A new approach to the preparation of ACTH antibody by immunization of the rabbit with an antigen-antibody complex. Immunization with antigen-antibody complex of ACTH produced sensitive ACTH antibody applicable to the radioimmunoassay. The antibody prepared by immunization with the synthetic 1-24 ACTH was mixed with the antigen porcine ACTH, and the mixture was incubated to form the antigen and antibody complex. Two rabbits were initially immunized with this complex, then further immunized with only the porcine ACTH. Both rabbits produced the ACTH antibody with a titer of 1:25,000, which could detect ACTH of 5 pg per tube when applied to the radioimmunoassay of the human ACTH. This antibody showed a strong crossreaction with synthetic 1-24 ACTH, which was confirmed by radioimmunoassay method and immunostaining technique. On the other hand, control animals immunized with only procine ACTH from the beginning showed no production of ACTH antibody. It was concluded that addition of ACTH antibody to the antigen for the first immunization took an important role in eliciting production of the antibody. Possible roles of the antigen-antibody complex for immunization were discussed.


Tyramine-like effect of cyclocytidine (2,2'-anhydro-1-beta-arabinofuranosylcytosine hydrochloride), an antineoplastic agent. Since cyclocytidine (2,2'-anhydro-1-beta-arabinofuranosylcytosine hydrochloride) was introduced as an antineoplastic agent for the treatment of lymphatic leukemia, sinus acceleration and an increase in systemic blood pressure has been reported as its systemic effects in the clinical cases. These cardiovascular effects of cyclocytidine were observed also in anesthetized dogs, but not in reserpine-pretreated animals. Increases in heart rate and in systemic blood pressure were prevented by propranolol and phentolamine, respectively. The mechanism of these sympathomimetic effects was further analysed in the excised, blood-perfused canine sinoatrial node and papillary muscle preparations with a support dog. Positive chronotropic and inotropic responses to cyclocytidine were abolished by desipramine, propanolol, and pretreatment with reserpine but not by tetrodotoxin and hexamethonium. The tyramine-like actions of cyclocytidine at adrenergic neuronal terminals were discussed in conjunction with the uptake mechanism of the drug into the tumor cells.


[Does cancer therapy program its failure, too? (author's transl)]. Is seems indispensable, in consideration of the present investigation results, to revise our actual therapeutic conception for cancer therapy! While palliative cancer therapy was greatly successful, it was not possible to obtain any decisive improvement of cancer recovery rates (in relation to similar stages or tumor volumes), in spite of all the therapeutic endeavour through the last twenty or twenty-five years. From almost 3000 analyses of metastatic growth and from numerous other experimental or clinical observations results as an explication that surgical treatment itself, on certain conditions, may release a relatively great number of metastases. Thus, the failure of our therapeutical endeavor is programmed, too, by the treatment! Consequences for diagnostics, precautions and therapy are discussed.


Radiation treatment of liver metastases. 19 patients with cancer of the liver treated with palliative irradiation are presented. In five of eleven cases jaundice disappeared (4) or diminished (1). In two of the eight patients with pain as the chief symptom pain disappeared, and in one case the enlarged liver diminished considerably. A total of eight of 19 cases responded to radiation treatment.


Modulation of T-dependent cell-mediated immune responses by antigen-reactive cell opsonization and active suppression. We have studied both specific and non-specific suppression in allogeneic combinations. On the one hand, achievement of specific suppression may circumvent both HVGR and GVHR, while on the other, Cy-resistant suppressor cells may exacerbate the GVHR in bone marrow graft recipients. A greater understanding of both of these aspects of modulation of immune responsiveness will be important in clinical bone marrow transplantation.


Close genetic relationships between determinants of the HLA-D region detected by MLR-I, MLR-II, and B-lymphocyte serology. The human Ia equivalent (Ly-Li system) or a very closely linked gene plays a preponderant role in secondary MLR, and also has an additive effect on the intensity of the primary MLR. PLTs developed in Li phenoidentity seem to detect still other determinants.


[Bladder outlet obstructions: the value of urodynamics (author's transl)]. The uroflowmetry has value (1) as a screening procedure in bladder outlet diseases, and (2) in assessing results of treatment. The results of measurement depend: (1) on the circumstances of micturition; (2) on the bladder volume, and (3) on how far the patient is cooperative. The interpretation of measurements must be related not only to maximum flow and micturition time, but also to a specific micturition pattern. As an isolated method the uroflowmetry has limitations. The value of this procedure may increase by pressure measurements during micturition. However, caution should be exercised in interpreting a resistance factor. Extensive information is presented by simultaneous cine-pressure-flow measurement. Additional urodynamic procedures, especially the urethra pressure profile, are of no value in bladder outlet obstructions.


Role of urinary alpha1-globulin fraction in formation of urinary calculi. With special reference to aggregating effect of serum alpha1-globulin on calcium carbonate suspension. The present study was undertaken to determine if urinary protein can produce urinary stones and what types of protein have such an effect. Normal human serum was fractionated first with ammonium sulfate and then with DEAE-cellulose. The stone-forming action of each fraction was estimated by calculating their ability to alter the sedimentation rate and zeta-potential of a calcium carbonate suspension. Finally, the proteins in each fraction were identified by cellulose acetate electrophoresis. The most marked aggregating and precipitating effect on a CaCO3 suspension was observed with a mixture of proteins of alpha1-globulin and albumin fractions. However, beta- and gamma-fractions had little aggregating effect on the CaCO3 suspension.


Chemotherapy for disseminated testicular cancer. Fifty patients with disseminated testicular cancer were treated with a three-drug combination consisting of cis-diaminedichloroplatinum, vinblastine, and bleomycin. Three patients were considered unevaluable due to early death. This chemotherapy regimen produced 74 per cent complete and 26 per cent partial remissions. Furthermore, five patients in partial remission became disease-free following the surgical removal of residual disease, producing an overall 85 per cent disease-free status. Toxicity, although significant during remission induction with cis-platinum, vinblastine, and bleomycin, was usually manageable. Maintenance therapy with vinblastine and BCG was very well tolerated, and only two patients in complete remission have experienced a relapse on maintenance therapy, one of whom had a central nervous system relapse. Thirty eight of these patients remain alive, and 32 remain alive and disease-free 6+ to 30+ months. We feel that this regimen represents a major advance in the management of patients with disseminated testicular cancer.


Biology of testicular tumors.

Biology of testicular tumors. Testicular tumors arise from the germ cell line and therefore exhibit characteristics of both neoplastic and normal growth and differentiation. Experimental model systems of animal and human tumors have been reviewed with emphasis on the biologic characteristics of these tumors. The embryonal carcinoma cell is the totipotential stem cell that resembles normal germ cells in many ways and is capable of differentiating along the somatic pathways to form endoderm, mesoderm and ectoderm cell types (teratoma) or along extraembryonic pathways to form trophoblast (choriocarcinoma) or yolk sac (endodermal sinus tumor). Markers of the extraembryonic cell types have been defined, and the cell surface characteristics of embryonal carcinoma cells are being intensively studied. Clarification of the biology of testicular tumors will provide the basis for future rational therapy.


[Histologic components of benign prostatic hypertrophy (bph) in relation to the androgen-estrogen status (author's transl)]. Histometric microscopic quantifications of stromal and glandular portions of BPH revealed a significant correlation of the amount of the stromal portion to the individual estrogens in the serum and to the estrogen secretion in the urine. The serum androgen level, the so-called androgen/estrogen ratio, and age had no influence.


[Complications following transfemoral embolization of renal carcinoma. Survey and experience (author's transl)]. A comprehensive survey of the complications following 151 transfemoral embolizations of renal carcinoma is presented, including 9 of our own patients. The main side effects seen after this procedure are (in decreasing frequency): elevation of body temperature, transient elevation of arterial blood pressure, impairment of renal function, infection of the necrotic tumor, thromboembolic incidents, and accidental embolization of other organs. Total lethality is about 3.3%. Possible contraindications and precautionary measures are derived from the discussion of the pathophysiologic reactions in the course of the complication: avoidance of therapeutic embolization immediately after diagnostic angiography, strict asepsis, addition of antibiotics to the embolization mixture, prophylactic administration of heparin, and the use of flowdirected balloon catheters.


Hematologic screening tests in patients with operative prostatic disease. One hundred sixty-five patients with operative prostatic disease were investigated for hematologic abnormalities. The tests were useful in the clinical management of 6 (3.7 per cent) patients. Preoperative hematologic screening tests are recommended in patients with prostatic cancer, potential sepsis, and in patients with a known bleeding tendency.


The efficacy of showers for control of ectoparasites of sheep. Ectoparasites of sheep in Britain include the tick Ixodes ricinus, the blowfly, Lucilia sericata, the ked, Melophagus ovinus and the lice, Damalinia ovis and Linognathus ovillus. The most important ectoparasite, however, is the mite Psoroptes communis ovis which causes sheep scab. This notifiable disease was eradicated from Britain in 1952 but was reported again in 1973. The control of ectoparasites depends largely on the efficient application of insecticide to the fleece and skin. Plunge dipping in a bath is generally regarded as the most efficient method and is compulsory for the control of sheep scab but it is not always the most convenient. After the eradication of sheep scab in 1952 plunge dipping was no longer compulsory and jetting, spraying and showering techniques were then employed for the other ectoparasites.


Xanthosis, an abnormal pigmentation of cattle. Xanthosis is seen in cattle in the abattoir. It is characterised by a dark brown colour of the heart muscle and certain skeletal muscles such as the masseter because of the presence of lipofuscin pigment. In a survey of its prevalence in 1000 cattle of varying breeds xanthosis was identified in about 25 per cent of Ayrshire cattle and the occasional Ayrshire cross. It was not seen in other breeds. The incidence of one affected and three normal suggests that this condition may result from the inheritance of a simple recessive gene. The relationship of xanthosis to brown atrophy is discussed.


[Resorption of colostral gamma-globulins and detection of antibodies to Bact. rhusiopathiaesuis, S. cholerasuis and beta-hemolytic Esch. coli in newborn pigs]. Traced was the resorption of colostral globulins and the production of antibodies against Bacterium rhusiopathiae suis, S. choleraesuis, and beta-hemolytic Escherichia coli organisms in newborn pigs. It was found that in the newborn pigs that had not yet started sucking there were no gamma-globulins and specific antibodies against the agents mentioned above. Such were observed after the animals had begun to suck, the titers of antibodies reaching their peak levels by the 10th--15th hour (erysipelothrix and paratyphoid) and the 24th--48th hour (hemolytic Escherichia coli). As against their mothers the titer of the antibodies in the sucklings was two to four times as lower. The gamma-lactoglobulins are resorbed along the whole intestinal mucous membrane, however, resorption is most intense in the duodenum and the jejunum in the course of the first 2 days after farrowing; from the fifth day on it ceases.


