[Carbohydrate metabolism in the kidneys of rats with dimethylnitrosamine-induced tumors]. Under study was anaerobic glycolysis, the activity of hexokinase, lactate dehydrogenase, gluco-6-phosphatase in rat kidneys in dimethylnitrosamine (DMNA) induced tumors in them. DMNA was administered perorally in the dosage of 10 mg/Kg during 4 weeks (25 mg per rat). Following 8 months tumors developed in the renal cortical substance. The tumor tissue, the renal cortical substance adjacent to the tumor, and the renal cortical substance without macroscopic tumor signs have been studied. An increased glycolysis, hexokinase and lactatedehydrogenase activity were noted, whereas the activity of glucoso-6-phosphatase was diminished in all tissues under examination. Changes of all indices were mostly pronounced in tumor tissue and least significant--in the renal cortical layer without any macroscopic tumor signs.


[Sudden deafness and virus infection (author's transl)]. A survey of the literature concerning sudden deafness caused by virus infection is followed by a discussion of 46 patients with the history of acute loss of hearing, who were subjected to virological-serological examination. In 9 patients the titre movement of the complement fixation reaction was regarded to imply a viral cause of the acute loss of hearing. This was corroborated in 5 cases by the history of recent viral infection. Pathogenetically, the significance of the viral endolymphatic labyrinthitis was underlined. The success of traditional therapy did not differ from the results in cases of sudden deafness due to factors other than viral disease. In the absence of specific therapy the importance of prophylactic measures is stressed.


[Virological investigations in peripheral idiopathic facial pareses (author's transl)]. Virological investigations were carried out on the serum of 62 patients suffering from peripheral facial pareses. The aetiology was definitely attributable to a virus infection in 12 of these cases. Neuropathological changes induced by these neurotropic viruses, predisposing anatomical features and pathogenesis are discussed. Since only symptomatic treatment is possible, the importance of active immunization, where available, is stressed in the prevention of virus diseases; a decrease in morbidity could lead to a reduction in neurological complications.


[Angiopasm and lesion of the ulnar nerve in Dupuytren's contracture (author's transl)]. 30 patients with Dupuytren's contracture were investigated by venous occlusion plethysmography of the index and ring fingers of both hands. The results are evaluated in respect to the clinical and electroneurophysiological findings. Special attention was given to the blood flow disturbances which have plethysmographically appeared to be a significant feature of Dupuytren's contracture and also to ulnar nerve lesions in individual cases. The finger venous occlusion plethysmography technique of Goetz (1934) has been further developed and a suitable apparatus constructed for the purpose of these investigations. Temporary vasopasm occurs in 77% of the patients suffering from Dupuytren's contracture when the fingers are cooled to 15 degrees C and a significant diminution of blood flow, as in the Raynaud syndrome, is evident. These neurovascular changes always appeared on the fingers of both hands and were similarly found in the region of the median nerve and of the ulnar nerve. They did not depend on the localization or the stage of the disease. 68% of the patients had symptoms suggestive of an ulnar nerve lesion, which corresponds with the findings of Mumenthaler (1961). In a comparison of the patients with normal plethysmographical findings and the patients with vasospasm, there is no correlation with the accompanying ulnar lesion. It is, thus, suggested that temporary vasopasm is not a consequence of the ulnar nerve lesion, but is related to an independent constitutional factor. In view of the high incidence of the ulnar lesion in patients with Dupuytren's contracture, a special neurological investigation is recommended and appropriate therapy, in addition to the fasiectomy, must be undertaken.


[Activation of vitamin D 3 and the mode of action of 1,25-hydroxycholecalciferol and 24,25-hydroxycholecalciferol]. A survey is given on the present state of the animal-biochemical research concerning the effectivity of the D-vitamins. The vitamin D3 is transferred in 25-hydroxycholecalciferol in the microsome fraction of the liver. Then in the kidneys a transformation into the physiologically active forms - the 1,25- and the 24,25-hydroxycholecalciferol - takes place. The kind of transformation depends on the Ca- and P-supply as well as on the level of the parathormone secretion. In the mucous membrane of the small intestine the 1,25- and the 24,25-hydroxycholecalciferol stimulate the formation of the Ca-transport protein. The 1,25-hydroxycholecalciferol is above all formed in hypocalcaemia or hypophosphataemia and furthers the mobilisation of Ca- and phosphate-ions from the bones. In a liver damage disturbances of the formation of 25-hydroxycholecalciferol and in renal damage disturbances of the formation of 1,25- and 24,25-hydroxycholecalciferol may appear. A reduction of the formation of the active forms of the D-vitamins leads to a decrease of the Ca-utilisation as well as of the growth of bones.


[Age-dependence of catecholamine effect in man. III. Influence of alpha- and beta-adrenergic agents on the lipolysis in the adipose tissue in vitro]. With the help of subcutaneous adipose tissue performed on 0,1- to 10-, 20- to 40- and 60- to 75-year-old test persons the effect of isoprenalin, adrenalin and noradrenalin on the release of glycerol or the unesterified fatty acids was investigated. Independent on age the quantity of the isoprenalin-stimulated lipolysis increases with the size of the fatty acids of the incubated tissues. The specimens of adipose tissue used do not show any differences in the size of the adipocytes between the individual age groups. Amaximum release of glycerol is achieved in a concentration of the medium of 10(-5) mol/l (isopernalin) to 10(-4) mol/l (adrenalin). Isopernalin effects an altogether larger increase of lipolysis in the adipose tissue of the human being of old age in already smaller concentrations compared with other age groups. These findings refer to a higher affinity of adrenergic beta-receptors of the adipocytes in this age period, but also to possible age differences in the chain of lipolysis mediated by cAMP.


[Serodiagnosis of rheumatic disorders].

[Serodiagnosis of rheumatic disorders]. For the serological diagnostics of the diseases caused by Streptococcus pyogenes (A-streptococci) and secondary diseases (rheumatic fever, acute glomerulonephritis) in the first place the anti-streptolysin reaction is at disposal. In the judgment age is to be taken into consideration and the proportion of the inhibitor in the serum is to be removed by absorption with dextran sulphate. Reliable evidence is to be expected only by the course of the titre. If possible, the antistreptolysin reaction should be supplemented by a second reaction, for which purpose the anti-desoxyribonuclease B-reaction is to be recommended. For supporting the diagnostics of the rheumatoid arthritis at least 2 reactions should be performed, i. e. a haemagglutination test (e. g. after Podliachouk-Harboe) and a particle agglutination test (latex fixation reaction). By means of them the rheumatoid factors (above all antibodies of the IgM-class against gamma-globulin) are proved. The haemagglutinations connect a high specifity with a more insignificant sensitivity, in the particle agglutinations the reverse is the case. Apart from the serological tests mentioned here other proved reactions are mentioned. Besides, data on the valuation of the results and their diagnostic importance are in this paper.


[Peculiarities of the clinical picture, diagnosis and prognosis of insulinoma]. It is reported on a patient with insulinoma whose diagnosis was made 16 years ago. Operation report: Insulinoma with the histological picture of a little expressed malignant degeneration. After 6 years recidivation of the clinical picture of an insulinoma. Operation report: Metastasis of a malignant insulinoma of the size of a hazel nut. After operation the patient had no complaints and was able to work for 8 years. Repeated hypoglycaemic conditions caused a third operation: In the cauda metastasis of a malignant insulinoma. After operation 18 months symptom-free with good health. The prognosis is discussed, emphasizing the unusually long course in malignant degeneration in the case described, as it hitherto was observed for the first time. It is also referred to some peculiarities of the carbohydrate metabolism of this patient. At length the necessity of an early diagnosis and a timely surgical treatment of the insulinoma is emphasized.


[Serum protein changes in liver transplantation in the dog]. Hemorrhage and shock gave rise to quantitative determination of serum protein changes by means of the two-dimensional immunoelectrophoresis according to Laurell. 5 proteins showed significant changes. There were no new protein peaks or products of decomposition of other serum proteins. The liver injured by ischemia can not alone be responsible for the shift of serum proteins. Rather probably the majority of lost proteins remains in the splanchnic area.


Histochemical and ultrastructural alterations of the duodenum in acute hypoxia. Laboratory animals were kept for 2, 8 and 16 hours in a pressure chamber, the air of which contained 8% O2 and 92% N2. Histochemical and ultrastructural examinations revealed the following duodenal alterations: 1. The alkaline phosphatase activity of the epithelium and glandular epithelium showed no alteration; the acid phosphatase activity was slightly increased in hypoxia. 2. The succinic dehydrogenase and cytochrome C oxidase activities of the glandular epithelium showed a marked decrease. 3. Two hours of hypoxia led to destruction of the microvillous epithelium. Prolonged hypoxia resulted in the destruction of the microvilli as well as of the cuticula. 4. Hypoxia of short duration had no damaging effect on glandular epithelial cells. After 8 to 16 hours of hypoxia, glandular secretion was reduced and the epithelial cells were evacuated. From the findings of the present investigation it is concluded that the decrease in the production of protective intestinal juice, due to the damaging effect of hypoxia on the epithelium and glandular epithelium as well as on the mitochondria, and the increase in the absorption of the intestinal content should be considered responsible of the additional damages to the intestinal epithelium.


Angiographic differentiation of thoracic aneurysms and neoplasms. The distinction between nondissecting aneuryms of the thoracic aorta and thoracic neoplasms may be difficult. The aortographic findings associated with aneurysms may be subtle. However, when the aortogram is properly performed and interpreted and the findings correlated with the plain chest roentgenograms the distinction between aneurysms and neoplasms may be made consistently. The thoracic aortogram should be filmed in at least 2 projections and abdominal aortography and ultrasonography should be performed. With aneurysms the aortographic signs include widening (often slight) of the aortic lumen, thickening of the aortic wall, small ulcer-like collections of contrast and non-filling of regional intercostal arteries. With neoplasms none of these radiological features is to be anticipated, while the aorta will be normal, displaced or narrowed.


[Long-term cultures of experimental CNS tumours as models in neurooncological research (author's transl)]. Experiences with the behaviour of long-term cultures of experimental CNS tumours of rats induced by methylnitosourea of ethylnitrosourea, resp., are reported. Differences in cell kinetic parameters result in a selection of the best adapted cell type among those ones existing in the primary tumour. In some long-term cultures of gliomas and neurinomas an increasing polymorphism is observed by which these lines gain the morphological appearance of a glioblastoma multiforme. The loss of cell-specific morphological differentiations is a further type of anaplastic changes. In neuroectodermal tumour strains these alterations are temporarily reversible by means of addition of dibutyryl cyclic AMP to the culture fluid. There is no relationship between the type of tumour and the degree of anaplastic changes in vitro. Some cell strains remain constant for years and retain their specific properties. Their application as tester strains in neurooncological studies is recommended.


