Steric hindrance of CON A receptor sites by antigen: a possible explanation of Ir regulated responses. Spleen cells from mice that respond poorly (C57BL/6) or well (CBA, C3H/HeJ AND B6D2F1) to DNP-BGG, an antigen under Ir gene regulation, were cultured with the T cell mitogen Con A and varying concentrations of DNP-BGG and DNP-KLH. It was found that DNP-BGG dpressed the responses of C57BL/6 spleen cells to Con A stimulation to a much greater degree than did DNP-KLH; the Con A stimulated responses of spleen cells from the other strains were impaired equally and less severely by both antigens. The possible implications of these findings with regard to Ir gene regulation of thymus-dependent immune responses were discussed.


Forssman antigen and phase specific fetal antigens: an evaluation of their role in SV40 tumor immunity. Forssman heterophile antigen was detected on hamster fetal cells which had been previously shown to be capable of eliciting transplantation resistance to syngeneic hamster SV40 tumors. The expression of Forssman antigen continued throughout fetal development and could be detected postpartum in the tissues of neonate hamsters. In contrast, fetal antigen(s) evoking immunity to SV40 tumors was also present on early fetal cells but, unlike Forssman antigen, was not expressed after the tenth day of gestation. Immunization of hamsters with guinea pig kidney cells or sheep erythrocytes which carry Forssman antigen failed to demonstrate significant protection against SV40 tumor development. Again by contrast, immunization with fetal cells was effective in evoking tumor immunity. Evaluation of serological responses to the FORSSMAN A ANTIGEN IN HAMSTERS INDICATED THAT THE HEMOLYTIC REACTIVITY PRODUCED BY IMMUNIZATION WITH GUINEA PIG KIDNEY CELLS OR SHEEP ERYTHROCYTES WAS ELICITED AGAINST ISOANTIGENS AND NOT THE Forssman antigen. A response to the Forssman determinant could only be detected in the serum from animals receiving exhaustive hyperimmunization with fetal cells or SV40 tumor cells. These data would eliminate a possible role of the Forssman heterophile antigen in the tumor protection evoked by immunization with fetal cells bearing embryonic antigens.


Effect of butyldiiodohydroxybenzoate on pituitary-thyroid interplay. The effect of BHDB, an analogue of thyroxine, on the pituitary-thyroid system was studied in the rat. BHDB produced low plasma T4 and T3 concentrations similar to those produced by methimazole, but failed to elevate plasma TSH and to produce goiter because of displacement of T4 from the binding protein. Low plasma thyroid hormone concentrations were due to an increase of fecal loss of thyroid hormones. By releasing excess iodide, BHDB blocked the development of goiter produced by methimazole.


Cell-mediated immunity in experimental allergic encephalomyelitis: cross reactivity between myelin basic protein and mycobacteria antigens. Guinea pigs injected with Freund's incomplete adjuvant emulsified with guinea pig spinal cord, purified guinea pig myelin basic protein, or human myelin basic protein showed dermal reactivity to both of the basic proteins as well as to mycobacteria antigens. Animals receiving only mycobacteria antigens expressed dermal reactivity to the sensitizing antigen in addition to basic protein. This cross reactivity may help explain the role of mycobacteria in inducing and protecting against EAE, and may have important implications concerning human demyelinating diseases.


Correlation of the critical micelle concentrations of surfactants with their effects on a bacterial demethylase. The activity of a sarcosine dehydrogenase isolated from a strain of Pseudomonas is enhanced by the addition of Triton X-100, Brij 35, and Tween 80, and is inhibited by deoxycholate and Sarkosyl NL-97. 2,6-Dichlorophenolindophenol, which is used as the oxidant in the dehydrogenase assay, has also been employed as an indicator in the spectrophotometric determination of the critical micelle concentrations (CMC) of both the nonionic and anionic detergents under conditions optimal for the enzyme analyses. A correlation between the activation or inhibitory activities of the surfactants and their CMC values has been established.


A comparison of three educational techniques used in a venereal disease clinic. The communications methods that could be used in educational programs for venereal disease patients were examined as to their relative effectiveness: a programed learning guide, an audiovisual (cinematographic) technique, and an interview method. An experimental design was used to study three groups of patients at a venereal disease clinic; (a) persons who were pretested, exposed to an educational method, and tested again, (b) a control group whose members were pretested and post-tested but not exposed to an educational method, and (c) another control group whose members were exposed to an educational method and then took a post-test. Each of those groups exposed to the educational techniques was further subdivided according to the technique applied. Analysis of the data collected from 443 subjects led to the following tentative conclusions: 1. Representation in the nine groups was demographically uniform as measured by age, sex, marital status, and ethnic origin. 2. All three educational techniques significantly raised the subjects' level of knowledge about venereal disease, as measured by their test scores. 3. All three techniques were favorably received by the subjects. The majority reported that the techniques were the right length (10 to 15 minutes), interesting, informative, useful, and anxiety-reducing. The three techniques apparently accounted for an increase of more than 20 percent in subjects' scores on tests about venereal disease, and the subjects perceived all three techniques as interesting and beneficial. The interview method proved significantly more effective than the other two techniques in raising the knowledge level. It was also the technique most favorably received by the subjects. As expected, those persons who entered the clinic with a low level of knowledge learned much more when exposed to an educational techniques than persons entering the clinic with a high level of knowledge. Reaction to the three methods did not differ significantly by the subjects' age or sex.


Turkey syndrome 65, oedema syndrome and Mycoplasma meleagridis. Comparisons of liver histology and serum protein characteristics from cases of oedema syndrome and from poults with Mycoplasma meleagridis induced ascites revealed that the two conditions, though presenting grossly similar post mortem appearances, are different entities. Serum albumin concentrations, but not total serum protein levels, were markedly reduced in poults with M meleagridis induced ascites and in those with turkey syndrome 65. Poults which were infected with M meleagridis but which failed to develop either of these conditions had more normal serum protein characteristics. It is argued that M meleagridis induced ascites may be an acute manifestation of a pathological process of which TS65 is the chronic form. It is also suggested that low serum albumin concentrations may play a primary role in the pathogenesis of TS65.


Electrophoretic separation, detection, and variation of amylase isoenzymes. An electrophoretic technique for demonstrating amylase isoenzymes is described. After separation in an agarose gel containing a linear polyacrylamide polymer to reduce electroendosmotic flow, the amylase fractions are visualized by incubation with a commercially available dye-starch polymer (Phadebas Amylase Test). The technique detects amylase fractions with activities below 10 U/l. Some characteristic changes in such diseases as acute and chronic pancreatitis, cystic fibrosis of the pancreas, macroamylasemia and inherited variants as well as after maxillofacial surgery are mentioned.


Thyroid function during erythrosine ingestion in doses encountered in therapy with conventional antibiotics. Six euthyroid patients without clinical or biochemical evidence of any renal or thyroid disorder received a diet of fixed composition. They were given no drugs. Urine was collected quantitatively throughout the whole investigation for determination of iodine and creatinine. After 5 days on diet they received 1.91 mumol of erythrosine, corresponding to approximately 7.88 mumol of iodine daily for 10 days. Thyroidal radioiodine studies were performed, levels of plasma inorganic iodine were calculated, and thyroxine, protein-bound iodine, and total iodine in serum were determined before and during erythrosine ingestion. A statistically significant increase in plasma inorganic iodine or in urinary iodine excretion was not found. The other test results of thyroid function remained virtually unchanged. Based on clinical aspects of thyroidal iodine metabolism we conclude that at most 7.8 per cent of the iodine content of the ingested erythrosine could have supplemented the iodine space.


The ultrastructure of the platelets in refractory anemia ("preleukemia") and myelomonocytic leukemia. We have conducted extensive morphologic studies of the platelets in 16 patients with preleukemia or myelomonocytic leukemia. Although the degree and frequency of the changes varied in the different cases, it was evident that the platelets in these two pathologic states often were structurally abnormal. The abnormalities include changes in size (mainly giant forms), shape (frequent presence of round cells), and quantitative (particularly decreases) as well as qualitative changes in the platelet granules. Quite remarkable has been the finding of giant granules of irregular contour and heterogeneous composition, perhaps the result of fusion of several single granules. Other changes have included overabundance of the membranous systems of the platelet.


The evaluation of fetal lung maturity by amniotic fluid analysis. The frequent necessity for termination of pregnancy before the spontaneous onset of labor requires that we be able to accurately predict fetal lung maturity. We have used amniotic fluid studies for evaluation of fetal lung maturity and have found that (1) a "fat" cell concentration of 30% or more, or (2) a creatinine concentration of 2.0 mg/100 ml or more, or (3) a lecithin:spingomyelin (L:S) ratio of 2.0 or greater all correlated well with fetal maturity. Since each of these studies is open to a variety of possible errors, the use of several different ones adds reliability to the estimation of fetal lung maturity.


RNA-polymerase activity in isolated nuclei of developing silkworm embryos. Nuclei isolated from developing embryos of the silkworm (Bombyx mori) are capable of RNA synthesis in vitro. The incorporation of C-14-uridine triphosphate (C-14-UTP) into the acid-insoluble fraction requires the presence of the other three ribonucleoside triphosphates; it is inhibited by actinomycin, olivomycin, and ethidium bromide, and is stimulated by ammonium sulfate. In a medium of moderate ionic strength C-14-UTP incorporation is slightly inhibited by alpha-amanitine (4 mug/ml), whereas in the presence of 0.2 M ammonium sulfate the same alpha-amanitine concentration reduces the incorporation by 90%. These data indicate that silkworm embryo nuclei, like nuclei from several other sources, contain two different RNA-polymerase fractions.


The functional state of the thyroid gland of the mother and fetus in the prenatal development of rabbits. The functional state of the thyroid gland of the mother and fetus was studied in different periods of intrauterine development of rabbits, as well as in newborn rabbits according to the level of protein-bound iodine (PBI) in the blood plasma and thyroid gland tissue. Similar studies were conducted after a thyroidectomy of females on the 10th-12th day of pregnancy in order to demonstrate the possibility of mutual compensation of the hormonal function under pathological conditions. The level of PBI in the blood plasma of the mother clearly increases in the second half of pregnancy and decreases sharply after birth. The content of PBI in the fetal blood plasma increases continuously beginning with the 22nd day of intrauterine development. The level of PBI in the thyroid gland tissue both of the mother and the fetus increases sharply at the end of pregnancy. In fetuses of thyroidectomized females the amount of PBI in the blood plasma and thyroid gland tissue on the 22nd day of pregnancy considerably exceeded that in normal fetuses.


