic esophagus for palliation of esophageal carcinoma. Curative resection is impossible in most patients with carcinoma of the esophagus or malignant tracheoesophageal fistulas, because of local tumor invasion or distant metastases. Optimal palliative therapy in these patients should relieve dysphagia and aspiration and restore the ability to swallow comfortably. This report describes a technique for palliation of carcinoma of the esophagus with a substernal gastric bypass after exclusion of the thoracic exophagus with the GIA surgical stapler. The results of this procedure in 10 patients with advanced malignant disease are discussed. Although postoperative morbidity and mortality rates were high, the quality of life achieved with this method of palliation was gratifying. Substernal gastric bypass of the excluded thoracic esophagus is an effective alternative to feeding tubes, prolonged radiation therapy, esophagogastrectomy, or colon bypass in patients with incurable, malignant esophageal disease.


Isocaloric diet changes and electroencephalographic sleep. Electroencephalographic (E.E.G.) sleep changes were studied in eight young healthy male subjects who were given a normal balanced diet or a high-carbohydrate/low-fat or low-carbohydrate/high-fat isocaloric diet, according to an experimental design. Significantly less slow-wave sleep (S.W.S.) was found after consuming a high-carbohydrate/low-fat diet than after consuming a normal balanced diet or a low-carbohydrate/high-fat diet. The latter two diets did not differ in terms of the amounts of S.W.S. Both high-carbohydrate/low-fat and low-carbohydrate/high-fat isocaloric diets, especially the former, were associated with significantly more rapid-eye-movement (R.E.M.) sleep than was the normal balanced diet. These findings emphasise the importance of daily diet for the following night's sleep.


Positive end-expiratory pressure in weaning patients from controlled ventilation. A prospective randomised trial. Twenty-five patients in acute respiratory failure were randomised to receive either 5 cm of positive end-expiratory pressure (P.E.E.P.) or no-P.E.E.P. while weaning from controlled ventilation. The use of P.E.E.P. resulted in a significant reduction in the increase in alveolar-arterial oxygen tension gradient (AaDO21) which occurred in the group of patients who were converted from controlled ventilation to spontaneous ventilation without P.E.E.P. Patients who weaned without P.E.E.P. had a mean increase in AaDO21 of 102+/-35 mm Hg S.E. while those who weaned with P.E.E.P. had a mean increase of only 10+/-22 mm Hg (P less than 0-03). The use of P.E.E.P. was also associated with a significant improvement in the vital capacity and the maximum inspiratory force. Patients who weaned with P.E.E.P. had an increase in vital capacity of 258+/-108 ml (P less than 0-05) and an increase in inspiratory force of -15+/-5 cm H2O (P less than 0-01), while patients who weaned without P.E.E.P. did not have significant changes in these measurements. The use of P.E.E.P. during weaning may be helpful in patients who fail to wean because of the development of hypoxaemia due to rapid alveolar collapse, since P.E.E.P. appears to minimise the increase in intrapulmonary right-to-left shunt which normally occurs during weaning from controlled ventilation.


Trials in man with live recombinants made from A/PR/8/34 (H0 N1) and wild H3 N2 influenza viruses. A long-term study is described of recombinant influenza viruses produced from the avirulent laboratory strain, A/PR/8/34 (H0 N1), and newly isolated H3 N2 influenza virus variants. A number of H3 H2 recombinants were found to be attenuated for man and capable of inducing antibody formation, and were therefore potentially usable as live vaccines. However, the volunteer trials as a whole suggested that, in this system, there might not be complete segregation of virulence and antigenic characteristics. No H3 N2 recombinants were detected which were non-infective for man, like the A/PR8 (H0 N1) parent, and reciprocal hybrids (H3 N1 and H0 N2) always reflected some of the virulence of the parent from which they had inherited their haemagglutinin. This property is not a feature of mouse influenza.


Pyrogenic reactions during haemodialysis caused by extramural endotoxin. Between July 24 and Aug. 19, 1974, an outbreak of pyrogenic reactions occurred in patients at a private haemodialysis centre in a suburb of Washington, D.C. 49 reactions characterised by chills, fever, and hypotension occurred in twenty-three of the seventy patients dialysed during this period. No infections could be documented in any of the affected individuals. Despite the fact that only low levels of gram-negative bacterial contamination of the haemodialysis system were found, high levels of endotoxin contamination of dialysis fluid and endotoxaemia in patients experiencing overt reactions were recorded using the Limulus lysate test. The cause of these reactions was traced to an increase in endotoxin contamination of the tap water used to prepare dialysate, possibly caused by an increase in the algae levels in the local water source. The installation of a reverse osmosis system for water treatment may be a solution to the problem of endotoxin contamination of water used to prepare dialysis fluid.


Is glucagon important in stable insulin-dependent diabetics? The role of glucagon has been evaluated in the everyday regulation of carbohydrate and lipid metabolism in insulin-dependent diabetic patients. Plasma concentrations of glucagon, growth hormone, cortisol, glucose, and free fatty acids and blood concentrations of glycerol, 3-hydroxybutyrate, acetoacetate, alanine, pyruvate, and lactate were measured in 38 fasting diabetic subjects deprived of their usual morning dose of insulin. The measurements were repeated in 25 of these patients after a further 3 hours of insulin deprivation and in 6 patients again at 6 hours. There was no correlation between the initial fasting levels of plasma-glucagon and those of the other biochemical measurements including glucose and ketone bodies. Furthermore, no correlation was found between changes in these measurements and in plasma-glucagon over a period of 3 or 6 hours. These findings suggest that glucagon is unlikely to play a role of primary importance in blood-glucose homoeostasis or ketone-body metabolism in ambulant insulin-dependent diabetic patients.


A new type of familial hypercholesterolaemia. Two members of a family (proband and daughter) with hypercholesterolaemia have an abnormal low-density lipoprotein which fails to suppress the activity of a rate-determining enzyme for cholesterol biosynthesis (3-hydroxy-3-methyl glutaryl-CoA reductase) in leucocytes of the patients and controls. However, the proband's leucocytes are inhibited by lipoproteins from other sources demonstrating that the mechanism for cellular regulation of the enzyme is intact. This mutant lipoprotein may have a role in the production of hypercholesterolaemia.


Evidence against breast-feeding as a mechanism for vertical transmission of hepatitis B. A follow-up study of 147 babies born to mothers known to be carriers of hepatitis B surface antigen (HBsAg) revealed no evidence for a relationship between breast-feeding and the subsequent development of antigenaemia in the babies. All babies were tested at three or more months of age, and the mean age at last follow-up was eleven months with a mean of three serum specimens per baby (not counting cord-blood specimens). The frequency of acquisition of HBsAg and anti-HBs was almost identical among breast-fed and non breast-fed infants. The frequency of other variables known to influence the development of antigenaemia among infants of carrier mothers did not vary according to breast-feeding status: mother's HBsAg titre, HBsAg positivity rate in cord-blood specimens, and HBsAg prevalence among siblings. 32 breast-milk specimens from carrier mothers were all HBsAg negative.


Epidemic of conjoined twins in Southern Africa? Eleven sets of conjoined twins have been born in Southern Africa in a period of just over twelve months. Analysis of the circumstance pertaining to the conception and delivery of these children revealed considerable ethnic, geographic, and socioeconomic differences. It is possible that a ubiquitous environmental agent is a precipitating factor in this situation.


Restoration of in-vitro lymphocyte responses with exogenous adenosine deaminase in a patient with severe combined immunodeficiency. Deficiency of adenosine deaminase (A.D.A.) occurs in an autosomal recessive form of severe combined immunodeficiency (S.C.I.D.). The role of this enzyme deficiency in the pathogenesis of the immune defects is not clear. A patient with A.D.A. S.C.I.D., studied during the first six weeks of life, was found to have B and T lymphocytes as well as 25% of normal lymphocyte responses to mitogens. This patient subsequently became severely lymphopenic with loss of mitogen responsiveness. Addition of calf-intestinal A.D.A. or human-erythrocyte A.D.A. to cultures of this patient's lymphocytes restored their ability to proliferate when stimulated with mitogens. These data indicate that A.D.A. deficiency is causally related to the cellular immune defects observed in A.D.A. S.C.I.D. and suggests a possible role for enzyme replacement in the therapy of this disorder.


"Incubation period" in Hodgkin's disease. Two clusters of patients with Hodgkin's disease are described. The interval between the first contact of the secondary cases with the index cases and the appearance of symptoms suggested a maximum "incubation" period of 2-6 months.


Chronic pancreatitis and alpha-1-antitrypsin. 110 patients with proven chronic pancreatitis have been studied to assess the prevalence of the various Pi phenotypes of alpha1-antitrypsin in this disease compared with a control group of 116 blood-donors. The phenotype PiMZ (including Mweak) was significantly more prevalent and PiMM significantly less so in the patients with pancreatitis. It is possible that a heterozygous deficiency of this protease inhibitor renders the pancreas more vulnerable to aetiological agents (e.g., alcohol).


Pathogenesis of neurogenic pulmonary oedema. Evidence suggests that the initial phase of neurogenic pulmonary oedema results from a centrally mediated, massive, sympathetic discharge. It is postulated that this produces intense, generlised, but transient, vasoconstriction with a resultant shift of blood from the high-resistance systemic circulation to the low-resistance pulmonary circulation. Pronounced increases in pulmonary vascular pressures and blood-volume then produce pulmonary oedema because of the hydrostatic effect of increased pulmonary capillary pressure. In addition, pulmonary hypertension and hypervolaemia injure pulmonary blood-vessels, altering pulmonary capillary permeability and producing lung haemorrhage. After the transient systemic and pulmonary vascular hypertension subside, the patient is left with abnormal pulmonary capillary permeability, so that pulmonary oedema persists in the face of normal haemodynamic and cardiac function.


Cerebral form of high-altitude illness.