[Mechanism of internal inhibition (role of the sympathetic nervous system in sleep phenomena)]. It has been shown on cats that the role of the sympathetic nervous system in sleep phenomena is of an adaptive nature and is effected through chain neurohormonal reactions in which adrenaline possessing a two-phase action plays a major part: it induces excitation followed by sleep. Sleep is regarded as a variety of internal inhibition, elaborated as an adaptive reaction to the changing conditions of environment, which later becomes a behavioral reaction.


[Amyotrophic lateral sclerosis with myoclonic bodies (Lafora bodies) (author's transl)]. In the present investigation 2 sporadic cases of amyotrophic lateral sclerosis with the occurrence of myoclonic bodies (Lafora bodies) in the CNS are reported. The patients died after about 14 respectively 8 months lasting disease at the age of 41 and 43, respectively under the clinical signs of an ALS. Morphology, staining qualities, and the distribution of the myoclonic bodies in our cases correspond to the adult form of the myoclonic body disease (type Lundborg). In the literature we found further 6 cases of neurogenic muscle atrophy with the occurrence of myoclonic bodies in the CNS so that one might suppose a syntropy of these two affections. The possible pathophysiological relations of neurogenic muscle atrophy to the occurrence of myoclonic body disease in adults are briefly discussed.


[Experiments with simultaneous immunization against cytomegalovirus infection and rubella]. An immunisation trial with simultaneously applicated attenuated rubellavirus (Cendehill) and attenuated cytomegalovirus (TOWNE 125) was done in adults. There was no difference in antibody-titers against both viruses and in side-reactions (local ones only) between simultaneous or single application of the two viruses. Adults immunized against cytomegalovirus two years ago still had IF-IgG-antibodies; in only 1 of 8 volunteers there was a significant antibody-decline.


[The effect produced by fine-dust extracts on cells in vitro, with particular regard to cancerogenic components (author's transl)]. Airborne dust is toxic for cells cultured in vitro and able to transform these cells to cancerous. The effect of extracts from atmospheric dust has been investigated. The dust samples were extracted by means of DMSO alone or in combination acetone-DMSO. Dosage of the extract was done according to its benzo(a)pyrene content (mug/ml medium). Dust extract with a concentration of 1 mug benzo(a)pyrene/ml exerted a toxic effect upon mouse macrophages (cell line IC-21) and human lymphocytes after stimulation. The degree of toxicity was estimated from the percentage of damaged cells seen in the dye exclusion test and from the amount of lactate dehydrogenase and lactate released into the medium in the case of macrophages. In the case of lymphocytes the degree of toxicity was estimated from the extent of inhibition of DNA synthesis. In the carcinogenicity test, hamster kidney cells were first treated with the extract and then incubated with Simian Virus (SV-)40. Treatment of the cell cultures with extract from airborne dust in a concentration of 0.01 and 0.1 mug benzo(a)pyrene/ml clearly enhances the rate of transformation caused by SV 40.


[Infections transmitted in swimming pools]. Public swimmingpools can be the source of infections due to micro-organism such as mycobacterium balnei, adeno and enteroviruses, the virus of plantar warts and molluscum contagiosum, the TRIC-Agent of swimmingpool-conjonctivitis and pathogenic fungi. The transmission of trichomonas vaginalis is considered unlikely-Water of pools, supposed to present satisfactory qualities by standard controls, was found to contain pathogenic staphylococci and pseudomonas aeruginosa. Effective preventive measures include the continuous recording of the redox-potential of the water, limiting the number of visitors to pool design specifications, better desinfection of sanitary installations, regular maintenance of technical equipment including frequent backwashing of filters and exclusion of visitors with communicable disease.


[Increased blood-CO-content in humans and animals by incorporated halogenated hydrocarbons (author's transl)]. Contrarily to the general opinion about the harmlessness of dichloromethane, clear functional disturbances of the central nervous system could be recorded by means of effect investigations as well in humans as in animals. The depressive effect on the REM-sleep of albino rats was especially well recognisable, similarly as with carbon monoxide exposure. Surprisingly the analytical investigations of the blood of these animals showed a clearly elevated blood-CO-content after exposure to dichloromethane. Further experiments during which albino rats were exposed three hours along to a dichloromethane-concentration equal to the TLV (1750 mg/m3!!) resulted in a blood-COHb-level of about 13%, corresponding to over 30 mug CO/ml blood. So high blood-COHb-levels are obtained after a three-hour-exposure to 120 ppm CO. Following these findings, a number of halogenated and oxygenated hydrocarbon compounds of the methane and ethane series were investigated relatively to their CO-forming capacity. Only the di- and trihalogenated methane derivatives were found leading to an increased blood-COHb-level. After a three hours-exposure to 1000 ppm respectively the jodoalkanes yielding about 23% COHb were strongestly, the bromoalkanes with about 20% COHb more strongly and the chloroalkanes with about 12% COHb strongly implicated in the endogenous CO-formation. By means of detailed experiments with human volunteers (non-smokers) it resulted that after eight-hours-exposure to 500 ppm dichloromethane (TLV) a mean value for CO-content in blood of about 30 mug/ml corresponding to 12% COHb was obtained, in one case raising as high as 60 mug CO/1 ml blood or 24% COHb. After an eight-hours-exposure to 100 ppm of the halocarbon, the blood-COHb-level reached 5%. The elimination was very slow, so that 24 to 26 hours were necessary to reestablish the original blood-COHb-level. These results show that the actually TLV for dichloromethane e.g. 1750 mg/m3 has to be revised, because a fifth of this value already leads to a blood-COHb-content equal to that produced by the TLV for carbon monoxide and that also eventually arising problems due to gas mixtures have to be considered and thoroughly investigated.


[Encephalitis (predilectiveness and "slow" infections)]. Chronic progressive forms of encephalitis (epidemic Economo, tick-borne) are considered from the concept of "slow infections" where the virus following the acute phase of the disease, in the latent state during many years, is persistent in the human organism. The author attributes herpetic encephalitis to this group of disorders. Unlike the slow, gradually developing forms of encephalitis and diseases with a protracted incubational period, herpetical encephalitis develops acutely and may be allocated to "slow infections" in respect to a protracted infection with a long-term persistent virus in the latent condition.


Cross-resistance of transformed mouse cells to some drugs. The Colcemid-resistant L--53 cell strain was examined for cross-resistance to metaphase inhibotors (Vincristine, Vinblastine, estradiol-17beta), an antitumor antibiotic (Rubomycin C) and an alkylating agent (Lycurim), compared with the Colcemid-sensitive L cells. The L-53 cells proved to be resistant besides colchicine to Vincristine, Vinblastine and estradiol-17beta concerning their antimitotic effect. The comparison of the viability of L and L-53 cells in the presence of Rubomycin C and Lycurim showed a resistance of the L-53 cells to Rubomycin C, while the effect of Lycurim was the same on both cell lines. The chromosome-mutagenic action of Lycurim was also equal on both cell lines.


Glycerolkinase--a regulatory enzyme of gluconeogenesis? 1. The development of glycerolkinase before and after birth was investigated in liver and kidney of rat and hamster. In rat liver, enzyme activity increased very slowly before birth and rapidly thereafter, reaching adult values at the 6th day of postnatal life. In hamster liver, glycerolkinase was considerably elevated already in utero, increased dramatically within the 1st day of postnatal life and reached adult values at the end of the 1st week. The development of hepatic glycerolkinase was compared with that of hepatic phosphoenolpyruvate carboxykinase of rat and hamster up to the 20th day of postnatal life. The different time-courses of the levels of these two enzymes before and after birth as well as the known kinetics of serum insulin, glucagon and corticosterone during that time suggested that none of these hormones is involved in the perinatal development of hepatic glycerolkinase activity. In contrast to liver, kidney glycerolkinase activity in both, rat and hamster, showed a delayed increase during the first week of postnatal life followed by a more pronounced elevation to adult values within the following 2 weeks. 2. When liver and kidney glycerolkinase activity was investigated during starvation (+/- refeeding), in alloxan diabetes(+/- insulin) and after adrenalectomy (+/- cortisol) no significant change in enzyme activity per g tissue could be detected either in liver or in kidney. However, total hepatic glycerolkinase activity was diminished during starvation as a consequence of decreasing liver weight. 3. Incorporation of U-[14C]-glycerol into CO2, lipids and glucose + glycogen by rat liver and kidney cortex slices was studied under the above gluconeogenetic conditions. Despite unchanged glycerolkinase activity in both organs, gluconeogenesis from glycerol was enhanced during starvation and in chronic alloxan diabetes, and could be reversed by refeeding and insulin replacement, respectively. 4. Feeding 20% of linolic acid to normal, alloxan-diabetic or adrenalectomized rats resulted in a significant increase in glycerolkinase activity in liver but not in kidney. 5. From the present findings it is suggested that the first step of gluconeogenesis from glycerol in liver and kidney is not influenced by glucagon, insulin and glucocorticoids, which are generally believed to regulate the rate of gluconeogenesis from non-glycerol precursors, but probably by the change in blood glycerol concentration.


[Inhibition of the cyclic AMP splitting myocardial nucleotide gydrolase by 5-methyl-7-diethylamino-s-triazol-(1,5-alpha)pyrimidine (rocornal)]. 5-Methyl-7-diethylamino-s-triazolo-(1,5-alpha)pyrimidine (Rocornal, trapidil), which has been introduced in clinical medicine as a coronary vasodilatator, competitively inhibits the cyclic AMP splitting nucleotidehydrolase (phosphodiesterase) from the heart muscle. The K1 value for Rocornal is 0.14 +/- 0.016 mM. The enzyme inhibition by this compound is abolished after an exchange of the diethylamino-group in C-7 position against dimethylamine and chloride. The proved triazolo-pyrimidines were without effect on myocardial adenylate cyclase activity. It is concluded that the vasodilatory effect of Rocornal may be realized in smooth muscle cells by an inhibition of cyclic AMP breakdown.


Mammary tumour virus (MTV)-specific immune complex deposites in renal glomeruli of MTV-infected tumour-free mice. Using direct and indirect immunofluorescence tests MTV-specific immune complex deposits were found in tumour-free female mice of the strains C3H/Bln, CBA/Bln, XVII/BlnfCBA/Bln, and CBA/BlnfXVII/Bln. These deposits consist of immunoglobulin, complement, and MTV antigen(s). The immune complex deposition increases with age. Antibodies eluted from renal tissue homogenate react with both MTV-A and -B particles in immunofluorescence tests performed on mouse mammary tumour slices. By these results the earlier finding of age-dependent spontaneously occurring anti MTV antibodies in naturally MTV-infected mice is confirmed and completed.


