Physiological evidence for habenula as major link between forebrain and midbrain raphe. The lateral habenula is one of the few forebrain areas that project to the midbrain raphe nuclei. Electrical stimulation of the habenula markedly suppressed serotonergic neurons in the midbrain raphe. The suppression was blocked by systemic or microiontophoretic administration of picrotoxin, which suggests that gamma-aminobutyric acid is the inhibitory transmitter in the habenula-raphe pathway. These results support the concept that the habenula may serve a pivotal role in funneling information from the forebrain to the midbrain raphe.


Circadian rhythm of synaptic excitability in rat and monkey central nervous system. Synaptic responses in hippocampal granule cells to stimulation of their afferent fibers from the entorhinal cortex fluctuate with a 24-hour period. The phase of this cycle for rats and monkeys depends on whether the animal is naturally nocturnal or diurnal. In a rat blinded by enucleation, the rhythm persists but drifts out of phase with the rhythm of sighted controls.


[Coagulation and acute disseminated lupus erythematosus. Apropos of 25 cases]. It is important to study coagulation during lupus disease, not only to detect circulating anticoagulants, which may be the cause of hemorrhage, but also in order to seek chronic hypercoagulability, which is more dangerous as it may favour the development of thrombosis on inflammatory arteritis or aggravate the development of glomerular lesions. We have thus explored in this way 25 patients with systemic lupus of which 17 had histologically confirmed renal disease. 25% had hypocoagulability, but 50% had hypercoagulability which justitied treatment with heparin.


[Auriculo-ventricular perforation in bacterial endocarditis. Surgical treatment]. The authors report a case of bacterial endocarditis during which the precise nature of the heart lesions were only discovered at operation. There left ventricle and right atrium. The characteristics of the systolic murmur and the findings on phonocardiography together with left ventricular angiography had suggested mitral incompetence. There were no conduction disorders in this patient which might have helped in preoperative diagnosis. In connection with this case, the authors recall the characteristics of aneuryms of the membranous septum and congenital or acquired communications between the left venticle and the right atrium.


[Variation in serum nonesterified fatty acids during glucose tolerance test in undernourished patients with anorexia nervosa and in obese patients]. Intravenous glucose tolerance tests (0,33 g glucose per kg body weight) are performed in 11 self starved women suffering from anorexia nervosa, 10 obese and 8 normal women. They have no genetic or chemical diabetes and belong to the same age group. Plasma concentrations of immuno-reactive insuline (IRI) and non esterified fatty acids (NEFA) are determined during these tests. The basal concentrations of NEFA are very high in the obese patients. In the starved women the elevation of the basal plasma NEFA concentration is less striking and statistically not significant. The plasma level of NEFA is reduced in all subjects by hyperinsulinism secondary to hyperglycemia. This drop in NEFA concentration is significantly reduced in the obese patients and markedly inhibited in the starved women. This observation points toward an increased resistance to the antilipolytic action of insulin in anorexia nervosa because, in these patients, the glucose load determines a normal increase in plasma IRI but the fall in plasma NEFA concentration is severely impaired.


[Angiofollicular lymphoid hyperplasia (Castelman's tumor) in the mediastinum. Apropos of 2 cases]. The authors report two new cases of angiofollicular hyperplasia of the mediastinum (Castelman's tumour). The only clinical peculiarity was a rapid increase in volume. The authors then review about 200 published cases. Emphasising the existence of 3 different histological types (plasma cell form, vascular hyaline form and intermediate form) and on the association in certain cases of hematological disorders such as anemia and hypergamma globulinemia. The significance of this lesion is discussed. An inflammatory theory with reactional hyperplasia of the beta-lymphocytes is proposed. It was supported by a direct immunofluorescent study of two cases (first study of this type carried out on such lesions) which showed polyclonal plasma cell hyperplasia predominating on the IgG.


[Inappropriate secretion of antidiuretic hormone: true and false Schwartz-Bartter syndrome. Apropos of 2 cases]. The authors report two cases and consider the various physiopathological mechanisms of inappropriate hypersecretion of antidiuretic hormone. An exploration including clearance of free water and, in some cases, estimation of ADH before and after a water load, then before and after administration of ethyl alcohol, permits one to determine the mechanism. It seems advisable to reserve the term Schwartz-Bartter syndrome to paraneoplasic syndromes linked to ectopic and autonomous secretion of ADH.


[Anemia in chronic lead poisoning. Apropos of 2 cases]. The authors report two cases of lead poisoning in which the diagnosis was made following anemia. They recall the clinical, laboratory and physiopathological characteristics of the blood signs of chronic lead poisoning. Anemia is the result of more rapid aging of the red cells, and of the effect of lead on erythropoiesis. The diagnosis is based on the finding of stippled red cells, on the rise in urinary delta-levulinic acid and on urinary lead after chelation.


[Chronic atrophying polychrondritis].

[Chronic atrophying polychrondritis]. After the description of the clinical signs (chondritis, arthritis, eye signs, cardiovascular signs) and laboratory signs of chronic atrophying polychrondritis, the authors study its pathology and the electron microscope findings, its diagnosis and the most recently proposed criteria, its course and therapeutic difficulties, its classification and finally discuss recent biochemical and immunologic data and the pathogenesis.


[Cutaneous manifestations in trisomy 21]. The possibility of cutaneous manifestations in Down's syndromes not a surprise because we known that this affection affects the three embryonic parts. This cutaneous disorder is described by many authors but it is variable and not specific. The authors had occasion to see four cases of alopecia areata in mongolian children. They do an analytic study of variable manifestations. They insist on frequency of hyperkeratotic lesions, alopecia areata, alterations of vasomotricity and elastic dystrophies. In the group of chromosomic aberrations, down's syndrome is alone where the cutaneous manifestations are studied because the patients have a good survival.


[Tuberculosis of migrant black Africans]. A study of 357 cases of tuberculosis in African negro immigrants seen between 1967 and 1971 showed the predominance of respiratory lesions especially pulmonary and/or hilar ganglio-mediastinal lesions compared with lesions elsewhere, e.g. lymph nodes, bones, joints, pericardium, peritoneum, livers, and the frequency of multiple lesions. Routine detection should be more frequent in high risk subjects, who are almost always allergic on arrival in France. In spite of frequent resistance, above all primary, treatment gave good results in 83% of cases. In future, we will have to take into consideration the possibility of relapses and perhaps more numerous resistances, including to rifamycin and ethambutol.


[Hyperlipemias and their manifestations in the rheumatological sphere]. It is fairly frequent to encounter hyperlipemia on a rheumatic unit. Firstly the symptoms of certain idiopathic hyperlipemias sometimes include rheumatic changes. The latter include firstly, arthritis and tendinitis, above all observed in Type II hyperlipoproteinemia but also mentionned in Type IV, and secondly, exceptional bony lesions (generally of xanthoma type) which seem to occur exclusively in severe hyperglyceridemia. A few bone and joint diseases, such as gout or aseptic necrosis, frequently coexist with dyslipemia. Furthermore, various diseases may be simultaneously responsible for secondary hyperlipemia and involvement of the locomotor apparatus. Finally, the iatrogenic manifestations of the locomotor system appear mainly due to hypolipemic drugs, e.g. the muscle disorders seen in a few patients treated with clofibrate.


[Treatment of the syndrome of inappropriate secretion of antidiuretic hormone with demethylchlortetracycline. Apropos of 2 cases]. Two cases of inappropriate antidiuresis are reported, one associated with small cell anaplastic bronchial carcinoma, the other secondary to acute hydrocephalus. ttreatment with demethylchlortetracycline proved effective in both cases. Treatment of the inappropriate antidiuretic syndrome is discussed and the advantages of demethylchlortetracycline emphasised. This antibiotic seems to represent the treatment of choice of the chronic syndrome of inappropriate antidiuresis.


[Intestinal bacterial flora in patients with colopathies. Study of samples obtained by colonoscopy]. This enquiry, the limits of which are easy to determine, permits one to note that in patients with chronic hemorrhagic colonic disease samples of digestive juice, carried, out at the level of the colonic mucosa, permit isolation of a large number of pseudomonadaceae, these bacteria are extremely various. A single patient may harbour 10 to 12 species. These bacteria, usually harmless, belong to the natural microbiocenoses, but they may under certain circumstances, increase in number and, according to Fabiani, induce severe symptoms or even be fatal. The mass of bacteria isolated and identified did not permit a study of bacterial sensitivity. The most seriously affected subjects clinically, usually had various bacteria which excludes the accusation of one species and eliminates any idea of bacterial specificity in the constitution of the syndromes observed. The disturbance seems to be a consequence of these chronic diseases and not the cause. In fact, no pathogenic germ was isolated, which one might consider to be responsible for the disease. Finally, it is wise to conclude that patients with irritable colon syndromes who formed part of this investigation, simply presented some imbalance in the bacterial flora which was sometimes very marked with a predominance of proteolytic Pseudomonas.


[Polyradiculoneuritis in visceral cancer. Review of the literature. Apropos of 2 cases]. One should distinguish two types of polyradiculoneuritis during visceral carcinoma. Metastic polyneuritis and paraneoplastic polyneuritis. They fulfil distinct anatomical criteria and their pathogenesis is different. Both, however, have clinical analogies and a similar course. The survival time in both types is usually a few weeks. It rarely exceeds one year.


A mastoid osteoma causing intracranial complications. A case report. A case report of a mastoid sinus osteoma with intracranial complications is presented. This is the first report of a mastoid osteoma causing intracranial complications. The tumour is one of the paranasal osteoma group. It produced displacement and compression of the posterior fossa structures. The patient was operated on by means of a combined intra- and extradural approach.


Reactivation of chick erythrocyte nuclei after fusion with enucleated cells. Inactivated Sendai virus was used to fuse nucleated chick erythrocytes with mouse L and A9 cells which had been enucleated by centrifugation in the presence of cytochalasinB. The enucleation step removed the nuclei from more than 99% of the cells. During the fusion step, chick erythrocyte nuclei were introduced into 20% of the enucleated mouse cytoplasms. This resulted in the formation of a large number of "reconstituted cells" where practically all the cytoplasm originated from the mouse cell while the nucleus was of chick origin. The chick erythrocyte nuclei appeared to become well integrated into the mouse cytoplasms since they increased dramatically in size and dry mass, formed nucleolus-like bodies, and resumed RNA synthesis. This, however, did not prevent a gradual decrease in the rate of protein synthesis in the cytoplasm after the removal of the mouse nucleus. Protein synthesis decayed at a similar rate in both reconstituted and enucleated cells. The majority of these "cells" died within 48 h and all of them within 5 days after enucleation/fusion. By contrast, the small number of L cells which failed to become enucleated multiplied rapidly. The results obtained suggest that the reactivation of the chick erythrocyte nuclei is not fast enough to rescue the enucleated mouse cytoplasms.