[Passive immunization in heterakidosis]. The sera of Heterakis-infected birds influence the course of the infection caused by the parasite, lowering its survival rate and delaying the shed of its eggs. Sera containing higher amounts of gamma-globulins from five-month-old birds confer higher resistance even when applied on the 12th day of Heterakis infection to intact birds as compared to sera containing lower amounts of gamma-globulins from one-month-old birds when applied on the 30th day of infection. The drop of the survival rate of the Heterakis parasite in injecting the birds with sera from Heterakis-infected birds is due to the activation of the caecum response.


[Group and type antigenic specificity of bovine adenovirus type 1 hexons]. Hexones were obtained from the bovine serotypes 1 and 3. They were investigated through the complement-fixation test along with intact virions in the presence of a hemotype and a heterotype antiserum. It was shown that the free hexones were twice as reactogenic in the homotype system as compared to the heterotype one. The hexones were found to possess two antigenic determinants--a typespecific one and a group-specific one. The latter proved sensitive to chymotrypsin. Intact vicions reacted chiefly type-specifically. Discussed is the problem of the space disposition of the type -and group-specific antigen determinants of the hexones in sito in the virions.


[Postoperative fructose infusion in a case of presumed hereditary fructose intolerance (author's transl)]. Hereditary fructose intolerance (HFI) was diagnosed in a 61 year-old male patient on account of liver dysfunction followed by prolonged shock immediately after the administration of a fructose and lactose infusion postoperatively. The diagnosis of HFI was based on an increased value of fructose, hypoglycaemia, lactic acidosis and diminution of the phosphate level in combination with the typical family history. The patient's children showed a normal reaction to fructose administration. The therapy included glucose, insulin and heparin administration, balance of acidosis and partial exchange of blood, which resulted in improvement in the glucose level, coagulation factors and acidosis, but could not prevent further liver damage and uraemia with a fatal outcome.


[Vascularization of the ganglion spirale cochleae of the rat (author's transl)]. Investigation into the vascularization of the Ganglion spirale of the rat showed an irregular, loose network of capillaries, with a somewhat denser vacularization of the marginal areas of the ganglion; the horseradish peroxidase benzidine test according to Sugar was used to demonstrate the vessels. At least of the blood supply of the ganglion is effected via the vessels which run parallel to the nerve fibres through the osseous canals from the modiolus into the Rosenthal canal. The density of vascularization of the Ganglion spirale is surprisingly small, namely 1.89% by volume. The comparative figure for the Ganglion spirale, also measured by means of stereological methods, is approximately 6.8% by volume, whilst the vessels in the Nervus cochlearis occupy 2.1% by volume. The vascularization density of the ganglion corresponds roughly to that of the Cortex cerebri. Electro-microscopical tests have shown that there are unfenestrated capillaries with a small number of pinocytotic vesicles. Possible conclusions as to the permeability of the capillaries are discussed in the paper. The blood supply of the Ganglion spirale has so far received only little attention. In the case of internal ear diseases of vascular genesis, attention is mainly given to changes in the vessels of the lateral wall of the cochlea. Experimental findings, however, show the high sensitivity of the nervous apparatus of the cochlea in the case of disturbed blood supply.


[Report on the application of various Kveim antigens in diagnostic of sarcoidosis (author's transl)]. In the Institute for Pulmonary Diseases and Tuberculosis, Novi Sad, a total number of 1500 patients was tested with a Kveim antigen prepared in this institute. Simultaneously these patients were tested with other antigens (SILTZBACH, BEHREND, DOUGLAS). Almost identical results could be found. In patients with sarcoidosis the Kveim test was positive in 60 to over 90%, depending on the stage of the disease. Within a cooperation 230 patients of the Research Institute for Pulmonary Diseases and Tuberculosis, Berlin-Buch, were tested with several Kveim antigens since 1972. 2/3 of these patients were suffering from sarcoidosis. All patients received Kveim antigen prepared in Novi Sad; one part of them was also tested with Kveim antigens prepared in Berlin-Buch. Dependent on the quality of the material processed the percentage of positive results was different. They varied from 65 to 30%. If there were less granulomas in the original material, as for the tissue of a spleen, used in Berlin-Buch, only 30% of sarcoidosis patients showed positive results. Therefore it is profitable to analyse the difficulties and the possibilities of improving the Kveim test as a valuable and rather simple diagnostical method.


Analysis and function of T and B cells subpopulations in sarcoidosis. Various technical procedure were applied to the purification of T and B lymphocytes subpopulation in sarcoidosis. Patients were selected according to the presence of a characterized deficit in cell-mediated immune functions. These purified lymphocytes populations were further analysed for their ability to release lymphokines in the presence of Con-A-sepharose or specific antigens. Among these factors, MIF, LIF and mitogenic factor (MF) were looked for. For the determination of MIF and LIF, a newly elaborated technique was deviced which allows a semi-quantitative approach of the lymphokine production. The following results were obtained: A decrease in the absolute number of T lymphocytes was observed among all our patients, and a increase in the number of Ig producing cells. A rather large percent (15 to 40%) of null cells which were carrying characteristic features of quiescent, non activable monocytes. The ability of T lymphocytes to release lymphokines was impaired in the presence of these monocytes but could be restored to normal levels when cells were removed. The results suggest that T cell function might be impaired, in sarcoidosis, by a non identified monocytes abnormal behaviour.


On the unmyelinated nerve glomuses in the bird's palate. The studies on the structure and morphological variability of nerve endings in the palate mucosa of Streptopelia decaocto Friv, have been carried out. Besides single loose or dense, irregular glomuses one can observe complex glomuses as well. The former and the latter do not possess of neither capsules nor tactile cells. The author suppose that both types of glomuses can correspond to free nerve endings and receptors in which the feeling of pain is coded.


[Health education through the teacher: recent development in the canton of Berne]. In the Canton of Berne, two working groups are currently developing a concept of school health education, in which the individual teacher assumes the principal role. In terms of documentation and availability of teaching aids, he is assisted by three addiction information centers, as well as other health institutions. Teaching goals are being formulated, socio-cultural conditions are being considered, and based on these, age specific lesson plans and exercises are being developed. On the other hand, the opportunity of a general reform of teacher training is being taken advantage of, in order to define main ideas, teaching goals and instructional contents for teacher training in human biology and health. The aim of teacher training in health education is twofold: on the one hand, it is to prepare the future teacher to include health education in his teaching skills; on the other hand, it is to enable the teacher to act appropriately, when faced with diseased or disabled pupils. The latter point becomes particularly important, as disabled children are being integrated into normal classes.


[Researches on possible applications of mycoserological methods of diagnosis in phytopathology. III. Information: about relations between the number of reacting epitops and the specificity of the reactions (author's transl)]. Several immunsera of rabbit were developed against 8 Fusarium ssp. on the basis of 10 intravenous injections with an increasing dose of the antigen. By means of these it was possible to differentiate several antigen-epitops by using the method of multidimensional double-diffusion. The number and the specificity of these epitops allows to get an insight as well into the reaction-behaviour of the Fusarium-species on test as in there serological relationship. Finally the serological result were discussed in comparison with the classification of the species within the present classification systems of Fusarium.


Demonstration of glycocalyx in the sweat gland. Skin specimens were taken without any anaesthesia from four volunteers before and after a 1 hour's exposure to heat. No glycocalyx could be demonstrated in the resting gland, but it usually appeared, however, after one hour of thermal sweating--although not in all the sections. The possible implication of this phenomenon is briefly discussed and new problems outlined.


Hydroxyproline to hydroxylysine molar ratio indicates collagen type. By using the molar ratio Hyp to Hyl, types I and II of collagen can be differentiated in 0.5 to 10 mg of dried, defatted tissue. Analyses on human skin, tendon, bone, aorta, cartilage, as well as nucleus pulposus, and annulus fibrosus of intervertebral discs are reported. Analyses of collagen of mesenchymal tissues of other vertebrates are also reported. From amino acid analysis of purified collagen samples published in the literature, the molar ratio Hyp/Hyl was calculated. Type I and type III collagen were differentiated from type II, and the latter was differentiated from type IV collagen. The molar ratios obtained with our analyses followed closely the values from previously reported amino acid analyses on purified collagen.


Immunofluorescence of the skin in allergic diseases: an investigation of patients with contact dermatitis, allergic vasculitis and atopic dermatitis. Skin biopsies for immunofluorescent studies were taken from patients with contact dermatitis (positive patch tests), atopic dermatitis and allergic vasculitis for comparison with normal-appearing skin from the same patients, and from healthy controls. A variety of deposits of immunoglobulins, complement  components and fibrinogen were demonstrated in 6 out of 20 patients with contact dermatitis, 7 out of 10 with atopic dermatitis, 8 out of 10 with allergic vasculitis, and in 4 out of 20 control individuals. No diagnostic pattern of deposits was found. Elevated serum IgE and eosinophilic counts were found in patients with atopic dermatitis, and high serum IgA and fibrinogen levels were found in the allergic vasculitis group.


Studies on the cutaneous sensitization reaction of guinea pigs to purified aromatic chemicals. The sensitization reactions to purified cinnamic aldehyde and its chemically related substances were investigated using the maximization test on guinea pigs. Mutual cross-sensitivities were also examined. Cinnamic aldehyde was found to be the most potent sensitizer in this series, and a strong cross-sensitizer. From the chemical structures of these substances, the following speculations were made. There was a tendency that as the number of hydrocarbons of alkyl groups replacing the alpha-hydrogen in the molecule increased, the rate of sensitization reaction declined. The conjugated system of double bonds was suspected to be a determinant factor in relation to the sensitization ability of the substances in this series.


Drug phototoxicity in mice.

Drug phototoxicity in mice. A series of agents with alleged photosensitizing properties has been studied in mice by a quantitative in vivo method for acute drug phototoxicity. The method, originally developed for phenothiazine studies, was found suitable for several drug groups with varying mechanism of action, such as tetracyclines, protoporphyrin and psoralens. In the sulfa group only sulfanilamide was active, although weakly. Phototoxicity in vivo, hitherto not demonstrated, was observed with griseofulvin, nalidixic acid, imperatorin, kynurenic acid and amiodarone.