Pseudomonas cytochrome c peroxidase. XII. Product inhibition studies. Kinetic studies of the reaction mechanism of Pseudomonas cytochrome c peroxidase (PaCCP) were made by the method of product inhibition using oxidized cytochrome C (551 P.aeruginosa) and oxidized Pseudomonas azurin as products. Inhibition by the two oxidized substrates was linearly non-competitive towards the respective reduced electron donor and towards hydrogen peroxide. Although a full kinetic analysis is experimentally impossible in a peroxidase-type reaction, the results do provide some evidence in favour of an ordered reaction mechanism in which hydrogen peroxide is the first to add to PaCCP and electron donor the second.


Corticosterone, 18-OH-deoxycorticosterone, deoxycorticosterone and aldosterone secretion in tissue culture of foetal rat adrenals in the presence and the absence of ACTH. A method for simultaneous analysis of the main corticosteroids secreted by the rat adrenal is described. Purification is performed using previously established steps involving dichloromethane extraction, ethanol-cyclo-hexane partition and Sephadex-LH-20 column chromatography. Deoxycorticosterone and aldosterone are then quantitated with radioimmunoassay and corticosterone and 18-hydroxy-deoxycorticosterone with gas liquid chromatography as their 0-methyloxime=trimethylsilyl ethers. The coefficient of variation of the method for these steroids in concentrations found in the tissue culture of feotal rat adrenals varies between 3.9-10.9 %. The secretion of these steroids in the tissue culture of foetal rat adrenals is studied. The steroid secretory pattern is correlated with a differentiation stage of the cultures as detected by electron microscopy. The initial secretory activity declines considerably after 15 days of cultivation to a low level. This is the case also with respect to aldosterone although the cortical cell population changed from the mixed population of the differentiated (zona fasciculata-like) and undifferentiated (zona glomerulosa-like) cells to homogenous undifferentiated growth. Addition of ACTH increased deoxycorticosterone secretion rapidly. Corticosterone, 18-hydroxy-deoxycorticosterone and aldosterone secretion was observed only after the differentiation of the cells (especially changes in their mitochondrial compartment) was evident morphologically.


Immunoreactive ACTH, immunoreactive human chorionic somatomammotrophin (HCS) and 11-OH steroids plasma levels in normal and pathological pregnancies. Plasma immunoreactive ACTH (I.R.ACTH), immunoreactive human chorionic somatomammotrophin (I.R.HCS) and 11-OH steroids levels were measured during normal and pathological pregnancies. Plasma I.R.ACTH levels were found to be above normal during pregnancy, with a slight decrease near term. This observation correlates well with the recent description of human chorionic corticotrophin (HCC), i.e. a factor of placental origin possessing a high biological adrenocorticotrophic activity and presenting partial immunological cross-reaction with human ACTH. The 11-OH steroids levels, as measured by a fluorimetric method, increased regularly during pregnancy but, unlike ACTH, reached their highest value near term, I.R.HCS increased progressively until term when a slight decrease was observed. In pathological pregnancies, I.R.ACTH levels behaved like other placental hormones. On the contrary, 11-OH steroids levels remained generally unmodified. Treatment with high doses of prednisolone caused no inhibition of the plasma I.R.ACTH and of plasma 11-OH steroids levels. These data suggest placental autonomy of the secretion of HCC and low adrenal responsiveness to endogenous ACTH variations throughout pregnancy.


Diagnosis of bronchogenic carcinoma through the cytologic examination of sputum, with special reference to tumor typing. The results obtained in the cytologic study of sputa from 630 patients are presented. There were 251 cases of bronchogenic carcinoma; diagnosis through sputum examination was possible in 57.4 per cent of the patients. Abnormal cells were detected in an additional 24.3 per cent. Sputum examination has proven to be a valuable complement by establishing the correct diagnosis when other methods failed. Cancer cells were unequivocally identified in 45.8 per cent of the cases with normal bronchoscopic examination and in 52.4 per cent of the cases in which bronchial biopsy did not include malignant tissue. The same proportion of cases with the various tumor types was obtained by cytologic and by histologic study. However, one of the methods often showed a higher degree of cellular differentiation than the other. The number of cases with undifferentiated cancer or unclassified tumors was markedly reduced when the information concerning cell differentiation available through both methods was used. In this manner, excluding the oat cell carcinomas, only 7.6 per cent of the cases of bronchogenic carcinoma did not show any cellular differentiation. The authors recommend wider use of the information provided by simultaneous evaluation of both cytologic smears and tissue sections in order to achieve a more accurate appraisal of tumor type.


Localization of certain phosphatases in the male sex accessory glands of Suncus murinus sindensis, Anderson, the common shrew. Histochemical localization of various phosphatases, alkaline phosphatase, acid phosphatase, adenosine-tri-phosphatase and glucose-6-phosphatase, have been carried out in the male sex accessory glands of Suncus murinus sindensis, ANDERSON. The seminal vesicle and the COWPER'S gland in Suncus display strong phosphatases activities in the epithelium, except the alkaline phosphatase in the in the COWPER'S gland which is more pronounced in the stroma. The possible role of these phosphatases in the secretory activities of the organ where they are localized have been discussed. In the prostate gland, no phosphatase activity could be revealed in the epithelium and the secretions.


Serum human placental lactogen (HPL) levels in patients with intact hydatidiform mole. Serum human placental lactogen (HPL) levels in forty cases of intact hydatidiform mole were measured by radioimmunoassay. The HPL values were generally lower than normal pregnancies of the corresponding period of gestation. However, normal and occasionally higher than normal values were observed in a few cases. Serum HPL level alone is of some clinical use in the diagnosis of hydatidiform mole. When combined with human chorionic gonadotropin (HCG), a low HPL/HCG ratio for the corresponding period of amenorrhoea is a useful index in the diagnosis of hydatidiform mole.


Cerebrospinal fluid cytology: diagnostic accuracy and comparison of different techniques. Cytologic examination of cerebrospinal fluid was performed in 1,021 patients, using Nuclepore and Millipore filter techniques. Positive findings were obtained in 89 cases, including 40 with primary central nervous system tumors, 24 with metastatic tumors and 25 with leukemic or lymphomatous involvement. When correlated with histologic findings, the overall detection rate was 32.2 per cent for primary tumors, 53.3 per cent for metastatic tumors and 65.8 per cent for leukemia and lymphoma. Highest degree of accuracy in the primary tumor group was achieved with medulloblastoma (61.9 per cent). Among metastatic tumors, those originating in the lung (70 per cent) and breast (83 per cent) were the one most often detected. Comparison of the two filter techniques indicated a slightly higher detection rate when the Millipore filter was used. The reasons for this are not entirely clear, but increased cellular yield with the Millipore filter may be an important factor. The cytocentrifuge method was found to be generally inferior to either of the filter techniques in quality of cell preservation. Our findings indicate that diagnostic usefulness of cerebrospinal cytology depends on collection and preparation methods as well as the anatomic distribution and biologic behavior of the lesions.


Defective neutrophil motility in hypovitaminosis D rickets. The chemotactic activity and random motility of neutrophils, was studied in 38 patients with hypovitaminosis D rickets, and compared with 29 healthy controls of matched age. The chemotactic activity derived from the activated rickets serum as well as the amounts of the complement components C4, C3 and C5 was normal, but the cell motility was clearly defective (p less than 0.001). A possible relationship between defective neutrophil movement and the recurrent infections seen in these patients is suggested. The possible mechanisms responsible for the defect could be the alteration in Ca/P metabolism or a defective action of the vitamin D on the neutrophils.


Basal and hormone-induced urinary cyclic AMP in children with renal disorders. The excretion of cyclic AMP in urine has been examined in normal children and in children with nephrogenic diabetes insipidus or moderate renal failure (predominantly defective concentrating ability) under basal conditions and in response to antidiuretic hormone (ADH) and parathyroid hormone (PTH). In contrast to other reported data, we could not confirm an ADH- and (PTH-unresponsiveness in hereditary, congenital nephrogenic diabetes insipidus, but our patients with structural renal disorders characterized by a defective urine concentrating ability did have reduced hormonal responses. It seems necessary to define nephrogenic diabetes insipidus very carefully, and until more data are collected, there appears to be no value in the measurement of urinary cyclic AMP level in the individual patient in the differential diagnosis of disorders due to renal concentrating defects.


Triglyceride storage disease. A report of two affected children associated with neurological abnormalities. Two children are described with congenital abnormalities (microcephaly, nystagmus, deafness, hepatomegaly) and the anomalous feature of triglyceride deposits in peripheral adipose tissue associated with severe malnutrition. Peripheral adipose tissue of one of these children displayed: (a) reduced sensitivity of adenyl cyclase to stimulation by noradrenaline (b) no response in tissue levels of cyclic AMP when stimulated by isoprenaline and (c) impaired release of glycerol following stimulation with isoprenaline. The other child, with similar clinical features, showed abnormal deposits of glycogen in the liver. It is postulated that a primary metabolic defect occurs in peripheral adipose tissue (and possibly at other sites such as the liver) that interferes with triglyceride (and glycogen) mobilization during prolonged malnutrition.


Histological typing of lung cancer. Application of the World Health Organization classification to 479 cases. Four hundred and seventy nine primary lung cancers were typed according to the WHO histological classification. The character of the material and the methods of investigation are described. All patients had been subjected to mediastinoscopy and 313 patients had been operated upon. Nearly half of the tumours (48 per cent) was epidermoid carcinomas. Small cell anaplastic carcinoma occurred in 25 per cent and around two thirds of these were of oat cell type. Adenocarcinoma was found in 22 per cent and the acinar type predominated. Bronchiolo-alveolar carcinoma occurred in 1 per cent and large cell carcinoma in 3 per cent. Typing of biopsy specimens was made in 289 cases in which a positive biopsy had been obtained during the pretreatment period. The result of the biopsy typing was checked against that of the final one. In the total group the preoperative histological diagnosis tallied with the final one in 88 per cent. In patients who had been subjected to surgery the pretreatment diagnosis of the epidermoid carcinoma was correct in 86 per cent, that of small cell anaplastic carcinoma in 92 per cent and that of adenocarcinoma in 100 per cent. The consistency was also high in the category of patients not subjected to surgery. Despite their critical attitude towards the delimitation of epidermoid carcinoma in the WHO-classification the present authors find it to be a reliable guide to routine typing of lung cancer.