Cerebral form of high-altitude illness. Twelve cases of severe altitude illness are reported in which the neurological signs and symptoms dominated the clinical picture. Pulmonary oedema, retinal haemorrhage, thrombophlebitis and pulmonary embolism, bronchopneumonia, and coronary-artery disease were also present in several of the patients but the primary problem seems to have been cerebral oedema. Other published cases support this impression. Patients who were returned to low altitude early in the disease fared well; two patients died, and in both cases evacuation had been delayed. The most effective prevention lies in slow ascent, though in one case reported here the rate of climb was well within the recommended limit. Recommended management is rapid descent to low altitude at earliest indication of cerebral or pulmonary oedema, intravenous dexamethasone or betamethasone in large doses, hydration, diuresis (frusemide has been most used), and perhaps other intravenous therapy with hyperosmolar materials such as mannitol, urea, 50% saline, or 50% sucrose. Prognosis is good if descent and treatment are started early, but permanent damage may be anticipated if the patient is unconscious for any prolonged period before descent.


Kuru. Epidemiological developments.

Kuru. Epidemiological developments. Important changes have occurred in the epidemiology of kuru since the last review in 1970. There has been a continued decline in the annual incidence, particularly in females. There is a change in the average age of onset in both sexes, and cases are no longer seen in children and adolescents. Alteration in the geographical distribution has resulted in kuru now being confined almost wholly to the South Fore region.


Glycosides of magnolia. II. Structural elucidation of magnolidin. Magnolidin, the major glycoside of Magnolia grandiflora L. consists of two moles of rhamnose, and each of glucose, caffeic acid and 3,4-dihydroxyphenethanol. Based on degradative and spectroscopic evidence, a structure is proposed for magnolidin as one of two possible alternatives which differ with respect to the position occupied by the O-caffeyl unit.


[Differential diagnosis of acute viral hepatitis and liver cirrhosis with severe activity (author's transl)]. Results of biochemical tests in 61 patients with acute viral hepatitis resp. 63 patients with subacute hepatitis were compared with laboratory findings of 27 patients with liver cirrhosis in the stage of severe activity of the disease. In acute and subacute viral hepatitis was the activity of GPT and CHE significantly higher than in active cirrhosis of the liver. In contrast to these findings was the activity of GLDH and the blood level of bilirubin in both groups of patients similar and for the differential diagnosis of no importance. Low albumin, high gammaglobulin and significant increase of IgG and IgA fractions of immunglobulins in serum are additionally to the results of the activity of some serum enzymes for the diagnosis of active liver cirrhosis in comparison to acute and subacute viral hepatitis of greatest value.


[Oral therapy of ectopic cardiac arrhythmias with Propafenon (author's transl)]. The antiarrhythmic effect of Propafenon administered orally in single doses of 600 resp. 900 mg (X = 10,2 Mg/kg/ bodyweight) was examined in 20 patients with chronic and stabile extrasystoles of either ventricular or supraventricular origin. In 18 patients the ectopic beats could be completely eliminated, 2 patients did not respond to antiarrhythmic therapy. The antiarrhythmic effect begins 30 minutes after administration of the drug and has its maximum 3 hours after application with a duration of more than 8 hours in most patients. Propafenon is an effective drug for oral therapy of ectopic cardiac arrhythmias.


Glycosaminoglycans from Ateroid and bovine duodenal mucosa and pancreas. Glycosaminoglycans (GG) were isolated from commercial Ateroid and compared with those from bovine duodenal mucosa and pancreas. The major GG in Ateroid is heparin. Heparan sulfate (HS) and dermatan sulfate were also found. HS, chondroitin sulfates, and heparin were isolated from duodenal mucosa after papain digestion, but a residue, non-digestible, was mostly heparin. Pancreas contains very little GG, and the GG composition is similar to that of mucosa. The heparin isolated from Ateroid and mucosa have similar lipoprotein lipase-releasing activity, but the former has considerably less anticoagulant activity. Interestingly, papain digestion of mucosa and pancreas did not release all heparin from the tissue, suggesting that the protein to which heparin is linked is not readily accessible to the enzyme.


The fractionation of cerebrospinal fluid proteins by cellulose acetate electrophoresis in children with infectious diseases of the central nervous system (author's transl). The increased permeability of the blood-brain barrier during acute inflammation of the central nervous system leads to changes of the cerebrospinal fluid (C.S.F.) protein pattern. Initially, in the cases of bacterial meningitis, cellulos acetate electrophoresis revealed decreased prealbumin, albumin and tau-globulin fraktion whereas alpha- and gamma-globulin fractions were found increased. In later stages of purulent inflammation a hydrocephalus occurred in five children, associated with an increased amount of albumin in the C.S.F. Cases of viral meningoencephalitis had a characteristic decrease of prealbumin and increase of gamma-globulin, the lowered prealbumin values were found more often. In three cases of congenital encephalitis pathological patterns of C.S.F. proteins were still found 1--1 1/2 years postpartum. Children with acute peripheral facial palsy and febrile convulsions had a normal C.S.F. protein profile.


[Correlation studies of some thyroid function tests (author's transl)]. The results of a thyroid test based on ion exchange and column chromatographic separation and of two radiochemical T4 and three T3 tests were carried out with commercially available reagent packs ready for use, and were compared with the PBI values found in the same serum sample in each case. This also tested the analytical precision of each method. A good correlation was found between the PBI and the T4 values, while the accuracy of the T3 tests was unsatisfactory.


[Contribution to information and genetic counseling in Mekkel's syndrome (author's transl)]. The deformity syndrome nowadays named after Meckel is characterized by the following principal features: occipital encephalocele, cystic kidneys and a polydactyly. According to the available findings in twins and families, an autosomal recessive lethal syndrome is involved. In 8 (= 16.6%) of 48 families, the parents of the feature carrier were blood relations. Heterozygous anlage carriers cannot yet be recognized as such. To make a statement in genetic counselling today, ultrasonic diagnosis and an amniocentesis must be carried out early in a pregnancy at risk.


[The fetal alcoholic syndrome. A case report on two siblings]. Two children of a mother suffering from chronic overindulgence in alcohol are reported. Both of them showed considerable signs of what Jones et al. (1973) called the fetal alcoholic syndrome. Delay in statokinetic, physical and mental development and craniofacial dysmorphism are prominent in the clinical picture. A direct toxis effect of the alcohol on the fetus is assumed to be the cause.


Beta2 microglobulin and lymphocytic infiltration in Sjögren's syndrome. We measured salivary beta2 microglobulin concentrations in 49 patients evaluated for Sjögren's syndrome with a labial salivary-gland biopsy. The salivary concentration was elevated and a significant correlation (P less than 0.001) was found between the concentration and the degree of inflammation seen in the biopsy. Serum concentrations were increased in 135 patients with Sjögren's syndrome. Striking elevations were seen in patients with associated renal or lymphoproliferative complications. Three patients have an increase in serum beta2 microglobulin concentration in association with exacerbation of their disease, and six a decrease after clinically efficacious therapy. These data indicate that determination of beta2 microglobulin in saiva may provide a simple, noninvasive technic for estimation of the degree of local inflammation in autoimmune disease.


Theory and practice for studies for peptides by 15N nuclear magnetic resonance at natural abundance: gramicidin S. The low-abundance isotope of nitrogen, 15N, is now accessible to study by the latest high resolution nuclear magnetic resonance techniques. Structure and motion in polypeptides of moderate size may now be usefully investigated in this way.


Cytological detection of mutagen-carcinogen exposure by sister chromatid exchange. A staining technique that detects sister chromatid exchanges (SCEs) has been used to examine the response of chromosomes in cultured Chinese hamster cells to a wide variety of mutagens-carcinogens. The test gives a very sensitive and rapid method for detecting chromosome mutagenicity of chemical agents and provides a powerful new method for detecting environmental mutagens.


Carcinogenesis.

Carcinogenesis. An examination has been made of the major chemicals which are known to be carcinogenic, either in animals or in humans. As a result, a generalized type of chemical property seems to be a prerequisite for the carcinogenic activity. In most cases, this is some kind of reactive electrophilic intermediate produced directly from the carcinogen or from one of its immediate metabolites. This electrophilic reagent is generally a positively charged ion of some kind. In the case of the hydrocarbons it seems to be an incipient carbonium ion; in the case of nitrogen compounds, it is a corresponding nitronium ion. There are a number of possible substrate materials (nucleophilic) in a cells, but the dominant one which has been suspected is the nucleic acid component, either the DNA or the RNA. The bases of these materials all have extra pi electrons susceptible to attach by the electrophiles of the carcinogen. Such a modification, particularly of the DNA, could lead to either major or minor changes in the genetic composition of the cell. Minor changes are usually rectifiable or are not visible, and this would include a large variety of point mutations.


Prostaglandin, slow-reacting substance, and histamine release from anaphylactic guinea-pig hearts, and its pharmacological modification. Prostaglandins (Pgs), slow-reacting substance of anaphylaxis (SRS-A), and histamine were released from anaphylactic isolated perfused guinea pig hearts. Pgs were to the greatest part of the F2alpha-type. PgE2 was found in traces only. Neither PgA2, nor the metabolites 13,14-dihydro-15-keto-PgF2alpha and 13,14-dihydro-15-keto-PgE2 were detected in the perfusates. Isoproterenol reduced the PgF2alpha output significantly. This effect was increased by the addition of theophylline. Propranolol did not reverse the effect of isoproterenol, but in a high concentration (5 mug/ml) reduced the PgF2alpha output for its own. Indomethacin completely abolished the anaphylactic prostaglandin release. The histamine liberation was significantly decreased only by the combination of isoproterenol and theophylline, and also by a high concentration of propranolol (5 mug/ml). In contrast to the Pg release, the anaphylactic SRS-A and histamine liberation was not abolished by indomethacin, but rather increased. The results are discussed in view of the possible role of the released substances  in the functional events of cardiac anaphylaxis.