Glomerular antigen complexes associated with transitional cell carcinoma. An immunofluorescent pattern consistent with glomerular complexes of tumor antigen bound to IgM antibody has been observed in a patient without clinical or pathologic evidence of renal disease. The findings support the thesis that tumors may shed antigen capable of eliciting an immune response which may or may not be associated with clinically evident glomerulopathy.


The effect of estrogen on the vascular endothelium and its possible relation to thrombosis. The effect of estrogen on the permeability of the endothelium of the aorta has been studied in the rat. The endothelium was subjected to different forms of chemical injury, and its permeability to silver ions was estimated in rats in a control group and in rats after estrogen treatment. In rats subjected to estrogen treatment, the degree of silver penetration through the endothelium was significantly higher than in untreated rats. This was interpreted as an increased vulnerability of the endothelium after estrogen treatment. Thrombosis in females using oral contraceptives often has an aberrant localization. These findings lead to a theory that an endothelial factor may be involved in the pathogenesis of this form of thrombosis.


[The morphogenesis of chronic synovitis in rheumatoid arthritis]. The synovial sheath obtained in synovectomy in 35 patients with rheumatic- and rheumatic-visceral forms of rheumatoid arthritis was studied histochemically and immunomorphologically. At early stages of exacerbation of the pathological process in the synovial tissue there were revealed predominantly catabolic processes: an increased permeability of vessels; mucoid oedema; fibrinoid changes in the subintimal layer. Further development of the disease was characterized by predominance of anabolic processes with proliferation of synoviocytes, subintimal histiocytes, productive vasculites, massive lymphoid-plasmocytic infiltration, diffuse, or in the form of lymphoid follicles. Using the immunofluorescent technique the authors revealed luminescence of the rheumatoid factor and gamma=globulin in plasmatic cells, extracellularly, and more rarely in macrophages. Pronounced immunological changes in the synovial sheath in the active course of rheumatoid arthritis were accompanied by a high level of metabolic processes and an intensive phagocytic reaction in synoviocytes and subintimal histiocytes. In observations with a low activity of rheumatoid arthritis the synovial tissue was characterized by low levels of enzymes of oxidative metabolism and hydrolysis, emptying of the capillary bed, processes of sclerosis, hyalinosis, amyloidosis.


Antigenic determinants of the W28 molecule different from but spatially close to W28 determinant. The existence of two allelic determinants, subtypic to W28 (named TO54 and TO55), and of an antibody cross-reacting W28 times HL-A10, is demonstrated. These new determinants have been studied by means of population and family studies and with the following serological techniques: absorption, elution, lysostrip and blocking by F(ab)-2 fragment. The results suggest that determinants TO54 and TO55 are very similar each other and are spatially close to the supertypic factor.


Ankylosing spondylitis and the major histocompatibility system. The purpose of this investigation was to see whether or not the hypothetical disease susceptibility locus to ankylosing spondylitis is linked to the MLC determinant 27a. Firstly, we discovered a strong MLC determinant which we called 27a because of its association with the second series specificity W27. Later, we found that this determinant was the same as that which Jorgensen et al. (1973) found to be associated with the second series specificity W5. These MLC determinants may, therefore, be in linkage disequilibrium with more than one HL-A specificity (in this case, of the second series) as previously described by Dupont et al. (1973). However, we found no association between 27a and ankylosing spondylitis. On the other hand, we confirmed the association of ankylosing spondylitis with W27 and also found an increase of HL-A2 of the first series which, however, was not statistically significant. In view of the high incidence of HL-A2 in the general population, more information is required to definitely establish such an association. We found no special association with specificities AJ and Hu (Sa 532), third series antigens, but confirmed their linkage disequilibrium with W27. Disease predisposition loci seem, therefore, to be associated with either type of MHS marker, multiple sclerosis and MLC determinant 7a, or ankylosing spondylitis and the second series antigen W27. It will be interesting to discover whether there is any special significance of the association of one marker rather than another.


The serological recognition of the human MLC determinants using a modified cytotoxicity technique. A new approach which presumably recognizes MLC determinants (or at least structures closely linked to MLC and different from the FOUR, AJ and LA series determinants) by serology is described. As the test can be performed within 10 h it could be used to match cadaveric kidney donors for these MLC determinants. Perhaps even more important is the fact that the antibodies detected by this technique could be used to study the immunochemistry of a class of determinants differing from the well known SD determinants.


A contribution to the question of the possible hepatocarcinogenic effects of lindane. The possible hepatocarcinogenic effect of lindane was studied in an 80-week study using 500 NMRI mice (strain Chbi : NMRI (SPF)). After giving doses of 12.5, 25 and 50 ppm in the food no compound-induced liver tumours were observed. Neither the occurrence of lymphatic leukemia, malignant haemangioendotheliomas, reticulum cell neoplasms nor liver cell adenomas could be related to the administration of the compound. In view of the actual residue level of lindane the probability of carcinogenic risk to man would appear remote.


Evaluation of platelet cryopreservation techniques by isolated kidney perfusion. The isolated perfused rabbit kidney, a model system used previously to assess platelet function, was adapted for evaluation of human platelet cryopreservation techniques. A new, simple, efficient device for controlling cooling rates before, during, and after freezing was used. Platelet concentrates frozen with 5 per cent dimethyl sulfoxide (DMSO) under different conditions were the most effective of those tried in maintaining the hemostatic function and vascular integrity of perfused kidneys. Our studies indicate that the isolated, perfused rabbit kidney can be used to evaluate platelet cryopreservation techniques and is potentially adaptable for studies of organ cryopreservation.


Management of adenocarcinoma of prostate with diethylstilbestrol diphosphate and cyclophosphamide. Eleven patients with terminal metastatic prostatic carcinoma were selected for a pilot study to evaluate how effective diethylstilbestrol diphosphate (Stilphostrol) and cylcophosphamide (Cytoxan) are in this disease.  Six of 7 patients had a good response when treated with diethylstilbestrol diphosphate.  The mean duration of response was 6.4 months.  All 6 patients given cyclophosphamide had marked relief of pain and increased mobility.  Of these, 3 died twelve, sixteen, and nineteen weeks, respectively, following initiation of therapy while still benefiting from pain relief.  The mean duration of response was 14.8 weeks.


[Synchronization of estrus in heifers by means of gestagenic preparations]. Studied were the synchronizing effect, the course of treatment, the combination of the gestagens CAP and MGA with PMS as well as their effect on the conception rate in heifers. A total of 143 heifers of the Bulgarian Brown breed (89 test and 59 control), aged 17--18 months, weighing 350--360 kg on an average, were used in the experiment, divided into three test and three control groups. I test group. Twenty-five animals were given daily one tablet of Synchrorosyn-Peach, the tablet containing 10 mg active chloromadinoacetate. The course of treatment lasted 15 days. II test group. Thirty-six animals were treated daily with 5 g of the premix preparation MGA-100 in the course of 20 days, the heifers being divided into two subgroups of 18 animals each. Each heifer of the first subgroup was injected with 2500 IU PMS. III test group. Twenty-eight animals were given MGA-100 at the same rate as in the II test group, but in the course of 14 days. Half of the test heifers were injected with 2500 IU PMS each on the day when the treatment with MGA-100 was discontinued. It was found that the oral administration of Synchrosyn-P for fifteen days and MGA-100 for 20 days results in a synchronized estrus in 84, resp. 44 per cent of the heifers, with a total conception rate of 76 and 94 per cent, respectively. The combined use of MGA-100 and PMS (2500 IU) enhanced the synchronizing effect. The shorter period of feeding with MGA-100 (14) days lowered both the synchronizing effect and the total conception rate, regardless of its combining with 2500 IU of PMS.


[An immunologic study of hyaluronidase of different animal origin]. Studied was the antigenic relatedness of hyaluronidase contained in the semen of breeder animals of homologic and heterologic species. The experiments were carried out by means of the immunodiffusion and the immunoelectrophoretic methods. The results obtained showed that the seminal hyaluronidase of bulls, rams and bucks is antigenically related, and that of stallions, boars and rabbits does not exhibit antigenic relatedness. Stallion semen is closely related antigenically with the above-mentioned three animal species' semen as manifested by two precipitation bands, but these are not identical with the hyaluronidase precipitation arc. The antigenic relatedness of seminal hyaluronidase is demonstrated by one precipitation line. This fact makes it reasonable to believe that the enzyme activity of hyaluronidase is to be manifested in one protein fraction only, and not in a protein complex. However, further investigations are needed on the biologic activity and the immunologic specificity of hyaluronidase.


Pituitary chromophobe adenomas consisting of prolactin cells: a histologic, immunocytological and electron microscopic study. Morphologic studies of pituitary neoplasms removed by srugery from 36 human patients revealed 8 chromophobe adenomas which differed clearly from the remaining tumors. The cytoplasm of the adenoma cells failed to stain with PAS, aniline blue, adehyde fuchsin, aldehyde thionin, orange G or light green, but positively stained granules were found by using erythrosine or carmosine. Immunoperoxidase technique disclosed the presence of prolactin in the cytoplasm of some adenoma cells. The adenoma cells exhibited distinct ultrastructural features such as well developed rough surfaced endoplasmic reticulum with Nebenkern formation, prominence of Golgi apparatus, presence of misplaced exocytosis as well as pleomorphism of secretory granules with a considerable variation of size ranging from 130 to 500 nm in diameter. Thus, by electron nicroscopy the adenoma cells showed a close resemblance to prolactin cells of the non-tumouous pituitary glands except for the reduced size and number of secretory granules. Thes chromophobe adenomas are regarded as representing a distinct pathological entity clearly distinguishable from other forms of pituitary neoplasms. In view of the morphologic findings and the elevation of blood prolactin level (measured in 3 patients) the term, "sparsely granulated prolactin producing pituitary adenoma", appears to be the most appropriate one to designate these tumors.


Deposits of immunoglobulins and complement C3 in clinically normal skin of patients with lupus erythematosus. Deposits of immunoglobulins and/or complement C3 were found in two-thirds of biopsies from clinically normal skin of 64 patients with systemic lupus erythematosus, as judged by well defined criteria. The incidence of deposits in clinically normal skin was identical in patients with and without clinical skin lesions. IgM was found more frequently in the deposits (88%) than was IgG (36%) but equally frequently in involved and uninvolved skin, whereas C3 was found more often in patients with skin lesions (59% in involved skin, 36% in uninvolved skin) than in patients without skin lesions (14%). The occurrence of IgG and IgA was less frequent than that of C3 but the distribution was similar to that of C3. In normal skin of 20 patients with chronic discoid LE, deposits were found in one. Deposits were found in the skin of one-third of patients with nuclear antibodies in their sera and symptoms compatible with SLE but with a score of symptoms too low to meet the criteria.