Biological conditions influencing the focal necrotic hepatitis test for differentiation between herpes simplex virus types 1 and 2. Some biological conditions of the focal necrotic hepatitis test for the differentiation between herpes simplex virus (HSV) types 1 and 2 were investigated. Most of 13 different strains of mice tested were found usable in the test. An upper age limit (4 weeks) for the appearance of focal necrotic liver lesions was found in one strain of mice, while this was not seen in another strain. The minimum dose in 3- to 4-week-old mice was found to be as small as 10(2) to 10(3) p.f.u. in 0.1 ml of diluent. Suckling rats and hamsters, aged up to 7 and 14 days, respectively, were found to be convenient as alternative test animals. Finally, it was observed that focal necrotic hepatitis did not develop in the nude mouse with thymic aplasia on intraperitoneal inoculation of HSV type 2. The possible involvement of the thymus in the pathogenesis of the focal necrotic lesions is briefly discussed.


Functional and ultrastructural studies of the effects of human interferon on cell membranes of in vitro cultured cells. The effect of human leukocyte interferon on cultured U-amnion cells was examined, and several biological parameters were registered. Multiplication of Vesicular stomatitis virus and the virus-produced cytopathogenic effect was prevented. The growth rate of uninfected cells was reduced, as well as the spontaneous release of 3H-uridine. These effects were observed following treatment with 10 units of interferon per ml. No morphological alterations could be detected by scanning electron microscopy after 24 or 72 hours treatment with up to 2000 units interferon per ml.


Crossed immunoelectrophoretic analysis of Bordetella pertussis antigens and of corresponding antibodies in human sera. Fourty-four antigens were demonstrated in sonicated preparations of Bordetella pertussis (B.p.), using crossed immunoelectrophoresis against antiserum obtained from rabbits. No qualititative differences between the four strains of the Danish pertussis vaccine were found. In preparations of B.p. culture medium, purified with respect to Lymphocytosis Promoting Factor (LPF) activity, one antigen was possibly related to LPF. In human sera, antibodies against five of the B.p. antigens were demonstrated by means of crossed immunoelectrophoresis with intermediate gel. Antibody production was demonstrable in children during the pertussis vaccination period and was most marked after the second vaccination.


Cross-reactions between Bordetella pertussis and twenty-eight other bacterial species. Cross-reactions between B. pertussis and 28 other bacterial species were studied by various quantitative immunoelectrophoretic methods. A sonicated B. pertussis antigen preparation and a corresponding pooled rabbit antiserum were used as reference system. Two of the B. pertussis antigens were cross-reactive with antigens from 17, respectively 19, other bacterial species mainly gram-negative species. As judged by absorption of antibodies, the degree of cross-reactivity of these B. pertussis antigens with antigens from other species was found to be in the range 25-30%. Antigens from B. parapertussis and B. bronchiseptica were found to cross-react very extensively with B. pertussis, and only 4, respectively 2, of the 44 antigens of the B. pertussis reference system could not be absorbed with antigens from these two Bordetella species.


An enterotoxin produced by Clostridium perfringens type D. Purification by affinity chromatography. Clostridium perfringens type D 9867 produced enterotoxin immunologically identical to that produced by types A and C which are responsible for C. perfringens food poisoning. Enterotoxin from type C 5386 and type D 9867 was produced in Duncan og Strong sporulation medium (DS medium). The supernatant fluid from DS-cultures was used for purification of the enterotoxin by affinity chromatography on a monospecific anti-enterotoxin-coupled CNBr activated-Sepharose 4B and activated CH-Sepharose 4B column. The enterotoxin purified by this one-step procedure proved to be of a purity comparable to that obtained by conventional methods, and possessed lethal activity in mice.


Identification of paramyxovirus-specific haemolysis-inhibiting antibodies separate from haemagglutinating-inhibiting and neuraminidase-inhibiting antibodies. 1. Sendai virus haemolysis-inhibiting antibodies. Egg-grown Sendai virus was used for preparation of rabbit hyperimmune sera directed against purified whole virus and pronasetreated projectionless virus particles. These sera and convalescent sera after natural Sendai infection in guinea pigs were studied in haemolysis-inhibition (HLI), haemagglutination-inhibition (HI) and neuraminidase-inhibition (NI) tests both before and after absorption with Tween 80-ether (TE) treated virus preparations. In addition, neutralization tests using the different sera were carried out. HI and NI antibodies and the major population of neutralizing antibodies in convalescent sera were removed by absorption with TE treated virus material without changing the titre of non-HI HLI antibodies. Rabbit hyperimmune sera directed against projectionless virus particles exhibited HLI antibody titres in marked excess of HI and NI antibody titres, whereas this was not found in sera against purified whole virus. In contrast, absorption of sera against projectionless particles eliminated HI antibodies without changing the titre of non-HI HLI antibodies. The protein composition of antigenic preparations used in absorption experiments and for preparation of sera was investigated by SDS-polyacryladmie-gel electrophoresis. TH treatment had no significant effect on the polypeptide pattern of Sendai virus. Pronase-treatment predominantly affected the two glycosylated proteins of Sendai virus. The larger glycoprotein was not detectable in pronasetreated projectionless virus particles, whereas the smaller glycoprotein was present in reduced quantities.


Antibodies to synthetic ACTH in asthmatic and rheumatic patients. The prevalence of antibodies against synthetic ACTH preparations and porcine gamma globulin was investigated in 29 asthmatic patients, in 28 rheumatic patients, and in 63 normal subjects of both sexes. Agglutinating antibodies were examined by a passive haemagglutination test and IgE antibodies by a radio-immuno assay. The incidence of agglutinating reactions against Synacthén and porcine gamma globulin was significantly higher in the asthmatic and rheumatic groups than in the group of normal subjects. Titres were generally low, attaining supposedly pathological levels (larger than or equal to 1/200) in about 10 per cent of the asthmatic patients and in 20-40 per cent of the rheumatic patients. In asthmatic patients, the incidence of ACTH specific IgE was higher than that in the normal group. This difference was not statistically significant in patients on routine treatment but it became satistically significant after ACTH booster treatment. In rheumatic patients the incidence of IgE antibodies against ACTH was insignificantly lower than that in the normal group. The incidence of agglutinating antibodies against vasopressin in asthmatic and rheumatic patients was also increased as compared with that in normal subjects and the titres were positively correlated to those against ACTH.


Responses of the denervated rat urinary bladder to alfa adrenoceptor stimulation. The contractile responses of the rat detrusor muscle to noradrenaline were increased 2-3 weeks after partial denervation but had returned to control values 6-9 weeks after the denervation, probably because of reinnervation of denervated muscle cells. 6-9 weeks after partial denervation the excitatory alpha-adrenoceptor mediated response to stimulation of the remaining intact nerves was predominant, masking the subsequent inhibitory beta-receptor response, which at this time was seen only after alpha-receptor blockade. The possibility of an outgrowth of adrenergic fibres activating alpha-receptors in muscle cells normally not innervated by adrenergic nerves is discussed.


Rescue of Rous sarcoma virus (RSV) from RSV-transformed human embryonic cells by cell fusion with chick embryo fibroblasts using lysolecithin. Heterokaryon formation and Rous sarcoma virus (RSV)-induction were studied by fusion of RSV-transformed human embryonic cells with chick embryo fibroblasts in the presence of lysolecithin. Heterokaryon formation was observed by autoradiography. RSV-induction was identified by focus formation, electron microscopy and density gradient centrifugation of 3H-uridine-labeled particles. The most effective concentration of lysolecithin for virus induction was 10 mug/10(6) cells/0.1 ml. Efficiency of lysolecithin in virus induction was not less than that of ultraviolet-inactivated Sendai virus (UV-HVJ).


Stereoelectrosubcorticography in epilepsy, the focus and epileptogenic system. According to the conceptual electrophysiological model for epilepsy worked out by the authors earlier (1968-1971) the development of the disease has the following stages: "epileptic" neurone epileptogenic focus epileptogenic system epileptic brain. The mechanisms of the II and III stages are analysed in the given paper. The critical volume of the neuronal population capable of functioning as a triggering focus is shown to be 10(3)-10(5) cells (Microsystem). On the II stage the control is achieved by the lateral inhibition. Further on epileptogenic macrosystems and subsystems of discharge reverberation (vertical and horizontal) are formed with complex hierarchy on a reciprocal principle. A morpho-functional organization of pathological systems in petit mal, grand mal, uni- and bitemporal epilepsy was found during ictal and interictal periods. Inhibitory systems (low pontine and caudate) and reciprocal inhibition during the III stage were found to act as controls.


Lymphocyte subpopulations: analysis of T-cell rosette characters. The data indicated that 2 populations of thymocytes existed: immature and mature types, identifiable by their rosette characters. The immature type was capable of changing spontaneously to the mature type, but was partially suppressed in vivo by the high concentration of thymic hormone present in the intrathymic environment. The mature types of thymocytes emigrated to the peripheral organ, accounting for their high percentage of small rosettes. Alternately, cells of peripheral organs might have originated from the immature type in the thymus. Once emigrated and exposed to a lower concentration of thymic hormone, they changed into the mature pattern. The fact that lymph node rosettes were less affected by culture in vitro indicated that once cells have changed to the mature pattern they have less ground for further differentiation.


Molecular and kinetic properties of 15-hydroxyprostaglandin dehydrogenase (PG-15-HDH) from human placenta. Some molecular properties of PG-15-HDH from human term placenta were investigated. Using a computer-based weighted linear regression analysis, intersecting initial rate patterns were received for the forward reaction with the prostaglandins (PG) E1, E2, and F2alpha, respectively, and NAD as substrates. NADH exerted a linear competitive inhibition with respect to NAD. The 15-ketoprostaglandins (15-keto-PG) E1 and F2alpha showed a linear noncompetitive inhibition with respect to their corresponding PG. The kinetic patterns suggest an ordered Bi Bi mechanism of PG-15-HDH reaction. The results are discussed with respect to their possible biological significance.


Kinetic studies on 15-hydroxyprostaglandin dehydrogenase from human placenta. The enzyme system 15-hydroxyprostaglandin dehydrogenase, which catalyzes the oxidation of the 15-hydroxy group of all naturally occurring prostaglandins, has been purified 1,270-fold by isoelectric focusing. Km values have been determined for prostaglandin E2 and NAD+ and were found to be 1 and 44 muM. The overall forward reaction was V1 = 450 nmol/min. Both the product 15-ketoprostaglandin E2 and the metabolite 13,14-dihydro-15-ketoprostaglandin E2 were noncompetitive inhibitors for the enzyme.


Kinetic evidence of a distinct regulatory site on 15-hydroxyprostaglandin dehydrogenase. 15-Hydroxyprostaglandin dehydrogenase was inhibited by xylocaine, furosemide, and ethacrynic acid, but was activated by imipramine and other related drugs. Inhibition by xylocaine was uncompetitive with respect to both NAD+ and PGE1. Activation by imipramine was also uncompetitive with respect to both substrates. Kinetic studies on mixed inhibitor and activator showed a competitive pattern of inhibition of xylocaine vs imipramine activation. These studies suggest that either inhibitors or activators interact with the enzyme at a site distinct from substrate and coenzyme binding sites, and that inhibitors and activators probably interact with the enzyme at the same regulatory site.