Decreased myelin basic protein content of the aged human brain. Myelin basic protein was extracted from frontal lobe white matter obtained at autopsy from seven individuals ranging in age from 72 to 78 years. Qualitative and quantitative comparisons were made between basic protein from this group and that extracted from another group of individuals ranging in age from 45 to 65 years. The basic protein content of the older brains was considerably lower than that of the younger brains. Qualitative studies that included assay for encephalitogenic activity, disk gel electrophoresis at pH 4.3, and immunoprecipitation did not reveal any difference in the basic protein derived from the two age groups. Possible factors that may help explain the decreased basic protein content of the aged brain are discussed.


[Oxprenolol in the treatment and prevention of cardiac arrhythmias]. Authors have analyzed the antiarrhythmic effect of oxprenolol, a beta blocking agent, in the treatment of various types of arrhythmias and in the prophylaxis of recurrences of auricular flutter and fibrillation. The results obtained in a group of 68 cases of different arrhythmias may be summarized in the following way: a) the drug efficiently reduces the ventricular rate in sinus tachycardia and in atrial flutter and fibrillation with high ventricular rate, even if resistant to treatment with digitalis; b) in patients with asynchronous pacemaker oxprenolol leads to disappearance or an important reduction of competitive rhythms; c) in supraventricular paroxysmal tachycardias the results are positive in the majority of cases (while on the contrary in 2 cases of ventricular tachycardias the drug was not effective). A group of 116 cases with auricular flutter or fibrillation (in which sinus rhythm had been restored with quinidine or cardioversion has been analyzed to study the prophylactic activity of oxprenolol in these arrhythmias. The cases have been divided at random into two groups and have been treated with quinidine (g 0.80 p.d.) or with an association of oxprenolol (mg 60 p.d.) and quinidine (g 0,60 p.d.). The observation period varied from a minimum of 1 month to a maximum of 3 years and 3 months. The curves showing the percentage of persistance of sinus rhythm in the two groups were very similar and after 3 years and 3 months 100% of patients observed presented a recurrence of arrhythmias.


[Results of selective posterior radiculetomy at the lumbar and cervical level]. At the light of authors' present experience, radicletomy appears as an excellent antalgic operative procedure in the case of roots with high functional risk (brachial plexus and lumbar plexus). In the absence of any motor deficiency or ataxia, it appears that radicletomy is of help in the cure of severe hypertonies of the extremities (sequelae of cerebral stem contusions). Conversely, in the spastic sequelae of hemi- or paraparesias, lumbar-sacral posterior selective radicotomy is a sure procedure that procures results nearly super-imposable to radicletomy with an appreciable gain in time. At last, for what concerns the motor involvements of the upper extremity ending in spasticity, selective radicletomy recovers its rights and has to be preferred to S.P.R. The indications may be summarized as follows: -- At the level of the lower extremities: in the case of paraparetic sequelae or of sequelae due to spastic paraplegia, a S.P.R. has to be performed; for what concerns antalgic surgery, in the absence of motor deficiency, the best indication is radicletomy. -- At the level of the upper extremities: in the case of dystonic sequeale of the cerebral stem, spastic pain bound with hemiplegia or with carcinoma etc. (herpes zoster..), radicletomy constitutes the ideal surgical procedure.


Ultrastructure of the white sponge nevus. An electron microscope study of tissue diagnosed as white sponge nevus suggested a more advanced process of cellular keratinization in the buccal mucosa than may be appreciated in histologic sections. Ultrastructural features which are normally associated with keratinizing epithelium were observed in the lesion and included (1) a marked increase in the intracellular content of tonofilaments, (2) numerous tonofilament-related keratohyaline granules, (3) membrane-coating granules that possessed an internal striated appearance, (4) the apparent accumulation in the intercellular space of the contents of the striated microgranules, and (5) the presence within some cells of a keratin-like material. Other features included the formation of perinuclear electron-lucent zones and the presence of elongated cytoplasmic processes which produced a complex pattern of interdigitation among the epithelial cells.


Why are white lesions white? Observations on keratin. It is proposed that oral keratoses appear white because of the ability of abnormal oral keratin to evenly reflect the visible light spectrum because of the hydration of the keratin layer in a manner similar to the reaction of the stratum corneum of the epidermis to water. Thickening of the keratin layer per se or the over-all thickness of the epithelium does not appear to be the primary factor in causing an intraoral lesion to appear white. The white appearance is related to thickness only insofar as it takes a certain amount of abnormal keratin to be clinically evident. It appears that an accumulation of only 10 to 20 microns of abnormal keratin is sufficient to cause a lesion to appear very white. This is about the amount seen on the normal human palate. It seems likely that, when a normally nonkeratinized area, such as the buccal mucosa or floor of the mouth, is stimulated to produce keratin, the keratin thus produced would be different from normally occurring oral keratin. This difference apparently manifests itself clinically as hydration of the keratin layer. A more complete understanding of why white lesions are white awaits further elucidation in regard to the role of lipids, keratohyaline granules, membrane-coating granules, and intercellular cement. Characterization of the oral keratins as to their amino acid residues and types of bondings, as well as insight into the events transpiring when the prickle cell becomes keratinized, may not only shed light on the etiology of these lesions but also have prognostic implications.


The release of membrane antigens into culture by adult Schistosoma mansoni. Antigens sharing determinants with surface membranes and soluble proteins of adult Schistosoma mansoni have been detected in culture media after incubation of radioactively labelled worms. The relative quantities of these antigens were measured with specific antisera raised in rabbits and with serum from an immune rhesus monkey. It was found that 12-16% of TCA-precipitable radioactivity in the culture medium consisted of membrane antigens and 6-8% consisted of antigens sharing determinants with proteins found in the soluble fraction of adult worms. Over half the membrane antigens were present in particulate form, while other antigens were present in solution. Surface labelling the adult worms with [125I]confirmed that some of the particles in the culture medium were derived from the surface membrane of the adult worm and electron microscope examination of such particles showed that large membrane fragments were present. These results support the hypothesis that antibodies against schistosome membrane antigens are induced by particulate membrane antigens released by the parasite.


Ultrastructural comparison of the cell coat in normal and chronic lymphocytic leukaemic blood lymphocytes by Concanavalin A labelling and cationic staining. The ultrastructure of the cell coat of normal and chronic lymphocytic leukaemic (CLL) blood lymphocytes has been compared by several cytochemical techniques. In CLL lymphocytes, there is no modification of Concanavalin A labelling, whereas a difference of stainability is observed with at least one of the three cationic dyes used: colloidal iron, colloidal thorium, or ruthenium red, signifying a modification of anionic reactive sites. This physico-chemical surface anomaly is discussed with regard to other biochemical and electrophoretic results given by other authors.


The impact of surgery on body image.

The impact of surgery on body image. Surgery has an impact on the patient's view of himself and his body. It is within the professional nurse's realm to skillfully assess, make a nursing diagnosis, plan, and follow through on findings of body image assessment. Operating room nurses can expand their roles by contributing to this dimension of care. Because of their close contact with the patient, they are in an ideal situation to attend to this patient need. O.R. nurses need not be "little psychiatrists" in order to do this--only caring, intelligent, resourceful persons who use the nursing process and truly place the patient's welfare above all else.


Protein kinase and its regulatory effect on reverse transcriptase activity of Rous sarcoma virus. We have studied the effect of protein phosphokinase (EC 2.7.1.37; ATP:protein phosphotransferase) and phosphoprotein phosphatase (EC 3.1.3.16; phosphoprotein phosphohydrolase) on reverse transcriptase (RNA-dependent DNA nucleotidyltransferase) activity of Rous sarcoma virus. Protein kinase from Rous sarcoma virus-transformed chick embryo fibroblasts was purified by DEAE-cellulose chromatography, Sephadex gel filtration, and isoelectric focusing. Purified reverse transcriptase from Rouse sarcoma virus was preincubated with protein kinase and ATP under conditions allowing incorporation of phosphate into substrate protein. After the preincubation, reverse transcriptase activity was assayed in the presence of poly(rA).oligo(dT) as template. A 2- to 5-fold increase of reverse transcriptase activity was found after the preincubation of reverse transcriptase with protein kinase and ATP. Incubation of reverse transcriptase with heat-treated, inactive protein kinase and ATP had no effect on transcriptase activity. When the transcriptase preparation was incubated with protein kinase and [gamma-32P]ATP and subsequently purified by chromatography on phosphocellulose and Sephadex gel filtration, significant amounts of 32P-labeled proteins were found in the fractions exhibiting reverse transcriptase activity, suggesting 32P incorporation into transcriptase or transcriptase-associated proteins. A 20-60% decrease of reverse transcriptase activity was observed after incubation of reverse transcriptase with phosphatase. The results suggest that phosphorylative modification of reverse transcriptase may be critical in the regulation of reverse transcriptase-catalyzed DNA synthesis.


Absence of H-2 antigens capable of reacting with cytotoxic T cells on a teratoma line expressing a T/t locus antigen. An established cell line of murine teratoma cells (F9), which lacks serologically detectable H-2 that is determined by a wild-type T/t locus gene. These cells are not killed and do not react with cytotoxic T cells sensitized to H-2 antigens in a cell-mediated lympholysis assay. Modification of spleen cells from the strain or origin (129) of this teratoma line with trinitrobenzene sulfonic acid allows the generation of syngeneic killer cells that display a cytotoxic effect against trinitrophenyl-modified splenic targets, but not against trinitrophenyl-modified F9 targets. Thus, the F9 antigen is structurally similar to H-2b but does not act as a target antigen in the cell-mediated lympholysis assay for anti-H-2b cytotoxic T cells, nor does it crossreact with H-2b antigens at the T cell level.