Leaching of nickel from stainless steel consumer commodities. Sweat and household detergents were shown to have the capacity to release nickel from stainless steel. This finding substantiates the thesis that the American-style stainless steel kitchen and other stainless steel commodities can be sources of skin contact allergy with nickel. Furthermore, a negative spot test (DMG) does not reflect the "safety" of a nickel alloy.


Immunofluorescent follow-up studies in patients with bullous dermatoses. Basement zone antibody titres were studied in two patients with bullous pemphigoid over a period of 1-1/2 and 3-1/2 years. Titres remained almost constantly even after a complete healing of all lesions, without any treatment. Direct immunofluorescence revealed basement zone antibodies in one of these two patients when examined after healing had occurred. Three patients with bullous dermatoses showed pemphigus antibodies at the inception of the disease. Basement zone antibodies were present simultaneously in one patient. In the subsequent course of observation in the two other patients, pemphigus antibodies were replaced by basement zone antibodies and in one case by nuclear antibodies too. These findings make the pathogenetic import of these "auto-antibodies" difficult to understand.


Enzyme activation and inhibition induced by cold provocation in a patient with cold urticaria. A 33-year-old female patient with acquired cold urticaria, together with her 8-year-old healthy daughter, was subjected to a brief period of cold exposure. The effect of this treatment upon a number of key factors of the plasma coagulation, kallikrein and complement systems was investigated. Cold air provocation caused increased fibrinolysis, together with a measurable consumption of the protease inhibitors alpha1-antitrypsin (alpha1AT), alpha2-macroglobulin (alpha2M) and C1Inactivator (C1INA). Kaolin activation of the patient's plasma elaborated exceptionally high levels of esterolytic activity, both before and after cold exposure, indicating pre-enzyme lability. Both subjects had abnormally high serum ratios alpha2M/alpha AT. Impressive leucocytosis was observed in the symptomless child.


HL-A27 and W10 in Reiter's syndrome and nonspecific urethritis. By means of a standard lymphocyte microcytoxic technique, the tissue types were fully determined in 41 patients with non-gonococcal urethritis and 25 patients with Reiter's syndrome. The antigen HL-A27 was identified in 14 of the patients with Reiter's syndrome and occurred in 3 of the patients with non-gonococcal urethritis. An excess of the genotype HL-A27/W10 was found in patients with Reiter's syndrome. There was no correlation between the duration or the severity of the clinical manifestations of the syndrome and the presence of the antigens. The possibility that the syndrome might result from various pathogenic mechanisms is discussed.


Examination of HL-A antigens and lymphocytotoxic antibodies in discoid lupus erythematosus. The distribution of HL-A antigens and lymphocytotoxic antibodies has been studied in the sera of patients suffering from discoid lupus erythematosus (DLE). A significant deviation in HL-A5 antigen has been found in the 33 cases investigated, while the lymphocytotoxic antibodies were present in only 8 sera. The possible cause of these findings are discussed.


Lipo-atrophy of the ankles and its relation to other lipo-atrophies. Two typical cases of lipo-atrophy of the ankles are described, one case of atrophy of the ankles with associated atrophy of the whole extremity, and one case of localized atrophy of the knee. For comparison, we present one case of atrophy in a diabetic patient due to insulin injections but developing at distant sites, and in one case, a child in whom atrophy followed antibiotic injections. Primary inflammatory vascular changes in the subcutaneous tissue were demonstrated in atrophy of the ankles, as in the early period of insulin-induced lipo-atrophy. Attention is called to the possible relation of the described lipo-atrophies.


A case of pigmentary hair naevus (Becker). A healthy 14-year-old Norwegian male developed a typical Becker's naevus on the left shoulder and upper scapular region, about six months after an intracutaneous BCG-vaccination in the homolateral junction of the shoulder and upper arm. The evolution of the lesion had been modified by exposure to sunlight during the following six years, with partial fading of the hyperpigmentation. Biopsies taken from the centre and from the edge of the lesion at the age of 19 years showed the usual histological picture seen in cases of Becker's naevus, but focal areas within the periphery showed a chronic granulomatous infiltrate of lupoid pattern in the dermis, mainly follicular and perifollicular in distribution. Acid-fast bacilli were not demonstrable in the sections, and in culture no tubercle bacilli were isolated from a central and histologically non-specific site. The implications of the histological findings are discussed, stressing the possibility that Becker's naevus may be a form of cutaneous tuberculosis caused by BCG or other mycobacteria of low virulence, precipitated by ultraviolet light and possibly modified by immunological factors.


Diffuse hair loss and psychiatric disturbance. 32 women complaining of diffuse alopecia were assessed by a psychiatrist, and daily hair loss and root counts were measured and compared with control women. Seven of the 32 women had severe marital difficulties, and 2 of these were overtly depressed. In these 7 women, daily hair loss and telogen counts did not differ significantly from the values for control women, whereas the remaining 25 women had a significant increase in hair loss and telogen counts. It is suggested that those women whose complaint of hair loss seems disproportionate to the objective degree of alopecia should be questioned as to symptoms of depression and marital difficulties.


Clofazimine-enhanced phagocytosis in pustulosis palmaris et plantaris. The phagocytic ability of neutrophil leucocytes was found to be impaired in patients suffering from pustulosis palmaris et plantaris (PPP). This ability was studied with the aid of the yeast particle method. In 78% of 27 patients whose PPP was in a static phase, the phagocytic function was enhanced, while the PPP abated concomitantly and the pustules disappeared. Impaired phagocytosis and the beneficial effect of clofazimine signify the pathogenic importance of defective neutrophils in PPP.


Keratinosomes in psoriatic skin.

Keratinosomes in psoriatic skin. Keratinosomes in psoriatic skin can be slightly larger than those in normal skin. Some seem to develop an unusual internal morphology, and some reach their full development while they are still within the immediate Golgi area. Observational evidence indicates that there may be more kerantinosomes in psoriatic skin than are generally found in normal skin. Keratinosomes appear extracellularly from the spinous layer through the horny layer. Some keratinosomes do not move to the outside of the cell and can be seen within cells of the horny layer. There appears to be an increased number of keratinosomes in and between the outer cells of sweat ducts. Keratinosomes are also present within the dark cells of the duct and the extracellular space between the dark cells contains material from keratinosomes.


A case of halo nevus with effete melanocytes. Epidermal melanocytes in the depigmenting lesion were examined in one typical case of halo nevus. Vacuolated melanocytes found in the upper layers of epidermis were not, as observed in serial sections, connected to the basal lamina. These melanocytes contained individual as well as aggregated melanosomes in what appeared to be autophagosomes. Part of the cytoplasm of these melanocytes appeared condensed and segregated and their nuclei were often pyknotic. These melanocytes were considered to be degenerated cells which had been detached from the basal layer and were being shed from the skin. Although epidermal keratinocytes, particularly basal cells, were also vacolated. Langerhans cells and non-specific dendritic cells were more or less intact. The total number of these dendritic cells seemed to be increased.


An approach to experimental scleroderma, using urinary glycosaminoglycans from patients with systemic scleroderma. As a result of intraperitoneal injections in mice of crude glycosaminoglycans obtained from the urine of patients with systemic scleroderma, a fibrotic process similar to the intial changes of human scleroderma was frequently observed, especially in the skin and esophagus when the glycosaminoglycans contained a probable variant of heparan sulfate. Furthermore, the scleroderma-like change was also observed, to some extent, in the ultrastructure of collagen fibers and glycosaminoglycans of the skin.


Alpha-1-fetoprotein and the heat stable alkaline phosphatase in some liver diseases. The presence of alpha-1-fetoprotein, the heat stable alkaline phosphatase and Australia antigen was examined in 103 patients with porphyria cutanea tarda, 300 patients with cirrhosis and 18 patients with primary liver carcinoma.  The heat stable alkaline phosphatase was determined in 46 percent of patients with porphyria cutanea tarda and in 61 percent of patients with primary liver carcinoma.  Alpha-1-fetoprotein was detected in 61 percent of patients with primary liver carcinoma and in 2 patients with porphyria cutanea tarda in whom primary liver carcinoma was proved later.  The simultaneous occurrence of alpha-1-fetoprotein and the heat stable alkaline phosphatase was found in 50 percent of cases with primary liver carcinoma.  Neither the patients with porphyria cutanea tarda nor the patients with cirrhosis were Australia-antigen positive.  Australia-antigen could be detected only in one patient with alpha-1-fetoprotein positive-carcinoma of the liver.


Quantitative studies of direct and indirect immunofluorescent staining of salmonella bacteria. Salmonella bacteria were stained with serial dilutions of anti-Salmonella conjugates of different F/P ratios and the staining intensity was measured quantitatively in an ultramicrofluorometer. In any given dilution of the conjugates, a stronger fluorescence was obtained with the more highly labelled conjugates. The dependence of fluorescence intensity of F/P ratio varied with the dilution of the conjugate. Similar results were obtained by the indirect immunofluorescence method. In four bacterial systems the direct and indirect immunofluorescent staining methods were compared quantitatively. The indirect method was 5 to 30 times more sensitive than the direct comparing the last dilutions giving a positive reaction by visual observations. The standard deviation of the intensity values of the stained bacterial cells was between 10 and 40 per cent of the mean. Different sources of variation in the quantitative measurement technique are discussed.


Complications of acute frontal sinusitis. The bone separating the frontal sinus from the anterior cranial fossa and the orbit is often quite thin. This, plus the interrelated venous drainage system of these areas, forms the anatomic basis for serious orbital and intracranial complications that must be recognized early. These include orbital cellulitis and abscess, cavernous sinus thrombosis, subdural and brain abscess and meningitis. Early hospitalization for intravenous antibiotic therapy and, occasionally, emergency surgical drainage are required.