Stimulation by TSH of prostaglandin synthesis in pig thyroid. The liberation of arachindonate in the thyroid occurs at the expense of two distinct pools of precursors. (1) the phosphatidylinositol through a process Ca2+-dependent and cyclic AMP-independent; and (2) the triglycerides by a cyclic AMP-dependent lipase, in which the involvement of cyclic AMP-dependent protein kinase has not yet been determined. The "PI pool" or "paracyclic AMP pool" is mobilized very rapidly by large doses of TSH but its physiological significance can be discussed. The "triglyceride pool" or "post-cyclic AMP pool" is mobilized more slowly by small doses of TSH and seems not to be implicated in the acute TSH stimulation of adenylate cyclase. The "post-cyclic AMP pool" of prostaglandins would be very important as third messenger or as "long-acting TSH hormone". Some recent works of Boeynaems and Van Sande (16) and Madaoui et al. (17) on the thyroid support this hypothesis, as aspirin or indomethacin inhibits DBc-AMP stimulation of glucose oxydation, iodine organification, or thyroid hormone secretion. On the other hand, in the absence of prostaglandin synthesis, TSH still stimulates the adenylate cyclase, which means that prostaglandins are not obligatory intermediates of hormonal action on cyclic AMP production. In conclusion, these results show a TSH action in the thyroid on the release of fatty acids, precursors of PG's, from their lipidic stores. Nevertheless, a second control step is not excluded in conversion of cyclic endoperoxide to PGE or PGFalpha.


Prostaglandin binding to membrane fractions from rat skin. [3H]PGE2 and [3H]PGF2alpha bound to PM and ER prepared from rat skin with high affinity and specificity. Maximum binding was achieved in the presence of Ca2+ (5.0 x 10(-4) M). Unlabeled PGE2 and PGF2alpha inhibited [3H] PGE2alpha binding to ER in a dose-dependent manner with approximately 90% inhibition at a concentration of 1.5 x 10(-10) M. PGF2alpha inhibited approximately 40% of the same concentration. A variety of fatty acids inhibited binding less than 30% at 3.0 x 10(-10) M. The [3H]PGE2 binding was inactivated by pronase, trypsin, and heat treatment. Decreased specific binding of [3H]PGE2 to membrane fractions of EFA-deficient rats was demonstrated in our experiments, whereas binding of [3H]PGF2alpha was elevated. These results indicate that the abnormality of skin under EFA deficiency alters the ability of the membrane preparations to bind prostaglandins.


Inhibition of adenylate cyclase in adipocyte ghosts by the prostaglandin endoperoxide PGH2. The prostaglandin endoperoxide PGH2 antagonized basal and hormone-stimulated adenylate cyclase activity in an adipocyte ghost preparation. The inhibition was readily reversible, and demonstrable on initial rates of cAMP synthesis. It is suggested that PGH2 may be an endogenous feedback regulator of lipolysis in adipose tissue.


Differential effects of prostaglandin synthetase inhibitors on prostaglandin E2 binding and on prostaglandin- or cholera toxin-induced cyclic AMP accumulation in the rabbit uterus. Cyclic 3',5'-nucleotide phosphodiesterase (PDE) activity in rabbit uterine homogenate was inhibited by indomethacin (10 mug/ml; 66% inhibition) or flufenamic and (10 mug/ml; 60%). Indomethacin (100 mug/ml) reduced uterine prostaglandin E2 (PGE2) content by 80%, but potentiated the stimulatory action of purified cholera toxin (choleragen; 800%) and of exogenous PGE2 (140%) on cyclic AMP accumulation, probably through its inhibitory effect on cyclic AMP destruction. These findings suggest that endogenous PGE2 is not an essential mediator of choleragen action. By contrast, flufenamic acid abolished choleragen and PGE2 action on cyclic AMP production. Unlabeled PGE2 (10 mug/ml), flufenamic acid, indomethacin, and aspirin (100 mug/ml each) inhibited [3H]PGE2 binding to uterine slices by 78, 73, 62, and 20% respectively. It is concluded that while indomethacin and flufenamic acid have similar effects on prostaglandin biosynthesis and PDE activity, only fenamates have an inhibitory effect on the biological action of exogenous PGE2 and choleragen on the stimulation of cyclic AMP production, probably through the inhibition of the binding of PGE2 and choleragen to its specific receptor sites. The diverse biochemical actions of the above drugs indicate that care has to be taken when using these drugs in analyzing the physiopathological roles of prostaglandins.


Inhibitory effects of prostaglandin E1 on responses of rabbit ear artery to nerve stimulation and on release of norepinephrine. PGE1 in concentrations of 7 x 10(-9) to 4.5 x 10(-7) M inhibited the vasoconstrictor responses of the perfused rabbit ear artery to nerve stimulation. The degree of inhibition was dependent on the concentration of PGE1, as well as on the train length and frequency of stimulation. The vasoconstriction produced by norepinephrine was not altered by 1.1 x 10(-7) M PGE1. This substance markedly reduced the stimulation-evoked outflow of 3H-norepinephrine from the artery. The findings indicate that PGE1 inhibits the vasoconstrictor responses of rabbit ear artery to sympathetic nerve stimulation by reducing the release of the sympathetic transmitter for adrenergic nerve endings.


Adrenocortical factors in hypertension. I. Significance of 18-hydroxy-11-deoxycorticosterone. Low renin essential hypertension and the syndrome of mineralocorticoid excess have two features in common, low plasma renin activity and volume-sensitive hypertension. The proposal that both disorders share a common mechanism--because of the ability of agents that inhibit or antagonize the adrenocortical secretion to lower blood pressure in the low renin hypertensive group--appears to be based on a circular argument. The beneficial effect of removal or neutralization of the adrenocortical contribution only constitutes evidence for volume-dependency or sensitivity, which is how the low renin group is defined. Any measure that blocks a component of the normal homeostatic chain for the maintenance of extracellular and intravascular volume including the adrenal cortex would be expected to have a beneficial effect in volume-sensitive hypertension. Evidence for an adrenal factor in low renin hypertension must rest on the isolation of an active substance that reproduces the effect when readministered. 18-Hydroxy-11-deoxycorticosterone (18-OH-DOC) does not meet these criteria. It is not significantly increased in experimental hypertension and, although its overproduction in unselected low renin essential hypertensive patients remains controversial, the magnitude of the reported elevations is insufficient in relation to the low biologic activity of the steroid to account for a significant effect. Apart from its increase in the 17alpha-hydroxylase defect, 18-OH-DOC is increased in primary aldosteronism and may also be an indicator of a histologic variant of the aldosteronoma. On the basis of a large body of evidence showing parallelism between the 11beta- and 18-hydroxylase functions of the fasciculata zone, we have proposed that both enzymic functions are functionally related and may involve the same enzyme protein and catalytic site. According to this view, the secretion of 18-OH-DOC would have no special significance of its own but would be an obligatory consequence of the secretion of fasciculata zone corticosterone.


Short term study of sucrose polyester a nonabsorbable fat-like material as a dietary agent for lowering plasma cholesterol. The efficacy, safety, and acceptability of sucrose polyester (SPE), a fat-like material that is neither digested nor absorbed, were assessed in 13 normal and seven hypercholesterolemic subjects for its potential as a cholesterol-lowering agent. Addition or substitution of SPE for culinary fats in the diets of the normocholesterolemic individuals produced a mean reduction of total and low-density lipoprotein cholesterol of 14 and 17%, respectively (P less than 0.001), despite the daily ingestion of a diet containing 800 mg of cholesterol and of dietary fat with a P/S ratio of 0.4. Total and low-density lipoprotein cholesterol were not significantly reduced by similar 10-day feeding periods of SPE in seven subjects with familial hypercholesterolemia. High-density lipoprotein cholesterol and triglycerides were not changed in normal or hypercholesterolemic subject receiving SPE. Plasma vitamin A and E levels were reduced by 10 and 21% (p less than 0.02 and less than 0.001) in both normal and hypercholesterolemic subjects on SPE. These returned to the basal levels when SPE consumption was discontinued. SPE was recovered quantitatively (greater than 97%) in the stools, with the last measurable SPE being found day 3 to 5 after cessation of SPE intake. Despite recovery of 50 g or more of unhydrolyzed SPE in stools during SPE feeding, there was no clinical or chemical steatorrhea. On subtracting SPE's input to total stool fatty acids, it was found that "non-SPE" fatty acids in the stool had not increased during SPE feeding, SPE was easily incorporated into routine foodstuffs in addition to, or in substitution for, conventional dietary fats. On the basis of this short term evaluation in humans and other investigations with the rat and dog. SPE appears to have potential as a cholesterol-lowering agent.


Metabolism of vitamin D: current status. There has been much progress in our understanding of the metabolism of vitamin D. It is now clear that vitamin D3 can be produced in the skin or ingested in the diet. It accumulates very rapidly in the liver where it undergoes 25-hydroxylation, yielding 25-OH-D3, the major circulating metabolite of the vitamin. 25-OH-D3 proceeds to the kidney where it undergoes one of two hydroxylations. If there is a biological need for calcium or for phosphate the kidney is stimulated to convert 25-OH-D3 to the 1,25-(OH)2-D3, a calcium and phosphate mobilizing hormone. If, however, the animal has sufficient supplies of calcium and phosphate, the l-hydroxylase is shut down and instead the 25-OH-D3 is converted to a 24,25-(OH)2D3. The role of the 24,25-(OH)2D3 remains unknown; it may be an intermediate in the inactivation-excretion mechanism. 1,25-(OH)2D3 proceeds to the intestine where it stimulates intestinal calcium transport and intestinal phosphate transport. It also stimulates bone calcium mobilization and probably has other effects yet to be discovered in such tissues as muscle. The 25-OH-D3-l-hydroxylase, which is located exclusively in renal mitochondria, has been shown to be a three component system involving a flavoprotein, an iron-sulfur protein (renal ferredoxin), and a cytochrome P-450. This system has been successfully solubilized, the components isolated, and reconstituted. The 24-hydroxylase, however, has not yet been thoroughly studied. 1,25-(OH)2D3 is necessary for the appearance of the 24-hydroxylase; parathyroid hormone represses 24-hydroxylation. It is possible that the 24-hydroxylase represents the major regulated enzyme, so that its presence or absence may determine whether 1,25-(OH)2D3 is produced. Two metabolic pathways for 1,25-(OH)2D3 are known, conversion by the 24-hydroxylase to 1,24,25-(OH)3D3, and conversion of 1,25-(OH)2D3 to an unknown substance. In the latter instance, there occurs loss of a side chain piece, including at least one of the 26 and 27 carbons. Whether 1,25-(OH)2D3 must be metabolized further before it carries out all of its functions has yet to be established. The primary excretion route of vitamin D3 is via the bile into the feces. Urinary excretion appears small in magnitude and no excretion products have yet been identified positively. Much remains to be learned concerning the metabolism and function of vitamin D and its metabolites. This should therefore, prove to be a fruitful area of investigation for many years to come, especially since 1,25-(OH)2D3, 25-OH-D3, and lalpha-OH-D3 have been shown to be effective in a number of metabolic bone disease states.