The influence of lindane on enzymes activity in the tissues of rats on protein rich diet. Lindane in the dose of 1/10 LD50 given to rats on standard diet decreases the activity of 3.1.3.1. and 3.1.3.2. alkaline and acid phosphatases (AP and AcP) in blood serum, 2.6.1.1. glutamic oxalacetic transaminase (GOT), 2.6.1.2. glutamic pyruvic transaminase (GPT) in liver and 1.1.1.27 lactate dehydrogenase (LDH) in blood serum, kidney and liver. The same dose of lindane but given to rats on protein rich diet induces much stronger inactivation of the discussed enzymes, the stated differences being statistically significant. On determining LDH isoenzyme activity in homogenates from kidneys, no statistically significant differences were noted either in the groups treated with standard diet or those on protein rich diet, as compared with the controls not given lindane.


Oncornavirus-like particles in human skin cancers. A high-molecular-weight RNA encapsulated with an RNA-instructed DNA polymerase in particles possessing the density characteristic of the RNA tumor viruses has been detected in 13 out of 14 human malignant melanomas. The [3H]DNA synthesized by these particles in an endogenous reaction hybridizes to RNA extracted from the human melanoma particulate structures, but not to RNA from normal skin. Similar particles containing RNA and enzyme have been found in basal cell and squamous cell carcinomas of the skin. The RNA of the melanoma particles is easily distinguishable by hybridization from the RNAs found in the particles of the basal and squamous cell carcinomas.


Role of mitochondrial calcium transport in failing heart. Mitochondrial calcium uptake, but not binding, like microsomal calcium uptake in failing human hearts, was less than the control values for dog, rabbit, and hamster hearts. Decrease in mitochondrial calcium binding and uptake was observed in genetically myopathic hamsters (BIO 14.6) at early, moderate, and late stages of congestive heart failure. Inhibitors of mitochondrial calcium transport, Dicumarol, dinitrophenol, and sodium azide, were found to produce a rapid fall in contractility of the isolated rat heart. Inability of rat hearts to generate contractile force on perfusion with Na+- or K+-free medium was associated with an increase in mitochondrial calcium uptake. A dramatic increase in mitochondrial calcium uptake was observed on perfusing rat hearts with control medium after CA++-free medium. No change in mitochondrial calcium uptake was noted in acute ischemic dog myocardium or hypoxic rat heart in which contractile force was severely depressed. Both mitochondrial calcium transport and contractility were decreased on perfusing rat hearts with substrate-free medium; however, the change in calcium uptake was secondary to the fall in contractile force. Decrease in pH, ATP:ADP ratio, ATP6AMP ratio, and K+:Na+ ratio were found to reduce the dog heart mitochondrial calcium uptake. It is likely that various factors such as pH, ATP:ADP ration, ATP:AMP ratio, and K+ :Na+ ration, in addition to damage in mitochondrial structure, play an important role in inhibiting mitochondrial calcium transport in failing hearts. The results also suggest that alterations in mitochondrial calcium transport are dependent upon the degree and type of heart failure.


[Venous vascular changes in prostatic adenomyomatosis]. An important role should be attributed to the prostatic venous complex and to its pathology in the clinical aspects of prostate adenoma. This appears to be responsible for the acute retention of urine as well as for the hemorrhages that accompany the disease. The authors, on the occasion of 50 adenomectomies by the trans-vesical method, have carried out histological investigations on the excised tissues and made a correlation with the microscopic aspects of the peri-orificial urethra and of the prosthatic urethra, in connection with the changes noted in the venous system. The veins have displayed more or less important changes in all the cases. These consisted in stasis, lacunar dilatations or of the varicose type, inflammations or parietal modifications of a different origin. At the same time were noted signs of inflammation in the submucosa as well as in the muscular layer of the bladder wall, which appeared to be distrophic. The pathogenic role is stressed of the venous system in the developement of the clinical aspects especially in type II and III of a personal classification.


Drug-induced agranulocytosis. A survey of twenty-three episodes. Twenty-three episodes of drug-induced agranulocytosis admitted to the Beilinson Medical Center between 1960-1972 are reported. An increased incidence in patients admitted with this condition was noted over the years. Dipyrone (6 episodes in 4 patients) and chloramphenicol (5 episodes in 5 patients) were the drugs most commonly associated with this condition. Four patients died in septic shock. The increased incidence of hospital-admitted patients with drug-induced agranulocytosis is related to the increased use of drugs in the Israeli population.


Serum proteins in diseases of the liver. In 9 groups of liver diseases, 11 serum protein parameters were studied. Prealbumin, retinol-binding protein, albumin, alpha-lipoprotein and Normotest (NT) were usually highly intercorrelated and separated best among groups with different types of functional impairment. Haptoglobin, C3 and total iron-binding capacity were probably also sometimes reduced by restricted protein synthesis but appeared to be more easily affected by other factors, alpha1-antitrypsin was often increased in different liver diseases, but a pattern compatible with the "acute-phase reaction" was regularly present only in hepatic tumors. Bile retention was often accompanied by relatively high levels of ceruloplasmin, C3, and alpha-lipoprotein and by high NT values.


Antibody response in C3H mice injected with CBA lymphoid cells as detected by membrane immunofluorescent staining. Lymphocytes from CBA mice are strongly responsive to cells from the H-2-identical strain C3H in vitro (MLC), whereas C3H lymphocytes are poorly reactive against CBA cells. Immunization of CBA mice with C3H lymphocytes did not yield any detectable specific antibodies. On the other hand, C3H mice immunized with CBA cells produced specific antibodies as detected by membrane immunofluorescence. Mice of the strains AKR and DBA/2 also possess this specific membrane alloantigen. We thus conclude that it is now possible to discriminate among lymphocytes of CBA and C3H origin.


Isolation of "speckled" nuclear antigen reactive with autoantibodies in patients with cancer and autoimmune diseases. An antigenic substance reactive with autoantibodies found in patients with cancer and autoimmune diseases was isolated from calf thymus. The purification procedure included extraction of the tissues with acetone powder, batch and column chromatography on DEAE-resins, ammonium sulfate precipitation, gel filtration on Sephadex G-200, and affinity chromatography on antibody-Sepharose 4B. Indirect immunofluorescence examination of cultured human embryo cells, using the serum of patients with nasopharyngeal cancer, showed a speckled nuclear pattern. The antigenic factor was a soluble acidic protein with a pI of 5.0 and a molecular weight of 250,000. The antigenic activities of this purified substance from calf thymus, and of the material on the cultured human embryo cells, were destroyed by proteases, ribonuclease, and alkaline phosphatase. The determinants were also sensitive to periodate oxidation. Thermal stability to 60 degree C and pH stability between 2.6 and 8.5 were demonstrated. Cross-reactivity of the antigenic substance with antibodies isolated from individuals with cancer and autoimmune diseases was shown by immunofluorescence, with appropriate blocking and absorption controls.


Incompatibility at irrelevant H-2 specificities augments in vivo stimulation of alloaggressive cells. Lymphoid cells of mice were sensitized in vivo either by H-2 strain-specific tumor allografts or by activation in lethally irradiated F1 hybrids and tested for cytotoxicity on 51Cr-labeled target cells. The release of 51Cr varied linearly with the logarithm to the proportion of effector lymphocytes to target cells and with the time of interaction. The release of 51Cr was immunologically specific and restricted to H-2 incompatibility. Spleen cells immune to public specificities of the target genotype were not cytotoxic. However, lymphoid cells immune to only one private specificity of a third-party target genotype were highly cytotoxic. The cytotoxicity of activated thymus cells on target cells sharing one private specificity with the genotype used for sensitization was significantly enhanced when the effector thymocytes were activated also against H-2 specificities not shared by the target strain. The results suggest that gene products that facilitate sensitization of effector cells may be determined both by the H-2K and the H-2D end of the H-2 complex. It remains to be shown whether the products of these loci, operating during sensitization in vivo, are body-wide correlated to the lymphocyte-defined specificities detectable during the mixed leukocyte culture interaction.


H-2 private specificity of in vivo-sensitized lymphocytes studied by adsorption on fibroblast monolayers. Spleen cells or thymocytes immune to one H-2 genotype are cytotoxic to allogeneic target cells of a third-party genotype, provided the target shares private specificities determined by either the H-2K or the H-2D locus of the H-2 complex with the H-2 genotype used for sensitization in vivo. The present results on elimination of cytotoxicity to specificities determined by one of the H-2 loci after adsorption of the immune lymphoid cells onto fibroblasts bearing this specificity suggest a state of diversity among effector lymphocytes reactive to the antigens determined by either the H-2K or the H-2D locus of the H-2 complex. Thymus cells activated in vivo were less specifically adsorbable than spleen cells of tumor-allografted mice.


Isolation and characterization of amyloid-related serum protein SAA as a low molecular weight protein. With direct immunoprecipitation or gel filtration under dissociating conditions, amyloid-related serum protein SAA has been isolated as a low molecular weight protein from the serum of two patients with rheumatoid arthritis but without known amyloidosis. The isolated protein SAA showed antigenic identity and an amino acid composition that was similar, but not identical, with isolated fibril protein AA. Molecular weight estimations suggest that protein SAA is approximately 50% larger than protein AA and has a molecular weight of 14,000-15,000 daltons. Preliminary results indicate that protein SAA from a patient with amyloidosis has a similar small molecular weight subunit.


Evolution of type C viral genes: origin of feline leukemia virus. Reiterated gene sequences related to the RNA of feline leukemia virus (FeLV) are detected in all tissues of domestic cats and their close Felis relatives but not in more distantly related Felis species. Partially homologous viral gene sequences are found in rodent, and particularly rat, DNA. Together with the immunologic relationships observed between FeLV and endogenous rodent type C viruses, the results lead to the conclusion that FeLV-related genes were transmitted from a rodent to cat ancestor and have been perpetuated in the germ line of cats.


Air pollution and health.

Air pollution and health. The effects of air pollution on human health are reviewed. Data from toxicology, epidemiology, clinical and laboratory exposures are presented as a basis for an emerging etiology. Sulfur dioxide, suspended particulates, nitrogen dioxide, photochemical oxidants, and carbon monoxide are examined as stress agents to the cardio-pulmonary system.