Control of the expression of a herpes simplex virus thymidine kinase gene incorporated into thymidine kinase-deficient mouse cells. When thymidine kinase-deficient mouse cells "transformed" by in activated herpes simplex virus and expressing the viral thymidine kinase (TK) are grown in nonselective medium, there is an exponential decay in the proportion of cells that continue to express the viral enzyme. However, the viral TK can be reactivated at a frequency of approximately 1 cell in 10(6) in every population that has lost TK activity. When cells in which the viral TK has been reactivated are grown in nonselective medium, a decay in the expression of the viral enzyme occurs again at the same rate as in the initial transformed population. Studies on the reactivation of viral TK indicate that reappearance of the enzyme is not induced by the selective medium (HAT) used to detect cells in which the enzyme has reappeared. Furthermore, treatments known to induce latent viruses in other systems--eg, exposure of the cells to mutagens or cell fusion--do not affect the frequency with which viral TK is reactivated.


The dose-response relationship for ethyl methanesulfonate-induced mutations at the hypoxanthine-guanine phosphoribosyl transferase locus in Chinese hamster ovary cells. The frequency of ethyl methanesulfonate (EMS)-induced mutations to 6-thioguanine resistance in a Chinese hamster ovary cells clone K1-BH4 was studied at many EMS doses including the minimally lethal range (0-100 microng/ml) as well as the exponential killing portion (100-800 microng/ml) of the survival curve. The mutation frequency increases approximately in proportion with increasing EMS concentration at a fixed treatment time. The pooled data for the observed mutation frequency, f(X), as a function of EMS dose X, is adequately described by a linear function f(X)=10(-6)(8.73+3.45 X), where 0 less than or equal to X less than or equal to 800 microng/ml. One interpretation of the linear dose-response is that, as a result of EMS treatment, ethylation of cellular constituents occurs, which is directly responsible for the mutation. Biochemical analyses demonstrate that most of the randomly isolated 6-thioguanine-resistant variants possess a highly reduced or undetectable level of HGPRT activity suggesting that the EMS-induced mutations to 6-thioguanine resistance affect primarily, if not exclusively, the HGPRT locus.


Simultaneous isolation of herpesvirus hominis type 2 and cytomegalovirus from the genital tract of a woman. Herpesvirus hominis and cytomegalovirus are closely related deoxyribonucleic acid viruses which have been isolated from the genital tract. This report describes the simultaneous isolation of Herpesvirus hominis type 2 and cytomegalovirus from the genital tract of a woman preceded by the isolation of cytomegalovirus from the semen and a probable herpetic penile infection in her sexual partner.


Heterotopic chondrogenesis and osteogenesis induced by transformed cells: use of nude mice as a model system. A subline of HeLa cells was shown to induce cartilage and bone formation in congenitally athymic (nude) mice when injected intramuscularly. The chondrogenesis and osteogenesis observed was similar to that found when other inducing epithelia are injected intramuscularly into cortisone-treated mice. A tumorigenic SV40 T antigen-positive human-mouse somatic cell hybrid with human chromosomes C7 and C6 did not induce cartilage or bone formation under similar conditions. The nude mouse may thus provide a system in which to investigate experimental host-cell differentiation without the complications of immunosuppression.


Intrathoracic chemodectoma with multiple localisations. In 1958 a mediastinal tumour was discovered in an asymptomatic woman with a history of vomiting and an oesophageal anomaly which had not been treated. A tumour of the anterosuperior mediastinum in relation to the aortic arch was extirpated and proved to be a chemodectoma or non-chromaffin paraganglioma. At subsequent follow-ups the mediastinum was never normal and the heart size progressively increased, the oesophageal anomaly remaining unchanged. A small opacity appeared in the left lung in 1974. An operation performed in 1975 revealed an osteochondroma in the lung, pericarditis, and an intrapericardial chemodectoma. The oesophagus was not explored. An intrathoracic chemodectoma is rare. The importance of angiography in its diagnosis is emphasised. Malignant degeneration is seldom observed. Therapy is surgical, the tumour being radioresistant. The possibility to be considered in our patient was either relapse of the tumour with degeneration or multiple localisations of the tumour.


Acute effects of intravenous infusion of conjugated estrogen on serum levels of LH and FSH in post-menopausal and castrated women. In order to quantify the changes of feed-back effect of estrogen on the release of pituitary gonadotropin which is regulated by the hypothalamic-pituitary-ovarian system, the responses of LH and FSH to the intravenous infusion of 20 mg of conjugated estrogen were studied in 49 post-menopausal and 20 castrated women. In the group of women within 1 year after menopause, serum LH levels were elevated following the infusion of the conjugated estrogen. The responses of serum LH and FSH levels were different between post-menopausal and castrated women. The data indicated that the difference between the two groups was probably due to the difference of secrection patterns of the gonadotropins in post-menopausal and castrated women.


A trial of quantitative classification of surgical stress. The severity of various surgical stresses was classified quantitatively on the basis of degree of adrenocortical stimulation by ACTH-Z. Urinary 17-OHCS (total, free and individual fractions) were dtermined in sixteen patients who underwent various operations and were injected some doses of ACTH-Z. The following quantitative classification of surgical stress was possible. In the group of ureterolithotomy and pyeloithotomy, the severity of operative stress appeared to be equivalent to the adrenocortical stimulation caused by injection of 0.125 mg to 0.25 mg of ACTH-Z. The severity in the group of ureterotomia externa was nearly the same as that in the above group. In the group of nephrectomy by oblique incision, the severity of stress appeared to correspond to the stimulation by injection of 0.25 mg or more of ACTH-Z. The group of total nephroureterectomy with partial cystectomy showed the severity which would correspond to the degree of stimulation by injection of about 0.5 mg ACTH-Z, and the group of transperitoneal nephrectomy, by injection of 0.25 mg to 0.5 mg of ACTH-Z.


Blood production rates of estrogens in women with differing ratios of urinary estrogen conjugates. On the basis of the ratios of the estrogen conjugates in their urine (estriol/estrone + estradiol: E3/[E1+E2]), 19 women were divided into two groups: 9 women had ratios less than 0.6 and 10 women had ratios greater than 1.3. All women had measurements made of endogenous estrogens in their plasma by radioimmunoassay. They were then given constant infusions of 3H-estrone, 3H-estradiol and 14C-estriol during days 5-7 and days 20-22 of their cycles, and metabolic clearance rates (MCR) and blood production rates (PB) of estrone, estradiol and estriol were determined. Despite the wide disparity in their ratios of urinary estrogens, no differences could be found between the groups for the MCR's and PB's for all estrogens at either time of the cycle. The mean ratios of PB's (PB3/[PB2+PB1]) of estrone, estradiol and estriol ranged from 0.07 to 0.10 for each group during the cycle. The amounts of estriol entering the blood are small compared to the amounts of estrone and estradiol and do not correlate with the ratios of their urinary conjugates.


Rejectability of virus-induced tumors and nonrejectability of spontaneous tumors: a lesson in contrasts. In contrast to the excellent surveillance against tumors induced by the ubiquitous viruses in their natural host species, spontaneous tumors developing naturally, without experimental interference, evoke little or no rejection reaction. This may be viewed in relation to the natural history of tumors. In most cases, tumors evolve in several steps, with a successful of clonal variants following each other, characterized by increasing independence of host regulations (including immune restrictions). This process is commonly designated as tumor progression. In all probability, selection for nonrejectability is part of this process. Selection of the host for rejecting capacity is unlikely to play any major role, since the overwhelming majority of the naturally occurring tumors arise after the host has passed the peak of its reproductive period. The nonrejectability of spontaneous tumors may be overcome by target-cell modification, e.g., by chemical coupling, somatic cell hybridization, or viral xenogenization. Furthermore, genetic analysis of the F1 resistance effect in relation to seemingly nonrejectable tumors may reveal the existence of specific immune-response (Ir) genes that can influence the recognition of tumor-associated membrane changes by the host immune system.


[Effect of ascorbic acid on glucocorticoid metabolism in guinea pigs]. Ascorbic acid administered for 18-20 days (daily by 100 mg per 1 kg of weight per os) causes redistribution of certain fractions of 17-OCS excreted with urine (a decrease in the content of free F and F/E ratio, an increase in the content of THF, THE and THS, a more frequent appearance of substances). In the blood plasm and adrenals concentration of 11-OCS rises. When determining the available functional reserves of the adrenal cortex under these conditions, an increase in the content of F, E and S unchanged forms is observed in response to ACTH administration as distinct from the initial state. The rise in concentration of 11-OCS in the adrenals and blood plasm is less pronounced than in the control. A conclusion is drawn that ascorbic acid affects metabolism of glucocorticoids and changes the reaction of the adrenaocortical system on the action of ACTH.


[Changes in alanine and aspartate aminotransferase activity in rabbit tissues following administration of hydrocortisone and ACTH]. Hydrocortisone and ACTH administration induced AlT- and AsT-activity changes in the brain hemispheres, liver, spleen, muscles and blood plasm of rabbits. The direction and rate of changes of the studied enzymes activity in the tissues was not the same after hydrocortisone and ACTH injections and depended on duration of the hormones administration. The changes in the AlT-activity were more essential than those in the AsT-activity for all tissues.


[Adenylate system of rat liver tissue during chemical carcinogenesis]. The ratio of adenylic nucleotides, activity of adenylatekinase and ATPase were studied in the liver subcellular fractions and in tumours of rats with cancerogenesis induced by diethylnitrozamine and p-dimethylaminoazobenzene. The adenylatekinase activity increases in the liver hyaloplasm of rats with tumours and in the tissue of the tumours themselves, the activity of ATPase is unchanged. An increase in the adenylatekinase activity in hyaloplasm is accompanied by a decrease in the level of ATP with the absence of changes in ADP and AMP, that results in a drop "of the adenylate energy charge" value (Atkinson reflecting the balance of adenyl nucleotides in a cell.