Advances in vitamin D metabolism as they pertain to chronic renal disease. Many clinical similarities between renal osteodystrophy and nutritional rickets have suggested that a defect in either the metabolism or action of vitamin D exists in chronic renal failure. The discovery of the kidney as the organ that manufactures the active metabolite of vitamin D has provided direct evidence for a relationship between renal failure and altered vitamin D metabolism. Other observations suggest that an abnormality of vitamin D action could underlie both osteomalacia and osteitis fibrosa (secondary hyperparathyroidism) observed in patients with chronic renal failure. The administration of the active vitamin D analogs, 25(OH)D3, 1,25(OH)2D3, and lalpha(OH)D3, to uremic patients with symptomatic bone disease is capable of reversing many of the abnormalities of divalent ion metabolism. The widespread availability of these agents in the future may provide the clinician the means to correct or even prevent the serious bone disease that frequently complicates the course of chronic renal failure.


Adrenocortical-related maturational events in the fetus. In various organs in fetal animals, maturation is inducible by corticosteroids and delayed by hypophysectomy. A surge of corticosteroid in the fetal circulation preceding parturition may cause rapid organ maturation and enhanced viability. Since this phase of accelerated maturation is linked to the parturitional mechanisms, the changes can be termed collectively "preparation for birth." Support for similar adrenocortical-related maturation of organs in the human fetus is less clear-cut. Nevertheless, evidence is accumulating to suggest that a similar concept can be usefully applied in man.


Dynamics of adenosine-3', 5'- monophosphate transfer among mother, fetus, and amniotic fluid in the rhesus monkey. Cyclic AMP exchange among the mother, amniotic fluid, and fetus was studied in normal rhesus monkeys at term pregnancy. Following a pulse intravenous administration of 3H-cyclic AMP into the mother, a small fraction of the dose appeared in less than 1 minute in fetal blood. It appeared in the amniotic fluid after 5 minutes and reached maximum level in 20 minutes. The accumulation of 3H-cyclic AMP in the amniotic fluid in 1 hour was 0.03 per cent of the injected dose. The amount and time course of 3H-cyclic AMP accumulation in the fluid were not altered by tying the umbilical vessels. The transfer of 3H-cyclic AMP injected in utero into the fetal femoral artery resembled that in the mother; in 1 hour the amniotic fluid contained 0.22 per cent of the injected dose. When injected directly into the amniotic sac, more than 65 per cent of the injected dose remained unchanged after 1 hour, with minimal transfer into the maternal and fetal compartments. This study showed rapid bidirectional exchange of cyclic AMP between the mother and the fetus. Both of these compartments can contribute cyclic AMP to the amniotic fluid, independently or in concert. It remained fairly stable in the fluid and was not readily metabolized or transported out.


Use of vidarabine in epidemic keratoconjunctivitis due to adenovirus types 3, 7, 8, and 19. Adenovirus types 3,7,8, and 19 were isolated during an outbreak of epidemic keratoconjunctivitis. There was no clinically recognizable difference in the severity of the disease produced by each adenovirus type. Twenty-nine patients with positive viral cultures were given either 3.3% vidarabine ointment or polyvinyl alcohol eyedrops within five days of the onset od disease, and were observed for at least 14 days. An observer unaware of which medication was prescribed found subepithelial corneal infiltrates in 81% of vidarabine-treated patients and in 63% of control subjects. Vidarabine was ineffective in preventing subepithelial corneal infiltrates in keratoconjunctivitis caused by adenovirus.


Herpetic stromal keratitis-evidence for cell-mediated immunopathogenesis. Immunofluorescence, histological, and electron microscopic observations were made on rabbit corneas from animals with experimentally induced stromal keratitis following intracorneal injection with the RE strain of herpes simplex virus. Electron microscopic observations were also made on human corneas obtained from patients with a history of herpetic stromal disease. Viral antigens were demonstrated by immunofluorescence in keratocytes of rabbit corneas with herpetic stromal keratitis. Electron microscopic observations and viral culture failed to reveal the presence of viral particles in these tissues. Lymphocytes, a major infiltrating cell type found in both the rabbit and human corneas, were often found in intimate contact with degenerating keratocytes.


En bloc removal of intrinsic neoplasms of the lacrimal gland. The management of intrinsic neoplasms primary in the lacrimal gland is of serious concern because some of the most malignant primary tumors of the orbit occur in this glandular structure and present surgical techniques may easily disseminate the neoplasm and contribute to death or recurrences. We propose a surgical approach in which the tumor and adjacent adnexa are removed in a one-stage procedure, that is, an en bloc resection of the neoplasm, its periorbital base, and surrounding bone. This technique will minimize seeding of the tumor, provide a more complete eradication of the neoplasm without loss of the eye, and assure either a cure or a longer interval free of local recurrences or metastasis than is presently attainable.


Impaired microtubule function correctable by cyclic GMP and cholinergic agonists in the Chediak-Higashi syndrome. The Chediak-Higashi (CH) syndrome of man and several animal species is characterized by the presence of abnormal giant granules in all granule-containing cells and by defects in chemotaxis and lysosomal degranulation during phagocytosis in polymorphonuclear leukocytes (PMNs). Since similar functional abnormalities have been reported in normal PMNs following exposure to colchicine and other agents that disrupt microtubles it was proposed that microtubule function may be impaired in the CH syndrome. The mobility of concanavalin A (con A)-receptor complexes on PMN membranes was used to test microtubule integrity. Normal PMNs showed a uniform distribution of membrane-bound con A. By contrast, con A was aggregated into surface caps on both colchicine-treated normal PMNs and untreated PMNs from mice and a patient with CH syndrome. This result is consistent with impaired microtubule function in the CH cells. The spontaneous capping response of CH PMNs was inhibited by cyclic GMP and by cholinergic agonists that can elevate cyclic GMP levels in neutrophils. This raised the possibility that the microtubule defect in CH cells may be correctable by treatments that increase cyclic GMP generation. Direct evidence for both the absence of microtubule assembly in con A-treated PMNs from the CH patient and for normal microtubule assembly in CH PMNs incubated with cyclic GMP and cholinergic agonists prior to con A treatment was obtained by electron microscopy. In addition, evidence for a direct relationship between the microtubule defect and the development of giant lysosomes in CH cells was obtained. Thus, CH fibroblasts grown in vitro developed abnormal lysosomes in the majority of cells. However, the same cells cultured in the presence of cholinergic agonists developed a majority of lysosomes that were morphologically normal at the level of the light microscope. Similarly, granule morphology appeared normal in peripheral blood leukocytes from mice treated chronically in vivo with cholinergic agonists.


Effectiveness of community services for discharged mental hospital patients. This study of 579 state hospital patients charts the pattern of their care in the community in the two or three years following hospital discharge, and examines the relationship of aftercare services to readmission rates. Findings suggest that, among the most chronic patients, a substantial number of aftercare visits may be related to lower hospital readmission rates.


Some secular changes in the growth of American-born and native Japanese children. Three hundred and sixteen (35%) of the American-born Japanese children whose height, weight, and skeletal age were recorded in 1956-57 were reexamined as young adults between 1968 and 1974, when they were found to be taller, heavier and shorter legged than men and women in Japan who were born in the same years as they. These differences between the American-born and the native Japanese adults were relatively smaller than they had been during childhood, due to both an acceleration in the growth rate of the native Japanese and a concomitant decline in that of the American-born Japanese during the intervening years. A comparison of our 1956-57 data with Kondo and Eto's findings in Los Angeles in 1971 shows that there has been very little increase in the size of California-Japanese children since 1956. The curves of average heights of native Japanese children 6 to 20 years of age, at 10-year intervals from 1900 to 1970, disclosed the changing rate at which they grew during different decates of that period. Those curves and other data discussed in this paper provide additional evidence of the biological superiority of the human female as compared with the male.


Phosphorylation of cardiac regulatory proteins by cyclic AMP-dependent protein kinase. Cardiac myofibrils were purified from canine myocardium, and the regulatory proteins (troponin + tropomyosin) were extracted and shown to contain endogenous cyclic AMP-dependent protein kinase activity. Other cyclic nucleotide stimulated the protein kinase activity but only at higher concentrations. The enzyme was able to catalyze phosphorylation of conventional substrates such as histones and casein as well as a component of the regulatory protein fraction with a molecular weight of 28,000 daltons. Endogenous phosphorylation required the presence of Mg2+ and was inhibited by Ca2+. A protein kinase inhibitor obtained from skeletal muscle inhibited the cyclicAMP-dependent phosphorylation. Escherichia coli alkaline phosphatase dephosphorylated the endogenous substrates. The level of phosphorylation found is severalfold higher than we have previously reported. A protein kinase, with its close association with the regulatory proteins, seems to be well suited to transmitting the message from the cyclic AMP to the regulatory proteins, a phenomenon that may influence the cardiac contractility via the troponin phosphorylation. The inhibitory effect of troponin on actomyosin might be changed by its state of phosphorylation.


Effect of parathyroid hormone on renal tubular permeability. The effect of parathyroid hormone (PTH) on renal tubular permeability has been studied utilizing micropuncture techniques in the rat kidney. After microinjection into superificial nephrons during control conditions, inulin (98.8 +/- 2.7%) and mannitol (97.2 +/- 2.4%) recovery from the experimental kidney was essentially complete. During intravenous infusion of PTH, inulin (99.3 +/- 2.9%) recovery was again complete. Mannitol recovery decreased signficantly after both early-proximal (84.7 +/- 5.8%, P less than 0.001) and late-proximal (89.7 +/- 2.8%, P less than 0.001) injections. There was no loss of either mannitol or inulin following distal tubular injection. Late-proximal TF/P inulin ratios during control conditions were 2.10 +/- 0.20 and decreased insignificantly to 1.99 +/- 0.21 during PTH infusion. Late-proximal TF/P mannitol rations were 2.09 +/- 0.21 during control periods and during PTH infusion decreased significantly to 1.78 +/- 0.19 (P less than 0.001). These results indicate that PTH induces a change in proximal tubular permeability to a usually impermeable nonelectrolyte, mannitol. The effects of PTH on proximal tubular transport could be partially explained by this alteration in permeability, which would increase passive backflux of actively transported species and decrease net transport while having no effect on active transport.