Effect of anabolic steroids on plasma antithrombin III. alpha2 macroglobulin and alpha1 antitrypsin levels. The effect of seven different anabolic steroids (Ethyloestrenol, Methenolone acetate, Norethandrolone, Methylandrostenediol, Oxymetholone, Methandienone, and Stanozolol) on three alpha-globulin antiprotease inhibitors of thrombin and plasmin was studied in men with ischaemic heart disease. In distinct contrast to the oral contraceptives, five of the six 17-alpha-alkylated anabolic steroids studied produced increased plasma Antithrombin III levels and five produced decreased levels of plasma alpha2-macroglobulin. The effect on plasma alpha1-antitrypsin levels was less clear-cut but three of the steroids examined produced significantly elevated levels. The increased plasma fibrinolytic activity which the 17-alpha-alkylated anabolic steroids induce is therefore unlikely to be secondary to disseminated intravascular coagulation.


Antithrombin activity of intact human platelets. Antithrombin activity has been identified in intact washed human platelets. An apparent activity was demonstrated at platelet concentrations above 0.31 X 10(9)/ml, when platelet suspensions were incubated with 2.0 NIH units/ml of thrombin. Neither red cells nor white cells revealed antithrombin activity. No significant loss of the platelet antithrombin activity was observed after ten successive washings or after treatment of platelets with antibodies to antithrombin III or alpha2-macroglobulin. Almost the same amount of antithrombin activity as normal platelets was demonstrated in the platelets from an afibrinogenemic patient. Pre-treatment of platelets with trypsin, papain, and neuroaminidase reduced the activity significantly, whereas lipase was without effect. The platelet antithrombin reacted with thrombin in less than 3 seconds, and this rapid reaction of platelet antithrombin was different from that of plasma antithrombin III or fibrinogen. The thrombin-like clotting activity of ancrod was inhibited by fibrinogen but not platelets. Also, unlike plasma antithrombin III or fibrinogen, brief exposure to heat (56 degrees C or 60 degrees C) reduced considerable amounts of platelet antithrombin activity. These results suggest that platelets possess a specific antithrombin with different characteristics from other known antithrombins.


An estimation of the recombination fraction between the MLC locus and the FOUR locus. Thirty-nine families with 167 children were typed for HL-A and studied in the MLC test. Two maternal recombinations between the FOUR and the MLC locus in two different families were found. An estimate of the recombination fraction between the FOUR and the MLC locus was calculated.


HL-A27 and anterior uveitis.

HL-A27 and anterior uveitis. HL-A types were determined in 90 successive patients with non-granulomatous uveitis. Fifty-one were HL-A27 positive (55.7%) compared to 8.2% of controls. Of 16 patients with ankylosing spondylitis, 13 were HL-A27 positive, as were two patients with a history of Reiter's syndrome. Twenty-eight patients were HL-A27 positive but had no evidence of rheumatic disease. The findings are discussed in relation to the possible pathogenesis of uveitis.


Definition in man of a polymorphic system of the normal colonic secretions. A study conducted in 30 normal human colons, obtained from cadaveric kidney donors, has evidenced the presence of two polymorphic antigenic specificities, W and Z, in the secretory cells of the colon mucosa. Three phenotypes have been demonstrated so far: W-Z- (frequency: 0.17), W-Z+ (frequency: 0.23), and W+Z+ (frequency: 0.60). Specific anti-WZ and anti-W alloantibodies, independent of anti-A and B agglutinins, were found in normal sera from blood donors. No apparent correlation was found between the WZ specificities and the ABH Lewis specificities, the other blood group systems specificities, and the leucocyte group (HL-A) specificities.


Identification of five lymphocyte activating determinants in man. Eleven putative LD-1 locus homozygous cell donors were found by MLC tests in non-consanguineous families. Lymphocytes from each of them were used as stimulating typing cells in MLC tests together with responding cells from the other homozygous cell donors and from 45 random unrelated individuals. Four of the stimulating typing cells were found to identify a determinant in non-random association with HL-A7; LD-7a, three other cells typed for a determinant non-randomly associated with HL-A8; LD-8a, and one cell seems to identify LD-W5 in non-random association with W5. Two possible additional LD-1 determinants, LD-oh and LD-om, were less well defined with two of the cells. The combined gene frequency of the five possible LD-1 determinants is approximately 0.45 among Norwegians.


Comparison between the retrograde axonal transport of nerve growth factor and tetanus toxin in motor, sensory and adrenergic neurons. In previous studies it has been shown that nerve growth factor (NGF) is taken up with high selectivity by adrenergic and sensory nerve terminals and is transported retrogradely to the corresponding cell bodies by a colchicine sensitive mechanism 10,11,23. The present study was designed to investigate whether this retrograde transport of NGF depends on properties of the nerve terminals which are common to all the neurons or restricted to those which respond to NGF either during the whole life cycle (adrenergic neurons) or during a restricted period of embryonic development (sensory neurons). In order to investigate the retrograde transport of NGF in motor neurons we injected [125I]NGF into the musculus deltoideus and measured the side differences of accumulation of radioactivity in the spinal cord (C6-C8) from 4-48 h. At no time was there a preferential accumulation of radioactivity on the injected side. In contrast, tetanus toxin was accumulated preferentially on the injected side and an approximate rate of transport of 7.5 mm/h was calculated. Astonishingly there was also a retrograde transport of tetanus toxin in sensory and adrenergic neurons. The rate of transport was identical to that of NGF and the transport could be blocked by transection of the corresponding nerve fibers and local administration of colchicine. After unilateral injection of [125I]tetanus toxin into the forepaw or the musculus deltoideus light microscopic autoradiographs revealed heavily labeled neuronal cell bodies in the dorsal root ganglia or the ventrolateral spinal cord of the injected side. It is concluded that the retrograde transport of [125I]NGF depends on properties of the neuronal membrane which are specific for adrenergic and sensory neurons, whereas that of tetanus toxin is determined by features which are common to all, or at least to all peripheral, neurons. The fact that the rate of transport for both NGF and tetanus toxin is identical in all examined neurons, supports the hypothesis that the specificity of retrograde transport is determined by specific uptake sites in the neuronal membrane whereas the retrograde transport system is non-specific.


Masking of pleomorphic glycogen sites by methanolic uranyl acetate. Rat liver tissue was fixed in 2.5% glutaraldehyde buffered with cacodylic acid (pH 7.3) for 2 hr, washed twice in buffer, and postfixed in 2% osmium tetroxide at 4 C for 1 hr. The tissue then was dehydrated, infiltrated with and embedded in Epon by routine procedures. The ultrathin sections from this tissue, when stained with spectroscopic grade methanol saturated with uranyl acetate (SMUA) for 1 min followed by aqueous lead citrate (PbCi) (Reynolds 1963) for 5 min at room temperature, showed a uniform staining of all major cellular components except glycogen. The SMUA appeared to be specific for ribonuceloprotein granules, rendering them more prominent in the cytoplasm due to the lack of glycogen staining. The question of glycogen removal from the sections due to SMUA treatment was evulated using various extractions and staining methods. It appeared that SMUA pretreatment alters the subsequent binding ability of lead salts, resulting in lack of glycogen staining, although it does not remove the glycogen from the sections.


Studies in gram staining.

Studies in gram staining. Gram-negative bacteria stained with crystal violet are decolorized by 95% alcohol within 2 min, whereas Gram-positive bacteria require at least 3 min treatment. Aqueous solutions of safranin, neutral red, and fuschsin replace crystal violet from stained Gram-positive bacteria more quickly than alcohol alone, and alcoholic solutions of these counterstains are in most cases still more effective.  Treatment of crystal violet-stained organisms with alcoholic safranin (0.25%) for 15 sec will distinguish Gram-positive bacteria (violet) from Gram-negative bacteria (pink). Alcohol containing very low concentrations of iodine generally decolorizes crystal violet-stained Gram-positive bacteria more quickly than alcohol alone. Increasing concentrations of iodine in alcohol reduce the rate of decolorization of stained bacteria, but stained Gram-negative bacteria are still readily decolorized. The addition of 0.1% iodine to alcohol increases the rate of extraction of crystal violet by alcohol from Gram-negative organisms, but delays extraction of dye from Gram-positive organisms, and this applies when counterstain is also present. A two-solution modification of Gram staining is described in which crystal violet-stained bacteria are treated with an alcoholic solution of safranin, fuchsin, and iodine.


Staining method for whole-body autoradiography. Sagittal whole-body sections of frozen mice were cut on a hydraulicly driven microtome in a cryostat at--15 C by applying cotton or nylon-backed adhesive tape to the mouse before cutting. Section thickness was 20 mu. The sections, still adhering to the tape, were dried in the cryostat (-15C) under atmospheric pressure. After autoradiography, the sections were pressed to a glass slide spread with a mixture of albumin and glycerin. The slide was immersed in xylene at 30 C for 15 min. The tape was then removed from the slide, where the section remained to be stained with hematoxylin-eosin. The section thus obtained enabled the tissue histology to be related to the autoradiogram. This method may also be applied to histochemical studies of substances insoluble in xylene.


Plastic sectioning for light microscopy of Pyrenomycetes. In preparation for light microscopy, ascocarps of Sordaria fimicola Ces. & DeNot. were embedded in Spurr's medium and sectioned at 1-1.5 mum on an ultramicrotome. Sections were floated on Giemsa staining solution at 60 C for 10-30 min, washed in distilled water, affixed to slides by drying, and mounted in immersion oil. Best preservation of the delicate sterile tissues of the centrum was obtained by fixation in 1% KMnO4 for 2.5-3 hr, followed by the Giemsa stain. This method is suggested for future studies on the morphology of perithecial ascomycetes.