Effects of lidocaine on impulse formation and conduction defects in man. The acute electrophysiologic effects of a bolus injection of 100 mg. of lidocaine were investigated in 39 patients with impulse formation and conduction defects by means of His-bundle recording and were correlated with plasma lidocaine levels. The effects of therapeutic plasma levels on conduction intervals and refractory periods were subsequently studied during sinus rhythm and atrial pacing. The sinus-node function was studied by measurement of the sino-atrial recovery time. Seventeen patients had conduction defects in or distal to the His bundle, six exclusively proximal to the His bundle, and nine at both levels. Nine patients had pre-existent sinus-node malfunction. Ten out of 39 patients suffered from acute myocardial infarction. Two patients were studied twice because of changed A-V conduction. Intravenous injection of 100 mg. of lidocaine within 20 seconds produced peak arterial plasma levels (mean 26.6 mug per milliliter) 60 seconds after the beginning of the injection. Seven out of 26 patients showed transient progression of their pre-existent infra-His conduction impairment, coincident with peak plasma levels, apparently due to drug toxicity. Even at therapeutic plasma levels, five out of 26 patients showed decremental intraventricular conduction during atrial pacing when compared to control tracings. His-Purkinje refractoriness was not shortened in these patients and increased in two. Lidocaine had no effect on ventricular automaticity in three patients with complete heart block. Lidocaine had no consistent effects on sinus rate, SART, atrial refractoriness, or A-V nodal conduction as measured by pooled AH intervals and the Wenckebach point, and on A-V nodal refractoriness. It is concluded that lidocaine is safe in patients with high degrees of A-V nodal block and in patients with impulse formation disturbances. However, patients with intraventricular conduction defects are prone to deterioration of their conduction disturbance due to drug toxicity. The drug should be given to such patients preferably if monitoring and pacemaker facilities are available and by the intramuscular route to avoid peak plasma levels.


Vagally mediated suppression of premature ventricular contractions in man. Twelve patients with PVC's were studied to assess the possible role of the vagus nerves in suppressing PVC's. All were without significant heart disease and under forty years of age. A series of five autonomically active drugs, including vagotonic and vagolytic agents, was administered intravenously, each drug being given after the effects of the previous one had abated. Two of the patients did not have PVC's at the time of study. Of the remaining ten patients, five showed vagally mediated suppression of PVC's. Phenylephrine (40 to 60 mug per minute) reduced HR, from an average of 63.2 bpm to 48.5 bpm by a vagally mediated reflex, and decreased PVC incidence in all five patients. The per cent of ventricular heart beats which were PVC's (per cent PVC) decreased from an average of 18.2 per cent to 3.2 per cent in these patients (p smaller than 0.005 in each case). Edrophonium (10 mg.) produced less bradycardia and less reliable PVC suppression. In two of these five patients, atropine (1.5 mg.) increased PVC incidence markedly, although the per cent PVC did not change significantly because of the concomitant tachycardia. These data suggest that strongly increased vagal tone can suppress PVC's in a significant percentage of such patients. This finding in man extends previous animal work which has shown a protective role of the vagus against ventricular arrhythmias under certain conditions.


Histamine induction and release following proteolytic enzyme exposure. The mechanism of biologic response from exposure to a 12% subtilisin Carlsberg preparation is shown to be one of histamine release in the guinea pig. Three groups of guinea pigs were pretreated by intradermal injections withsaline solution of (1) the commercial proteolytic enzyme preparation containing 12% subtilisin Carlsberg, (2) an alkaline protease preparation obtain from Aspergillus oryzae that was isolated from cotton dust, or (3) a nonproteolytic mixture of proteins and lipases obtained from cotton seeds.  The histamine content of the ling, liver, and ear tissues of guinea pigs that were pretreated with any one of the three preparations showed an in untreated animals.  Following challenge by intratracheal injection of a saline solution containing the subtilisin preparation, the guinea pigs pretreated with the same preparation showed a markedly reduced liver histamine level. Challenge by inhalation exposure to the subtilisin preparation of guinea pigs that were pretreated with any one of the above preparations resulted in a lower histamine concentration in the lungs and livers.


Seasonal exposure to dust in flax processing in Egypt. Previous evidence suggested that interruption of worker's exposure to flax dust may lead to severe symptoms of byssinosis on their return to work. In the present study, the prevalence and severity of byssinosis was studied in a sample of flax workers (n=577) who had been exposed to dust for six months each year. Byssinosis prevailed in 36.9% of them, and 32.3% of them had their FEV 1.0 sec reduced 10% at the end of the first morning work period (4 to 6 hours) of the week. Both syndromes were higher among seasonal workers than what would be predicted if they were pemanently exposed to flax dust. A hypothesis has been presented to interpret this finding.


Diagnosis and quantification of arrhythmias in ambulatory patients using an improved R-R interval plotting system. An improved technique for identification, diagnosis and quantification of arrhythmias during rest or ambulatory electrocardiographic recording is described. With simultaneous plotting of the R-R interval and the QRS duration and QRS vector measurement of each beat versus time, all periods of arrhythmias or abnormal complexes can be identified and characterized. Analog electrocardiographic samplings are used to confirm the diagnosis of the arrhythmia and to exclude artifact. The availability of a permanent record for the characterization of each QRS complex enables the physician to check the technician's analysis of the recording and to relate all events to the patient's heart rate and clinical symptoms. This technique also provides data for quantification of ventricular arrhythmias.


Correction of platelet dysfunction and bleeding in cyanotic congenital heart disease by simple red cell volume reduction. Red cell volume reduction corrected the platelet aggregation abnormality and bleeding tendency in four boys, aged 5 to 16 years, with severe cyanotic congenital heart disease and polycythemia. Red cell volume was reduced by replacing 15 to 20 ml/kg body weight of the patient's blood with plasma in 50 ml increments over a 1 to 2 hour period. Within 3 days, platelet aggregation was restored essentially to normal, and previous bleeding symptoms disappeared. Platelet aggregation remained normal during 3 weeks of follow-up study and hematocrit values remained at palliative levels. The procedure was safe and simple, and it had beneficial effects not only on bleeding but also on other symptoms related to polycythemia. These preliminary observations suggest that red cell volume reduction may be useful preoperatively in patients with cyanotic heart disease and defects in platelet function to lessen the risk of serious bleeding during the early postoperative period. Palliation in severely cyanotic children whose condition is inoperable is another possible indication for this procedure.


Motor-sensory cortex-corticospinal system and developing locomotion and placing in rats. Normal and abnormal development of movement in the rat were studied by investigating the growth and organization of the motor-sensory cortexcorticospinal tract system (MSC-CST) and the functional and morphologic effects of ablating the MSC or quadrants of it at different ages. Major growth of the MSC outflow, the CST, in the brain stem and rostral cord occurred in the second and third weeks postnatally, coinciding approximately with the normal mid-week transition from infantile to mature locomotion. Ablation of the MSC at birth revealed that while the MSC-CST was not essential for ordinary locomotion on flat terrain, its presence hastened normal development of this kind of movement, and that it was absolutely essential for locomotion on difficult terrain. The MSC quadrants showed quite different, and in some domains mutually exclusive, CST projection patterns to forebrain, diencephalon, brain stem, and spinal destinations (determined by Fink-Heimer-Nauta fiber degeneration studies). Ablation of some quadrants produced distinctive syndromes of disordered movement: the posterolateral quadrant related to active grasping in positioning limbs, while the posteromedial quadrant related to tactile motor-sensory positioning of limbs. Thus in addition to the classic somatotopic organization of the MSC, there was another kind of organization into regions concerned with components of integrated movement of a number of parts of the body. Several forms of aberrant circuitry developed after MSC ablations in infants, but their possible roles in functional adaptation remain to be determined.


Models of ionic transport in biological membranes. Raman spectroscopy as a probe of valinomycin, gramicidin A', and rhodopsin conformations. There is evidence that membrane proteins can serve as the functional units of ionic transport in biological membranes. Laser Raman spectroscopy has been used to probe specific molecular interactions inside two models of transport membrane proteins, valinomycin and gramicidin A. Conformational changes of these molecules, as well as specific interactions with ions, can be detected and may help elucidate how membrane transport proteins such as Na+ minus K+ ATPase and rhodopsin function. Resonance Raman spectroscopy has also been used to study conformational changes and protein-chromophore interactions in rhodopsin, the membrane protein that acts as the primary unit of visual excitation in the eye.


Hepatocellular carcinoma: relation to alcohol, HB-antigen and alpha-fetoprotein. Thirteen of 16 patients with primary cancer of the liver were heavy alcoholics. Fifty per cent of them had positive alpha-fetoprotein and 25% had HB-Ag in their blood. The association of alcoholism with cancer of the liver is thus very striking and hence alcohol should be proclaimed as a carcinogenic substance.


Interactions in the uptake between catecholamines and estradiol in the human uterus. Optimal conditions of pH, dose, time and temperature for the in vitro uptake of radioactivity from 3-H-E or 3-H-NE by the human endometrium and myometrium were established. Uptake was dependent on temperature but not on pH. Uptake of radioactivity from 3-H-NE was always higher (p smaller than 0.05) in both tissues than the uptake of radioactivity from 3-H-E at all the studied times but 10 minutes. Only the uptake of radioactivity from 3-H-NE by the myometrium increased continuously from 2 to 90 minutes. E2 increased the uptake of radioactivity from 3-H-E and decreased the one from 3-H-NE, being both effects more significant (p smaller than 0.05) in the myometrium. Both E and NE increased significantly (p smaller than 0.05) the uptake of 3-H-E2 by the myometrium but not by the endometrium. These results indicate that the interactions between E and NE and E2 are more marked in the myometrium. The uterine tissues studied corresponded to the secretory phase of the menstrual cycle, which was established by the endometrial histology and plasma levels of progesterone.


Prenatal detection of neural tube defects. Comparison between alpha-fetoprotein and beta-trace protein assays. The prenatal diagnosis of neural tube defects is now possible in about 90 per cent of cases by assaying the amniotic fluid for alpha fetoprotein. The accuracy of beta-trace protein assays on amniotic fluid samples from defective fetuses was compared to alpha-fetoprotein studies. At present, alpha-fetoprotein studies provide more reliable results.


Auto-tutorial method for teaching manual skills. This paper describes a self-learning method for teaching craft and activity techniques developed by the faculty at St. Mary's Junior College, Minneapolis. The basic assumption is that, in order for learning to take place, the student must be actively involved in the learning-teaching process. Personalized instruction was simulated in an auto-tutorial laboratory where the student was responsible for organizing his time and for mastering specified craft and activity techniques.