[Mechanism of calcium ion transport in brain microsome fractions]. The influence of Ca2+ in rising concentrations on the ATP-dependent Ca2+-binding system of the brain microsome fraction, the inhibitory effect of SH-reagents on it and the protective effect of ATP correlate with the properties of the Mg2+-dependent Ca2+-activated ATPase of this fraction. Such properties of the system as inactivation with an increase in Ca2+-concentration effect of phosphate and oxalate, relation to detergents cannot be explained from the view point of the tri-phosphoinozitid-dependent binding of Ca2+. These data indicate that the general mechanism of Ca2+ transport in the brain microsome fraction is similar to the mechanism of this process in the sarcoplasmatic reticulum and is realized with participation of Mg2+, Ca2+-ATPase.


[Activity of carbohydrate metabolism enzymes in loach embryos under the influence of hormones]. The activities of hexokinase, glucokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, and fructose-1,6-diphosphatase were determined in loach embryos developed in solutions of insulin, hydrocortisone, estrone and thyroxin at different stages of embryogenesis. Glucokinase and fructose-1,6-diphosphatase activties are shown not to change markedly under the influence of the above-mentioned hormones. During some periods of early development the hexokinase activity is inhibited by insulin, estrone and thyroxin. The glucose-6-phosphate dehydrogenase activity is suppressed by each of the used hormones at all the stages of early embryogenesis while the glocose-6-phosphatase activity decreased only under the influence of insulin at the cleavage, blastula and gastrula stages. Insulin increased the activity of phosphofructokinase at the cleavage, blastula and early gastrula stages and hydrocortisone, estrone and thyroxine during certain periods of these stages. From middle gastrula two last hormones decreased the phosphofructokinase activity in the loach embryos.


Prostaglandins, nonsteroidal anti-inflammatory agents and eye disease. The prostaglandins produce elevation of intraocular pressure and breakdown of the blood-aqueous barrier. They act via the secondary messenger system, cyclic AMP. Although the pathogenesis of many forms of ocular inflammation, both external and internal, is unclear, it is evident that some forms of ocular inflammation are prostaglandin-mediated, at least in part. Others may be totally mediated by prostaglandin synthesis. At present the corticosteroids are the mainstay of therapy of these conditions. However, the corticosteroids are poor inhibitors of prostaglandin synthesis and have many deleterious side effects such as induction of ocular hypertension, cataract, and infection. The search for new agents that will obviate these side effects and be more specific for the disease process is crucial. The discovery that the mode of action of many nonsteroidal anti-inflammatory agents is via inhibition of prostaglandin synthesis places a premium on elucidating which of these agents is most effective and least toxic in the eye and by which route of administration. The arachidonic acid screening model is ideal for initially choosing which agent has the greatest potential clinically. Arachidonic acid, a PGE2 precursor, when given topically also elevates intraocular pressure and aqueous humor protein, and these effects are blocked by the nonsteroidal anti-inflammatory drugs. This occurs if the arachidonic acid is injected into the vitreous humor, too, providing evidence that this in vivo model involves intraocular mechanisms. Utilizing the arachidonic acid system, a comparative study of nonsteroidal inhibitors of prostaglandin synthesis shows that the most effective of 14 agents were flurbiprofen solution and suspensions of polysorbate-dispersed indoxole, meclofenamic acid, indomethacin, and clonixin. Animal uveitis is not an ideal model for the human condition. Nevertheless, proving the superior efficacy of a screened drug in this system will identify those drugs to be tested in the human disease states. Only after the very few best drugs of this nature are identified should the ultimate steps of human testing be initiated.


Morphology of human cells, carrier of measles virus, using nomarski optics and scanning electron microscopy. A human cell line (Lu106) carrier of measles virus was studied in a Nomarski interference-contrast microscope (NICM) and a scanning electron microscope (SEM). The results from this were correlated with fine structure findings obtained from analyses made in the transmission electron microscope (TEM). In both the NICM and SEM it was possible to identify intracellular perinuclear structures, which most likely represent aggregates of measles nucleocapsids. These structures appeared in the NICM as opaque vesicles and in the SEM as bulges in the flattened cells. The SEM also proved to be used for determining cell surface characteristics specific for the carrier culture, which were lacking in uninfected Lu106 cells. In the carrier culture, there were vesiculated cells with bled-like polymorphic and ridged projections, and cells with webbed cytoplasmic extensions. Ridges and transverse striations observed on these cellular protrusions and on microvilli possibly denote oriented viral nucleocapsids at the cell membrane. Furthermore in the carrier cells, the microvilli were more heterogenous in length and diameter and were more frequently branched or fused together when compared to microvilli in uninfected cells. The results are discussed in view of the available information on the appearance of virus-infected or virus-transformed cells in the SEM, also inregard to the various factors, other than virus infection, which play a role in determining the surface features of monolayer cells.


In vitro binding of 3H-estradiol to eosinophil and neutrophil granulocytes in various tissues (normal and neoplastic) of newborn and adult rats. In vitro uptake and binding of tritiated estradiol to the specific granules of eosinophil granulocytes has been observed by ultrastructural radioautography in various tissues of the rat (liver and spleen of newborn, small intestine and bone marrow of adult animals). Binding of 3H-estradiol to granules present in the cytoplasm of neutrophil granulocytes has also been observed in bone marrow and in a cholangioma produced by chemical carcinogenesis. Neither type of granulocyte bound 3H-testosterone.


Mitotic histiocytes and intranuclear Langerhans cell granules in histiocytosis X. Several mitotic histiocytes containing Langerhans cell granules were found in the lymph nodes of Letterer-Siwe disease. Some histiocytes of Hand-Schüller-Christian disease contained Langerhans cell granules within the nuclei. These Langerhans cell granules were not in 'nuclear pseudo-inclusions,' but were freely scattered inside the nuclei. We suggest that the Langerhans cell granules may get trapped in the nucleus during mitosis, since several investigators have suggested that mitosis causes other intranuclear organelles to get trapped. We also speculate that cells containing Langerhans cell granules may divide and increase by mitosis.


Immunoelectrophoretic investigations on Sendai virus envelope antigens in relation to host antigens. The different antigenic fractions characteristic of egg-cultivated Sendai virus envelopes were studied by immunoelectrophoresis. Virus-specific and host-specific fractions were identified. It was proved that incorporation of the host membrane fragments into the viral envelopes is not a passive phenomenon. During the last stages of its assembly and release, the virus incorporates into the envelopes some host glycoproteins, after an active biochemical processing resulting in a considerable reduction of their molecular weight, while the host antigenic determinants remain almost unaltered.


The role of some viruses in acute pneumonias in adults. Virological and bacteriological investigations were performed in 85 patients with acute pneumonias and virus isolation or serological evidence of virus infection were obtained in 37.6% of the cases. Influenza A2 and B viruses were incriminated in 14.1% of the patients; parainfluenza viruses in 7% and adenoviruses in 17.2% of the cases. Coxsackie virus was isolated from one patient's blood, and poliovirus 3 was recovered in 3 cases. In 5 cases associated virus infections were detected.


[Phosphoribosyl pyrophosphate and its metabolic enzymes in the erythrocytes in certain forms of anemia]. Content of phosphoribosyl pyrophosphate and the activity of ribose phosphate pyrophosphokinase and AMP-pyrophosphorylase were studied in erythrocytes of healthy persons and of patients with various types of anemia. Deficiency of phosphoribosyl pyrophosphate and a decrease in the activity of enzymes studied were observed in erythrocytes under microspherocytic and hypoplastic anemia. The alterations correlated with impairments in energy metabolism. At the same time an activation of phosphoribosyl pyrophosphate enzymatic system and an increase of its content in erythrocytes did not depend on energy metabolism in Marchiafava--Micheli disease.


[Insulin-like effects of taurine].

[Insulin-like effects of taurine]. A single administration of taurine at a dose of 200 mg per kg of body weight increased the insulin-like activity in blood plasma, elevated two-fold the content of glycogen in liver tissue, decreased content of sugars in blood. In vitro taurine increased the consumption of glucose by isolated diaphragm and increased the insulin activity. The adenilate cyclase activity was increased in incubation mixture, containing the diaphragms and taurine added. The data obtained and the recognized insulin-like effect of 3',5'-AMP and theophylline suggest that the insulin-like action of taurine is mediated through the cyclic 3',5'-AMP.


[Study of the role of endogenous 3',5'-cyclic AMP in the radioresistance of the cell]. A survival period of irradiated rat thymocytes was studied after administration of several possible modifiers of intracellular 3',5'-cyclo AMP. Theophylline, which inhibits 3',5'-cyclo AMP phosphodiesterase, adrenaline, ATP and adenosine possessed a radioprotective effect if they were added before the irradiation or just immediately after it. Imidazole activated 3',5'-cyclo AMP phosphodiesterase and, being added within the above-mentioned periods, it shortened the survival period at the irradiated cells. When theophylline and imidazole were added within 30 min after the irradiation, their effect was completely altered: imidazole increased but theophylline decreased the survival period of the irradiated cells. 3',5'-cyclo AMP and N6-2'-0-dibutyryl-3',5'-cyclo AMP did not affect the viability of thymocytes after the irradiation.


[Enzymatic activity of glucose-6-phosphate metabolism in the liver during the administration of a hepatic carcinogen]. In liver tissue of mice, administered with diethyl nitrosamine (2.5 mg/kg of body weight) within 2-8 months, activities of hexokinase and glucoso-6-phosphate dehydrogenase were increased and the activity of glucose-6-phosphatase was decreased . Termination of the administration of diethyl nitrosamine, which was carried out during 1-2 months, caused the temporary normalization of the enzymatic activity, but later on the alterations typical for carcinogensis were developed. After more prolonged administration of diethyl nitrosamine the period of normalization gradually disappeared. The distinct alterations in the enzymatic activity, after termination of diethyl-nitrosamine administration, were closely related to development of tumors in liver tissue.


[Effect of cortisol on the state of adenyl cyclase system in rabbits]. Content of 3',5'-cycloAMP was estimated in rabbit blood plasma and urine; activities of adenylcyclase and phosphodiesterase were determined in liver tissue, adipose tissue and adrenal glands within 5, 24 and 48 hrs after hydrocortisone administration. Concentration of 3',5'-cycloAMP was found to be increased 4-6-fold in plasma and urine after the hormone administration. Cortisol was shown to increase also the activity of adenylcyclase and phosphodiesterase in liver tissue within 5 hrs and in adipose tissue--within 24 hrs and 48 hrs after the administration. In adrenal glands hydrocortisone caused an inhibitory effect on the adenylcyclase activity at early steps of the experiment.