Thin layer chromatography of certain preformed metal complex dyes used in biological staining. Thin-layer chromatographic systems are described for the analysis of various performed metal complex dyes (aluminon-chromium (III), carminic acid-aluminum, carminic acid-chromium (III), carminic acid-iron (III), celestine blue-chromium (III), gallamine blue-chromium (III), gallocyanin-chromium (III), hematein-aluminum, hematein-chromium (III), purpurin-aluminum) and their parent dyes. Certain of these dyes have also been analysed by agar-gel electrophoresis or gel-filtration chromatography. The merits of the three analytical methods are discussed.


Evaluation of six fluorescent protein stains for use in flow microfluorometry. Flow microfluorometric (FMF) analysis of stained cells has provided protein distribution histograms for large populations of cells. Spectral data and staining protocols were evaluated for six fluorescent protein dyes suggested for staining cells in liquid suspension. The requirements for dyes and/or staining protocol included minimal cell clumping and cell loss, near-optimal dye excitation at existing laser wavelengths, and tenacity of the dye/protein interaction. These criteria were best satisfied by fluorescein isothiocyanate (FITC) and rhodamine B isothiocyanate (RITC). Both fluorescamine and 8-aniline-1-naphthalene sulfonic acid (ANSA) showed potential applicability for use in systems where excitation wavelengths in the ultraviolet range are available. Protein staining with fluorescamine was extremely rapid. Brilliant sulfaflavine and 1-dimethyl-aminonaphthalene-5-sulfonyl chloride (DANSYL) were found unsatisfactory in these studies, since the former dye tended to diffuse from the cells, while the latter induced excessive cell clumping and cell loss. These techniques have application to immunofluorescence analysis and can also be profitably employed in dual-parameter analysis systems in connection with double-staining techniques for simultaneous DNA and protein analysis.


[Studies on combined lesions. 22. Studies on serum proteins by means of CAF-electrophoresis in mice, treated with whole body radiation and with open skin wounds]. After combined injuries, much more pronounced changes in the protein composition of serum develop than simply after skin wounding or irradiation. A decrease was found in the prealbumin, albumin, alpha1-globulin and gamma-globulin fractions while the alpha2-globulin and beta-globulin fractions increased. If skin wounds were inflicted prior or almost simultaneously to irradiation, the serum protein changes as induced by irradiation become normalized earlier. I1 skin wounds were inflicted after irradiation they caused very pronounced alteration in the protein picture which develops in a course parallel to the increasing lethality. Only if the skin wounds were inflicted 21 days after irradiation, that they appeared to have nearly no influence in the form of augmenting protein changes. The gamma-globulin content increased considerably after the 14th day after irradiation. An additional skin wound, however, caused a depression of the gamma-globulins; but the values were still significantly higher than normal.


Serum factors and red cell enzymes in Carib and Arowak Indians from Surinam. The results of the electrophoretic phenotyping of some genetic markers (haptoglobin, group specific component, transferrin, haemoglobin, glucose-6-phosphate dehydrogenase and 6-phospho-gluconate dehydrogenase) in two tribal Indian populations from Surinam are presented. Most of the gene frequencies fit well into the pattern of frequencies of the Amerindian Carib group. The finding of Hb AS and GDA in a small number of individuals, mainly Caribs, demonstrates some admixture by Negroes.


Evaluation of the crossed-over electrophoresis test for the immunodiagnosis of human hydatid disease. The crossed-over electrophoresis (COE) test for hydatidosis was evaluated with sera from preoperative, surgically-confirmed hydatidosis cases, postoperative hydatidosis patients, healthy donors and persons with other parasitic and non-parasitic diseases. The sensitivity and specificity of the test varied with the use of concentrated or unconcentrated serum and when test positivity was based on readings carried out before or after citrate treatment of slides or after their staining. Although the sensitivity of the COE test was higher than that obtained by the immunoelectrophoresis (IEP) test, it was not possible to differentiate hydatid from non-hydatid sera by the former technique. The IEP test based on the detection of the Echinococcus granulosus arc 5 as criterion of positivity was found to be the test of choice for this purpose. No false positive results were obtained in non-hydatid sera.


Application of the immunoelectrophoresis test for hydatidosis in patients with a presumptive diagnosis of the disease. The Echinococcus granulosus diagnostic arc 5 was detected by the immunoelectrophoresis (IEP) test in 43 of 51 sera from patients with a presumptive clinical diagnosis of hydatid disease when stained slides were examined. In 22 of these, however, the arc 5 was readily recognized in the reading following citrate treatment of the slide. The routine reading of slides after 24 and 48 hours of incubation is recommended in an attempt to provide the clinician with an earlier immunological confirmation of hydatidosis by the IEP test. The definitive reading of the stained slide has the added advantage of detecting a larger number of uncharacterized precipitation bands which may be of value in preoperative lydatid sera lacking the diagnostic arc and in the post-operatory serological monitoring of hydatid cases.


Prostatitis: Man's hidden infection.

Prostatitis: Man's hidden infection. Prostatitis exists when inflammation of prostatic glands and tissues results from infection or allergy. Gram-positive and negative bacteria cause most prostatic infections, but infections may also be caused by fungi, mycoplasma, viruses, and other nonbacterial infecting agents. Precise diagnostic localization of infection to prostatic glands is accomplished by obtaining divided urinary specimens and prostatic fluid and observing numbers of bacteria (or other infecting agents) present in each specimen. Treatment of prostatitis remains difficult because of several factors: patients may lack the normal prostatic antibacterial factors and only a few commonly used antibiotics pass the plasma-prostate barrier and enter prostatic fluid. For proper therapy, one must select antibiotics known to penetrate into prostate tissue and fluid and to which the infecting organism is demonstrated to be sensitive. Even so, optimal cure rates following antibiotic therapy seem no better than 33 per cent. Nonspecific methods of treatment such as surgical excision of prostatic tissue, prostatic massage, sitz baths, relaxants, and supportive psychologic therapy contribute to the rehabilitation of patients with prostatitis. Relapse or recurrence of prostatitis is frequent. Longterm (in excess of six months) follow-up is required to ascertain cure.


Is colony count necessary?

Is colony count necessary? Evidence presented herein suggests that: (1) If the Gram stain of the spun urinary sediment is negative, there is no need to do a culture, sensitivity test, and colony count since significant bacteriuria and urinary infection are not present. There are very few false negative results. (2) Since there are many false positive Gram stains, the test is not specific. A positive Gram stain of the spun urinary sediment does not mean that bacteriuria is present. (3) The test is very sensitive in that practically all bacteriuric subjects had a positive Gram stain. (4) Because the Gram stain of the spun urinary sediment is so sensitive, a positive spun urinary sediment and culture should be treated regardless of the colony count.


Megestrol acetate in treatment of benign prostatic hypertrophy. In this study we found no significant effect on benign prostatic hypertrophy due to megestrol using standard clinical criteria. However, there is evidence using urinary drop spectrometer data which makes one suspect that megestrol does have a positive effect. If there is an effect, it is apparently so small as to be undetectable using the clinical protocol of this investigation. Since the urodynamic evidence does indicate a possibility of a positive effect, it appears reasonable to investigate further using a different protocol - perhaps a higher dosage and/or a more controlled test population.


Massive prostatic hypertrophy.

Massive prostatic hypertrophy. An unusual case is presented in which an enormously enlarged prostate gland, producing minimal urinary tract symptoms and changes, was removed via the retropubic route without operative complications and with a benign postoperative course. Applicability of the retropubic procedure in such cases is emphasized. A brief review of the literature is tabulated.


Periprostatic abscess. Unusual complication of transurethral prostatectomy. Many large series analyzing the results and complications of transurethral prostatectomy have failed to mention the occurrence of periprostatic abscess. A case is described which followed perforation of the posterior capsule at the time of transurethral prostatic resection. This complication was successfully managed by transperineal needle aspiration and high-dosage antibiotic therapy.


[Surgical aspects of the acid-producing function of the stomach in peptic ulcer]. In the paper, the results of studies on the acid-producing function of the stomach in ulcerous disease and its dependence on regulatory disturbances (neuro-humoral) and the type of an irritant are analysed. It was found that patients with ulcerous disease were characterized by dysfunction of the vegetative nervous system, and as a result of it there is a pathological irritability of acid-producing cells being one of causes of fluctuations in acidity at all stages of gastric secretion. It is concluded that gastric secretion may not be used in pathogenetic foundation of surgical methods of treatment for ulcerous disease, and for this purpose one should act in accordance with the state of neuro-humoral mechanisms of regulation of the gastric function concerned.


[Experimental study of a combination preparation of a ferrodextran complex, gamma-globulin, trace elements and vitamins]. A combined preparation was produced, containing the Bulgarian ferrodextran complex, edema-disease gamma-globulin, microelements (Co, Mn, Cu), and vitamins (B1, B6, PP), pro uso veterinario. It was found that the product (B-50), kept under ordinary conditions in the course of one year, does not change its physicochemical properties and is not distinguished substantially by toxicity (Fe3+/kg liveweight) from the initial ferrodextran complex, but is resorbed more slowly following its muscular application to rabbits. B50 combines the properties of the fast-resorbing ferrodextran preparations giving slight local coloration with those of preparations having antianemic, growth-stimulating, and resistance enhancing effects.


The effect of flavins and enzyme inhibitors on 4-nitrobenzoic acid reductase and azo reductase of Ascaris lumbricoides var suum. 1. The effects of inhibitors and activators on the azo- and nitro-reductases of Ascaris lumbricoides var suum have been investigated. Both types of reduction were inhibited by FAD, FMN, riboflavin, allopurinol, dicoumarol, 5-nitro-2-furaldehyde, azide and cyanide at concentrations of 1 mM. Neither reaction was inhibited by menadione, nitrofurantoin, SKF 525-A or fluoride. Both reactions were stimulated by addition of hypoxanthine. 2. The enzyme preparation contained no detectable aldehyde oxidase or xanthine oxidase activity. 3. The differences in the effects of flavins and inhibitors on mammalian and nematode azo- and nitro-reductases might have practical significance in the development of anthelmintic synergists.