Possible mechanism of histamine release during active vasodilatation. Continuous electrical stimulation of the cut synpathetic innervation to perfused gracilis muscles restored vasoconstrictor tone and active dilatation resulted when stimulation was terminated. This dilatation was unaffected by cholinergic blockade but was blocked by the antihistamine tripelennamine. Prior vasoconstriction was not required to produce active dilatation since sympathetic stimulation applied during infusion of xylocholine (betaTM10) produced no vasoconstrictor response yet an antihistamine-sensitive vasodilatation appeared when stimulation ceased. This dilatation was also blocked by the alpha-adrenergic receptor blocker phentolamine even though adrenergic vasoconstrictor tone was absent. These results suggest that the release of histamine from its storage site is mediated by an alpha-receptor mechanism. Since betaTM10 abolished adrenergic vasoconstriction but preserved histamine-mediated vasodilatation that could be prevented by alpha-adrenergic blockade, it is proposed that histamine release may be under the control of separate adrenergic fibers without a vasoconstrictor function. This mechanism may underlie the process of active reflex vasodilatation since upon reflex withdrawal of tonic sympathetic activity an antihistamine-sensitive vasodilatation occurs.


Relative analgesic potencies of morphine and hydromorphone in postoperative pain. Because of discrepancies in the estimates of the relative analgesic potencies of hydromorphone and morphine, the drugs were compared in two four-point, double-blind bioassays. In the first study, hydromorphone, 1 and 2 mg, was compared with morphine, 5 and 10 mg, in 31 postoperative patients; in the second, hydromorphone, 0.5 and 1 mg, was compared with morphine, 5 and 10 mg, in 112 postoperative patients. Subjective responses to nurse-observer questions were used to quantitate analgesia for postoperative pain. Hydromorphone is more potent than commonly believed: approximately 0.9 to 1.2 mg is equianalgesic with 10 mg of morphine, with a similar incidence of side effects.


Combination of delta9-tetrahydrocannabinol with oxymorphone or pentobarbital: Effects on ventilatory control and cardiovascular dynamics. Marijuana is widely used, yet few data concerning its actions combined with other drugs exist. Psychologic, respiratory and cardiovascular effects of delta9-tetrahydrocannabinol (THC), the active component of marijuana, combined with oxymorphone (OXM) or with pentobarbital (PBL), were studies in 15 healthy volunteers. Oxymorphone, 1.0 mg/70 kg, iv, caused sedation and ventilatory depression (minute ventilation: 24.9 plus or minus 11.9 SD to 14.1 plus or minus 4.9 1/min with PETCO2 held at 50 torr) in eight volunteers. TCH (27, 40, 60, 90, and 134 mug/kg, iv) increased sedation and further decreased ventilation with each TCH dose to 6.6 plus or minus 3.7 1/min after 134 mug/kg. The combination of OXM and THC decreased the CO2-ventilation slope from 2.23 to 0.88 1/min/torr. When THC, 134 mug/kg, was added to OXM, which alone caused no significant cardiovascular change, cardiac index (4.1 plus or minus 1.3 to 5.0 plus or minus 2.2 1/min/m-2) and heart rate (66 plus or minus 12 to 107 plus or minus 31 beats/min) significantly increased and total peripheral resistance (1,030 plus or minus 260 to 660 plus or minus 200 dynes-sec/cm-5) decreased. Heart rates exceeded 150 beats/min in two subjects after 27 and 134 mug/kg THC. Pentobarbital alone, 100 mg/70 kg, iv, caused no significant ventilatory or cardiovascular change. THC, after PBL pretreatment, induced hallucinations and anxiety in five of seven volunteers; four failed to complete all five doses of THC becuase of the severe psychologic effects. The combination of PBL and 40 to 134 mug/kg THC did not affect ventilation significantly. After PBL pretreatment, THC significantly increased heart rate (76 plus or minus 17 to 130 plus or minus 32 beats/min). Cardiac index also increased (3.8 plus or minus 0.8 to 5.6 plus or minus 1.9 1/min/m-2) and total peripheral resistance decreased (1,070 plus or minus 240 to 720 plus or minus 300 dynes-sec/cm-5). Three subjects developed heart rates esceeding 150 beats/min after 27, 27, and 90 mug/kg THC; in all three, heart rates fell from maximal value with a further dose of THC.


Inhibition of multiplication of Mycobacterium leprae by several antithyroid drugs. Multiplication of Mycobacterium leprae in the mouse footpad was inhibited when mice were fed, mixed in their diet, 0.05 per cent methimazole, 0.066 per cent USP thyroid powder, methimazole plus thyroid powder, 0.15 per cent 5-n-heptyl-2-thioxo-4-thiazolidinone, 0.1 per cent propylthiouracil, and 0.1 per cent thambutosine for 154 days, beginning on the day of inoculation. All of the treatment regimens, except for the 2 containing thyroid powder, decreased the plasma concentrations of thyroxine and protein-bound iodine. It is suggested that the 2 antithyroid drugs, methiomazole and propylthiouracil, and the 2 antimicrobial agents, heptylthioxothiazolidinone and thiambutosine, all of which possess structural features in common, may exert the antithyroid and antimicrobial effects through a common mechanisms.


Immunosuppressive alpha globulin from bovine thymus and serum: mode of action upon afferent and efferent arcs of the mouse immune response. Immunosuppressive bovine alpha globulins of both serum and thymus origin were analyzed for in vitro effects upon the afferent and efferent arcs of the immune system. Although considerable variation in potency occurs between preparations, the functional identity of thymus and serum fractions is apparent. Antigenic recognition and effector capability are not altered whereas the proliferative lymphocyte response is either augmented or suppressed, depending upon the concentration of alpha globulin. A rather selective effect is noted on DNA synthesis and is followed by parallel changes in the development of effector capability, as measured by the development of alloimmune cytotoxic lymphocytes.


Factors influencing activation of B-cells in immunity. The hypotheses so far advanced for B-cell activation by antigen are based on the assumption that the interaction between antigen and the Ig receptors delivers at least the initial triggering signal. There are few, if any, experimental findings to support this assumption. On the contrary, a variety of findings indicate that the Ig receptors do not deliver any signal to the cells, whereas activation can be regularly achieved without participation ofIg receptors. The available evidence forces us to suggest that antigen-induced B-cell triggering is always caused by one nonspecific signal, which is delivered to the cells by surface structures, which are not the Ig receptors. For distinctive features of this hypothesis see One Nonspecific Triggering Signal. Various competing hypotheses for B-cell activation have been analyzed, but none of them appears to satisfy the experimental findings.


[DNA cytophotometry on cells of dermatofibrosarcoma protuberans (author's transl)]. Determination of DNA content was performed by Feulgen staining of tumour cell smears and DNA measurement with an integrating microdensitometer, In 3 cases of Dermatofibrosarcoma protuberans there was a DNA distribution in the range of 2 c: only a few cells showed a DNA content in the range between 2 c and 4 c; no atypical DNA distribution curves were found. The rate of proliferation in these cases of Dermatofibrosarcoma protuberans is small, there are no cytophotometric indices for malignancy.


An assessment of Mustard's operation as a palliative procedure for transposition of the great vessels. Ten patients in whom palliative Mustard operations have been performed for transposition of the great vessels with ventricular septal defect and elevated pulmonary vascular resistance are reported. There has been early or late mortality in this group of patients, and postoperative morbidity has been minimal. Five of them have been recatheterized, and the results indicate substantial improvement in postoperative arterial oxygen saturation with change in pulmonary vascular resistance. The operation is reserved for those patients in whom peripheral desaturation is the major cause of symptomatology. Clinical improvement has been gratifying, and the continued use of the operation in selected patients seen indicated.


Clinical evaluation of priming solutions for pump oxygenator perfusion. Various hemodilution agents are now used routinely to prime heart-lung machines for cardiac operations. Hemodilution has resulted in considerable conservation of blood as well as diminution of plasma and corpuscle damage by decreasing the concentration of these elements in blood during extracorporeal circulation. Controversy has existed regarding the relative efficacy of various hemodilution solutions. This study covers 68 patients, divided into three groups, for whom hemodilution was done as follows: (1) the pump was primed with a 5% dextrose solution containing no colloid; (2) Ringer's lactate solution containing approximately 1% low-molecular-weight dextran was used; and (3) a new plasma expander, hydroxyethyl starch, was used as the colloid component of an electrolyte solution. Evaluations and comparisons were carried out for flow rates, blood pressure, urine volume, hematocrit, BUN, blood loss, clotting factors, and the patient's clinical course with regard to pulmonary and neurological complications. We conclude that a colloid is beneficial, especially with longer perfusions.


Quinidine hepatitis.

Quinidine hepatitis. Long-term administration of quinidine was associated with persistent elevation of serum concentrations of SGOT, lactic acid dehydrogenase, and alkaline phosphatase. Liver biopsy showed active hepatitis. Discontinuance of quinidine therapy led to normalization of liver function tests. A challenge dose of quinidine caused clinical symptoms and abrupt elevation of SGOT, alkaline phosphatase, and lactic acid dehydrogenase values. We concluded that this patient had quinidine hepatotoxicity and believe that this is the first case reported with liver biopsy documentation. This report also suggests that, even after long-term administration, the hepatic toxicity is reversible.


Blood protein fraction comparisons of normal and schizophrenic patients. Whole blood, plasma, or serum levels of various components were measured in fasting, drug-free control subjects and drug-free schizophrenic patients. Compared to normal controls, chronic schizophrenic patients showed increased alpha2-globulins and decreased plasma cholinesterase activity and ceruloplasmin activity, and acute schizophrenic patients showed decreased alpha2-globulins. Compared to chronic patients, acute schizophrenics showed decreased alpha2-globulins and IgA. Compared to normal controls of similar age, chronic schizophrenic patients weighed less, were shorter, and had smaller body surface area. The acute schizophrenic patients were significantly younger than the normal subjects or chronic schizophrenics but there was no difference in the other physical measurements. The present study indicates no gross disturbances in the blood variables studied. That some differences are statistically significant from controls is of scientific interest, but of no clinical value in the diagnosis of schizophrenia.


Aneurysmectomy in the aged.

Aneurysmectomy in the aged. The records of 206 aneurysmectomy patients over the age of 70 years were reviewed. Increased three- and five-year mortality was seen with a variety of risk factors--cerebral vascular disease, cardiac disease, diastolic hypertension, renal disease, and cigarette smoking--but 30-day mortality was not affected. Age was not a significant risk factor. It is recommended that patients with aneurysms less than 7.5 cm be observed if multiple risk factors are present. Almost all patients with aneurysms greater than 7.5 cm should have resection to prevent death from rupture, although this will be short-term palliation in patients with multiple risk factors.