Transcutaneous nerve stimulation and itching. The response to transcutaneous nerve stimulation (TNS)--a method used for treatment of chronic pain--was studied in 41 patients with itching of diverse etiology. At a first trial, 63% of the patients found that TNS ameliorated their itching, 20% reported complete relief. As a rule the effect lasted for many hours, although TNS was given only for 5-30 min. In 15 of the patients, having suffered from extensive pruritus for more than one year, TNS was given several times a day for 5-47 days. During this time the effect declined. Twelve patients were relieved initially, either partially or completely, but ultimately only 6 had a partial relief and in none had the itching disappeared completely. Only one patient wanted to continue the TNS therapy. The decreasing efficacy is discussed; probably there was an initial placebo effect which declined during the course of treatment. The results indicate that TNS is of limited value for treating chronic itching.


The effect of occlusion on carbon dioxide emission from human skin. The effect of occlusion on the carbon dioxide (CO2) emission rate (CDER) of human skin was determined. Occlusive plastic tape elevated the CDER 4.5 times (90nl/cm2/hr) over the normal CDER (20nl/cm2/hr). This increase was noted within a 3-hour period. Non-occlusive paper tape had no effect on CDER. Quantitation of the amount of CO2 under plastic tape revealed that CO2 was present at a concentration of 8-10%. Removal of the plastic tape after 24 hours allowed the CDER to return to approximately normal values within 2 hours. The mechanism by which occlusive plastic tape mediates this dramatic effect on CDER as well as the significance of elevated CO2 concentrations under occlusion are discussed.


The clinical significance of cutaneous reactions to trichophytin in dermatophytosis. An intracutaneous test was performed in 114 patients with dermatophytosis verified by culture and in 32 control subjects, unsing purified trichophytin (according to the ethylene glycol method) and commercially available trichophytin. Immediate reactions occurred with both trichophytin antigens at a similar frequency in 12-14% of cases. Delayed reactions occurred significantly more often to the purified trichophytin in patients with dermatophytosis (36%) but in none of the controls. Immediate reactions to purified trichophytin occurred in 26% of the chronically infected patients. Delayed reactions were correlated to patients with tinea cruris (50% positive reactions), to infections with Epidermophyton floccosum (50%) and to patients not chronically infected. Thus, chronic dermatophytosis was characterized by immediate reactions to purified trichophytin and few delayed reactions. In contrast, patients not chronically infected were characterized by delayed reactions and few immediate reactions.


Dose-dependent effect of topical corticosteroids on blood flow in human cutaneous tissue. In seven healthy subjects the dorsum of the hand was treated with beta-methasone valerate cream in increasing concentrations, from 0.1 to 1.0%, and with hydrocortisone butyrate 0.1% with or without plastic occlusion. Under conditions of controlled room temperature, blood flow in treated, placebo-treated, and untreated cutaneous tissue was measured using the local 133Xenon wash-out technique. Placebo creams did not affect cutaneous blood flow, but beta-methasone valerate 0.1% reduced blood flow and 1.0% increased it. An increase in blood flow was also observed after use of hydrocortisone butyrate under plastic occlusion. The results indicate a dual effect of potent corticosteroids on cutaneous blood flow.


Plasma levels of 8-methoxypsoralen and phototoxicity studies during PUVA treatment of psoriasis with meladinin tablets. A new tablet formulation of 8-methoxypsoralen was used in PUVA treatment for psoriasis. The 8-Mop plasma level showed a maximum at about 1 hour after ingestion (mean values: 1/2 hr, 284 microgram/1; 1 hr, 275 microgram/1; 1 1/2 hr, 198 microgram/1; 2 hrs, 129 microgram/1). Phototoxicity tests showed the optimal time for exposure to be about 1 hour after peroral intake of 8-MOP.


The effect of transfer factor on cystic acne. A chromatographically purified component of human dialysable transfer factor, previously described as causing a non-specific stimulation of cell-mediated immunity, was used as a therapeutic agent in three cases of stage IV cystic acne. The treatment caused a marked strengthening of skin test responses and had a promising effect on skin eruption in each case.


Oral zinc therapy in geriatric patients with selected skin manifestations and a low plasma zinc level. A geriatric population comprising 585 inhabitants of an institution for the aged was studied. Twenty-six persons with a mean age of 82 years were selected because of skin manifestations suggestive of chronic zinc deficiency. In 10 of the patients a subnormal plasma zinc level was found. This hypozincaemic group underwent a 4 week trial with zinc sulphate tablets, 0.6 g daily. The therapy failed to alleviate the skin condition in any of the patients, thus indicating that the changes were not caused by zinc deficiency. In the hypozincaemic group, plasma albumin was subnormal in all patients and significantly lower than in the normozincaemic subjects. The correlation between plasma zinc and plasma albumin levels in all 34 patients studied was highly significant (rs = 0.69, p less than 0.001). As plasma albumin tends to fall to subnormal concentrations with age, this explains why plasma zinc may be low in the elderly without indicating a state of zinc deficiency. After 2 and 4 weeks' zinc therapy, the mean plasma zinc concentration of the hypozincaemic group rose significantly from 9.5 to 17.6 and 23.4 mumol/1. This increase is higher than the rise observed in younger patients receiving an identical zinc sulphate dosage.


Topical treatment of penile condylomata acuminata with podophyllin, podophyllotoxin and colchicine. A comparative study. The effect of alcoholic solutions with 20% podophyllin from Podophyllum peltatum and Podophyllum emodi, 8% podophyllotoxin, and 8% colchicine, when applied to penile condylomata acuminata in 227 men, were statistically alike. Of the patients initially judged to be cured after 1-2 applications, 13% showed recurrence, thus bringing down the permanent cure frequency to only 43%. Local side effects were absent after only half the series of colchicine applications, whereas as much as about 3/4 of the treatment course with podophyllin and pure podophyllotoxin could be completed without provoking discomfort. Warts in the urinary meatus healed significantly less well than warts on the other genital mucous membranes. Eighty-nine per cent of patients who had previously been cured of concylomata became wart-free after 1-2 treatments, as opposed to only 40% of those who had never had this wart type previously. The use of the commercially available colchicine offers an opportunity to establish a standardized therapy; following application of an 8% solution, rinsing off should be performed after 6-8 hours.


Multiple keratoacanthomata. A unique case and review of the current classification. A case of multiple keratoacanthomata is described, with involvement of the palms and soles, and erosive lesions of the eyelids and penis. Several lesions healed spontaneously, leaving circular scars. Some were atypical clinically, taking the form of keratotic tumors. Methotrexate produced marked improvement of all lesions but had to be abandoned because of thrombocytopenia. The current classification of keratoacanthomata is reviewed.


Chlamydia trachomatis urethritis in men attending a venereal disease clinic: a culture and therapeutic study. Urethral specimens from 459 male patients attending a venereal disease clinic were studied for presence of Chlamydia trachomatis and Neisseria gonorrhoeae. Of the 459 patients, 362 had symptoms suggestive of urethritis. In these 362, gonorrhoea was diagnosed in 78 (22%), while 88 (24%) harboured C. trachomatis; 15 harboured both organisms. Of those patients from whom C. trachomatis was isolated, 17% had no subjective symptoms of urethritis; the same percentage of symptomless carriers of gonococci was found. Watery discharge occurred more frequently in patients with chlamydial urethritis than in patients with gonorrhoea, while in the latter condition purulent discharge was more often found. Treatment with doxycycline for 9 days rendered 28 of 29 chlamydia-positive patients culture negative at control.


Third generation infantile syphilis--an unusual presentation. A case of third generation early congenital syphilis with unusual features is reported and discussed. The infant presented with Livedo reticularis and an ulcer on the right forearm since birth; the underlying radius and ulna showed osteomyelitic changes with sequestrum formation and a pathological fracture. The rest of the skeletal system was normal. The blood STS (VDRL) was reactive at 1:64. The child showed no other evidence of congenital syphilis. Livedo reticularis and bony lesions resolved promptly with penicillin therapy, but abnormal movements at the wrist joint persisted. The mother had pathognomic Hutchinsonian incisors and a reactive VDRL test.


Serum levels of 8-methoxypsoralen 2 hours after oral administration. Serum levels of 8-methoxypsoralen (8-MOP) were determined 2 hours after oral administration and found to vary considerably among psoriatic patients. There was no definite correlation between the 8-MOP serum level, the dose of 8-MOP/kg body weight ingested, and the minimal phototoxic UVA dose.


Periodic, functional disuse of limbs: report of a case. The case is presented of a patient who developed periodic loss of function in individual limbs, and associated cyanosis and hyperkeratosis. Investigation excluded organic disease, and the condition responded to physiotherapy.


Oral injury caused by fellatio.

Oral injury caused by fellatio. A 34-year-old Caucasian woman is presented with a circular hemorrhagic lesion located on the soft palate and caused by fellatio. The lesion consisted of erythema, petechiae, dilated blood vessels and vesicles. It healed in a few days. No evidence of the major clinical alternatives such as thrombocytopenia, venereal disease, candida infection or pathomimia were found. Injuries due to fellatio must be considered as an etiological factor to hemorrhagic changes of the oral mucosa, and with a positive history, patients can be spared from other investigations.


Parakeratosis in some epidermal tumors: fine structural and immunohistochemical similarity between parakeratosis and "Hornmark" -like structure. Both parakeratosis and "Hornmark" -like structure are basic histopathologic changes found in a variety of skin lesions. In order to investigate more closely the architecture and components of these two structures, three cases of epidermal tumor which showed both parakeratosis and "Hornmark" -like structure were studied by using routine histology and histochemistry, immunofluorescence technique, and electron microscopy. In the intercellular space of the stratum corneum in these two structures, diastase-resistant PAS-positive substance was found. This substance also showed positive immunofluorescence for immunoglobulins, complement, and fibrinogen. Electron microscopically, this substance was moderately electron-dense and fine granular, and was located in the intercellular space and in part in the cytoplasm of the horny cells. On the basis of these findings, this substance was judged more likely to be derived from the components of plasma protein than a result of the degeneration of epidermal cells. Only quantitative difference was observed between these two structure. This substance was considered to play an important role on the increased cohesiveness of the horny cells. However, whether this is a product of antigen-antibody reactions, or the result of the process similar to blood coagulation, remains to be elucidated.