[Subcellular distribution of hexokinase in hepatoma and its electrophoretic properties]. In hepatomas of various malignancy contrary to normal and regenerating liver tissue a considerable part of hexokinase (HK) activity was bound with mitochondria. The HK activity, estimated in nuclei, microsomes and apparently in cytoplasma membranes, was due to contamination with mitochondrial fraction. High specific activity of HK in mitochondria of tumors might be responsible for the increased glycolysis, when these organelle preparations were added to the soluble fraction of cells. The HK of tumors was extracted from the preparations by alternative pathways. Reversible binding of some part of the enzyme with mitochondria was regulated by concentration of metabolites (ATP and G6P) similarly to the bound HK from normal tissues (brain, retina). At the same time the other part of unregulated HK activity (isozyme I only) was found in hepatomas to be intercalated into lipoprotein membranes; it was not controlled by metabolites.


[Biosynthesis and properties of collagen forming in the cartilage of chick embryos in the presence of various proline analogs]. Effect of proline analogues on biosynthesis and properties of collagen in chick embryo cartilage was studied. Azethidine-2-carboxylic acid, 3,4-dehydroproline, cis-fluoro-proline, cis-hydroxyproline and thiazolidine-4-carboxylic acid were found to inhibit the incorporation of 14C-proline into proteins by 66-89%. Introduction of proline analogues, instead of the amino acid, into the polypeptide chains of collagen caused the impairment of the enzymatic hydroxylation of the proline residues (formation of hydroxyproline). 3,4-dehydroproline possessed the highest inhibitory effect (80%) on formation of hydroxyproline. When it was introduced into alpha-chains of protocollagen, 3,4-dehydroproline inhibited 1.5-6-fold the cleavage of the protein by bacterial collagenase.


Transsphenoidal microsurgery for selective removal of functional pituitary microadenomas. The transphenoidal approach to the pituitary gland is emerging as the safest and most efficacious procedure for the management of pituitary tumors. With the aid of the microscope large tumors producing visual symptoms can be removed and microadenomata producing only signs and symptoms of endocrinopathies can be safely and adequately approached. The procedure is described in this report. The results of its use in 29 patients with selected illustrative case reports are described.


[Determination of 11-hydroxycorticosteroids in stress-evoking interventions as an endocrinological test]. Determinations of the 11-hydroxycorticosteroids (11-OHCS) in intervention evoking stress proved as advantageous method for the estimation of the ACTH-reserve. After pneumencephalography or transethmoidal-transsphenoidal operations of the hypophysis intensive increase of 11-OHCS in the plasma and urine were observed, when the ACTH-reserve was intact. The investigations give the possibility of renouncing additional special functional tests.


E1The mechanism of action of Lupidon.

E1The mechanism of action of Lupidon. Since quite some time relapsing herpes simplex virus infections of the skin are clinically successfully treated with a heat-inactivated vaccine Lupidon G and Lupidon H respectively, although nothing is known as yet regarding the working principle of this therapy, which bases on immunological reflections. It was, therefore, examined by the complement fixing and neutralizing antibodies against herpes simplex virus of 11 patients and 3 control individuals if repeated injections of this vaccine cause alterations of the specific antibody titer. Skin tests were made in addition with 9 patient prior to and 8 weeks after therapy at the earliest. During the entire eamination period of at least 8 weeks up to 9 months the complement fixing as well as the neutralizing antibody titer remained practically constant and in none of the examined cases the skin tests caused any reaction. Since it is, however, known, e.g. from the examinations by Lehner, that seropositive individuals reacta to herpes virus with symptoms of an allergy of the delayed type, is must particularly be considered in furture examinations on the working mechanism of Lupidon that the Lupidon solutions for intracutaneous testing must be of considerably higher concentration. The questition of the site of action of Lupidon at the interferon mechanism remains pending in addition.


[Therapy of recurrent herpes simplex].

[Therapy of recurrent herpes simplex]. The topical and systemic possibilities of treatment of herpes simplex recidivans are discussed in a brief report. The antigen therapy with Lupidon is mentioned in detail. A selection of important clinical reports on Lupidon is commented. These reports demonstrate a good to very good therapeutic effect of Lupidon in relapsing herpes simplex with more than 1500 controlled patients. A statistically confirmed result of the long-term antigen therapy with Lupidon was particularly demonstrated in controlled double blank tests. Up to now there were not observed any severe side effects with this great number of patients.


[Long-term effect of hormonal contraceptives on the behavior of serum lipids]. In order to check the long-term effects of oral contraceptives used in the GDR on certain serum-lipid-fractions, triglycerides, phospholipids, total and free cholesterol, and beta-lipoproteins were determined in four groups of 15 women each, taking the contraceptive preparations Ovosiston, Nonovlon, Gravistat, and Deposiston. Determinations were carried out before and following 3, 6, 12, and 18 month of drug administration. Statistically significant increases of triglycerides occurred under the combined preparations, of phospholipids under Ovosiston and Deposiston and of the beta-lipoproteins under Ovosiston and Gravistat. Total cholesterol showed a slight decrease under all preparations tested. At present the prognostic significance of these slight alterations of serum-lipid-concentrations cannot be estimated completely.


[Neurophysiologic analysis of the effect of ACTH and hydrocortisone on conditioned reflex behavior in cats]. In defensive behaviour of cats, ACTH eliminated extinction delay, evoked by electrical stimulation (with constant parameters) of the midbrain reticular formation, and enhanced the activating influence of the thalamus reticular zone. Hydrocortisone produced opposite effects. In alimentary behaviour, the adaptive hormones enhanced the facilitating effect on extinction, induced by stimulation of non-specific structures and the hypothalamus. However, during hydrocortisone action, encephalographic signs of the reflex remained for a long time after extinction of effector manifestations. Thus, ACTH and hydrocortizone, by changing the interaction between brain structures, exert certain influences on the behavioral processes. The hormonal effects, in turn, depend on the initial co-excitation of the centres.


Electron-microscopical observations on the development of vaccinia, cowpox and monkeypox viruses in pig skin. Multiformal abnormal configurations of virus particles and virus factories were observed in pig skin inoculated with vaccinia, cowpox and monkeypox viruses. The discussion is based on the data of multiplication of the viruses and production of circulating antibody.


[Biochemical characteristics of subcellular components of the visual system following light deprivation]. A study was made of the influence of prolonged light deprivation (ten weeks) at early stages of the rabbit postnatal ontogenesis on the state of specific enzyme activity (of cytochromoxidase, AChEase, K-Na-ATPase, monoaminoxidase and ATPase) in the synaptosomes and cellular mitochondria of the visual cortex and superior colliculi. A specific and oppositely directed change has been found ro each enzyme and subcellular structures. Restoration of sensory impulse activity in two weeks was attended with normalization of the revealed metabolism changes, likewise dissimilar for different subcellular components.


[Effect of alcoholic intoxication on the body's natural resistance to exposure to infectious and toxic agents]. The influence of alcoholic intoxication on the resistance of albino mice to bacterial toxins and staphylococcus cultures was investigated. Five-day administration of 40% ethyl alcohol to the animals was accompanied by a significant increase of their resistance to the intoxication caused by C1. perfringens toxins and staphylococcus. Thirty-day alcoholic intoxication promoted a marked reduction of albino mice resistance to the both toxins used and the staphylococcus cultures.


Interaction of elongation factor 2 from wheat germ with guanosine nucleotides and ribosomes. 1. The amino acid composition of wheat germ EF2 differs to some extent from that of elongation factors from mammals and bacteria. 2. The purified wheat germ EF2, similarly as the factors from other sources, is active in the: EF1-dependent polymerization of phenylalanine; ribosome-dependent GTP hydrolysis; binding of guanosine nucleotides; and ADP-ribosylation in the presence of diphtheria toxin. Fusidic acid at a concentration of 1 mM inhibits all these EF2-dependent reactions. 3. Diphtheria toxin in the presence of NAD+ inhibits polymerization of phenylalanine but does not effect GTP binding to EF2. 4. Binding of GDP to wheat germ EF2 is inhibited by ribosomes. During interaction with ribosomes, GTP in EF2-GTP complex is rapidly hydrolysed to GDP. Both GTP and 5'-guanylmethylenediphosphonate competitively inhibit formation of the ribosome-EF2-GDP complex due to the replacement of GDP from the complex. The latter is stabilized by fusidic acid.


[Comparative-biochemical study of phosphoinositides as functionally active components of excitable nerve fiber membranes]. The effect of acetylcholine (ACh) and cyclic 3',5'-adenosine monophosphate (cAMP) on phosphoinositide (PI) metabolism and associated changes of the permeability of the nervous fibers in the crustaceans Carcinum maenas and Eriphia spinifrons, as well as in the frog Rana temporaria, has been investigated. It was shown that ACh induces a significant decrease in the content of triphosphoinositides (TPI) in the nervous fibers of the crabs and increases their potassium permeability, which in its turn results in depolarization of the fibers. ACh did not affect frog nervous fibers. cAMP significantly increases the incorporation of 32P into TPI fraction of crab nervous fibers during conduction of excitation and also facilitates repolarization of the fibers after application of ACh. Proserine effectively protects nervous fibers from the influence of ACh, indicating possible participation of acetylcholinesterase in TPI hydrolysis. The data obtained suggest that PI are involved into the regulation of membrane permeability of crab nervous fibers to potassium ions.


Analysis of diameters of human pituitary hormone secretory granules. Measurements were made on electron micrographs of six human anterior pituitary glands of the maximal diameters of secretory granules in 130 cells, average 91 granules per cell. This was done in an attempt to classify the various hormone types solely by differences in the mean diameters of the secretory granules. The range of diameters in nanometers could be segregated into six subgroups of the following suggested functions: 135.5 +/- 13.6 TSH, 181.6 +/- 9.3 LH, 226.0 +/- 19.4 FSH, 356.8 +/- 30.5 ACTH/MSH, 452.9 +/- 23.8 GH, 559.9 +/- 38.0 prolactin.