Hepatic artery ligation and cytotoxic infusion in treatment of liver neoplasms. Since 1970, 38 patients with multiple primary or secondary liver neoplasms have been treated by hepatic artery ligation and distal cytotoxic infusion with fluorouracil. There have been two postoperative deaths. Although liver enzymes (alkaline phosphatase, serum glutamic oxaloacetic transaminase, and lactic dehydrogenase) rise markedly during the first three days, they usually return to preoperative levels within eight days. The median survival time of all patients, including the two postoperative deaths, was 13.3 months. The longest patient survival was 44 months. In the eight patients still living, the median survival time is 17 months, ranging from 11 to 27 months. Substantial palliation can be achieved by hepatic artery ligation and infusion with minimal morbidity and mortality.


[Testicular morphology in the early and late stages of prostatic cancer]. A total of 31 biopsy specimens in patients with cancer of the prostate (18 with I and II stages and 13 with III and IV stages of the disease) were investigated.  The results obtained were collated with those of the control group (22 observations).  Involutional changes in the testes in the patients with cancer of the prostate started earlier and were more pronounced than those in the corresponding age of the control group.  The testes in the patients with cancer were characterized by a specific mucoid oedema of the intertubular stroma with outcome into sclerosis.  At early stages of the cancer hyperplasia and hypertrophy of Leydig' cells were noted.  At final stages of the diseases their number normalized.  At the same time the number of Sertoli's cells increased and signs indicating to intensification of their activity appeared.


[Morphogenesis of coronarosclerosis in rheumatism]. Post-mortem studies of 72 hearts of persons who when alive had suffered from rheumatism were carried out.  A complex genesis of sclerotic processes in the vascular walls was noted.  They were occurring as a result of the desorganization of the connective tissue, as well as of "wearing out" of hemodynamic adaptation structures and development of atherosclerosis.  The dependence of the character of sclerotic changes in vessels upon the peculiar features of the clinical course of the disease is shown.  In cases with a high activity of the rheumatic process and considerable increase in the vascular-tissue permeability the development of hyalinosis was noted, and in cases with a slow course of rheumatism an increased fibrillogenesis was observed.  Simultaneously, lesion and perish of the smooth-muscle fibres of the media with outgrowth therein of the connective tissue occurred.  The dependence of the extent of atherosclerosis in various branches of the coronary arteries upon a morphofunctional characteristics of this defect was established.  The most extensive atherosclerotic lesions were found in those vessels which supplied with the blood the functionally burdened regions of the myocardium.  A higher activity of lipolitic enzymes in the vessels and the cardiac muscle was observed in persons with rheumatism, as compared with that in persons free from cardiovascular diseases, and particularly in patients with atherosclerosis.


[Acid polysaccharides (glycosaminoglycans) of the articular cartilage in rheumatoid arthritis]. As a result of histochemical investigation of the articular hyaline cartilage in 22 pateints with rheumatoid arthritis data were obtained on the decrease and redistribution of acid polysaccharides glycosamine glucane including keratosulphates, which led to an impartment of the cartilage supply and development therein of destructive processes.  It was established that the most pronounced changer occurred in the main substance of the cartilage; changes in chondrocytes, according to the authors, were of secondary nature.


[Smooth muscle cells of the blood vessels and internal organs of the vertebrates in normal and pathologic states]. The article presents a review of present day literature data on the structure of the smooth-muscle cells of vertebrates in the norm and pathology.  The smooth-muscle cells of blood vessels and internal organs of vertebrates possess a contractile apparatus the same as in striated muscle and are characterized by two main functions: contractile and synthetical.  The latter manifests itself in the capability of the muscle cells to synthesize all the components of the interstitial matter.  General pathology of the smooth muscle includes disorders of ultracirculation, metabolic disturbances, necrobiotic changes and necrosis of the muscle cells, compensatory-adaptive processes predominantly of the type of hyperplastic-hypertrophic reaction and regeneration.


Mucous glands in the developing human nose. In 56 fetuses the development and spread of the nasal glands were studied by three different whole-mount methods. Development starts anteriorly in the nose and proceeds with a given regularity backward. The anterior nasal, serous glands are found only most anteriorly in the nose. They are laid down in the 11th week by the formation of long ducts that grow backward. Small seromucous glands start forming in the 13th week. They gradually spread backward in the middle and inferior meatus and hence to the medial and lateral surfaces of the inferior and middle conchae. They are present in all parts of the respiratory region except in a small area above and behind the nasal vestibule and behind the conchae, Bowman glands start developing in the 16th week, in the roof of the nose, and gradually spread down through the entire olfactory region. They are very small, tubular, and serous. Bythe 23rd week gland formation has been completed.


Middle ear mucosa and chronic ear disease. III. Enzyme studies of thick noncholesteatomous epithelium. Thick mucosa removed from the promontory in cases with chronic otitis media showed prominent PAS-positive glands and epithelial secretory cells. Alcian blue positivity was less pronounced, contrary to the mucosa from glue ears. Enzyme activity in the epithelium and propria was comparable to that in glue ears, with some increase in alkaline phosphatase and some decrease in proprial lactate dehydrogenase and malate dehydrogenase activity. Removal of thick, permanently altered mucoas is recommended even in the absence of squamous epithelium. Steps should be taken to allow regrowth of thin, normal middle ear epithelium on the promontory.


Myoepithelioma of minor salivary gland origin. Light and electron microscopical study. A gingival tumor that invaded the anterior maxilla was removed from a 14-year-old boy and studied by light and electron microscopy. The tumor was composed exclusively of myoepithelial cells and appeared to be malignant. By light microscopy, the tumor appeared to be a poorly differentiated epithelial neoplasm of undetermined origin; however, electron microscopical examination showed myoepithelial differentiation, indicative of a salivary gland origin. To our knowledge, the present case represents the only confirmed myoepithelioma that shows features indicative of malignant potential. Myoepitheliomas may be related to mixed tumors of salivary glands.


[On the sex chromatin and sex chromatin-like nuclear structures in human Purkinje-cells]. Animal experiments have shown that in the course of chromatolysis the nuclear sex chromatin of nerve cells of female mammals changes its customary location at the nucleolus and migrates to the nuclear membrane; moreover, in the nuclei of nerve cells of males there occur under similar conditions nuclear structures which resemble the sex chromatin. It was, therefore, thought of interest to see if similar findings also apply to human Purkinje-cells. The cerebellum of 100 female and 52 male corpses of various ages was examined. Paraffin sections, 2-5 mum thick, were stained with haemalumeosin and, after hydrolysis by hydrochloric acid, with cresyl violet of Schiff's reagent (Feulgen stain). In each cerebellum 100 Purkinje-cells, whose nuclei showed a well developed nucleolus and an obvious Barr body, were studied. In the cerebellum of 29 female corpses the cells examined showed a marked cytoplasmic chromatolysis; in the Purkinje-cells of the remaining 71 female, and of all the male corpses the stage of chromatolysis was classified according to the degree of dissolution of the Nissl bodies as "feeble", "marked", or as the stage of restitution, characterized by nuclear caps. The sex chromatin was seen as a, mainly, round and compact chromocenter with a maximal diameter of 0.6--1.6 mum. The larger Barr bodies were seen more frequently, if chromatolysis in the corresponding cells was marked. With increasing chromatolysis the Barr body, which usually occupies a perinucleolar location, tended to be found more often at or near the nuclear membrane. In the cerebellum of the males 17.4% of the Purkinje cells studied showed heteropyknotic nuclear structures which could not always be distinguished in size or in appearance from a sex chromatin. They occupied predominantly a perinuclear position. but with increasing chromatolysis they too were seen more frequently in a location which tended to be intermediary or near the nuclear membrane. Not infrequently the nuclei simultaneously presented a granular hyperchromatosis. The change in the location of the sex chromatin in the nucleus is considered to be associated with compensatory processes following chromatolysis. These in turn are accompanied by an intranuclear current of materials, such as RNA, towards the periphery of the nucleus, or by changed electric potentials which develop in the affected cells. The variations in size of the Barr body should be attributed to a variable condensation of the corresponding X-chromosome, rather than to polyploidy of the nerve cell nuclei. The sex chromatin-like chromocenters, which are seen in "male" Purkinje-cells in the course of chromatolysis, could be attributed to certain chromosomal segments which have a tendency to heterochromasia...


Frequency potentiation and postextrasystolic potentiation in patients with and without coronary arterial disease. Frequency potentiation and postextrasystolic potentiation of myocardial contractility were induced in 17 patients found not to have cardiac disease (group 1) and in 10 patients with coronary arterial disease (group 2). Atrial stimulation was performed starting at a rate of 110/min and going up to 200/min (frequency potentiation). Single, premature ventricular beats with decreasing coupling intervals were induced every fifteenth beat during basal atrial stimulation at 125/min, after which compensatory pauses were provided (posts used an an index of contractility. With increasing heart rate dp/dt max was augmented equally, in both groups of patients, by frequency increases and premature beats (the coupling interval of the extrasystole being expressed as heart rate). dp/dt min and left ventricular systolic pressure remained unchanged while left ventricular end-diastolic pressure decreased in both groups of patients with the two forms of potentiation It was concluded that both these forms of potentiation have the same augmenting effect on myocardial contractility. Shortening the coupling intervals of premature beats caused a decreased in left ventricular end-diastolic pressure, suggesting that the Frank-Starling mechanism was not involved in postextrasystolic potentiation. Patients with coronary arterial disease had lower values of dp/dt max, dp/dt min, and higher values of left ventricular end-diastolic pressure during rest and stimulation procedures, while the systolic pressures equalled those in the control group. Though individual case values from the healthy and diseased hearts might be similar, it was only under the stress of potentiation that the true state of contractility was made apparent. Impairment of dp/dt min was not found without an impairment of dp/dt max in the presence of myocardial ischaemia.


Cytology as a guide to the presence of chlamydial inclusions in Giemsa-stained conjunctival smears in severe endemic trachoma. Microscopical examination of 927 Giemsa-stained conjunctival smears from children with chronic trachoma in southern Tunisia showed 93 (10 per cent.) with typical trachoma (chlamydial) inclusions in epithelial cells. The accompanying cytological features were a useful indicator for inclusions. Inclusions were found only in slides with numerous polymorphonuclear neutrophils (PMNs) and separation of the epithelial cells. When these two features alone were present, 3 per cent. of the smears were inclusion-positive; when many lymphocytes were present also, 25 per cent. were inclusion positive; when other cytological features (plasma cells, macrophages, blastoid, and stem cells) were present as well, 70 per cent. of the smears were inclusion-positive. The occurrence of these sets of cytological features can be a useful guide for selecting smears for intensive examination for chlamydial inclusions. Immunofluorescent (FA) staining and Giemsa staining of 527 pairs of matched smears detected trachoma agent in 67 (13 per cent.); in thirty by both methods, in thirteen by Giemsa staining alone, and in 24 by FA alone. The examination of Giemsa-stained smears for chlamydial inclusions is a useful technique for the diagnosis of trachoma or inclusion conjunctivitis by laboratories that do not have the specialized facilities for the identification of these chlamydial infections by the technically more complex procedures of immunofluorescent staining or isolation in embryonated eggs or tissue cultures.