Operating room nurses' psychomotor and driving skills after occupational exposure to halothane and nitrous oxide. Concentrations of halothane and nitrous oxide were assayed by gas chromatography throughout a working day in three operating theatres and in the end-tidal air of 19 nurses 15 and 60 min after leaving the theatres. Perceptual, psychomotor and driving skills were measured in these nurses and in 11 younger nurses working in the wards of the same hospital. A complicated psychomotor test battery and a driving simulator were used. End-tidal air concentrations of halothane and nitrous oxide were positively correlated with the exposure level of these gases in the operating theatres. Some of the operating room nurses had greater amounts of halothane in their end-tidal air (average 15 to 10 ppm) than student volunteers 4.5 h after 3.5 min of general anaesthesia with a combination of halothanenitrous-oxide oxygen (10 ppm halothane). These volunteers had worse psychomotor and driving performances when measured than controls who had not been anaesthetized. No correlations were found between the concentrations of halothane or nitrous oxide in end-tidal air and psychomotor or driving performance. Despite their higher age and exposure to the operating room environment, the driving skills of the operating room nurses were similar to those of the ward nurses. The results suggest that tolerance to anaesthetic gases develops among operating room personnel. No impairment of driving skills can be expected after daily exposure to halothan and nitrous oxide among long-term employees in operating theatres.


Concentration elimination of anaesthetic gases in operating theratres. Influence of anaesthesia apparatus leakages. Halothane and nitrous oxide (N2O) concentrations were measured in operating theatres, in the areas corresponding to theinhalation zones of the anaesthetists and operating nurses. The measurements were performed in an operating theatre with a non-recirculating air exchange rate of 20/h. This was performed partly in model experiments and partly during the administration of anaesthesia by intubation. In the model experiments. the measurements were taken both with and without a specially constructed scavenging system. During anaesthesia, the measurements were taken exclusively with the scavenging system, although well-defined leakages were fitted into the otherwise gas-tight anaesthetic system. The results were supplemented by smoke experiments which showed the air distribution patterns. The investigation showed that the gases were concentrated over and around the operating table. Activities during surgery diluted this concentration. Furthermore, it was shown that leakage in the anaesthetic system significantly influences the achieving of a low gas-air mixture. Halothane concentrations in the inhalation zone of the anaesthetist and operating nurse can be reduced to 0.02 and 0.01 p.p.m. respectively, if the anaesthetic system is completely gas-tight.


Nerves and nerve endings in the skin of tropical cattle. The nerves and nerve endings in the skin of tropical cattle were studied using histological and histochemical techniques. Many nerve trunks and fibres were present in the reticular and papillary dermis in both hairy and non-hairy skin sites. In non-hairy skin locations such as the muzzle and lower lip, encapsulated endings akin to Krause and Ruffini end bulbs, which arise from myelinated nerve trunks situated lower down the dermis were observed at the upper papillary layer level. Some fibre trunks seen at this level extended upwards to terminate within dermal papillae as bulb-shaped longitudinally lamellated Pacinian-type endings, while other onion-shaped lamellated nerve structures were located either within dermal papillae or near the dermo-epidermal area. Intraepidermal free-ending nerve fibres, appearing non-myelinated were observed in areas with thick epidermis. Intraepidermal free-ending nerve fibres, appearing non-myelinated were observed in areas with thick epidermis. On hairy skin sites, however, organized nerve endings or intraepidermal nerve endings were not readily identifiable.


A sliver-gold impregnation technique for routine neuropathological use. A silver-gold impregnation technique for routine neuropathological use is presented. It is easy to perform, gives reproducible results and the ingredients are chemically well characterized. It has been successfully applied to formalin-fixed paraffin-embedded material from human brain, where nerve cell processes, neurofibrillary changes and melanin-containing neurons are distinctly visualized. Axons in peripheral nerves are impregnated and cross striations in muscle cells can also be demonstrated.


Translative and transformative growth of the rat mandible. The growth of the rat mandible was studied during a period from 14 to 30 days of age. Roentgencephalometric and alizarin vital staining techniques were employed. Growth in length doubles the growth in breadth; the angle between the mandibular halves decreases slightly. Bone remodeling patterns were revealed with the alizarin technique. Posteriorly facing surfaces and the anterior end of the incisal process show apposition. Lateral facing surfaces of the posterior part of the mandibles were resorptive. A medio-posterior growth direction of these parts were found. The intermandibular articulation plays no role in the translative growth movements, in contrast to other articulations between skull bones as sutures and synchondroses, but serves primarily during biting and chewing.


An evaluation of the quantitative parameters applied in bone histology. An evaluation of the following histomorphometric parameters: absolute trabecular bone volume (ATBV), osteoid surfaces (OS), osteoid volume (OV), resorption surfaces (RS), and mean size of periosteocytic lacunae (POL) was carried out. Double determination on sections, obtained from an area 2 cm below the summit and 2 cm behind the anterior, superior, spine of the iliac crest from 20 normal individuals aged 20-40 years, showed that the precision of method by far outweighed the inter-individual variation. Parameters obtained from 9 different localizations within the iliac bone revealed that the volume of bone was the only parameter which was influenced if the bone specimen was removed more than 2 cm below or behind the standard localization. Randomly selected sections alternately stained with Masson trichrome and toluidin blue were used for the study of the influence of the staining method on the osteoid parameters. It was shown that Masson trichrome staining would generally result in a slightly higher value of osteoid surfaces. There was, however, a high correlation between the parameters obtained with the two methods. (OS: r = 0.96; OV: r = 0.87).


Histomorphometric analysis of normal bone from the iliac crest. Bone specimens from a standardized area of the iliac crest were obtained at autopsy in 105 individuals after sudden unexpected death and at biopsy in 30 living volunteers. Seven micron thick sections of the plastic embedded undecalcified material were produced and stained. The amount of cancellous and cortical bone and the parameters attached to description of bone remodelling were determined by point counting and simple measurements, in order to establish normal mean values and range in a Danish population. A decrease in the amount of bone, trabecular as well as cortical, was found with increasing age in both males and females. The extent, volume and width of osteoid seams and the osteoclastic resorption were found to be age-independent. The osteoclastic resorption in cortical bone in males decreased, however, with increasing age. The reported values are of the greatest importance for the use of histomorphometric analysis of bone biopsies as a diagnostic tool in metabolic bone diseases. It is stressed, however, that supplementary information of the dynamic aspects of the bone remodelling would be necessary for the understanding of the pathogenesis of bone changes. Such information might be obtained by using tetracyline double labelling.


Quantitation of human granulocyte protease inhibitors in non-purulent bronchial lavage fluids. The predominant inhibitors of granulocyte proteases in plasma (alpha1-antitrypsin, alpha1-antichymotrypsin, and alpha2-macroglobulin) were quantitated in unconcentrated bronchial lavage fluids obtained from non-infected individuals, together with the acid-stable low molecular weight inhibitor with activity against granulocyte elastolytic and chymotrypsin-like enzymes. This latter inhibitor accounted for about 90% of the total molar concentration of granulocyte protease inhibitors in the bronchial lavage fluids. The remaining 10% consisted mostly of alpha1-antitrypsin and alpha1-antichymotrypsin. About 85% of the bronchial inhibitor was in a free form with preserved enzyme reactivity. The remaining 15% of the immunoreactive bronchial inhibitor exhibited a molecular size indicating complexation with enzymes. The major portion of alpha1-antitrypsin and alpha1-antichymotrypsin showed electrophoretic mobilities and molecular sizes similar to the native proteins but had no enzyme reactivity.


Plasmid borne virulence of Enterobacter hafniae. The strain classified as Enterobacter hafniae has been isolated in a severe epidemy of porcine diarrhoea. Its pathogenicity has been found to be cotransmissible with resistance to oxytetracycline when the strain was grown in a mixed culture with some nonpathogenic E. hafniae strains as well as with Escherichia coli. Toxinogenity seems to be responsible for virulence of the strain.


Studies on the experimental infection of Hyalomma dromedarii (Koch) ticks with tick-born encephalitis virus. The replication dynamics of 4 strains of tick-borne encephalitis virus, differing in neurovirulence towards white mice, and their penetration to the salivary glands and ovaries of H. dromedarii were examined. The ticks were infected by being artificially fed a large dose of the virus and were observed for 44 days. The virus actively multiplied in whole ticks and examined organs. A relation between the neurovirulence of the strains towards white mice and persistence of infection in the ticks and their organs was observed.


An attempt at the use of immunological methods for the detection of enzymes of BCG substrains. Immunological methods have been used to visualize peroxidase and dehydrogenase activities of substrains of BCG mycobacteria. Immunodiffusion (ID) and immunoelectrophoresis (IE) in agar gel and two-dimensional immunoelectrophoresis (2D-IE) in agarose gel were employed. In all these tests part of the ID, IE, and 2D-IE preparations were stained with Amido Black 10B (AB 10B) to visualize the total number of precipitin lines and part were stained at the same time with histochemical methods for vizualization of peroxidase and dehydrogenase activities.


The use of two-dimensional immunoelectrophoresis for the characterization of antigens of BCG substrains. The usefulness of the method of two-dimensional immunoelectrophoresis (2D-IEP) in comparative studies and characterization of the antigenic spectra of various BCG substrains have been estimated. The BCG substrains used were: substrain BCG-Rio de Janeiro, substrain BCG-Poland, form-rough (R) and substrain BCG-Poland, form-smooth (S). The 2D-IEP technique was found to give characteristic immunoelectrophoretic patterns of antigenic composition of the different BCG substrains. The number of precipitin peaks was usually over 20, that is more than detected by conventional immunoprecipitation techniques such as immunodiffusion and immunoelectrophoresis in agar gel (ID, IE).


Some properties of partially purified phytase from Aspergillus niger. Phytase was purified from Aspergillus niger culture fluid by molecular sieve filtration on Sephadex G-200, followed by thermal inactivation of acid phosphatase and CM-cellulose chromatography. The 12-fold purified enzyme had two pH optima at 2.7 and 5.5 and was characterized by high thermal stability in alkaline environment and broad substrate specificity. The Michaelis constant of phytase relative to myo-inositol hexaphosphate sodium salt is 4.8 X 10(-4) M and activation energy 9,217 cal/mole. The molecular weight of the enzyme is estimated at 200,000.