Studies on the mechanisms of somatostatin action on insulin release. IV. effect of somatostatin on cyclic AMP levels and phosphodiesterase activity in isolated rat pancreatic islets. The effects of somatostatin on insulin release and cyclic AMP metabolism were studied in collagenase-isolated islets of Langerhans from the rat. Ceoncentrations from 500 to 2000 ng/ml significantly inhibited glucose stimulated insulin release, while 100 and 200 ng/ml were ineffective. Somatostatin (2000 ng/ml) inhibited insulin release and [3H]-cyclic AMP accumulation induced by 16.7 mM glucose after 10 and 30 min of incubation. In dose-response studies, the inhibition by somatostatin of the effect of glucose on [3H]cyclic AMP and insulin release could be overcome by a high concentration of the hexose (44.9 mM), suggesting competitive inhibition. In the absence of glucose, somatostatin inhibited [3H]cyclic AMP accumulation induced by the phosphodiesterase inhibitor, IBMX, while no inhibition was seen, again in the absence of hexose, when the [3H]cyclic AMP levels had been raised by the adenyl cyclase stimulator, cholera toxin. Somatostatin did not affect phosphodiesterase activity when added to islet homogenates, but preincubation of the islets with the peptide before homogenization decreased the activity by about 30%. It is suggested that somatostatin-induced inhibition of insulin release is, at least partially, mediated by cyclic AMP, probably through an action on islet adenyl cyclase.


Physiological regulation of rat liver phosphoenolpyruvate carboxykinase (GTP) by insulin. Insignificance of a cyclic AMP-independent mechanism. The effect of re-feeding glucose, protein or fat and the effect of insulin injection on the activity of hepatic phosphoenolpyruvate carboxykinase (GTP: oxaloacetate carboxy-lyase (transphosphorylating) EC 4.1.1.32), the concentration of hepatic cyclic AMP and the level of serum insulin was investigated in starved rats. Under all conditions examined the concentration of serum insulin was elevated to a high degree. However, only rats re-fed with glucose responded to the increase in serum insulin with a decrease in PEP carboxykinase activity, while the activity of the enzyme remained unchanged or was elevated after re-feeding protein or fat or after insulin injection, respectively. Since under all conditions there was a close correlation between cyclic AMP concentration and PEP carboxykinase activity, but not between the insulin level and enzyme activity, it is concluded that the hormone physiologically regulates PEP carboxykinase activity by decreasing the intrahepatic cyclic AMP concentration rather than by the postulated cyclic AMP-independent inhibition of specific mRNA translation.


Extremely high levels of corticosteroids and low levels of corticosteroid binding macromolecule in plasma of marmoset monkeys. Marmoset monkeys were shown to have extremely high resting plasma corticosteroid levels compared to those of macaque monkeys and humans. A major component of corticosteroids seems to be cortisol. Levels of total 11-deoxy-17-KS in plasma of marmoset monkeys were very low (less than 0.01-0.04 microng/ml). Following the injection of ACTH, plasma corticosteroid levels of marmoset monkeys increased by 18-62% (at 1 h), and by 62-160% (at 2 h). Concentrations of plasma corticosteroid binding macromolecule in marmoset monkeys were extremely low (less than 10 nM). It was suggested that in these monkeys, the majority of plasma corticosteroids exists in non-protein bound forms.


The effect of calcium and dibutryl-cAMP on the secretion of parathyroid hormone by human parathyroid adenomas in organ culture. The effect of different calcium concentrations as well as dibutyryl-cyclic adenosine 3',5'-monophosphate (DB-cAMP) on the secretion of parathyroid hormone by human parathyroid adenomas taken from patients with primary hyperparathyroidism (pHPT) was studied in organ culture. Their influence on the release of hormone was determined. The tissue was incubated in culture medium for 4 h; the medium was changed hourly and analyzed for immunoreactive parathyroid hormone (PTH) by radioimmunoassay. The hormone secretion showed an inverse relationship to different calcium concentrations in the medium and could be stimulated independently of the calcium concentration by adding DB-cAMP. These results suggest that the examined parathyroid adenomas are sensitive to physiological stimuli.


Studies on the mechanism of somatostatin action on insulin release. V. Effect of somatostatin analogues on arginine induced release of insulin and glucagon from the perfused rat pancreas. Eighteen analogues of somatostatin have been used in order to elucidate the structure-activity relationship of the peptide on the release of insulin and glucagon from the isolated perfused rat pancreas. Neither the amino terminal nor a free carboxyl terminal seemed to be essential for the activity of the cyclic peptide. Addition of amino acids to the amino terminal did not decrease the activity. On the other hand, minor changes in the structure of linear somatostatin, which lead to the loss of ability to form a cyclic peptide, impaired the activity. Deletion of Asn5 was accompanied by decreased action on glucagon but not on insulin release. It seems that the major actions of somatostatin on the pancreas are bound to the amino acid sequence 4-13 in the molecule and to the ability of the molecule to cyclize.


Lack of effect of prolactin inhibition by alpha-bromoergocriptine (CB 154) on plasma aldosterone in anephric and non-nephrectomized patients on regular haemodialysis. To investigate whether a direct influence exists between the prolactin suppressive effect of alpha-bromoergocriptine (CB 154) and the aldosterone response to a potassium stimulation, the present study was performed in 7 anephric patients and in 7 non-nephrectomized patients, all on regular haemodialysis. The increase in the plasma potassium concentration between dialysis was used as a stimulus to the adrenals, and was correlated to the increase in the plasma aldosterone concentration (PAC). Plasma samples were obtained during a control period and during a corresponding period of treatment with bromocriptine. Despite a significant fall in the prolactin levels during the bromocriptine treatment, no differences in the aldosterone response to the increasing potassium concentration in the two periods were found neither in the anephric nor in the non-nephrectomized patients. It is concluded that depression of prolactin levels by the dopamine agonist (bromocriptine) has no influence on the ability of the adrenals to react with an increase in aldosterone secretion following potassium stimulation in dialysis patients with and without preserved renin-angiotensin system.


Effects of ACTH and dexamethasone on the zona glomerulosa of the rat adrenal cortex: an ultrastructural stereologic study. The effects of a chronic treatment with ACTH and dexamethasone on the zona glomerulosa of intact rat adrenals were investigated by morphometric methods and electron microscopy. It was found that ACTH increases the volume of the zona glomerulosa, of the cells, nuclei mitochondrial compartment as well as the surface of SER and mitochondrial compartment as well as the surface of SER and mitochondrial cristae. Also noticeable was the hypertrophy of the Golgi apparatus. Opposite effects were obtained after dexamethasone treatment. These findings are interpreted as indicating that ACTH is involved in the maintenance and stimulation of the growth and steroidogenic capacity of the adrenal zona glomerulosa.


Demonstration of an FSH receptor in a functioning granulosa cell tumour. The effect of gonadotrophin treatment on its viability following transplantation to nude mice. Hormone production in a patient suffering from a late recurrence of a granulosa cell tumour has been studied pre- and post-operatively, and a vein on the tumour surface was cannulated at operation to collect tumour vein blood for pre-operative studies. Elevation in the plasma oestradiol level and depression in FSH and LH were found pre-operatively, and elevations were found in tumour vein oestradiol and 17alpha-hydroxyprogsterone. Plasma oestradiol level returned to normal postoperatively whereas FSH and LH levels were persistently depressed. FSH receptors were found in this tumour, and on the basis of this finding, gonadotrophins were given to athymic nude mice in an attempt to support the growth of the granulosa cell tumour implanted in these animals. We demonstrated that gonadotrophins have supported the tumour tissue, but not promoted growth.


Erythrocyte galactose-1-phosphate uridyltransferase and galactokinase levels in twins. The levels of the two enzymes, GAL-1-PUT and GAL-KIN, have been examined in a sample of 35 MZ and 45 DZ twin pairs of both sexes. The activities of these enzymes do not appear to be influenced by sex. The role of genetic factors appears to be rather limited in the case of GAL-1-PUT, but much higher in the case of GAL-KIN.


Transmission of excitation from muscle to nerve under in situ conditions. In order to investigate the excitatory effect of the muscle on the adjacent nerve experiments were performed on nerve-muscle and whole leg preparations of the frog. The results showed that muscular activity could generate excitation of the nerve in contact with the muscle under in situ circumstances, and that a well-defined part of the muscle could play a significant role in the transmission of excitation from muscle to nerve. The results support the hypothesis of being an additional way for muscle activity to influence the regulatory mechanism of the nerve-muscle function during excitatory processes.


The clinical classification of maculopathies in adults. A survey. The development of fluorescein angiography and the introduction of laser technology into the treatment of macular diseases has considerably widened our knowledge of the pathological processes in the macular region. A number of clinicopathological reports have confirmed the angiographic findings and interpretations. The aetiological factors that lay behind the clinical lesions are, however, still unknown. The clinical pictures have, as a result of the above, more relation to the histological than to the aetiological classifications. Clinical classification includes an analysis and categorization of the individual diseases. This process takes place daily in the surgery of every ophthalmologist by means of the ophthalmoscope. The ophthalmoscopical examination is enhanced by knowledge of the angiographic picture of the lesion. This means that in the great majority of cases it is possible using the ophthalmoscope alone, to evaluate the type and anatomical localization of the pathological lesions. Fluorescein angiography is the most important single supplementary examination, both with regard to the diagnosis, indication for treatment and the follow-up. The present work describes 9 clinically and histopathologically well-defined lesions, which isolated or in combination are seen in the majority of adult macular diseases.


Mesenteric vascular occlusion in infants and children: report of two cases and review of the literature. Mesenteric vascular occlusion is a rare disease in the paediatric age group. The pertaining literature is reviewed and two cases are reported. In the first one the vascular obstruction developed after a Wilms tumour on the right side had been removed. Following bowel resection and end-to-end anastomosis the patient died of uraemia. Post mortem examination revealed a diffuse membranous glomerulonephritis and pseudoxanthomatosis in the remaining left kidney, the function of which had probably been affected by the shock associated with mesenteric thrombosis. In the second case a mixed mesenteric vascular occlusion was found without any previous disease; after ileal resection and ileo-coecal anastomosis the baby made a smooth recovery.


Severe disseminated adenovirus infection successfully treated with a thymic humoral factor, THF. Adenovirus and other usually benign viral infections may occasionally be associated with severe fulminant disease, often accompanied by acute acquired cellular immunodeficiency. Thymic humoral factor derived from calf thymuses has been demonstrated to have the capacity to restore the immunocompetence of immature, incompetent T cells. This factor was used in the treatment of a 3 1/2-year-old boy who was critically ill with an adenovirus infection and presented evidence of immunocellular deficiency. Within less than 48 hours after the institution of treatment with thymic humoral factor there was a dramatic, progressive clinical improvement, with restoration of the cellular immunocompetence. It is suggested that thymic humoral factor may be beneficial in the treatment of severe viral infections associated with depressed cellular immunocompetence.