Mechanisms of lysosomal enzyme release from leukocytes. IV. Interaction of monosodium urate crystals with dogfish and human leukocytes. In order to determine the possible mechanisms whereby interactions between phagocytic cells and crystals of monosodium urate (MSU) lead to cell death with simultaneous release of both cytoplasmic and lysosomal enzymes, phagocytic leukocytes of the smooth dogfish shart Mustelus canis were studied by means of light and electron microscopy, and biochemistry. Lysosomes of these cells can be stained supravitally with toluidine blue and are large enough (0.7-0.8 mu) to be clearly resolved with the light microscope. Light microscopic observations showed that of cells exposed to MSU 87% of those containing visible ingested crystals died within 1 hour, whereas 92% of adjacent cells in the same wet mount without such srystals survived. Cell death occured after a latent period of 10-15 minutes following fusion of lysosomes with crystal-containing phagosomes. Electron microscopic examination of both dogfish and human leukocytes exposed to MSU for more than 1 hour and then fixed in situ revealed occasional discontinuities or ruptures in secondary lysosome membranes. Endogenous peroxidase activity could be cytochemically localized in primary and secondary lysosomes and in the cytoplasm adjacent to such ruptured secondary lysosomes. It was not seen adjacent to primary lysosomes, a result indicating that the cytoplasmic reaction product was not a diffusion artifact. To exclude the possibility that crystals were exercising their affect primarily upon the plasma membrane, suspensions of dogfish buffy coat cells were incubated with cytochalasin B (5 mug/ml, 10 minutes), which inhibits phagocytosis but not exocytosis of lysosomal enzymes by stimulated phagocytes. Whereas cells exposed to MSU crystals released 30% of their content of lysosomal beta-glucuronidase activity and 28% of their cytoplasmic lactate dehydrogenase (LDH) activity within 3 hours, preincubation with cytochalasin B reduced the release of LDH activity within that period to 6% but reduced the release of beta-glucuronidase activity only to 20%. Preincubation with 10-3 M cyclic adenosine monophosphate (cAMP) and theophylline (10-3 M), which inhibit lysosomal fusion, reduced the release of both LDH and beta-glucuronidase activities to 7% and 6% respectively. Cells that were preincubated with both cytochalasin B and cAMP + theophylline released only 1% LDH activity and 4% beta-blucuronidase activity. These results are compatible with the "suicide sac" hypothesis of lysosomal enzyme release mediated by MSU for the following reasons: a) cell death was seen to follow uptake, not mere exposure to crystals, b) ultrastructural studies indicated that the primary injury was to the secondary lysosome membrane, and c) cell death was reduced when either phagocytosis or lysosomal fusion was inhibited.


Acute myelogenous leukemia of the Wistar/Furth rat: establishment of a continuous tissue culture line producing lysozyme in vitro and in vivo. A transplantable myelogenous leukemia of an inbred Wistar/Furth rat has been established in tissue culture and cloned. The resulting transplantable leukemia line demonstrates in vitro doubling time of 20 hr, colony-forming efficiency of 5% in liquid and methylcellulos-containing medium, and a saturation density of 3.0 x 106 cells/sq cm in liquid medium. Following intraperitoneal inoculation, newborn rats developed solid tumors, ascities, and leukemia with ld50 of5 x 103 cells and mean latency of 60 days. The tumor cell morphology was consistent with that of acute myelogenous leukemia. Histochemical staining for myeloid enzymes revealed no evidence of myeloperoxidase, esterase, or leukocyte alkaline phosphatase; however, fluorescent antibody staining for lysozyme was markedly positive. Serum, urine, and ascitic fluid from rats with transplanted leukemia also contained elevated levels of lysozyme. There was no detectable type-CRNA virus production by this cell line after as long as 100 days in vitro. This inbred rat myelogenous leukemia should provide a useful model for studies of chemotherapy and immunoltherapy of human acute myelogenous leukemia.


Microscope fluorometric investigations on the reticulocytic maturation distribution as diagnostic criterion of disordered erythropoiesis. A microscope fluorometric technique is described which permits not only the visual identification of reticulocytes under the fluorescence microscope but also the determination of their relative stage of maturation to normocytes. The technique is based on a specific staining procedure which results in a fluorescent complex between the reticulocytic RNA and acridine orange. Thus, the relative mass of RNA in the individual reticulocytes can be measured by means of mciroscope fluorometry. As the reticulocytic RNA content decreases and finally disappears during the final maturation process of reticulocytes after their release into the peripheral blood stream, the fluorescence signal indicates the relative degree of this maturation. A characteristic frequency distribution of this parameter can be obtained for a given blood sample by microscope fluorometry measuring 200 to 300 reticulocytes. The preliminary use of this technique for following up the course of two cases of hemolytic anemia and one of pernicious megaloblastic anemia during their treatment demonstrates the potential diagnostic value of this technique of identifying the change of the reticulocyte maturation distribution in addition to the reticulocyte count. Satisfactory agreement between the microscope fluorometric results and those obtained by counting separately the four reticulocytic maturation stages according to Heilmeyer and Wesbäuser has been achieved. The possibility of obtaining quantitative and comparable results by use of this method may be considered a general advantage and a promising basis for the development of an automated technique.


[Influence of ultrasonic waves and enzymes on antigenic properties of human erythrocytes. I. Ultrasonic waves]. In order to desintegrate the membranes and to isolate Rh antigens erythrocytes with well defined Rh patterns are treated with ultrasonic waves. The results of investigation of the homogenous sonicates allow the following tentative conclusions: The Rh antignes (C and E) are combined obviously with certain functional membrane areas of a given size. After sonication the activity of the sonicate to neutralize specific antibodies is greater than the activity of the same amount of untreated cells. It is supposed that this effect is caused by making accessible hidden antigens that are inaccessible in the intact membrane. Immunization of rabbits with the sonicates does not stimulate Rh-specific antibodies.


Inhibition of immediate hypersensitivity reactions in laboratory animals by a phenanthroline salt (ICI 74,917). 1. The activity of a new anti-allergic compound, I.C.I. 74,917, has been studied in the rat, mouse and guinea-pig. 2. Following intravenous administration, I.C.I. 74,917 inhibits in a dose-dependent manner passive cutaneous anaphylaxis induced in rats and mice by heat-labile homocytotropic antibody. In rats, its potency is approximately 300 times that of disodium cromoglycate. 3. To achieve maximal inhibition, it is necessary to administer I.C.I. 74,917 at the same time as antigenic challenge; dosing before or after challenge has much less effect. 4. Liberation of histamine, provoked by the antigenic challenge of mast cells passively sensitized in vitro by IgE-like antibody, is reduced in the presence of I.C.I. 74,917. 5. Intravenous administration of the compound has no significant effect upon local blueing reactions provoked in the rat by intradermal injection of histamine, 5-hydroxytryptamine or Compound 48/80. It has only a slight effect at high doses upon passive cutaneous anaphylaxis induced in the rat by heat-stable homocytotropic or heterologous (guinea-pig) antibodies. 6. Although not a bronchodilator in the guinea-pig, I.C.I. 74,917 partially inhibits systemic anaphylaxis. A consistent reduction in the severity of antigen-induced bronchospasm was demonstrated in the Konzett-Rossler preparation at doses comparable to those inhibiting passive cutaneous anaphylaxis in the rat. However, there was only slight inhibition of passive cutaneous anaphylaxis in the guinea-pig. 7. I.C.I. 74,917 itself induces bronchospasm when administered to anaesthetized guinea-pigs or to a guinea-pig isolated lung preparation. This effect is reversed by salbutamol, but is not prevented by the prior administration of mepyramine, atropine or methysergide. 8. These results indicate that in the rat, mouse and guinea-pig, I.C.I. 74,917 is a potent inhibitor of certain types of immediate hypersensitivity reactions.


The distribution and dosimetry of 111-IN-bleomycin in man. The distribution of 111-In in the human body was studied after the injection of -111-In-bleomycin for tumour localization. Uptake in body organs was measured by quantitative scanning using a dual detector scanner. The estimated absorbed dose from an injection of 1 mCi was 0.3 rad to the whole body, and approximately 1 rad to bone marrow, kidneys, liver and spleen.


111-In-labelled bleomycin; clinical experience as a diagnostic agent in tumours of the thorax and abdomen. The potential value of indium-labelled bleomycin as a diagnostic scanning agent has been investigated in patients with a variety of malignant neoplasms involving the thorax, abdomen or pelvis. Sixty-five patients were scanned on 72 occasions, the optimum time to perform the examination being 72 hours after the intravenous injection of 2 mCi 111-In chelated to 2 mg bleomycin. Tumour uptake was visualized in 53 out of 62 scans in which tumour was present, but the extent of tumour was underestimated in seven cases, and over-estimated in five others. The latter were mostly due to uptake in infective lesions. These results indicate that the situations in which indium bleomycin is most likely to provide clinically relevant information are the distinction between recurrent tumour and post-radiotherapy changes in the thorax and pelvis, the diagnosis of recurrent carcinoma within the pelvis, and the distinction between bony metastases from carcinoma of the prostate and Paget's disease. Further clinical trials are necessary to assess these situations.


Progressive peripheral neuropathy in patient with primary hyperoxaluria. In a patient suffering from primary hyperoxaluria with oxalosis a progressive peripheral neuropathy was associated with intra-axonal deposition of microcrystals of calcium oxalate. Probably his neuropathy was the result of mechanical obstruction of axoplasmic flow.


Origin of urinary fibrin/fibrinogen degradation products in glomerulonephritis. To elucidate the origin of the fibrin/fibrinogen degradation products (F.D.P.) occurring in the urine in glomerulonephritis 28 patients with glomerulonephritis were examined for renal fibrinolytic activity, F.D.P. in urine and serum, and blood fibrinolytic activators and blood fibrinolytic activators and inhibitors. Unlike the glomerful of healthy kidneys, which were fibrinolyticly inactive, those of kidneys with glomerulonephritis constantly showed fibrinolytic activity. The presence or absence of fibrin in the glomeruli was almost always accompanied by, respectively, the presence or absence of urinary F.D.P., which suggested a renal origin of urinary F.D.P. in glomerulonephritis. The low fibrinolytic activity of the blood and the absence of F.D.P. in the serum of these patients make it unlikely that the urinary F.D.P. in glomerulonephritis result from glomerular filtration.