Photobiological behaviour of bacteria and phages supplemented with aza-analogoues of nucleic acid bases. The photochemical stability of anomalous nucleic acid bases of the azatype, 5-azacytosine (I), 5-azacytidine (II), 6-azacytosine (III), 6-azacytidine (IV), 6-azathymine (V), 6-azauracil (VI), and 8-aza-adenine (VII) to U. V. light of the wavelength 254 nm differs from the U. V. stability of the normal constituents. Changes of the U.V. inactivation of Escherichia coli K12 C600, E. coli B, Bacillus cereus, as well as E. coli phages gamma cb2 and gamma b2b5 supplemented with azaderivatives prior to irradiation were investigated. It was found that I, II, III, IV, and VII are more, V and VI less sensitive to U. V. light compared with corresponding natural nucleic acid bases. Their changed U. V. sensitivities are reflected in the survival curves after U. V. -irradiation in as far as azabases are incorporated into the nucleic acids in vivo. This explains the increase in U.V. sensitivity of E. coli K12 C600, E. coli B, and B. cereus supplemented with I, II, III, IV, and VII and the decrease in U.V. sensitivity of Streptococcus faecalis supplemented with V (the latter information was taken from Gunther and Prusoff 1967). The lack of any significant influence on inactivation curves of E. coli K12 C600 by V and VI, and on E. coli phages gamma cb2 and gamma c2b5 by II, is discussed in terms of too small incorporation rates. No discrimination was put forward with respect to DNA and RNA incorporation.


[Maternal serum-alpha-fetoprotein for monitoring risk-pregnancies (author's transl)]. This study confirms essentially the results of other investigators who found a good correlation between fetal risk and maternal AFP level. This adds an immuno-chemical technique to well-known methods of monitoring risk-pregnancies (ultra-sound, HPL, estrogenes) which enables us to measure a specific fetal metabolic product, alpha-feto-protein, in amniotic fluid, umbilical blood and maternal serum.


[Immunohistochemical studies on non neoplastic and neoplastic gastric mucosa. Determination of embryonic and specific antigens (author's transl)]. The distributions of acid alpha1-glycoprotein, alpha1-fetoprotein, beta-galactosidase and gastrin in gastric carcinoma and gastric ulcer as well as in the neighbourhood of these lesions were studied by means of immunohistochemical methods on imprint preparation. We could not find significant differences between gastric carcinoma and the nonneoplastic lesions, except for the acid alpha1-glycoprotein. The results of this first study indicate that the immunochemical and immunohistological assay of acid alpha1-glycoprotein might be of practical value in diagnosing malignant changes of gastric mucosa.


[Low molecular weight IgM in human sera (author's transl)]. During evolution of vertebrates 7S-IgM-antibodies are the first developed specific antibodies. In man monomeric IgM is not observed in sera of healthy newborns, children or adults. The detection of 7S-IgM in monoclonal gammopathies (Waldenström's disease 71.4%, IgA-myeloma 47.8%, IgG-myeloma 24.2%, benigne monoclonal IgA-gammopathy 37.5%, benigne monoclonal IgG-gammopathy 15.5%) autoimmune (SLE 26.6%, multiple sclerosis 18%, chronic atrophic gastritis 14%, chronic aggressive hepatitis 35%) and in some infectious diseases (virus hepatitis 25%) is believed to be an atavistic primary IgM response, occurring in case of elevated humoral immune reactions and disorders of lymphatic tissues.


[Effect of sparteine sulfate on the predamaged conduction system of the heart]. Antiarrhythmic drugs are known to cause AV-blockade. In animals and healthy humans the alcaloid of the gorse sparteine sulphate has been reported not to cause those side effects. We have studied in 10 patients with predamaged conduction system the grade of AV-blockade, the AV-interval and the intraventricular excitation spread by e.c.g. after i.v. injection of 200 mg sparteine sulphate (ajmalin, 50 mg i.v. as control). In 6 out of 10 patients no side effects have been observed. In 4 patients both sparteine and ajmalin injection caused higher graded AV-blockade. Our results suggest that sparteine sulphate like other antiarrhythmic drugs should not be administered to patients with a predamaged conduction system.


[Genetic aspects in anencephalus].

[Genetic aspects in anencephalus]. According to one case of repeated anencephalic pregnancy the etiology of anencephaly has been discussed. The possibilities of prevention of repeated anencephalic pregnancies are described. To determine the alpha-I-fetoprotein in amniotic fluid and the ultrasonic diagnosis are most important in risk pregnancies. The significance of genetic counselling and examination in definitive risk population is advised.


Investigations on the carcinogenic burden by air pollution in man. XIII. Assessment of the contribution of passenger cars to air pollution by carcinogenic polycylic hydrocarbons. A total of 100 passenger cars were tested with regard to the amount of polycyclic aromatic hydrocarbons (PAH) emitted during the EUROPA-Test (E.-Test, simulate city driving; 4 times 195 s). As determined by frequency of registration, the 20 most common car models were chosen. Each model was represented by 5 cars. The total amount of selected 14 PAH emitted by all test vehicles during an E.-test is in the range of 1-16 mg. As can be seen from the average of fuel consumption (409.4 g/E.-test) and benzo(a)pyrene emission (41.6 mug/E.-test), 1000 kg of burned fuel yield 101 mg of benzo(a)pyrene. Based on the consumption of gasoline in 1973 in West Germany (18508200 tons), an annual amount of 1.85 tons of benzo(a)pyrene is produced by gas engine vehicles. However, the biological effect of the automobile exhaust is still larger because it contains additional carcinogenic PAH. - A statistical evaluation of the results shows that different car models can not be distinguish by their PAH emission. When evaluating individual vehicles after 5 repeated E.-tests, the margin of error for any single PAH is between 6.3-10.9% (variation coefficient) for this car. A larger margin of error is obtained by pooling 5 different vehicles of the same model.


[Experiences with the macrophage electrophoresis mobility test (MEM test) in the diagnosis of malignant gynecological diseases]. In 1970, Field and Caspary reported that lymphocytes from patients with a malignant disease could be stimulated by an encephalitogenic factor, the myelin basic protein from human brain. After in vitro incubation with this protein the stimulated lymphocytes release a factor ("macrophage slowing factor") which reduces the electrophoretic mobility of guinea-pig macrophages. In general, this effect was not found in lymphocytes from patients with non-malignant disease. On the base of this unexpected finding the hitherto most successful way to an universal and early in vitro test for cancer detection was established. Experiences are reported with the macrophage-electrophoretic-mobility-test (MEM-test) at 38 patients with malignant and 16 patients with non-malignant gynaecological disease in various stages of disease and treatment. The test was positive in all malignant diseases. Significance and perspectives of the test system with respect to the tumour diagnostic were discussed.


[The effect of fluoridated phenylethanolamines on hyperglycemia induced by catecholamines in the rat]. 10 compounds from the 2.4- and 3.4-difluorinated phenylethanol-amines series were tested for their antagonistic action against a hyperglycemia induced by catecholamines in rats, and the ED50 and AD50 values were determined. All the substances acted beta-adrenolytically, with the glycogenolysis enhanced by isoproterenol being blocked more potently by 3.4-difluorophenylethanolamines than by the corresponding 2.4-difluoroderivatives. An exception in the series is 2.4-difluoro-n-butylnoradrenalin, which acts 10fold more beta-adrenolytically than the 3.4-difluoroderivative, and has 3 times the effect of the comparative substance dichloroisoproterenol.


Papillary thyroid carcinoma in Denmark 1943-68. II. Treatment and survival. A comparison of the present non-selected, nation-wide material with series from hospitals abroad indicates that the prognosis may be improved by more extensive operations on the thyroid gland, avoiding complications such as paralysis of the recurrent laryngeal nerve and tetany. The surgical efforts should also be supplemented with postoperative suppression of the TSH production. In seeking to explain the differences from American data, it should not be overlooked that papillary thyroid carcinoma may be inclined to take a more serious course in Denmark than in a number of other countries. Moreover, a nation-wide material must by necessity show less favorable results than data from specialized units. In the present retrospective study it was not possible to report 20- and 30-year survival rates. This is a task for the future, like the planning of prospective studies which, in the case of a disease as rare as papillary thyroid carcinoma, should be established on an international basis.


Squamous-cell carcinoma of the anus.

Squamous-cell carcinoma of the anus. Twenty-nine patients treated for squamous-cell carcinoma of the anus were studied. Fifteen patients (52%) died from recurrent disease within 3 years of treatment, including patients treated palliatively only. Among 24 patients treated curatively 19 had an abdominoperineal resection. Ten of these patients were alive without recurrence 3-11 years after the operation. Of 5 patients treated with local excision, 4 were alive without recurrence at follow-up 3-6 years later. The prognosis and the type of treatment in relation to the location of the tumour-in the anal canal or at the anal margin-are discussed.


Embryology of the epidermis: ultrastructural aspects. II. Period of differentiation in the mouse with mammalian comparisons. A detailed light and electron microscopic study of the cellular morphology of the epidermis in the 13 through 16 day mouse fetus reveals that an occasional intermediate cell is interposed between the basal and peridermal layers on day 13. All layers are mitotically active. Tonofilaments, unassociated with desmosomes, are present within the basal cell cytoplasm and the mitotic axis of the basal cells has changed from a parallel to a perpendicular plane with respect to the epidermal surface. At 14 days, a complete stratum intermedium, composed of one or two cell layers, is present. Rarely, developing hemidesmosomes are observed. Pools of glycogen are present in all cells below the periderm. The periderm is dense and no longer mitotically active. The skein of filaments, present in the inferior cytoplasmic region of the basal cells on days 12 and 13, is now absent. In the 15 day fetus, numerous developing hemidesmosomes are present. The stratum intermedium contains three to four layers of cells, and filaments are located deep within the cytoplasm of these intermediate cells. Rarely, a few developing keratohyalin granules and keratinosomes are present. A stratum intermedium is no longer present in the 16 day fetus. This region is now composed of a stratum spinosum and a stratum granulosum. Numerous keratinosomes are located in the upper stratum spinosum and lower stratum granulosum. The cells in the stratum granulosum are nucleated and the uppermost cells contain large keratohyalin granules. Three heterogeneous and one homogeneous type of keratohyalin granule is described. Dense bodies are present within mitochondria, nuclei, glycogen pools and the peridermal cytoplasm. The periderm is no longer dense and glycogen and keratohyalin granules are not observed in this layer.