Cord serum lipid and lipoprotein-cholesterol values in normal and betamethasone-treated newborns of varying gestational age. Cord serum total cholesterol, very low density lipoprotein-, low density lipoprotein-, high density lipoprotein-cholesterol and triglyceride was determined in 30 AGA infants and 35 SGA infants born between the larger than or equal to 37th less than or equal to 42th week of gestation and in 26 AGA infants born between the larger than or equal to 33th less than 37th week of gestation. In SGA infants significantly higher VLDL-cholesterol and triglyceride values were found than in AGA infants. In AGA infants less than 37 weeks of gestation total cholesterol, LDL-, and HDL-cholesterol concentrations were higher than in AGA infants larger than or equal to 37 weeks of gestation. In 10 betamethasone-treated AGA infants less than 37 weeks of gestation HDL-cholesterol was higher than in 16 untreated AGA infants less than 37 weeks of gestation.


Infantile convulsions: transient infantile hypocalcemia associated with skeletal deformities. An infant with skeletal deformities and hypocalcemic convulsions is described. The convulsions, which were first noted in the 5th week of life, as well as the low serum calcium level were transient. The skeletal deformities consited of deformation of the terminal phalanges of the right third finger and right second toe, syndactyly of the third and fourth finger of both hands and left pes equinovarus. X-ray examination revealed abnormal shape and structure of some bones of the hands. The most likely diagnosis is transient congenital idiopathic hypoparathyroidism, which has not yet been described in association with congenital skeletal anomalies.


Adaptation of neuromuscular junction to transmission of impulses after inactivation of acetylcholinesterase. Adaptation of neuromuscular junction to transmission of impulses after inactivation of acetylcholinesterase. Acta Physiol. Pol., 1977, 28 (1): 23-30. Isolated preparation of rat diaphragm with phrenic nerve was incubated in paraoxon solutions which caused complete inactivation of acetylcholinesterase. This inactivation was associated with disturbances of neuromuscular transmission in the form of blockade of the tetanic response, post-tetanic inhibition of twitch responses and a decreased amplitude of the second response after the first one when two stimuli at a short interval were used. These disturbances were withdrawn somewhat during further incubation of the preparation, although it was kept in paraoxon solution which maintained complete inactivation of acetylcholinesterase. It is suggested that the observed recession of transmission disturbances may be caused by partial adaptation of blockade of the tetanic response, post-tetanic inhibition of twitch blockade of enzymatic hydrolysis of acetylcholine.


The effect of lipiodol injected into the pulmonary artery on blood pressure in pulmonary artery and thoracic aorta in dogs. The effect of lipiodol injected into the pulmonary artery on blood pressure in pulmonary artery and thoracic aorta in dogs. Acta Physiol. Pol. 1977, 28 (2): 143--151. The purpose of the experiments, carried out on 10 anaesthetized dogs, was to trace changes in pressure in aorta and pulmonary artery within 2 hours after injection of lipiodol Ultra-Fluide into the pulmonary artery of dogs. In individual experiments a gradual fall, rise or maintenance of normal pressure was found in the aorta. Pressure changes in the pulmonary artery were similar. Statistical analysis failed to demonstrate any significant correlation between the pressure in the aorta or in the pulmonary artery and the time of measurements of these pressures during the two-hour experiment.


X-ray analysis of enzymically purified elastin from bovine ligamentum nuchae. Insoluble elastin has been isolated from bovine ligamentum nuchae by treatment with quanidine and dithiothreitol followed by digestion with collagenase, purified by affinity chromatography. The preparation was subjected to both wide- and low-angle X-ray analysis. The wide-angle diffraction patterns of relaxed and stretched specimens showed only two broad diffraction rings, corresponding to spacings of 4.5 and 9.3 A. No significant reflections were visible in the low-angle diffraction pattern of unstretched specimens, but on stretching an equatorial reflection was produced, corresponding to spacings of between 45 and 50 A.


Myospherulosis. An electron-microscopic study of a human case. An electronmicroscopic study of a human case of myospherulosis, which involved the nose and maxillary sinus, is reported. Large parent bodies limited by a thick electron-dense wall, enclosing variable numbers of spherules, were seen in cystic tissue spaces or adjacent connective tissue. Free spherules and shrunken degenerative forms were present as well. Similarity of these bodies to sporangium-like structures is suggested. The etiology of the disease remains unsettled.


A case of cerebral gigantism and hepatocarcinoma. A 14-year-old boy, who had the physical and neurological characteristics of cerebral gigantism (Sotos syndrome), developed hepatocarcinoma. This tumor is rare in children and has never, to our knowledge, been recorded in a patient with cerebral gigantism. An autopsy was performed, the first we are aware of in a patient with cerebral gigantism without increased size in ventricles.


Prevention or modification of varicella using zoster immune plasma. Zoster immune plasma (ZIP) was given to 31 susceptible immunocompromised children one to seven days (median, two days) following household, playmate, or hospital exposures to varicella. The average amount of ZIP transfused was 7 ml/kg. Twenty-one children did not develop varicella or persistent antibodies to varicella-zoster virus (VZV). Eight (26%) of the 31 contracted clinical varicella. Seven cases were mild, but in one child, who was given ZIP seven days after exposure, visceral disease developed and the child died. Two children had subclinical varicella that was documented by persistence of VZV antibodies for at least ten months after passive immunization. Because none of the 30 children given ZIP one to six days following exposure had severe varicella, we conclude that ZIP is effective in preventing or modifying varicella in immunocompromised patients if given shortly after exposure.


SV40 T-antigen expression in skin fibroblasts from clinically normal individuals and from ten cases of Fanconi anemia. Previous studies of the expression of SV40 genetic information by skin fibroblasts included limited numbers of cell donors and failed to adequately consider possible effects of age, sex, and ethnic origin on assay results. A population of 76 healthy subjects were selected for study following determination of personal and family disease history and karyological analysis. Skin fibroblasts from these individuals were tested for expression of SV40 T-antigen by indirect immunofluorescent assay. The data were normally distributed and showed no significant differences between the age, sex, or ethnic groups tested. The occurrence of rare karyological anomalies in this control population had no effect on T-antigen expression. Fibroblasts from 10 Fanconi anemia patients demonstrated significantly elevated expression of T antigen compared to the well-defined control population, based on simple statistical criteria. T-antigen expression was elevated in two young patients prior to the onset of anemia and did not appear to correlate with the incidence or severity of other specific symptoms. Thus, elevated T-antigen expression in Fanconi anemia fibroblasts reflects an actual defect at the cellular level, rather than clinical, age, sex or ethnic factors not previously considered.


The Philadelphia variant of galactokinase. We have previously reported the existence of a polymorphism that causes black populations to have lower mean RBC galactokinase activity than comparable white populations. We have designated this allele the Philadelphia variant, GALKP, and have suggested that it is common in blacks and rare in whites. GALKP individuals have normal WBC GALK activity, in contrast to the half normal WBC GALK activities of heterozygotes for the allele (GALKG) that causes the galactokinase-deficient form of galactosemia. In one family, we have presented evidence for the existence of two sisters heterozygous for both GALKG and GALKP alleles. These individuals have 50% normal WBC GALK activity and less than 50% normal red cell activity. The latter finding indicates that the two variant GALK alleles additively affect RBC activity. The WBC results suggest that the low activity of GALK in RBC of individuals with the GALKP allele is due to its relative instability. We could obtain no evidence for such instability from studies of high reticulocyte bloods or RBC fractionation. Furthermore, we could not demonstrate that the GALK in WBC from GALKP individuals has altered electrophoretic migration.


Clinical and laboratory correlates of molar pregnancy and trophoblastic disease. From January 1, 1970 to July 1, 1976, 128 women had hydatidiform moles evacuated at the Los Angeles County-University of Southern California Women's Hospitals. Of the 121 patients with follow-up, persistent trophoblastic disease (TD) was diagnosed in 32 (26.4 per cent). Remission was achieved in all treated patients. The frequency of TD was significantly increased in pregnancies large for dates (47.8 per cent), with a uterus greater than 20 weeks' gestational size (45.0 per cent) or with theca-lutein cysts greater than 5 cm. in diameter (50.0 per cent). A normal regression curve for serum beta-human gonadotropin as measured by radioimmunoassay has been constructed as an aid to the early recognition of postmolar TD (invasive mole and choriocarcinoma).


Immunosuppression and eye disease. First Vail lecture. Several viral, fungal, and protozoal diseases of the eye are significantly associated with immunologic deficiencies. Of the viral agents, cytomegaly and herpes simplex and zoster cause a discrete necrotizing retinopathy that has the characteristics of vascular occlusion. Measles may result in a delayed retinopathy that is predominantly macular and associated with subacute progressive encephalopathy. Of the fungal agents, Candida and Aspergillus are apt to involve the eye, beginning as choroidal lesions with extension forward to involve the pigment epithelium and retina secondarily. Mucor and Cryptococcus are less common. Toxoplasmosis is the one ocular protozoal disease whose incidence is increased by immunosuppression, and, like the viral diseases, is characterized by a discrete necrotizing retinopathy and probably results from activation of dormant organisms in the retina. Autoimmunity undoubtedly plays an important role in eye disease but its ocular pathogenesis is obscure.


Cutaneous dissemination of herpes simplex virus in individuals fifteen years of age and older. We have reported the case histories of two individuals with underlying atopic dermatitis who developed extensive vesicular eruptions. In both cases herpes simplex virus type l was isolated from skin lesions and both individuals ultimately recovered. These two cases represent only the third and fourth instances of this syndrome proven to be caused by herpes simplex virus type l that have been reported in older individuals. In addition we have reviewed the literature relative to cutaneous disseminated herpes simplex virus infections occurring in individuals over the age of 15 and have presented a comprehensive overview of this disease.


Assessment of physical maturation and somatomedin levels during puberty. The chronologic age, skeletal age, and somatomedin level of thirty-nine Caucasian girls of various developmental stages were compared. The results showed that there was a significant difference between the somatomedin levels in the plasma of circumpubertal and postpubertal females. No significant difference was noted between the prepubertal and the circumpubertal subjects tested. In addition, the skeletal age appears to be a better indicator of physical maturation than does the chronologic age of an individual. In order to substantiate the concept of somatomedin as a true marker for the pubertal growth spurt, this study should be continued on a longitudinal basis utilizing rate-of-growth data.