Glucose oxidase activity of actinomycetes. The ability of 311 actiomycete, belonging to 12 species to produce glucose oxidase was studied. It was found that 174 of them formed exoenzymes on solid medium and 133 in liquid medium. The composition of the nutrient medium has an essential effect on the amount of enzyme formed. Strains with considerably higher activity form a greater amount of exoenzymes on soya meal medium and on synthetic medium with KNO2. The highest activity of the culture liquid of some strains was observed between the 6th and 7th day of cultivation. During this phase of growth the highest productivity of the biomas was established.


Nitrogen fixation by Rhizobium in pure cultures. Strains of Rhizobium trifolii and Rhizobium meliloti were tested for their asymbiotic nitrogen fixation ability. From among ten tested strains two R. trifolii and one R. meliloti expressed nitrogenase activity within the range of 1.3--9.3 nM C2H4/h/mg protein. Asymbiotic nitrogen fixation was affected by the composition of the medium.


Extracellular release in Chlorella vulgaris culture and the role of bacteria accompanying - algae in this process. The effect of different concentrations of nitrogen and phosphorus on extracellular release was investigated. Phosphorus induced the enhanced extracellular release of metabolites by Chlorella vulgaris. No influence of nitrogen on extracellular release was observed. In the initial stages of C. vulgaris culture the algae release was observed. In the initial stages of C. vulgaris culture the algae release compounds readily assimilated by the accompanying bacteria, hence the observed drop of percentage of extracellular release (PER) in culture medium caused by the bacteria. Both, the glycolic acid and the products of photoassimilation released to the environment in the first stages of cultivation were assimilated by the bacteria accompanying-algae at a similar rate. The ageing of C. vulgaris culture resulted in the accumulation of extracellularly released metabolites and increase of PER. These products were not assimilated by the bacteria present in the algal culture.


Primary production and extracellular release by phytoplankton in some lakes of the Masurian Lake District, Poland. The primary production and extracellular release by phytoplankton were measured at different depths of Mikołajskie Lake, Ryńskie Lake and Bełdany Lake (Masurian Lake District, Poland). The release of dissolved organic compounds was found to be related to the rates of primary production. The percentage of extracellular release (PER) of organic matter in the photic zone showed an inverse relationship with particulate production and chlorophyll alpha concentration. The highest PER was determined in the epilimnion of the studied lakes, where also increased release was observed. The higher release of algal products of photosynthesis in the photic zone than in the profundal is probably caused by the inhibition of physiological activity of bacteria by antibacterial substances produced by algae. The substances released by algae in the profundal are taken up by aquatic bacteria which explains the lower release and PER measured.


[Studies on antigenspecific immunosuppression: Influence of 6-mercaptopurine-BGG-conjugates on BGG binding cells (author's transl)]. The rosette forming cell (RFC) response of different lymphoid organs (spleen, lymph node, peripheral blood) of guinea pigs was examined by immunocytoadherence. The method has been adapted to work with the soluble antigen BGG. The number of antigen binding cells following immunization with BGG in CFA reached the highest level on day 6 in Ln. popliteus and on the 10th day in spleen and peripheral blood. It is shown that the highest level of antigen binding cells appears generally before the maximum of circulating antibodies. After i.p.-immunization to alum-adsorbed BGG we only detected a small number of RFCs. After pretreatment with 6-mercaptopurineI-25-BGG (MP-BGG) and a control substance (toluylI-25-BGG) over 8 days and in increasing doses we obtained an antigenspecific suppression of BGG binding cells following MP-BGG treatment. In contrast to these findings the antibody titres were only slightly decreased in the beginning of the immune response.


Sea-blue histiocytes in a patient with lymphoma. A middle-aged man with lymphocytic lymphoma had numerous sea-blue histiocytes in his bone marrow, splenomegaly and thrombocytopenia. Thus, his illness mimicked that of patients with the primary syndrome of the sea-blue histiocyte. However, the paucity of sea-blue histiocytes in his spleen, the absence of neurologic disease, his age and the ultrastructure of his abnormal histiocytes were all evidence for the presence of the acquired syndrome. The pathogenesis of sea-blue histiocytosis and the relationship between acquired cases and the primary syndrome are discussed.


Histology and histochemistry of the normal superficial corneal epithelium of rabbit. The superficial epithelial cells of normal cornea are in a process of gradual metabolic shutdown. Nuclear DNA may be depolymerized. Loss of DNA also occurs by extrusion in small quantities into the cytoplasm. There is a small quantity of RNA in these cells. The cytoplasm shows the presence of some vicglycols. The superficial corneal epithelial cells do not keratinize.


Pituitary cytology of the Indian carp Labeo rohita (Ham.). In the adenohypophysis of Labeo rohita eight cell types could be identified on the basis of their different tinctorial response to various staining techniques. The rostral pars distalis has 3 types of cells. Type 1 is stained with erythrosin, orange G, and acid fuchsin. Type 2 cells are lead hematoxylin positive and give an amphiphilic reaction in response to tri and tetrachrome techniques. Type 3 cells are stainable with PAS, ATh, AB, AF, and aniline blue and are distributed in an area comprises of anteroventral RPD and anterodorsal PPD. Apart from type 3, the PPD has two more cell types. The classical acidophils forming the type 4 cells readily take up orange G, erythrosin and acid fuchsin. Type 5 cells have affinity for PAS, ATh, AB, AF and aniline blue as that of type 3 cells, but they are relatively smaller. Pars intermedia has type 6 and 7 cells which are PbH and lightly PAS + ve respectively. Eight cell type is constituted by the chromophobes which are seen in all the components of the adenohypophysis, they might be the immature or degranulated chromophils. On the basis of colour reactions cell types 1, 2, 3, 4 and 5 of Labeo rohita are comparable to the prolactin, ACTH, TSH, STH and gonadotropin secreting cells described in other teleosts by earlier workers using comparable techniques. However, functional interpretation based on staining reactions is tentative and needs experimental verification.


The cingulate bridge between allocortex, isocortex and thalamus. The Fink-Heimer silver impregnation and the autoradiographic methods were used to study the fiber projections of the cingulate cortex in the squirrel monkey. It was found that this cortex provides inputs to the straitum, thalamus and several areas of isocortex. Evidence was found for a number of fiber projections (1) Fibers from the anterior limbic area were traced to the central part of the head of the caudate nucleus, putamen, septum, dorsomedial nucleus of the thalamus, anterior hypothalamus and lateral basal nucleus of the amygdala. (2) Projections from the cingulate area were traced to the lateral part of the head of the caudate nucleus, putamen, and to the centromedian, anterior, lateral dorsal, and lateral ventral thalamic nuclei and to medial nuclei of the base of the pons. (3) There were porjections from the retrosplenial area of the anterior, lateral dorsal, dorsomedial, and posterior thalamic nuclei and lateral nuclei of the pons. These results indicate that most of the cingulate gyrus is an intermediate structure between the thalamus and overlying cortex. The anterior limbic area forms a bridge between the thalamus and other areas of the cingulate gyrus and the frontal cortex. (4) the retrosplenial area and the posterior part of the cingulate area bridge the adjacent visual snesory association cortex and pelvic areas of the snesory motor cortex, respectively. These areas of the cingulate gyrus project directly to the striatum as well as to the thalamus, structurally providing limbic system input to subcortical motor structures.


Pleural effusion from malignancy.

Pleural effusion from malignancy. Pleural effusion from metastatic malignancy can cause major impairment of respiratory function and eventual death. Although cure is not possible, successful palliative treatment allows months to years of productive life, obviating the need for continuous hospitalization and repeated thoracenteses. Successful palliative treatment requires obliteration of the pleural space. Literature survey indicates that a wide variety of medical agents and surgical methods have been used with variable success. Medical methods include instillation of antineoplastic agents, antimicrobial agents, or colloidal radioisotopes into the pleural space; quinacrine and tetracycline are moderately to highly effective agents, but the toxicity of the former is substantial. Bedside talc poudrage with thoracostomy-tube drainage is a safe and highly effective alternative. Pleurectomy is the definitive method of preventing reaccumulation of pleural fluid that results from metastatic malignancy, even when other methods have failed, but thehigh morbidity and mortality of the procedures mandate careful patient selection.


[Demonstration of Q bands on mitotic chromosomes of the amphibian urodele Pleurodeles poireti Gervais, after staining with quinacrine mustard. Comparison with Pleurodeles waltii]. Preparations of metaphase chromosomes of the amphibian urodele Pleurodeles poireti were obtained by squashing cells from tailbuds of ten days old embryos which had been in 50% acetic acid. The Q-bands karyotype is described. Frequently the induced secondary constrictions exhibit a bright fluorescence, as do the centromeres, except for that of chromosome XII. In contrast, satellites on chromosomes III, IV, and XI exhibit little fluorescence. This pattern is compared with that in Pleurodeles waltlii. Differences are observable in centromeres of chromosomes III and XII and the proximal part of the long arm of chromosome VII, differences which can be used as chromosome marker in case of hybridization.


Improved microbiological assay procedures for dihydrostreptomycin residues in milk and dairy products. Because dihydrostreptomycin can remain as a slowly removed antibiotic residue in dairy animals and because of the need for more sensitive procedures with which to provide information concerning antibiotic residues in food products, procedures were developed in more sensitive assays of dihydrostreptomycin in milk and some representative dairy products. The cleanup procedures that aided these improvements were (i) precipitation of milk proteins by acidification and (ii) centrifugation to extract cheeses and to remove physical barriers to diffusion in the cylinder plate assay. In addition, a thin, single seeded assay layer was used to maximize diffusion. Levels of dihydrostreptomycin as low as 0.06 microgram/ml in milk and 0.2 to 0.4 microgram/g in cheeses were measurable; these levels were some fourfold more sensitive than those presently recommended by the Food and Drug Administration.


[Evaluation of the contractile reserve of the myocardium by post-extrasystolic potentiation in aortic insufficiency]. Calculations were made of the indices of ventricular performance during the ejectional phase in 10 patients with a normal left ventricle and in 24 patients with aortic aneurysm, both under basal conditions and in the presence of extrasystoles produced incidentally during left biplanar cineventriculography. The fact that these indices were constantly raised implies the presence of post-extrasystole potentiation associated with an increase in contractility without significant changes in load. This technique, which provides a dynamic study of the behavior of the left ventricle in aortic incompetence allows us to assess the contractile reserve, and thus to give a more accurate prediction of the potential for recovery after operation.


[Prognosis in severe dyslexia].