Alteration in the surface morphology of synchronized B-16 melanoma cell during the cell cycle. B-16 melanoma cells were synchronized for G1-S periods by mitotic shake-off and S-G2 periods by thymidine block. The surface morphology of the B-16 melanoma at low density partially confluent culures revealed that, as in other cell systems investigated, the surface morphology could be correlated with four periods to cell cycle: G1, S, G2 and M. G1 cells were rounded and possessed microvilli, blebs and ruffles (late G1). During S period, blebs and microvilli diminished and disappeared, but ruffles were more evident. Late G2 cells acquired microvilli, surface blebs, and extended filopodia and began to thicken and round themselves for mitosis.


Urinary excretion of 5-S-cysteinyldopa in patients with primary melanoma or melanoma metastasis. Urinary excretion of 5-S-cysteinyldopa was studied in 9 patients with primary melanoma. All had 5-S-cysteinyldopa excretion in the normal range. In 8 of the patients excretion values decreased after removal of the tumour. Twenty-four patients with clinical signs of melanoma metastasis were examined for 5-S-cysteinyldopa and dopa+dopamine in the urine. 16 of the 24 had pathologically increased excretion of 5-S-cysteinyldopa and 7 of the 24 had pathological excretion of dopa+dopamine. Six of the latter belonged to the group with increased 5-S-cysteinyldopa excretion and one patient had a borderline value of 5-S-cysteinyldopa. Determination of 5-S-cysteinyldopa seems to be of value in the follow-up of patients operated on for primary melanoma.


Use of affinity chromatography for purification of tyrosinase. The possibility of using affinity chromatography for the purification of tyrosinase was explored. When purified mushroom tyrosinase was employed, almost all tyrosinase became bound to Sepharose containing 3-iodotyrosine, an inhibitor of tyrosinase. When crude extracts from B16 melanoma were employed, partial purification of tyrosinase and separation of two or possibly three forms of tyrosinase could be obtained. The results indicate that affinity chromatography could possibly be employed for the purification of tyrosinase during the final stages of the purification procedures.


B lymphocytes, T lymphocytes and phytohaemagglutinin responsiveness in atopic dermatitis. The spontaneous binding of sheep erythrocytes to human lymphocytes with the formation of rosettes was used as a measure of thymus-derived lymphocytes and the rosette formation with complement-coated sheep erythrocytes as a measure of bursa-dependent lymphocytes in the peripheral blood of patients with atopic dermatitis. Both percentage proportion and the absolute number of thymus-derived lymphocytes were slightly but significantly reduced. In a few patients with atopic dermatitis the percentage and absolute number of bursa-dependent lymphocytes were increased. However, when all values were considered, no significant differences were demonstrated. The responsiveness of cultured lymphocytes to phytohaemagglutinin was normal when the culture medium contained foetal calf serum. The response of normal lymphocytes was not impaired by serum from patients with atopic dermatitis. However, the response was depressed when atopic dermatitis lymphocytes were cultured in medium containing autologous serum, indication that a partial lymphocyte defect becomes manifest only in the presence of a serum factor, presumably IgE.


Abnormal cutaneous reactions in dermatitis herpetiformis. In 94% of the patients with dermatitis herpetiformis, a locally applied ointment with an ester of nicotinic acid (Trafuril) induced an abnormal reaction with erythema, edema, papules, and often vesicles. The appearance of the reaction to Trafuril is similar to DH lesions. It differs markedly from the reactions to iodide where, as a rule, only one large blister results. The reaction is most pronounced 12-24 hours after application of Trafuril. The reactivity is strongest in the predilection areas for dermatitis herpetiformis. Strongly increased reactivity to Trafuril in DH is induced by pretreatment with streptokinase, streptokinase-streptodornase, or urokinase. Diminished reactivity to Trafuril is seen after pretreatment with injections of Compound 48/80, tranexamic acid, cromoglycate, or application of fluocinolone-acetonide, as well as after stroking the skin.


Deposits of immunoglobulins and complement in the dermoepidermal junction of patients with anaphylactoid purpura. Skin biopsies from 3 patients with anaphylactoid purpura examined by an immunofluorescence technique revealed deposits of immunoglobulins, complement C3, and fibrinogen in the dermo-epidermal junction and in vessel walls of clinically involved as well as uninvolved skin. The deposits in the dermo-epidermal junction are similar to those seen in the skin of patients with systemic lupus erythematosus.


On the diagnosis of Fabry's disease.

On the diagnosis of Fabry's disease. Fabry's disease is a recessive X-linked inborn error of metabolism due to deficiency of the lysosomal enzyme alpha-galactosidase. The large variety of symptoms may make the diagnosis difficult. A severely afflicted female patient is presented. For several years she had been treated under the diagnosis polyarteritis nodosa until the characteristic cutaneous lesions of Fabry's disease were recognized. Enzymatic studies and electronmicroscopic examinations confirmed the diagnosis. A symptomatic effect of corticosteroid treatment was proven. The grave prognosis, the recent attempts at enzyme substitution therapy and the possibility of preventing new cases by prenatal diagnosis should stimulate the efforts of the clinician to diagnose the disease.


Treatment of psoriasis with oral psoralens and longwave ultraviolet light. Therapeutic results and cytogenetic hazards. The purpose of the present investigation was to study the usefulness of oral treatment of psoriasis with psoralens and longwave ultraviolet light and the possible cytogenetic hazards of this therapy. 8-methoxypsoralen (8-MOP) in doses between 15 and 60 mg orally followed 2 hours later by UVA irradiation of one side of the body gave a healing of the irradiated side in 24 of 40 cases and an improvment in another 11 cases while only one case healed on the side of body that was not irradiated. The most common undesired side effect was pruritus on the irradiated side of the body. The cytogenetic study showed that 8-MOP and UVA treatment of lymphocytes in vitro gives rise to chromosomal aberrations. In a combined in vivo-in vitro study where the lymphocytes had been isolated from a patient 2 hours after intake of 60-80 mg 8-MOP and then irradiated with therapeutic UVA doses, a significant increase in chromosomal aberrations was found. When chromosome analyses were made on the patients whilst the 8-MOP treatment was temporarily withdrawn and when the lymphocytes were not irradiated in vitro, no increased frequency of chromosomal abberations was found on comparison with a group of psoriatic patients receiving dithranol therapy.


Herpes simplex: cicatricial type.

Herpes simplex: cicatricial type. An example of a cicatricial form of recurrent herpes simplex is presented. Although the initial appearance of the lesions was identical with non-scarring forms of herpes simplex, this patient's lesions progressed insidiously to eschar formation. Healing was delayed for four to seven weeks, with subsequent atrophic scar formation. Scarring and local recurrence could be prevented by curettage, and acridine orange and ultraviolet light therapy within 48 hours of an attack. Other modalities employed over a fourteen year period were largely ineffectual. It was concluded that the ulceration and scar formation were an intrinsic part of the herpetic process in this patient.


Sezary syndrome with arthropathy. Report of a case. A 65-year-old black female with Sezary syndrome had generalized intractable pruritus, erythroderma, alopecia, onychogryphosis, lumphadenopathy and hepatomegaly. Abnormal lymphocytes with large, convoluted and grooved nuclei (Sezary cells) were identified in the skin and peripheral blood. A striking feature of her disease was severe, deforming arthropathy of the hands and knees, a clinical finding which has been described previously in only one patient with Sezary syndrome. At necropsy no associated lymphoma was found.


Pachyonychia congenita. A clinical, histological and microradiographic study with special reference to oral manifestations. This paper rresents a clinical, histological and microradiographic study of three patients with pachyonychia congenita with special reference to oral manifestations. The patients, who are relatives, exhibited thickening of finger- and toe-nails, follicular keratosis, palmoplantar keratosis and hyperhidrosis, oral leukokeratosis, and natal teeth. It is stated in the discussion that natal teeth and oral leukokeratosis may constitute the earliest clinical manifestations of pachyonychia congenita and that they appear to accur earlier than nail lesions. When there is a hereditary disposition for pachyonychia congenita, it is important to inspect the oral cavity at an early stage.


Treatment of familial benign chronic pemphigus by skin grafting. A report on a patient with familial benign chronic pemphigus, resistant to all conservative therapy, treated in several stages by surgical excision of the most affected areas and reconstruction with split skin grafts. The follow-up period of the treated sites varies from two to eight years. All grafted sites have remained totally asymptomatic and there has been no sign of recurrence. Outside the grafted areas the disease is still as active as before.


Biochemical approach to bovine leukemia. Many bovine leukemic lymphocytes produce virus particles when kept in survival cultures in Eagle's Minimum Essential Medium supplemented with 20 percent of inactivated fetal calf serum. Virus particles equilibrate at a density of 1.16 g/ml in sucrose gradients and at a density of 1.12 g/ml in metrizamide gradients. Simultaneous detection tests show that a high molecular weight RNA-reverse transcriptase complex exists in these viruses. Hybridizations between total RNA from bovine leukemic lymphocytes and C-DNA prepared in various known RNA oncogenic viruses show that the virus associated with bovine leukosis is unrelated to RLV, SSV-1, MSV-Ki, FSV-Ga and FLV-Ri.