Effect of dichloromethane diphosphonate on calcium homeostatic mechanisms in pregnant cows. The administration of 4 mg/kg/day of dichloromethane diphosphonate (Cl2MDP) subcutaneously to pregnant cows fed a low-calcium diet significantly reduced bone resorption as indicated by microradiographic evaluation of endosteal surfaces of cross sections of ribs. Plasma parathyroid hormone levels were similar between Cl2MDP-treated and control cows prepartum, during EDTA infusions, and near parturition. Ultrastructurally, chief cells of the parathyroid glands of both groups of cows were in the active stage of the secretory cycle. The chronically stimulated chief cell from cows administered Cl2MDP had a large cytoplasmic area containing many lipofuscin granules and lysosomal bodies and a few secretory granules near the large Golgi apparatus or aligned along the plasma membrane. Uptake of calcium 45 by the duodenal mucosa incubated in vitro was greater in Cl2MDP-treated cows compared to control cows. The administration of Cl2MDP significantly reduced rapidly mobilization calcium reserves. Following an intravenous EDTA infusion and the spontaneous calcium drain associated with parturition and the beginning of lactation, Cl2MDP-treated cows developed severe hypocalcemia. The rapid mobilization of calcium reserves in cows administered Cl2MDP prepartum was impaired mainly because of diminished resorption of bone despite adequate parathyroid hormone secretion in response to severe postpartal or EDTA-induced hypocalcemia.


Virus-induced lysosomal enzyme dissolution of nasal turbinate cartilage. The mechanism of laryngotracheitis virus-induced dissolution of chick nasal turbinate cartilage was studied by lysosomal enzyme histochemistry. Five-day-old chicks were infected by intranasal instillation, and changes in lysosomal enzyme distribution were followed at daily intervals through the tissue regeneration stage, Day 28. In the mucosa the lysosomes were activated beginning on Day 1, and glycerol acid phosphatase and a diffuse form of beta-glucuronidase were released concomitant with tissue cell destruction. In the chondrocytes (where glycerol acid phosphatase was absent), beginning on Day 2, particulate (lysosomal) beta-glucuronidase decreased as diffuse beta-glucuronidase increased and extended out into the matrix. The cartilage lost its metachromatic staining properties and became soft and pliable. Regeneration of the mucosa started on Day 6 and gradual reappearance of metachromatic staining of the cartilage began on Day 8 with considerable recovery of original turbinate structure by Day 12. A lysosomal membrane labilizer, vitamin A, exacerbated the cartilage pathology, whereas a stabilizer, cortisone, retarded it.


An examination of the federal psychiatric training grant peer review process. The authors present some of the criticisms that have been leveled against the federal peer review system of approving or disapproving monetary grants. They then summarize the process used by the National Institute of Mental Health's Psychiatry Education Branch to judge grant applications, focusing on the disposition of 527 applications reviewed in November 1974-January 1975. They found that the wide distribution of the reviewers by geography, subspecialty, experience, sex, and ethnicity, plus the steps taken to guard against bias and ensure fairness, were effective, refuting many of the criticisms of the group peer review process.


Definition of the antigenic pattern of Entamoeba histolytica, and immunoelectrophoretic analysis of the variation of patient response to amebic disease. The antigenic anatomy of Entamoeba histolytica and the variation in response of 148 patients with amebic disease are described. Immunoelectrophoretic patterns and indirect hemagglutination titers were studied in sera obtained from patients with amebic disease acquired in several areas of the world, i.e. Canada, Vietnam, Afric, India, Central America, and southern United States. The various populations are compared and similarities and differences are discussed.


Experimental amebiasis. I. Pathogenicity of axenically cultured Entamoeba histolytica in the brain of the newborn mouse. Axenically cultured Entamoeba histolytica inoculated intracerebrally into newborn Swiss mice invaded the cerebrum and produced multiple abscesses containing viable trophozoites. As few as 20 amebae of a virulent strain (HM-1:IMSS) occasionally produced fatal disease, 200 killed about 75% of animals and higher doses regularly killed all animals. In contrast, avirulent strains (HK-9 and HB-301:NIH) failed to produce acute brain disease in comparable time periods even when mice were inoculated with as many as 20,000 amebae. Two other strains (1295 and H-458:CDC) were of intermediate virulence. High doses of avirulent amebae often produced hydrocephalus as a late manifestation. In newborn, 3 week-old, and 6-week-old mice resistance to infection increased with age, and older animals often responded late to virulent strains by developing hydrocephalus.


Experimental amebiasis. II. Hepatic amebiasis in the newborn hamster. Newborn hamsters inoculated intrahepatically were highly susceptible to infection by axenically cultured Entamoeba histolytica. Inoculations were performed through the abdominal wall, and lesions could be observed through the skin as early as 4 days after inoculation. The most virulent amebal strain, HM-1:IMSS, produced liver lesions in 19% of newborn animals inoculated with 20 amebae, and in about 90% receiving 2,000 amebae. Eleven other strains similarly tested either produced no lesions with 20,000 amebae or were of intermediate virulence. Two hamster strains did not show appreciable differences in susceptibility to the HM-1:IMSS amebal strain. Newborn hamsters were more susceptible to HM-1:IMSS amebae than animals which were 2, 4, or 7 days old at the time of inoculation. Three-week-old animals were resistant to doses below 20,000 virulent amebae.


Vascular exclusion in surgery of the liver: experimental basis, technic, and clinical results. Because liver exeresis and surgery for liver trauma still carry  a great mortality by hemorrhage or air embolism due to suprahepatic or vena cava  injuries, temporary vascular exclusion of the liver is considered. Based on hemodynamic, biologic, and anatomopathologic experimental and clinical data, a catheter was designed that allows isolation of the retro-and suprahepatic portions of the inferior vena cava and consequently vascular exclusion of the liver for 30 minutes. We report on seven patients in whom this technic was utilized (4 requiring hepatectomy and 3 traumatized), confirming the utility, ease, and efficacy of this method.


Prognosis and treatment in minimal breast cancer. Of 176 patients with minimal breast cancer, 138 had intraductal carcinoma in situ, 21 minimally invasive carcinoma, and 17 lobular carcinoma in situ. Various modalities of treatment were used including radical, modified radical, and simple mastectomy with and without radiation therapy. Long-term postoperative follow-up was available in all but five patients and ranged from one year to twenty-one years. Actuarial analysis projected a twenty year survival of 93.2 per cent for the entire group. Analysis of survival figures based on each of the several treatment modalities showed no definite advantage of one form of treatment over another. The data suggest that minimal breast cancer is a prognostically favorable diagnosis, provided invasive carcinoma is not present or does not develop in the opposite breast. It is also indicated that breast cancer is potentially a bilateral disease and that follow-up and treatment of the opposite breast must be of major concern in the care of these patients.


Evidence for the involvement of microtubules in wound contraction. Many theories have been proposed for the mechanism of wound contraction, that phenomenon of wound closure in which the skin surrounding the tissue defect is drawn into the open wound. When agents that inhibit microtubular function, such as vinblastine and colchicine, were topically applied to actively contracting wounds, contraction stopped. Cytochalasin B, an agent that reportedly disrupts microfilaments, did not alter contraction. These results suggest that wound contraction is related to the functioning of microtubules in fibroblasts within the wound and is proceeding at its maximal rate. The results tend not to support the theory that the microfilament components of cells are involved in wound contraction.


Recovery of neuromuscular transmission following desensitization block. Depolarization and desensitization neuromuscular blockade was induced with suxamethonium. Rate of recovery of neuromuscular transmission did not vary with the nature of the blockade.


Effect of cytosine arabinoside on Herpes virus infection in renal allograft recipients. Cytosine arabinoside (Ara-C) was used for treatment of severe symptomatic cytomegalovirus (CMV)-herpes infections that were seen in nineteen of 174 renal allograft recipients. Ara-C was administered by continuous intravenous infusion at a mean dose of 35 mg/m2 daily for three to four days. Side effects were few and minor in nature. All cases of herpes simplex and herpes zoster, which usually have a prolonged and sometimes unfavorable course in immunosuppressed patients, cleared promptly with no recurrence. All nine patients, except one who had CMV infection with the symptom complex of fever and retinitis or pneumonitis, responded satisfactorily. In the three patients in whom the CMV titers were available, there was a significant decrease in titer within two weeks after treatment. This pilot study of Ara-C in treatment of CMV-herpes infections in immunosuppressed renal allograft recipients suggests a degree of efficacy and safety in the drug that would justify a carefully designed, controlled study.


Investigations on the turnover of adrenocortical mitochondria. VI. An autoradiographic study of the effect of ACTH on the radioactivity decay in the mitochondrial compartment from the zona fasciculata of 3H-thymidine injected rats. The radioactivity decay of the mitochondrial compartment from the zona fasciculata of the adrenal cortex of 3H-thymidine-injected rats was followed by high resolution autoradiography. The number of days in which the radioactivity of the mitochondrial compartment was reduced to a half was calculated from the semilogarithmic plots of radioactivity versus time. Since DNA is a very stable molecule, it was assumed that this parameter can be an estimate of the half-life of adrenocortical mitochondria. The half-life of mitochondria from the zona fasciculata of the normal rat averaged 11.17 days, and ACTH was found to increase significantly this figure to about 15 days. It is hypothesized that the ACTH-elicited stimulation of the growth of rat adrenal zona fasciculata mitochondria involves not only hypertrophy and proliferation of the organelles (Nussdorfer et al., '74b), but also the slowing down of the degeneration rate of mitochondria.


Effect of isometric handgrip on systolic time intervals in patients with ischemic heart disease and cyclic amp phosphodiesterase inhibitor pretreatment. The effect of cAMP phosphodiesterase inhibitor EG626 on the left ventricular function was studied in 23 patients with ischemic heart disease at rest and during the IHG test. Administration of a single dose of the substance produced changes in STIs indicating an increase in cardiac output and a possible enhancement of myocardial contractility during the IHG test. EG626 may have a beneficial effect on impaired left ventricular function in patients with ischemic heart disease.


Comparative neuromuscular effects of lincomycin and clindamycin. The effects of lincomycin and clindamycin on neuromuscular transmission in vitro were studied. Standard microelectrode technics were used to measure miniature endplate potential (MEPP) amplitude and frequency, and endplate sensitivity to acetycholine on the frog sartorius muscle. Twitch tension and nerve terminal acetycholine release were also studied. In the drug concentration range where twitch tension changes occurred, both drugs caused marked decreases in MEPP amplitude and decreases in endplate sensitivity to iontophoretically applied acetylcholine. Lincomycin did not alter MEPP frequency but decreased acetylcholine release. Clindamycin increased MEPP frequency and increased acetylcholine release. The study shows that both lincomycin and clindamycin cause blockade of neuromuscular transmission through a postsynaptic action. However, at high concentrations, lincomycin has a nerve-terminal depressant effect, while clindamycin has a marked presynaptic stimulatory effect.