Midbrain neuronal responses to local and spinal cord temperatures. Water-perfused thermodes were implanted over the lumbothoracic spinal cord and unilaterally in the midbrain of urethan-anesthetized rabbits. Single-unit activities were recorded with steel microelectrodes from the thermosensitive neurons in the midbrain reticular formation (MRF), and the effects of heating and cooling of the spinal cord were studied. Of 38 cold-sensitive MRF neurons studied, 7 units decreased their firing rate upon elevation of spinal cord temperature (Tsc) and 3 units showed the opposite type of response to Tsc. The remaining 28 cold units were not affected by the changes in Tsc between 30 and 43 degrees C. Of 17 warm units, 3 units increased and one unit decreased the firing rate during spinal cord heating. These results suggest that the temperature signal arising from thermosensitive structures in the spinal cord may be transmitted to some of the locally thermosensitive neurons in the MRF.


Simulation study of control of hepatic glycogen synthesis by glucose and insulin. The plausibility of various hypotheses concerning the effects of glucow dynamic model of glucose metabolism in the liver. The model consisted of six compartments representing extracellular glucose, and intracellular glucose, glucose 6-phosphate, glucose 1-phosphate, uridine diphosphate glucose, obtained from literature reports, the model predicted values of intermediates which were close to those reported for the liver, sampled from fasting animals. The model predicts that glucose can generate significant glycogen deposition by engendering the inhibition of glucose-6-phosphatase, but not by mass action, glycogen synthase activation, or phosphorylase deactivation. The model predicts that, although insulin can inhibit glucose production by lowering phosphorylase and gluconeogenesis, only an insulin-mediated induction of glucokinase can account for insulin's action to potentiate the effect of glucose alone on glycogen synthesis.


Janeway Lecture: Pediatric cancer treatment: a model for oncology. Advances in pediatric oncology are reviewed using Wilms's tumor as a model. From the period when Wilms's tumor was treated by surgery alone to the time when adjuvant radiation and chemotherapy enabled attainment of an 80% survival rate, true collaboration among surgeons, radiation therapists, and pediatricians has been the key to success. The National Wilms's Tumor Study seeks to further refine treatment so that survival rates are maximized with minimum morbidity. The lessons applicable to all in cancer management are that a team approach is essential, all forms of treatment should be weighed early, treatment should be skilled and vigorous from the beginning the biology and natural history of the tumor should be considered in treatment planning, and toxicities of all forms of treatment should be respected and ways designed for their reduction.


Cryoultramicroscopy of lower vertebrate retina. Cryoultramicroscopy was carried out in the retina of lower vertebrates. Myeloid bodies of the pigment epithelium of turtles and synaptic vesicles and ribbons of frogs were stained negatively. Numerous altered, shaped, dense bodies, containing granular and myelinlike matrices, were found in the retinal pigment epithelium of turtle, and were thought to be lysosome. The advantages and disadvantages of this method are discussed.


[Ultrastructural aspects of chloroquin-keratopathy (author's transl)]. This reports deals with ultrastructural findings in chloroquin-keratopathy on the basis of three cases. Cytoplasmic inclusions are found in the corneal epithelium, alternately in the form of lamellar bodies, dense bodies, or as vacuoles with a variable content. Similar results are reported in the literature with other drugs and permit the conclusion that a pathologic mechanism depending on the amphiphilic character of these substances is involved. Thus they are able to undergo reactions with phosphilipids, disturbing the normal phosphilipid catabolism and leading to a drug-induced phospholipidosis.


Hormones and hormonal target cells in the testis. Studies over the last few years have greatly increased our knowledge about target cells for sex hormones and gonadotropins in the testis. A diagram illustrating our present state of knowledge is given in Fig. 1. LH is the principle stimulus of testosterone secretion by the Leydig cells. Direct effects of estrogens and androgens on these cells might modulate the response to LH. Androgens are apparently influencing the differentiation and the contractility of peritubular cells. FSH is the principle stimulus for Sertoli cell secretory function before puberty, although androgens are acting synergistically with FSH. After puberty, androgens alone are capable of maintaining on optimal secretory function of the Sertoli cells. In addition to normal secretory activity of the Sertoli cells, direct stimulation of the germ cells by androgens is needed in order maintain spermatogenesis.


Isolation and characterization of a virus associated with progressive pneumonia (maedi) of sheep. A virus with growth and morphologic characteristics of progressive pneumonia (maedi-visna) virus was isolated from the lungs of sheep with typical clinical and postmortem changes of chronic progressive pneumonia. The virus grew slowly in cultures of embryonic ovine lung cells, causing syncytial formation and degeneration. Syncytia developed much slower and involved fewer cells than reported for other similar viruses isolated from sheep. As seen with the electron microscope, the virus reproduced by budding from cell surfaces. Two types of virions were seen-a large particle (120 to 140 nm) with an electron-lucent center and dense laminated outer rim, and a small particle (80 to 110 nm) with an electron-dense core surrounded by a single membrane. Viral structures and fragments similar to the large extracellular particles were seen in the cytoplasm of a few cells. These characteristics are reported for other viruses isolated from sheep with progressive pneumonia.


Vaccination of newborn pigs with an attenuated strain of transmissible gastroenteritis virus. Clinical signs of transmissible gastroenteritis were not observed in newborn pigs orally inoculated with the high-passaged vaccinal transmissible gastroenteritis virus (TO-163 strain). Vaccinal viral multiplication in digestive tract of newborn pigs fed colostrum before inoculation and kept at 21 to 22 C was diminished, but was not diminished in those fed colostrum and kept at 10 to 11 C. Other groups of newborn pigs inoculated with the attenuated vaccinal virus and kept at 18 to 22 C or at 31 to 34 C were challenge exposed with virulent intestinal virus on the 1st, 2nd, . . ., or 6th postinoculation (PI) days. In the groups kept at 18 to 22 C, 2 of 7 inoculated pigs challenge exposed with virulent virus on the 3rd PI day, 4 of 7 pigs exposed on the 4th PI day, and all of the pigs exposed on and after the 5th PI day survived the exposure. In the groups kept at 18 to 22 C, the attenuated vaccinal virus was distributed mainly in the respiratory organs and lymphatic tissues. On the contrary, in the groups kept at 31 to 34 C, all of the pigs died in 2 to 5 days after challenge exposure, and the attenuated vaccinal virus was scarcely detected in any of the pigs.


Leukocyte-aggregation assay for transmissible gastroenteritis of swine. An in vitro leukocyte-aggregation assay was developed to detect the exposure of swine to transmissible gastroenteritis virus. Leukocytes in heparinized blood samples aggregated when mixed with test antigen prepared from transmissible gastroenteritis-infected swine testicle cell cultures. Twenty-two of 23 swine exposed 3 days or more were positive or suspects in the assay; 6 nonexposed swine were negative. Aggregation was shown as early as 3 days postexposure in 1 sow and persisted for as long as 14 months in another. Persistence of the assay was proved by repeated evaluations on 2 experimentally exposed swine.


Effects of metyrapone and ACTH on intestinal absorption of immunoreactive bovine IgG in cesarean-derived pigs. Newborn cesarean-derived pigs were injected with 5.0 mg of metyrapone/kg, or 1 USP U of ACTH/kg, or the vehicle 1.0 ml of 44 mM sodium tartrate and 88 mM NaCl soon after delivery (0 hour) and again 4, 8, and 12 hours later. Beginning at 2 hours, each pig in the 3 groups was given 40 ml of pooled bovine colostrum/kg by stomach tube every 8 hours for the duration of the experiment. Four hours after each feeding, pigs were killed; plasma and serum were collected and assayed for cortisol and bovine immunoglobulin (IgG), respectively. Some nonfed, nontreated pigs were killed at 0 hour also. Metyrapone significantly decreased plasma cortisol (hydrocortisone) concentrations at all times tested, whereas ACTH-treated pigs demonstrated a biphasic increase of plasma cortisol. Immunoreactive serum bovine IgG was not detected in nonfed, nontreated pigs. In vehicle-injected control pigs, bovine IgG was present in the serum at 6 hours; the concentration increases consistently to 22 hours, but not significantly thereafter. The concentration of bovine IgG in the serum of metyrapone-treated pigs also increased steadily before plateauing at 22 hours, but the values were significantly less than those of the controls at 14, 22, 30, and 38 hours. The concentration of bovine IgG in the serum of ACTH-treated pigs did not differ significantly from the control values at any of the times tested.


Scanning electron, light, and immunofluorescent microscopy of coronaviral enteritis of turkeys (Bluecomb). Intestinal sections from both experimental and field cases of turkey coronaviral enteritis (TCE) were examined by scanning electron microscopy and light microscopy through 10 days after inoculation and by a direct fluorescent antibody test for TCE through 12 days. Serums were collected for an indirect fluorescent antibody test for TCE through 160 days after inoculation. Lesions observed with the scanning electron microscopy were catarrhal enteritis with hemorrhage per diapedesis, epithelial desquamation, and villous atrophy which developed and regressed within 6 days after inoculation. Light microscopy demonstrated similar lesions, except that villus-to-crypt ratios remained depressed 10 days. The direct fluorescent antibody test demonstrated the presence of coronaviral antigen throughout the sampling period, and serum antibodies to TCE were present until at least 160 days, when the experiment was terminated.


In vitro interferon production by bovine tissues: effects of hydrocortisone. The effect of hydrocortisone on bovine interferon production in vitro was studied. Infectious bovine rhinotracheitis virus was used as an inducer. Interferon was assayed by the plaque-reduction method in bovine fetal kidney cultures, using vesicular stomatitis virus as challenge virus. Hydrocortisone decreased interferon production in bovine fetal spleen and peripheral blood leukocyte cultures. Hydrocortisone did not decrease interferon production by bovine alveolar macrophages, in 1 experiment. Properties of viral inhibitors were those of interferon.