[Prognosis in severe dyslexia]. 37 children with a mean reading retardation of 4,3 years were placed full time in a specialized centre. All had failed in school in spite of remedial training and/or psychotherapy. The goal of the centre is to separate linguistic and non-linguistic subjects. The non-linguistic subjects were taught with the aid of audio-visual methods in order to relieve the dyslexics of the burden of written language. If progress with reading and spelling was slow, audio-visual instruction enabled these children to reach or exceed 5th grade level in non-linguistic subjects. 80% of them were able to go on to vocational schools. At the same time, there was a very favorable improvement in their behavior (P less than 0.001), which is a prerequisite in the prevention of juvenile delinquency and an essential step in social and professional integration. These favorable results emphasize the part audio-visual instruction should play in severe dyslexia.


Changes in plasma proteins during pregnancy. Changes in maternal plasma proteins during pregnancy are now well documented. These changes may be quantitative, as seen in the electrophoretically separated fractions of serum and in the various binding globulins; or they may be represented by the appearance of a protein which is present only in the serum of pregnant women. These include the placental isoenzyme of alkaline phosphatase, oxytocinase, human chorionic gonadotropin and the "pregnancy-associated plasma proteins." Other constituents, such as alpha-fetoprotein, salivary amylase, prolactin and the proteins of the "pregnancy zone," which are present in small quantities in non-pregnant women as well as in men, show a substantial increase in concentration in the maternal circulation during pregnancy. An important factor in the etiology of protein changes is the effect of hormones, especially estrogen, on the synthesis and degradation of these proteins. While certain quantitative changes such as those seen in hormone binding proteins may interfere with diagnostic procedures, a number of pregnancy-associated changes in protein composition of the maternal circulation may be used to follow the course of pregnancy by monitoring placental function as well as fetal maturity and well being.


[Study of PLi genes action on the cell wall structure of "Saccharomyces cerevisiae" Hansen (author's transl)]. A study of the composition of cell walls extracted from a wild strain and three mutant strains "smooth colony" of Saccharomyces cerevisiae had been done. It points out differences in the mannose/glucose ratio and in the concentration of some other components of the cell wall in the mutant strains. The immunological study of the cell wall shows that "smooth colonies" mutants and wild strains differs in their mannoproteins.


Immunoperoxidase techniques: practical and theoretical aspects. Immunoperoxidase methods have much in common with established immunofluorescence procedures. Both have the potential for specific demonstration of cell and tissue antigens, with similar limitations demanding rigorous control of specificity. In any study the choice of an immunofluorescence method or an immunoperoxidase method can be made on rational grounds, according to the desired objective, the degree of morphologic detail required, the material available for study, and the ease of access to specialized ultraviolet microscopy. In this article the relative merits of the various immunoperoxidase procedures are examined, and theoretical and practical aspects governing the application of these methods are discussed in detail.


Ectopic hypophyseal hormonal cells in benign cystic teratoma of the ovary. Light microscopic histochemical dye staining and immunoperoxidase cytochemistry. Histologic study of the hypophyseal component of a benign cystic ovarian teratoma disclosed elements that resembled sellar adenohypophysis, pars intermedia, and neurohypophysis. Histochemical dye methods revealed secretory cells with cytologic and granule-staining characteristics of somatotrophs, mammotrophs, melanocorticotrophs, and thyrotrophs. Nongranulated follicular cells and salivary gland rest cells also were present. Indirect immunoperoxidase staining with monospecific antisera to anterior pituitary hormones revealed abundant prolactin-containing cells, which comprised more than 50% of all chromophilic cells, as well as numerous cells that contained growth hormone and thyroid-stimulating hormone. Gonadotrophic cells could not be demonstrated by either tinctorial stains or immunostaining.


The clinical significance of human alpha-fetoprotein. Deviations from the normal of alpha-fetoprotein (AFP) concentrations in fetal serum, amniotic fluid, maternal serum and adult human serum can be explained by understanding the normal physiology and the pathophysiology of AFP synthesis and metabolism. AFP is the prototype of oncofetal markers. Emphasis is given to the usefulness of elevated serum AFP levels on the diagnosis and management of primary hepatomas and tumors of germ cell origin. The ability to detect neural tube defects early in gestation by monitoring maternal serum and amniotic fluid AFP concentrations is discussed.


Continuing experience with palliative chemical splanchnicectomy. Forty-one patients underwent open phenol splanchnicectomy for control of pain at the time of initial laparotomy for what was thought to be unresectable pancreatic carcinoma. Twenty-three patients underwent concomitant biliary and/or intestinal bypass procedures. In no patient was laparotomy performed only for the purpose of performing splanchnicectomy. The operative mortality was 15%. In no patient could the addition of splanchnicectomy be implicated as the cause of death. Eighty-eight per cent of patients experienced relief of pain postoperatively. The mean duration of pain control was 4.3 months. The mean postoperative survival was five months. No postoperative complications could be attributed to the addition of splanchnicectomy. Open phenol splanchnicectomy is a highly successful and safe ancillary procedure for control of pain and is recommended at the time of initial laparotomy in patients found to have advanced intra-abdominal neoplasm.


Pancreaticojejunostomy for chronic pancreatitis. Two- to 21-year follow-up. Between 1954 and 1975, 80 pancreaticojejunostomies were performed on 77 patients for intractable pain of chronic pancreatitis. All patients had a history of chronic alcoholism. Drainage operations done primarily for pseudocysts were excluded. Operative procedures included seven caudal pancreaticojejunostomies, 42 longitudinal pancreaticojejunostomies with splenectomy and implantation of the pancreas into the jejunum, and 31 side-to-side pancreaticojejunostomies. Eighty-one percent of the patients noted substantial improvement or complete resolution of their abdominal pain on follow-up that ranged up to 21 years. The operative mortality was 5%. Thirty-two patients died during the period of the follow-up. Continued alcohol abuse, carcinoma, and cardiovascular disease were the leading causes of mortality. Data from this review confirm the effectiveness of pancreaticojejunostomy in relieving the pain of chronic relapsing pancreatitis.


[The role of mepartricin in the medical treatment of benign prostatic adenoma]. A "cross over" study was carried out in a group of 22 subjects with prostatic hypertrophy in different stages, first treated with chloroformic extract of Pygeum Africanum (4 capsules/die for 30 days) and afterwards, when the symptoms reappeared, with mepartricin (3 gastroresistant tablets of 50,000 U. each/die for 30 days). Both substances proved to be active against the urinary symptomatology; however the polyene induced a significant decrease in the prostate size (evaluated by cystography), justifying the 77% of "excellent" results against the 13% obtained with the reference drug.


Neoantigen of the membrane attack complex of human complement: Occurrence on peripheral blood leukocytes from patients with systemic lupus erythematosus. Since complement activation and hematological abnormalities occur in systemic lupus erythematosus (SLE), the present study is an investigation of whether the membrane attack complex of complement might be bound to peripheral blood leukocytes (PBL) in vivo. Assembly of the membrane attack complex results in the generation of neoantigen (neoAg) which is complex-specific and not expressed by any of the individual complement proteins. FITC antiserum specific to neoAg was employed to detect the membrane attack complex on PBL from 7 normal donors, 12 patients with SLE, and 2 patients with rheumatoid arthritis (RA): 3 +/- 1% of normal, 25 +/- 13% of SLE, and 23 +/- 11% of RA PBL were positive. The majority of the neoAg positive PBL in SLE were polymorphonuclear neutrophils (PMN) as shown by adherence to plastic, phagocytosis of carbonyl iron, and differential cell counts. The PBL were greater than 98% viable as indicated by the trypan blue exclusion technique. These observations strongly suggest that the membrane attack complex may be bound to viable PBL in patients with SLE and RA, and further raise the possibility that the membrane attack complex, may have a function other than lysis.


Eye hue and the oculocardiac reflex.

Eye hue and the oculocardiac reflex. During operations for squint nodal rhythm and other more serious arrhythmias such as heart block and multifocal ventricular extrasystoles, as well as the oculocardiac reflex, are shown to occur more frequently in patients with brown or hazel eyes than in patients with blue or grey eyes.


The emission yields of delayed and prompt fluorescence from chloroplasts. 1. The decay of delayed fluorescence from chloroplasts blocked with 3-(3,4-dichlorophenyl)-1,1-dimethylurea and uncoupled with gramicidin has been measured in the time range 0.75--45 ms by use of a laser phosphoroscope. 2. The decays have been analysed as the sum of three first-order components of approximate half-lives 0.2, 2.5 and 300 ms by a computer-assisted least-squares fit procedure. 3. The prompt fluorescence yield of the chloroplasts was manipulated by changing the cation concentration of the chloroplast-suspending medium. 4. Analysis of the concentration dependence of the components of the delayed fluorescence decay and of the prompt fluorescence inductions indicates that the emission yield of the intermediate (tau approximately 2.5 ms) component of the decay is equal to the fluorescence yield of a Photosystem II photosynthetic unit with an open trap, and that for the slow (tau approximately 300 ms) component the emission yield is equal to the total Photosystem II prompt fluorescence yield. 5. It is concluded that the delayed fluorescence yield in the time range studied is a complex function of time, which may be due to there being different mechanisms leading to delayed fluorescence production at short and long times after cessation of illumination.


Occurrence of novel branched-chain fatty acids in Refsum's disease. Two novel branched-chain fatty acids, which appear to be unsaturated analogs of phytanic acid, have been observed in sera and urine of patients with Refsum's disease. They occur in both phospholipids and neutral lipids, and have been isolated and characterized.


Renaturation of a reduced Taiwan cobra cardiotoxin. Refolding of a denatured protein obtained by reducing cardiotoxin from the Taiwan cobra with mercaptoethanol has been carried out in aqueous and non-aqueous solutions. Oxidation of the reduced protein in 0.05 M phosphate buffer (pH 7.2) resulted in isolating an active protein which showed, as compared to native cardiotoxin, identical conformation and biological activities such as lethality, antigenicity and muscle contracture inducing activity. On the other hand, the reduced protein was undergoing incorrect SS-pairing and several inactive products were formed in a mixture of 1,2-ethanediol and 1-propanol (1 : 1; v/v).