Diagnosis of hypothyroidism: a comparison of statistical techniques. From replies to a postal questionnaire used in a radioactive iodine follow-up scheme patients had to be classified as either "suspected hypothyroid" or "euthyroid." A comparisons has been made of the effectiveness of published statistical techniques in making this classification. Two main conclusions emerged. Firstly, all except one of the methods identified an acceptable proportion of the hypothyroid patients, and, secondly, the results given by these methods were remarkably similar. Thus the simplest, which required only a count of the number of symptoms present, was selected for use.


Kinetically-based multiple drug treatment for advanced head and neck cancer. A multiple drug regimen was given to 36 patients with advanced carcinomas of the head and neck. In 19 of the 24 patients who were assessable the tumour regressed more than 50%; in one it regressed by 25%; and in four it did not respond at all. Multiple drug chemotherapy should be given much earlier in the course of these cancers, preferably as an adjuvant to surgery or radiotherapy.


Mercaptoethanol-resistant human serum antibodies reacting with endotoxin from Neisseria gonorrhoeae. Sera from fifty patients with gonorrhoea, thirty with non-specific urethritis, and eighty blood donors were treated with mercaptoethanol (ME) and examined by the indirect haemagglutination test for antibodies against endotoxin from gonococci. Erythrocytes sensitized with determinant a of endotoxin from Strains 8551, V, and VII, or determinant b from Strain V were used. The percentage of sera active in the haemagglutination test was much higher in the gonorrhoea group than in the controls. The geometric mean titre was also significantly higher in the gonorrhoea group. This applied for all four antigens used. Results obtained in an anti-globulin test indicated that the titre of ME-treated serum was determined by IgG antibodies against the endotoxin. Many sera had titres which varied according to the strain origin of the antigen used in the test. The sensitivity of tests for antibodies was increased by using endotoxin from several different strains of gonococci for the examination of each serum. A simplified procedure for determination of antibodies against endotoxin from different strains of gonococci was elaborated.


Rapid axonal transport in trigeminal nerve of rat. The rat trigeminal nerve was investigated as a model system for axonal transport to identifiable sensory nerve endings. Following stereotaxic injection of [3-H]proline into the ganglion, the distribution of label in protein and other extracts of ligated or unligated infraorbital nerve was measured in replicates at various time intervals from 30 min to 3 days. In unligated nerves the average maximum velocity of somatofugal protein transport was 228 mm/day. Light microscope autoradiography demonstrated rapid intraaxonal transport of radioactive material to nerve endings in molar teeth and vibrissae. The system appears suitable for investigating the fate of axonally transported material at peripheral receptors.


Changes in brain hydrolytic enzyme activities in rats treated with cholesterol biosynthesis inhibitor, AY9944. Intraperitoneal administration of AY9944 causes accumulation of 7-dehydrocholesterol, appearance of abnormal neuronal cytoplasmic lamellar inclusions containing acid phosphatase activities, and degeneration of oligodendroglial cells. In the present study, we attempted to correlate appearance and disappearance of abnormal inclusions, oligodendroglial degeneration, activities of lysosomal enzymes, and accumulation of 7-dehydrocholesterol. One group of 5-day-old rats received daily injection of AY9944, 30 mg/kg, for 30 days. Other groups received the same daily dosage but only in 10 consecutive days, starting from 5, 15, 25, and 35 days, respectively. Activities of 13 brain hydrolytic enzymes were determined. In the first group, activities of most enzymes increased over the controls, reaching the peak between the 15th and 25th day, corresponding to the maximum appearance of the neuronal inclusions and degenerating oligodendroglia. Despite the continued administration of AY9944 and the high tissue concentration of 7-dehydrocholesterol, activities of most enzymes declined after 25 days to relatively steady levels somewhat higher than controls. In the group which received 10-day injections, enzyme activities reached the peak at the end of the injections and then rapidly returned to normal within 10 days thereafter, corresponding to the appearance and disappearance of the abnormal inclusions. However, 7-dehydrocholesterol continued to increase for 10 days after the drug administration was discontinued. AY9944 had no direct effect on any of the enzymes in vitro. There appears to be generalized lysosomal activation concomitant with formation of abnormal neuronal inclusions in the experimental conditions.


Studies on the development of the chick optic tectum. IV. An autoradiographic study of the development of retino-tectal connections. The normal pattern of innervation of the optic tectum has been studied autoradiographically in a series of chick embryos which were injected intraocularly with [3-H]proline at intervals between the 6th and 21st days of incubation. From the distribution of the radioactively labeled proteins transported in the rapid phase of axonal flow, it is evident that retinal fibers first enter the tectum late on the 6th day of incubation and then spread across its surface from its rostrolateral aspect to its caudo-dorso-medial pole during the ensuing 6 days. At the 9th day, when the fibers have grown across the surface of the rostral half of the tectum, there is no indication that the terminal portions of the axons have left the stratum opticum to enter the outer layers of the stratum grieseum et fibrosum superficiale. The first suggestion of such an invasion of the stratum grieseum et fibrosum superficiale is found at day 10, when labeled fibers can be seen in this stratum, over a restricted, oval, area near the center of the tectum. Over the course of the next 2 days the region of the stratum grieseum et fibrosum superficiale occupied by retinal fibers expands, more-or-less concentrically, until by day 14 some labeled fibers are seen in the outer part of the stratum, throughout the tectum. Concurrent with the ingrowth of optic nerve fibers the final cytoarchitectonic differentiation of the outer layers of the tectum occurs so that by day 18 the autoradiographs show a pattern of labeling of layers a-f of the stratum griseum et fibrosum superficiale similar to that seen in mature, post-hatched chicks. Since the region of the tectum which is first innervated by retinal fibers corresponds to the projection field of the region around the upper end of the choroid fissure where the first ganglion cells are generated, it would appear that the axons of the first-formed ganglion cells grow over the rostral surface of the tectum before establishing the first retino-tectal synapses near the central portion of the tectum. Subsequently, as the ganglion cell population grows concentrically from around the area centralis, there is a parallel expansion of the region in which retino-tectal synapses are being formed in the tectum.


Evaluation of [3-H]proline for radioautographic tracing of axonal projections in the teleost visual system. The efficacy of [3-H]proline radioautography for tracing retinal ganglion cell projections to the optic tectum of the jewel fish, Hemichromis bimaculatus, has been compared with that of degeneration techniques. There was good agreement between the various methods. Retinal projections to the optic tectum of two other teleosts, the oscar, Astronotus ocellatus, and the goldfish, Carrasius auratus, were examined radioautographically. In addition to conventional methods of analysis, radioautograms were scanned in a slit microdensitometer and by an automated isodensity scanning system. Results of studies with the protein synthesis inhibitor, cycloheximide, are compatible with the suggestion that axonally transported proteins labeled with [3-H]proline may release diffusible precursors that are reincorporated into protein in adjacent regions. The possible advantages and limitations of radioautography of [3-H]proline-labeled axonally transported protein in brief or extended studies are discussed in terms of the results obtained in the teleost visual system.


Feulgen hydrolysis and chromosome banding in Chilocorus (Coleoptera: Coccinellidae). Prolonged Feulgen hydrolysis of chromosomes of Chilocorus orbus Csy. and C. stigma Say produces banding patterns that are the reverse of those revealed with quinacrine; brightly fluorescing regions are unstained, but nonfluorescent regions remain relatively darkly stained. This differential reactivity at hydrolysis times that otherwise yield intense Feulgen staining confirms the need for caution in the determination of DNA values with the Feulgen reaction in material with well-defined quinacrine bands. The coincidence of DNA-specific Feulgen bands with Q-, G-, and C-bands supports the view that, in Chilocorus at least, bands reflect differences in DNA composition along the chromosome.


Quinacrine fluorescence and Q-banding patterns of human chromosomes. I. Effects of varying factors. Various factors involved in the production of "Q-bands" have been studied. It was found that a Zeiss standard WL fluorescent microscope required a shorter exposure time for photography as compared to a Zeiss photomicroscope. The minimal exposure time was obtained when the standard WL microscope was equipped with a UV light source containing a DC powered mercury burner and a concave mirror. Further, the pH and type of water used in the staining, washing and mounting of the slide were also important factors in producing clear and well differentiated "Q-bands". It also appears that the factors involved in the production of "Q-bands" effect the enhancement or quenching of fluorescence by poly d(A-T)-poly d(A-T) and salmon sperm DNA or poly dG-poly dC respectively. This preliminary report also suggests that DNA or polynucleotides with a specific base sequence may play an important role in Q-banding patterns on chromosomes.


Virologic and immunologic studies of human prostatic carcinoma. Morphologic, tissue culture, immunologic, and biochemical methods have been used in an attempt to detect and characterize oncogenic viruses or their subviral components in cells derived from human prostatic carcinoma (PrCa) or benign prostatic hyperplasia (BPH). Electron microscopy was used to characterize the ultrastructural features of normal and neoplastic prostatic tissue. Examination of specimens of prostatic tissue from 34 patients with PrCa, ten patients with BPH, and three patients with bladder tumor (BT) revealed the presence of particles resembling type-C virus in three cases of PrCa and structures resembling budding type-C virus particles in one case of BPH. Fifty human prostatic tissue specimens have been set in tissue culture, of which 30 have been successfully grown for varying periods of time. Of 20 currently active cultures, nine consist primarily of epithelial cells. Immunofluorescence and mixed hemadsorption tests of cells derived from benign and malignant prostatic tissue and sera derived from patients with PrCa, BPH, BT, and other types of tumors, and from normal donors revealed that sera from patients with PrCa, BPH, or BT contain antibodies to antigens in cells derived from PrCa, BPH, or BT. The nature of these antigen-antibody reactions is under study. Initial biochemical studies have not detected reverse transcriptase in the tissue culture fluid from a small number of sparsely growing PrCa cultures nor specific gene sequences homologous to murine leukemia virus-Rauscher genomic RNA in preparations of either normal or malignant prostatic cell DNA. The results of these preliminary studies have demonstrated the applicability of the techniques employed to the study of the relationship of viruses to human PrCa and have provided a number of promising leads for further investigation.