In vitro interferon production by bovine tissues: induction with infectious bovine rhinotracheitis virus. The interferon-inducing ability of infectious bovine rhinotracheitis (IBR) virus was determined in tissue cultures of bovine origin inoculated with untreated and ultraviolet (UV) irradiated IBR viruses. Interferon was assayed by the plaque-reduction method in bovine fetal kidney (BFK) cell cultures, using vesicular stomatitis virus as challenge virus. Highest interferon concentrations were produced by cultures of bovine fetal (BF) spleen cells and aveolar macrophage cultures derived from adult cattle. Moderate interferon concentrations were produced by peripheral blood leukocyte (PBL) suspension cultures from adult cattle with serum-neutralizing antibodies against IBR virus. Cultures of PBL from 1 cow without detectable serum-neutralizing antibodies against IBR virus did not produce detectable interferon in response to IBR virus. Cultures of PBL from cattle with or without detectable serum-neutralizing antibodies against IBR virus produced interferon when stimulated with phytohemagglutinin (PHA). Low levles of viral inhibitors were detected infrequently in monolayer cultures of BFK and BF nasal mucosa inoculated with UV-irradiated IBR virus and in BF tracheal organ cultures inoculated with untreated IBR virus. Interferon was not detected in fluids collected from IBR virus-exposed monolayer cultures of primary and secondary BF lung, secondary BF tracheal mucosa, secondary BF liver, secondary BF adrenal, and PBL in the 4th and 7th passages. The antiviral inhibitors from BF spleen, bovine alveolar macrophage, and PBL cultures induced with IBR virus, as well as inhibitors from PBL cultures induced with PHA, had the usual properties of interferon.


Hydrogen sulfide intoxication. A case report and discussion of treatment. The toxicity of hydrogen sulfide is thought to be due primarily to reversible inactivation of the respiratory enzyme, cytochrome oxidase, with resultant inhibition of aerobic metabolism. A patient with severe hydrogen sulfide poisoning and consequent profound metabolic acidosis was treated successfully with nitrites and oxygen. The nitrite-induced methemoglobin, by competitively binding the toxic hydrosulfide anion until detoxified, presumably reactivated and protected cytochrome oxidase and therby aided the patient's recovery by enhancing aerobic metabolism. His rapid recovery adds clinical support to the efficacy of nitrite therapy in sulfide poisoning. Therefore, we recommend that severe cases of sulfide poisoning be treated with nitrite-induced methemoglobinemia in addition to vigorous supportive care.


Naloxone.

Naloxone. Narcotic analgesics and related drugs act as agonists on several receptors that are responsible for their effects on pain perception, mood and feeling state, and respiration, as well as other pharmacologic actions. Naloxone is the first discovered antagonist that is devoid of agonistic activity and appears to be a competitive antagonist at several receptors. The ability of naloxone to displace or prevent the binding of agonistic narcotics is partly responsible for its antagonistic effects. The ability of naloxone to rectify narcotic-depressed homeostats and precipitate abstinence is also related to its antagonistic activity. Certain cautions and principles apply in the use of naloxone in treating narcotic overdose, reversing surgical analgesia, and the treatment of neonates and children. Unapproved uses of naloxine include reversing the psychotomimetic effects of certain agonists-antagonists, terminating narcotic-induced convulsions and coma, reversing non-narcotic depression, diagnosing physical dependence, and treating narcotic addicts.


Immunotherapy with nonviable microbial components. Structural components of microorganisms have been studied for immunopotentiating effect with the aid of transplantable (line 10) tumors in syngeneic guinea pigs. Microbial components were associated with oil droplets, suspended in Tween-saline, and injected intralesionally. BCG cell walls, given in this way, produced regression and cure of 50-60% of established tumors, as did viable BCG. Lipid extraction markedly reduced the tumor-regressing potency of cell walls, but P3, a trehalose mycolate present in the extract, restored full activity to the cell wall residue. P3 alone was nonsensitizing and had no antitumor activity, but it enhanced the latter property of various other microbial products. For example, the cure rates produced by cell walls of M. tuberculosis, M. bovis, M. phlei, or M. smegmatis were enhanced from 20-60% to as much as 90% by addition of P3. P3 also conferred antitumor activity on products from unrelated microbes, such as cell walls of E. coli, and in combination with endotoxins from rough Re mutant salmonellae, it produced cure rates of up to 93%. These results suggest that P3 is essential to the immunopotentiating activity of mycobacteria and that it may be broadly applicable in immunotherapy of cancer with microbial agents.


[Carboyydrates localization on ultrathin sections of "Brucella" and "Escherichia" cells in smooth (S) and rough (R) phase (author's transl)]. Carbohydrates localization on ultrathin sections of Brucella abortus, melitensis and Excherichia coli cells has been studied by the periodic acid thiocarbohydrazide-silver proteinate (PATAg) and phosphotungstic acid (PTA) methods. Carbohydrates are mainly localized on the cell envelope of Brucella and Escherichia but there are several differences between these two bacteria. The differences are discussed and a Brucella polysaccharide envelope model is proposed. The PATAg method gives the same silver grain deposits on Brucella S and R and Escherichia S and R. The phosphotungstic acid method differenciates Brucella S and R cells by lack of contrast on the outer leaflet of the outer membrane of the latter, but does not differenciate E. coli S or R cells. The Brucella outer membrane contains less polysaccharides than that of E. coli. There is a seemingly symetric distribution of polysaccharide in the Brucella outer membrane as compared to an asymetric distribution in E. coli. The peptidoglycan of Brucella reacts strongly as compared with that of E. coli. The polysaccharides present a dispersed pattern in Brucella cytoplasm, whereas in E. coli they appear as dense, strongly reactive clusters very close to the cytoplasmic membrane.


[Interactions of Shope papilloma virus with SV40 in adult domestic rabbit cell lines derived from normal skin or from Shope papilloma virus infected skin (author's transl)]. Three cell lines from adult domestic rabbit are infected with SV40: LP 17 and LP 45 derived from normal skin and LP 42 PS derived from skin infected for 24 h with Shope papilloma virus. The fibroblastic morphology of the cultures is not changed. SV40 is not recovered and T antigen is only detected in LP 42 PS cell line after 29 passages. To know if Shope papilloma virus facilitates penetration of SV40, cultures of LP 45 are first infected with Shope papilloma virus for 2 h and for 24 h, then superinfected with SV40. There is no cellular alteration, and T antigen induced by SV40 is only detected in cells pretreated for 24 h with Shope papilloma virus, after 20 passages. When cultures LP 45 are  infected with Shope papilloma virus neutralized with a high titer antiserum and superinfected with SV40, T antigen is not detected. Superinfected cells containing specific SV40 T antigen do not induce tumors either in new born hamsters or in rabbits but they are able to grow in colonies in soft agar. LP 42 PS cell line and LP 45 cells infected with Shope papilloma virus for 24 h containe Shope papilloma virus genome which is able to modify the permissivity of rabbit cells to SV40.


[Alkyl sulfates and alkyl aryl sulfonates as inhibitors of penicillinase]. The kinetics of inhibition of penicillinase of Bac. licheniformis 749/c by various alkyl-sulphates (with a long hydrocarbon chain from C8 to C16), n-toluolsulphoacid and alkylbenzol-sulphonate (R-C12--C16) was studied. The inhibition rate increased with elongation of the alkyl radical and rising of the inhibitor concentraiton. This means that the determining factor in inhibition process was hydrophobic interaction of the alkyl chains and not the electrostatic interaction with the enzyme. In-vitro experiments with penicillinase-producing strains of staphylococcus showed that non-bactericidal concentrations of the alkylsulphates and alkylben zolsulphonates increased the effect of benzylpenicillin, ampicillin and methicillin. The highest increase in the antibiotic activity, as well as in the enzyme inhibition was observed with respect to the compound with the hydrocarbon chain fron C12 to C16. The increase in the activity of methicillin against the staphylococcal strains resistant simultaneously to benzylpenicillin, ampicillin and methicillin was indicative of possible using of the above surface active substances as inhibitors of the realization process of various mechanisms of penicillin resistance.


[Effect of antibiotic action on the submicroscopic structure of Salmonella. The action of monomycin on S. typhi]. The effect of subinhibitory concentrations of monomycin on the submicroscopic structures of 2 strains of S. typhi, 5 and 799 was studied. It was shown that formation of filamentoue forms, separation of the cell wall, thinning out of the cytoplasm granular component, increasing of the size of the matter with low electron optic density of fine granular structure were common in the cell response of both strains. Formation of vacuoli containing the thinned out granular component, filterable elements and complex membrane structures followed by their liberation into the medium and formation of the forms devoid of the cell walls was a characteristic peculiar property of the cell response in strain 799. The cells of strain 5 were characterized by formation of large granular osmiefilic matters and their excretion from the cells.


[Experimental study of the organotropic side-effect properties of polymyxin B]. Toxicity of Soviet polymyxin B and its effect on the central peripheral nervous system, blood circulation, respiration, smooth muscles, functional liver and kidney state, growth and development of young animals, the picture of the peripheral blood were studied in acute and chronic experiments on various species of animals. It was found that polymyxin B had a suppressing effect on the peripheral n-cholinoreactive systems of the neuromuscle synapses of the skeletal muscles and ganglia of the sympathic and parasympathic innervation and deprimizing effect on the central nervous system. Caffeine, adrenaline and calcium chloride proved to be the antagonists of the neurotoxic effects of polymyxin B. The chronic experiments revealed that polymyxin B induced disorders in the kidney function and morphological changes in the glomeruli after its repeated administration. No significant effect of polymyxin B on the growth and development of the young animals, the functional state of the liver and the picture of the peripheral blood was observed when the drug was used in doses corresponding to the therapeutic ones in clinics.


Effect of sodium nitrite inhibition on intracellular thiol groups and on the activity of certain glycolytic enzymes in Clostridium perfringens. Activities of glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12) (GAP-DH) and aldolase (EC 4.1.2.13) in cells of Clostridium perfringens that had been inhibited with sodium nitrite were investigated. A complete loss in GAP-DH activity and a 67% decrease in aldolase activity were observed when growth of C. perfringens was inhibited. There was also a 91% decrease in the concentration of free sulfhydryl groups of soluble cellular components. Dithiothreitol restored some activity to inactive GAP-DH from sodium nitrite-inhibited cells, indicating that a loss of reduced sulfhydryl groups was involved in the inactivation of the enzyme. The evidence presented suggests that sodium nitrite inhibition of C. perfringens may involve an interaction of sodium nitrite as nitrous acid with sulfhydryl-containing constituents of the bacterial cell.


Concentration of viruses from large volumes of tap water using pleated membrane filters. A method is described for the efficient concentration of viruses from large volumes of tap water in relatively short time periods. Virus in acidified tap water in the presence of aluminum chloride is adsorbed to a 10-inch (ca. 25.4 cm) fiberglass depth cartridge and a 10-inch pleated epoxy-fiberglass filter in series at flow rates of up to 37.8 liters/min (10 gallons/min). This filter series is capable of efficiently adsorbing virus from greater than 19,000 liters (5,000 gallons) of treated tap water. Adsorbed viruses are eluted from the filters with glycine buffer (pH 10.5) and the eluate is reconcentrated using an aluminum flocculation process. Viruses are eluted from the aluminum floc with glycine buffer (pH 11.5). Using this procedure, viruses in 1,900 liters (500 gallons) of tap water can be concentrated 100,000-fold in 3 h with an average recovery of 40 to 50%.