Simultaneous determination of hydromorphone, hydrocodone and their 6alpha- and 6beta-hydroxy metabolites in urine using selected ion recording with methane chemical ionization. A selected ion recording using chemical ionization (methane) is described for the simultaneous measurement of hydrocodone, hydromorphone and their respective 6alpha- and 6beta-hydroxymetabolites in human urine. The samples were acid-hydrolyzed, extracted and derivatized by silylation. Only partial resolution of the components on 3% OV-17 was achieved but was sufficient for their determination. The [M+1]+ ions of the drugs and metabolites as well as the [M+29]+ ion of the internal standard were recorded. The assay was sensitive down to c. 0.01 microgram ml-1. The relative standard deviation of standards processed along with the samples ranged from 4.5-8.2%. Hydrocodone was found to be metabolized in man primarily by O-demethylation and 6-keto reduction. Hydromorphone was excreted mainly in the unchanged form (after acid-hydrolysis) with only minor amounts of the 6-hydroxymetabolites being detected. A lack of stereoselectivity in the metabolic reduction ofhydrocodone was observed.


[Haptoglobin- and group-specific component-phenotypes in healthy carriers of antibodies to hepatitis B surface antigen (author's transl)]. No significant differences could be observed when the haptoglobine and group-specific component phenotypes of 51 unrelated, healthy carriers of antibodies to Hepatitis B surface antigen were compared with normal controls. These findings are contradictory to the suggestion of Prokop [2].


The influence of myoneural blockers on intracranial dynamics. A series of animals was studied to evaluate the effect of commonly used myoneural blockers (curare, succinylcholine, gallamine, and pancuronium) on intracranial physical dynamics. Of this group, only curare alters intracranial pressure. Histamine release secondary to curare administration results in bronchoconstriction with subsequent major alterations in pulmonary ventilation. Resultant hypercarbia along with a decreased cerebral vascular resistance affects intracranial dynamics by alterations in cerebral blood flow; changes in CSF flow patterns passively reflect the alterations in intracranial pressure. These changes can be blocked by prior treatment with antihistamines.


Intra-axonal ferric ion-ferrocyanide staining of nodes of Ranvier and initial segments in central myelinated fibers. Ferric ion and ferrocyanide were used to stain central nervous tissue from the spinal cords of rats following fixation in cacodylate-buffered aldehydes. At the nodes of Ranvier in myelinated fibers, the stain was localized primarily on the inner surface of the unmyelinated nodal axolemma, as had been reported previously for peripheral nodes. Unmyelinated initial segments of myelinated neurons were similarly stained, but the axon hillock, cell body and dendrites were not stained. Synapses also exhibited no staining. Details of stain localization and comparison of these results with other ultrastructural data suggest that the stain is specific for the node of Ranvier and the axon initial segment, and are consistent with the idea that the axolemma at these sites may be structurally different from the cell membrane in other regions of the neuron, including paranodal and internodal regions of the axon. The electron-dense substance underlying the cytoplasmic surface of the membrane at the nodes and initial segments may represent a substrate that serves to bind together membrane structures in specialized regions of the axolemma.


Two-dimensional gel electrophoresis of proteins in rapid axoplasmic transport. Two-dimensional electrophoresis of proteins has allowed high resolution analysis of the protein species rapidly transported in the frog sciatic nerve. The 7th, 8th and 9th dorsal root ganglia were selectively labeled with [3H]leucine or [35S]methionine in one compartment of a lucite chamber. Transport of TCA-precipitable material was monitored in the spinal roots and sciatic nerve kept in another compartment. Fastest transport rates were 75-90 mm/day at 18 decrees C. Ligation of the nerve 30 mm distal to the 8th ganglion at the beginning of the experiment resulted in accumulation of label during a 24 h period. This material was subjected to two-dimensional electrophoresis (pI 5-8; mol.wt. 10(4)-10(5) daltons) in 3 mm nerve segments. Autoradiographs or fluorographs from segments proximal to the ligature yielded a pattern of about 140 spots. Of these, at least 60 were considered to be independent protein species. Neither actin nor tubulin were present among these rapidly-transported, labeled proteins. No pattern was observed from segments distal to the ligature. Blocking protein synthesis with 18 micrometer anisomycin reduced the accumulation of label proximal to the ligature by 98%. Direct labeling of nerve segments produced patterns significantly different from the pattern of transported proteins.


Thalamic afferents to the limbic cortex in the cat studied with the method of retrograde axonal transport of horseradish peroxidase. Thalamic afferents to the limbic cortex in the cat were studied with the method of retrograde axonal transport of horseradish peroxidase. The anterior limbic region receives fibers largely from the anteromedial nucleus and partly from the anterodorsal and anteroventral nuclei. There appears to be a dorsoventral organization of cortical projections of the anteromedial nucleus to the anterior limbic region. The cingular area has its main input from the anteroventral and anteromedial nuclei. The lower bank and fundus of the splenial sulcus receive fibers from the anteroventral nucleus, particularly its parvocellular part. The retrosplenial area receives projections from the naterodorsal, anteroventral and anteromedial nuclei. The agranular retrosplenial area (area 30) recieves hardly any fibers from the anterior thalamic nuclei. The postsubicular and presubicular areas receive cortical afferents from the anterodorsal, anteroventral (both magnocellular and parvocellular parts) and anteromedial nuclei. In addition, the limbic cortex receives many fibers from the dorsal lateral, medial pulvinar and lateral pulvinar nuclei, and few fibers from the intralaminar and midline nuclei.


Fluorescent probes of chromosome structure and replication. Procedures employing fluorescent dyes or Giemsa stain have been utilized to differentiate methaphase chromosomes into longitudinal segments termed bands. In spite of the immense practical utility of chromosome banding, the chemical basis of banding patterns remains incompletely understood. Physical chemical studies have elucidated the modes and specificities of the interaction of fluorescent dyes such as quinacrine, 33258 Hoechst, daunomycin, chromomycin A3 and 7-aminoactinomycin D with DNA and chromatin. However, it is not clear that all aspects of chromosome staining are explainable in terms of the optical properties of soluble dye-DNA complexes. BrdU-dye techniques in which chromosome staining depends on the schedule of BrdU incorporation by cells, have been used for cytological studies of chromosome structure and replication. These procedures have revealed a close association between quinacrine or Giemsa bands and late replicating chromosomal regions. Biochemical studies on chromatin differentially labelled according to replication timing may thus prove useful for investigating the molecular basis of chromosome banding.


Reticuloendothelial system function and humoral factor deficiency following acute hemorrhage. The present study has shown that following acute hemorrhage (equivalent to 3% body weight withdrawn over 20 min) in the rat, there is a large reduction (56% of control) in circulating alpha-2-glycoprotein opsonic activity. The reduction in this plasma opsonic activity was near maximal by the completion of blood withdrawal and was maintained throughout a 2-h hypotension period. There was no trend toward recovery of the opsonic activity when evaluated 15 min following reinfusion of shed blood in animals that were hypotensive for 0, 30, and 120 min. Reticuloendothelial system (RES) phagocytic function, as assessed from the carbon clearance rate (phagocytic index) following reinfusion of the shed blood, was depressed in animals that were hypotensive for 0, 30, and 120 min. Thus, phagocytic index followed a time course similar to the depression of opsonic activity. The observed close temporal relationship between alpha-2-glycoprotein opsonic deficiency and depression of RES clearance further supports the possible role of a humoral opsonic deficiency in mediating the RES phagocytic depression during circulatory shock.


Immunohistochemical localization of a choriogonadotropin-like protein in bacteria isolated from cancer patients. By the use of specific antibody to human chorionic gonadotropin (CG) as well as to its beta-subunit, and the application of the indirect fluorescein-labeled and peroxidase-labeled antibody techniques, we have demonstrated the presence of a membrane (wall)-associated CG-similar immunoreactive protein in 15 strains of bacteria isolated from tissues of patients bearing malignant neoplasms. These microorganisms were classified as S. epidermidis, (12) E. coli (2), and a single strain of P. maltophilia (ATCC 13637). The absence of the CG-like antigen in other "cancer associated bacteria", Streptococcus faecalis (ATCC 12818) and Pseudomonas aeruginosa (from patient with cancer of  colon), demonstrated that not every "cancer associated bacteria" has the capability to synthesize the trophoblastic-like protein. The negative results obtained with a number of "noncancer control" bacteria of known origin, obtained from ATCC and from clinical samples, strongly supported the idea that the existance of these CG-like protein producing microorganisms is not a ubiquitous finding. The demonstration of a de novo bacterial biosynthesis of a protein having similar antigenic and biophysical properties to those of the human trophoblastic hormone, has great biological implications, especially if its biosynthesis is proven only in bacterial strains growing in the presence of cancer cells in which we have already demonstrated the presence of a similar antigen. The explanation of the phenomenon is unknown. Because of their origin, the potential of "genetic exchange" with subsequent expression of the mammalian gene by the bacterial cells becomes a possibility. It is also possible that the gene coding for the CG-like protein is normally present but inactive or repressed in all bacteria.


Chondroma of soft parts.

Chondroma of soft parts. The clinical and pathological features of 104 cases of chondroma of soft parts are presented. The tumor occurred predominately in the third and fourth decades, was slightly more common in male (61%) than in female patients, and affected chiefly the soft tissues of the hand (64%) and feet (20%). The presenting  symptom was usually a slowly and insidiously growing mass, occasionally causing tenderness or pain. Nearly always the tumor was well demarcated and  lobulated and measured between 1 and 2 cm in greatest diameter. Microscopically, most of the tumors were composed of adult-type hyaline cartilage,  undergoing calcification in a large percentage of cases. In addition, histologic variants with giant cell proliferation and chondroblastic activity could be distinguished. Despite the slight cellular pleomorphism and the plump appearance of many cartilage cells in the chondroblastic variants, there was no evidence that these tumors behaved differently from the tumors composed predominately of adult-type hyaline cartilage. Of the 56 patients with follow-up information (median follow-up period, 5.7 years) 44 were alive and well with no evidence of recurrence in the follow-up period. In 10 patients the tumor had recurred once. Multiple recurrences or metastatic lesions were no observed. Two patients died of unrelated cause. Complete local excision appears to be the treatment of choice.