Neuromuscular block by antibiotics: polymyxin B. Characteristics of neuromuscular block produced by polymyxin B (PXB) were examined in 12 anesthetized cats, using sciatic nervetibialis anticus muscle preparations. The ED50 was 6.7 (+/- 1.4, SD) PXB base/kg body weight. The ED95 was 10.8 (+/- 2.4) mg/kg. Spontaneous recovery from 25 percent of control to 75 percent of control required 72 (+/- 16) minutes. During a 50 percent block, train-of-four twitches elicited at 2 Hz faded with a train-of-four ratio of 0.42 (+/- 0.13), but the tetanus did not fade. Edrophonium Cl, neostigmine methylsulfate, and pyridostigmine Br at sub-clinical dosages weakly antagonized the block but enhanced the block at anti-curare dosages. All 3 cholinesterase inhibitors were short acting, lasting 10 to 15 minutes, and noncumulative on repeated injection. The potency ratio was approximately 20:10:1 in the order of edrophonium, neostigmine, and pyridostigmine on a weight-for-weight basis. Calcium partially antagonized the block. The authors conclude that neuromuscular blocks produced by various antibiotics differ from each other and from that produced by other groups of neuromuscular blocking agents, including curare.


Discussion paper: dual effects of tumor antigens: induction of tumor resistance or tumor growth enhancement. TA3-HA nonspecific tumors growing in ascites form shed their membrane components into the ascites fluid. This product can induce tumor growth enhancement if given together with or after i.p. tumor inoculation in relatively large quantities, but if given i.m. in small quantities, several days before tumor challenge, the mice show an elevated resistance to the tumor. The strictly strain-specific TA3-St line does not release such membrane components into the ascites fluid. It has also been found that the TA3-HA cells have a larger membrane fluidity than the TA3-St cells, as measured by membrane microviscosity, using the Shinitzki procedure. Isolation and gross chemical analysis of the TA3-Ha ascites fluid component was carried out. Results, so far, indicate that the active site of this product is probably carbohydrate in nature. The possible mode of action of such component in tumor growth enhancement is most probably by overwhelming and neutralizing immunocytes capable of recognition and eventually cytotoxic action.


Discussion paper: loss of cellular antigens during malignant transformation. Normal human diploid cells, such as WE-38, transformed by an oncogenic virus, SV40, are greatly depleted of a cathodal esterase isozyme using both immunological and enzymatic criteria. This cathodal esterase is primate-specific and associated with lysosomes of many different tissue cells. It provides a clear example of antigenic loss associated with malignant change.


Discussion paper: specific paralysis of the antitumor cellular immune response produced by growing tumors studied with a radioisotope footpad assay. The kinetics of the antitumor cellular immune response of mice with progressively growing syngeneic tumors were determined in vivo using a quantitative radioisotopic footpad assay. A close correlation was found between the size of the tumor and the degree of the cellular immune response. An initial phase of cellular immune stimulation was followed by specific suppression and subsequent immunologic paralysis as the tumor grew larger. This immune paralysis was attributed to increased tumor load since a homogenate of an SV40 transformed fibrosarcoma injected intraperitoneally into tumor-immune mice specifically depressed their cellular immune response. The fraction of the tumor homogenate that brought about this depression was present in the high speed supernatant and pellet of a 3M KCl extract of the tumor. The specificity of the depression was determined in vivo by the radioisotopic footpad assay and in vitro by a 51Cr cytolysis assay. Unwashed spleen cells harvested from mice bearing large tumors were unreactive in a local adoptive footpad assay. However, reactivity could be restored by repeatedly washing the spleen cells.


Inhibition of tumor and fetal tissue growth in newborn recipients. A comparative study of growth of a variety of fetal tissues and transplantable tumors in syngeneic newborn and adult mice was carried out. Tumors used in the experiments arose spontaneously (hepatomas, mammary gland adenocarcinoma) or resulted from malignant conversion of ectopic transplants either of fetal tissues (urinary bladder carcinoma, adenocarcinoma of small intestine, stomach sarcoma) or of adult animal tissues (ovary carcinoma) in syngeneic system. The growth of "teratomas" developed after transplantation of minced tissues of 18-20-day fetuses was considerably inferior in newborn syngeneic recipients as compared to analogous transplants in adults. Inhibition of tumor growth was also observed in newborn animals. It was manifested in prolongation of latent period before tumor node appearance as well as in slowing down of growth rate of developed tumors. Only one tumor, mammary gland adenocarcinoma, proved to be an exception, its growth being equally progressive in newborn and adult recipients. At transplantation of tumor cells mixed with lymphocytes of adult mouse spleen, stimulation of tumor growth in newborns and inhibition of growth in adult recipients was observed. It is suggested that there exists a special type of cellular or humoral mechanism controlling tumor growth in newborns. The activity of such factors is conceivably based on fetal antigens as targets.


Optochiasmatic syndrome from adhesive arachnoiditis with coexisting hypophyseal adenoma: case report. Adhesive arachnoiditis is an occasional finding during neurosurgical operations for pituitary adenoma, previously treated by radiation therapy. A case where an arachnoidal process was found in combination with an eosinophilic pituitary adenoma, which had never been treated by irradiation, is reported. A 44-year-old woman at the time of surgery with scarce endocrinologic symptoms had suffered visual loss from 2 episodes, 18 years apart. Analysis of her symptoms, neuro-ophthalmologic findings and neurodadiologic features suggest that her visual damage was due to an optochiasmatic arachnoiditis, rather than to the tumor itself.


[Histochemical and ultrastructural study of cytochrome-oxydase in basal cell epithelioma]. The activity of cytochrome-oxydase is less pronounced in the basal cell epithelioma than in the basal cells of the surrounding normal epidermis. The electron microscopic study of the localisation of the enzyme reveals that the cells of the basal cell epithelioma contain two types of mitochondria, the first of which having the same size as the epidermal mitochondria, and the other being giant mitochondria. The latter seem to be less active. The weak reactivity of the basal cell epithelioma for cytochrome-oxydase is probably due to the reduction of the cristae in mitochondria and to the functional deficiency of the giant mitochondria.


Prognosis of carcinoma of the breast in women under 25 years of age. In 1960 to 1969 twenty six women below 25 years were operated on because of mammary carcinoma. All eighteen patients in stage 0 and I had a five-year cure. The corresponding rate for seven women in stage II was 43%. Of eight women with a poorly differentiated or anaplastic growth, 38% survived for more than five years. The corresponding figure for those with a well differentiated tumour was 100%. The prognosis in young women is thus good provided the malignant breast tumour is diagnosed and treated in good time, and it is better than that in elderly women.


Adenoidcystic carcinoma (cylindroma) of the parotid gland. Adenoidcystic carcinoma or cylindroma of the parotid gland is a slow-growing, relentless, and often lethal disease which kills usually by local occurrence and direct extension of the disease. The reported incidence of adenoidcystic carcinoma with reference to other parotid malignancies varies from 5% to 37%. The incidence in this series is 36%. The presence of facial nerve involvement adversely affects the long-term survival. Some authors regard facial nerve involvement as an indication of noncurability. The incidence of local pain is reported to be as high as 50% and is thought to be caused by perineural invasion by the tumor. This is well-documented histopathologically. There is no uniform or standard treatment for this disorder. Extensive resection of the parotid gland (including the facial nerve if there is any indication of involvement), followed by external irradiation to the parotid area and upper neck is the most rational approach to the problem. This is supported both in the review of the literature and from the present series. A radical neck dissection is not included as part of initial therapy unless there are clinically suspicious cervical nodes. Postoperative radiotherapy appears indicated in all cases of adenoidcystic carcinoma of the parotid gland. Four case histories are presented which demonstrate the hallmark characteristics of the disease, i.e. multiple cranial nerve deficits, facial pain and subsequent death by direct intracranial extension of disease. The protracted, relentless course of the disease is well-documented in one case in which 25 local recurrences developed over an 18-year period.


A quantitative study of the ABH red cell antigens in the Kulamwo of Ivory Coast. The agglutination percentages given by various erythrocytes with reference sera have been compared in blood samples from Kulamwos living in the Ivory Coast and of blood donors of the regional transfusion centre of Toulouse. The study of O, A, B and AB phenotypes shows: 1. in O Kulamwos a higher agglutination percentage with anti-H than in Toulousains; 2. in B Kulamwos a higher agglutination percentage with anti-B than in Toulousains; 3. in A Kulamwos a very marked frequency of A intermediate which can be classified in different categories due to the variability of their agglutination percentage with anti-A1 and anti-H sera.


Experience with a new agar culture medium for demonstrating the presence of anaerobic bacteria. In view of the fact that anaerobic diagnostics have become a matter of primary importance, the authors have developed the RCM medium with certain modifications. Owing to its good keeping quality, this medium can be used also on smaller laboratories for demonstrating the presence of anaerobic bacteria and for carrying out germ counts. It constitutes and adequate base for the anaerobic blood medium and for the Wilson-Blair medium, and also for the determination of the antibiotic resistance of the anaerobic bacteria. The sensitivity of this medium surpasses that of the thioglycollate medium, and is suitable in its carbohydrate-free form also for testing the strains for their sugar-fermentative capactiy. Our work was aimed at serving the anaerobic diagnostics of clinical laboratories, and at serving at the same time the method of demonstrating the presence of anaerobes becoming increasingle important in the food industry.


Diffuse otitis externa: clinical and microbiologic findings in the course of a multicenter study on a new otic solution. This report reviews the literature on the epidemiology, pathogenesis and bacteriology of diffuse otitis externa. Four departments of otolaryngology undertook identical studies of these factors, as well as the efficacy and safety of two similar antibiotic-corticosteroid formulations; one a suspension and the other a clear solution. A total of 239 patients, or 283 ears, were studied, utilizing objective clinical as well as correlative bacteriologic criteria. A high degree of clinical and bacteriologic efficacy was demonstrated by the medications irrespective of the formulation, infecting organism, patient's age, length of disease history, severity, or geographic location. There was no statistical difference between either formulation, both achieving a clinical efficacy rate of 97% and a bacteriologic efficacy rate of 83%. Drug related side effects occurred in 1.9% of the patients given the solution and in 1.1% of those given the suspension.