Malignant lymphoma, small lymphocytic type: a clinicopathologic study of 84 cases with suggested criteria for intermediate lymphocytic lymphoma. Clinical and histopathologic findings were reviewed in 84 cases of malignant lymphoma of the small (well differentiated) lymphocytic type. The slides were studied without clinical information, and the following morphologic features were evaluated: pattern of growth, number of large lymphocytes, mitotic rate, degree of capsular involvement, presence of plasma cells and/or plasmacytoid lymphocytes, and presence of residual germinal centers. Subsequently, clinical information was obtained. The minimum follow-up period on living patients was 5 years. The patients were divided into 3 clinical categories: 1) monoclonal gammopathy (MG)-11 cases, 2) chronic lymphocytic leukemia (CLL) without MG-56 cases, and 3) those without MG or CLL at the time of lymph node biopsy-17 cases. The criterion for CLL was an initial absolute lymphocyte count less than 4000/mm3. Four of the patients with MG also had CLL, and 6 of those in the third group later developed CLL, from 1 to 61 months after lymph node biopsy. Generalized lymphadenopathy was the usual presentation in all 3 groups, and bone marrow examination was positive in all but 1 of the 49 cases, representing all 3 groups, in which it was performed. Median survival for the 84 patients was 51 months. The only clinical parameters which showed a significant association with poorer survival were age above 60 and anemia (Hb. conc. less than 11.0). There was no significant relationship between morphologic characteristics and clinical categories other than the association of plasmacytoid cells with MG in 6 cases. A mitotic rate of 30 or more mitoses per 20 high power fields (HPF), found in 5 cases with at least 1 in each clinical category, showed a highly significant association with decreased survival (p = .01). Variations in mitotic rate between 0 and 29 mitoses per 20 HPF and other morphologic parameters did not show a significant relationship with prognosis. It was concluded that malignant lymphoma of the small lymphocytic type is a definite clinicopathologic entity which may or may not exhibit MG or CLL, and it is proposed that the term "intermediate lymphocytic lymphoma" be applied only to those cases showing histopathologic characteristics of small lymphocytic lymphoma and a mitotic rate of 30 or more mitoses per 20 HPF.


Detection in human ovary and prostate tumors of DNA polymerase activity that copies poly(2'-O-methylcytidylate) . oligodeoxyguanylate. Particulate DNA polymerase activity that copied poly(2'-O-methylcytidylate) . oligodeoxyguanylate and banded at a density of 1.15 to 1.20 g/ml in sucrose gradients was detected in 8 of 16 human ovary tumors and in 11 of 16 malignant prostate tissues. None of the 10 nonmalignant ovary and prostate tissues examined contained detectable particulate DNA polymerase activity that copied poly(2'-O-methylcytidylate) . oligodeoxyguanylate. Since poly(2'-O-methylcytidylate) . oligodeoxyguanylate is effectively copied by oncornavirus RNA-directed DNA polymerase (reverse transcriptase) although not by the known species of human cell DNA polymerase, these results are interpreted as supporting the concept that some malignant human tissues contain particle-associated reverse transcriptase activity.


Early histological and functional alterations of ethionine liver carcinogenesis in rats fed a choline-deficient diet. The effects of feeding a choline-deficient (CD) or a choline-supplemented diet upon the early stages of DL-ethionine carcinogenesis in rat liver were investigated. Low levels of DL-ethionine (0.05 and 0.10%) when fed with a CD diet were found to induce within 4 weeks a massive proliferation of oval cells without significant cell necrosis or presence of inflammatory cell infiltrates. The same levels of ethionine when fed with a choline-supplemented diet caused no significant histological alteration of the liver. In rats fed the CD plus ethionine diets concomitant with the proliferation of oval cells, there was a marked elevation in the content of alpha1-fetoprotein in both liver and plasma. After specific immunofluorescence staining, oval cells stained intensely for albumin and alpha1-fetoprotein. Hepatocytes stained only for albumin, and bile duct cells stained for neither albumin nor alpha1-fetoprotein. These results indicate that a diet deficient in choline markedly alters the response of rat liver to carcinogenetic doses of ethionine. Thus, ethionine hepatocarcinogenesis in rats fed a CD diet may be a useful model for the exploration of the mechanism(s) whereby a dietary factor influences hepatocarcinogenesis.


Identification of type C viruses by electron microscopy. The cores of a small proportion of the particles in purified preparations of type C viruses are characterized by two concentric shells that have a "double-ring" appearance in specimens prepared for electron microscopy by negative staining or thin sectioning techniques. This distinctive feature allows such particles to be recognized as viral in impure preparations. Detectability of double-ring particles is considerably enhanced by treating the specimens with a non-ionic detergent before fixation and negative staining. The limit of detectablity of type C virus (identified by the double-ring feature) in the presence of a large excess of nonviral particulates of similar size and density was assessed.


Identification of beta-oncofetal antigen in cervical squamous cancer and its demonstration in neoplastic and normal tissues. An extract of a human cervical squamous carcinoma was used to produce rabbit antiserum with immunoreactivity against an antigen in several types of normal and neoplastic tissues. This antigen was abundant in cervical cancer as well as in normal adult and fetal kidney and liver. The antigen had a beta mobility in immunoelectrophoresis and a molecular weight range of 74, 000 to 90,000 as determined by gel chromatography. Since some of its properties were similar to those of the beta-oncofetal antigen described by Fritsche and Mach, a comparison was undertaken that indeed revealed identical immunoreactivity of the anti-beta-oncofetal antigen and anti-cervical cancer antisera when reacted in immunodiffusion against a cervical cancer extract. These results do not support the designation of this antigen as an oncofetal antigen.


Interaction of 4'-(9-acridinylamino)methanesulfon-m-anisidide with DNA and inhibition of oncornavirus reverse transcriptase and cellular nucleic acid polymerases. 4'-(9-Acridinylamino)methanesulphon-m-anisidide (AMSA) (NSC 141549), an acridine derivative with activity against a variety of laboratory tumors in vivo, is presently undergoing Phase 1 clinical evaluation. The interaction of AMSA with DNA and its effects on nucleic acid-polymerizing enzymes were examined in an attempt to define the site of cytotoxicity of AMSA. Binding of AMSA to DNA, as demonstrated by equilibrium dialysis and spectrophotometric methods, appears to be similar to other aminoacridines, in that two types of binding sites (type 1 and type 2) were observed. Fluorescence studies and thermal denaturation studies gave strong evidence that AMSA type 1 binding was by intercalation into DNA. The binding of AMSA to DNA was without marked base-pair specificity. Furthermore, the effect of AMSA on nucleic acid-polymerizing enzyme activities (mouse embryo DNA polymerase alpha, avian myeloblastosis virus reverse transcriptase, and Escherichia coli RNA polymerase) was studied. Inhibition of enzyme activity by AMSA appeared to be independent of DNA base sequence. The relatively high concentrations of AMSA required for inhibition of these enzymes as compared to the concentrations of AMSA necessary for cytotoxicity in vitro suggest that the interaction with DNA alone might not fully explain its antitumor activity.


Immunohistochemical study of a large molecular fragment of thyroglobulin in parafollicular cells. Thyroglobulin-like immunoreactivity of the parafollicular cells was studied by an immunoperoxidase bridge technique using antisera against dog thyroglobulin fragments. 1. The dog parafollicular cells were specifically stained by anti-peak I (27S and larger components fraction) antiserum absorbed with peak II (19S fraction). By this method, they were easily distinguishable from the non-reactive follicular cells and colloid droplets. More sensitive staining of the parafollicular cells was possible with anti-peak I'' (larger components fraction) antiserum. The staining reactions indicated that the antigenic material responsible for immunoreactivity of the parafollicular cells was due to larger molecular components of thyroglobulin corresponding to 32S, 37S or greater than 37S, and was not due to either the 19S thyroglobulin or to the 27S iodoprotein. 2. A conspicuous decrease of the immunoreactive material in the parafollicular cells occurred in the dog after both chronically induced hypercalcemia and antithyroid drug treatment. This coincided with movement of secretory granules containing calcitonin as shown by staining with silver impregnation, HCl-basic dye, and lead-hematoxylin. 3. The antisera against larger molecular components of dog thyroglobulin showed a high degree of cross-reactivity to the parafollicular cells of most of the mammalian species investigated; rats, rabbits, hamsters, mice, cats, lions, goats, cows, and human.


The alpha2-plasmin inhibitor levels in liver diseases. Concentrations of alpha-2 plasmin inhibitor, which is a primary and fast-reacting inhibitor of plasmin, were measured immunochemically in sera of patients with liver diseases and compared with normal controls. Serum level of alpha2-plasmin inhibitor was significantly decreased in liver cirrhosis and other severely affected liver diseases. The decrease appeared to be dependent upon the extent of liver damage, and the level of alpha2-plasmin inhibitor was closely correlated with parameters of liver functions of protein synthesis such as albumin concentration and cholinesterase activity in serum. The level of alpha2-plasmin inhibitor was fairly well correlated with the fibrinolysis inhibitor activity of serum. In contrast to alpha2-plasmin inhibitor, levels of alpha2-macroglobulin and alpha1-antitrypsin were increased significantly in liver cirrhosis. It was suggested that the reduction of alpha2-plasmin inhibitor level contributes substantially to the increased fibrinolytic activity observed in liver cirrhosis.


Intracellular distribution of 57Co-bleomycin. Since the first promising results of Nouel et al. 1972, additional positive experience has been obtained with 57Co-Bleomycin (57Co-BLM) as a tumour-localizing agent. In this preclinical study, mice with transplanted osteosarcoma and lymphosarcoma were used and rats with transplanted rhabdomyosarcoma. 57CoCl2 served as a control substance. 57Co-BLM had concentrated in the tumours with a factor 2 to 10 as compared to the (normal) liver of the animals. No preferential concentration in the tumours was found when 57CoCl2 was used. The highest specific activity of 57Co-BLM (cpm/mg protein) was found in a fraction containing mitochondria and lysosomes. Evidence for a lysosomal localization of this diagnostic compound was obtained from experiments in which the mitochondrial-lysosomal fraction was treated with hypertonic media of different osmolarities. Conditions could be found in which many lysosomes burst while almost all mitochondrial were intact. From these experiments it appeared that the radioactivity in the particles obtained from animals injected wtih 57Co-BLM was released very rapidly. It is concluded that 57Co-BLM is preferentially localized in the heavy lysosomes sedimenting together with most of the mitochondria of the cell and that these structures are more fragile than the light lysosomes.


Association of nucleolus organizer chromosomes in domestic sheep (Ovis aries) shown by silver staining. The nucleolus organizer regions of domestic sheep (Ovis aries), as shown by silver staining, are located terminally on chromosomes 1, 2, 3, 4, and 25. Significant differences between individuals in the number of Ag-NORs per cell were found. The frequency of involvement of individual chromosome pairs in nucleolar organization was found to be a characteristic of individual animals. Association frequencies of individual chromosomes were accounted for by their frequency of participation in nucleolar organization. No evidence for nonrandom association of chromosome pairs was found.