[Colonic cancer and diverticulitis of the large intestine]. The authors report 17 cases of colonic carcinoma associated with diverticulitis. They differentiate between carcinomas arising above and below the diverticular area and emphasise the coexistence of both diseases on the same segment of colon. The diagnosis may be made in two different circumstances depending on whether the association presents as diverticulosis or as diverticulitis with  complications. Careful examination of the barium enema whenever possible is the basic factor in diagnosis. The operation is rendered more difficult by inflammatory phenomena or suppuration of the sigmoiditis and the prognosis is aggravated by cancer.


[Reflexions on the surgical treatment of diverticular sigmoiditis. Apropos of 62 cases]. The authors report 62 cases of operated diverticular sigmoiditis, note the indications for surgery and the method adopted. Apart from acute complications comparison of the clinical, laboratory and radiological data permit one to decide on a cold operation for prophylactic purposes. For acute generalised or localised peritonitis, the authors remove the lesions straight away when local and general conditions permit it. They emphasis the severity of the complications and the dealy with which these patients are still too often admitted on a surgical unit, which explins the persistently poor prognosis in spite of present conditions of resuscitation.


[Chyloperitoneum causing intestinal obstruction]. The two cases reported here show intestinal obstruction may occur by coagulation of lymph around the loops. They permit us to better understand the physiopathology of blockage of the lymph vessels whether congenital as in the first case or traumatic as in the second case. Traumatic rupture of the cisterns chyli is exceptional. The histological lesions observed on clamped biopsies show clearly the pathology of protein-losing enteropathy.


[Spontaneous pneumothorax in women].

[Spontaneous pneumothorax in women]. Among cases of spontaneous pneumothorax, female cases are extremely rare. They represent only about 10% of observed cases and form a special clinical type. The authors discuss 20 cases out of a total of 261 cases of pneumothorax observed over a period of 7 years. A certain number of facts were noted which distinguished the female forms from the male forms of this disease. Although there is no difference in the symptoms, the disease tends to occur later in women, in the fourth decade of life, and only three of the 20 cases in this series were idiopathic. On the other hand, among the secondary cases, the frequency of E.N.T. or respiratory disease is remarkable for it concerned 75% of cases. None of the cases observed responded to the usual criteria of menstrual pneumothorax although seven occurred during the menstrual period. However the forms which relapse during the periods should lead to a search for pelvic endometriosis. Finally the proportion of rib malformations is not negligible. These facts emphasise that pneumothorax in women, contrary to men, appears much more as a complication of another disease than as an autonomous pleural disease.


Fanconi's anemia: chromosome anormalies. Two types of chromosome abnormalitie are observed in the bone marrow and the blood of a patient with Fanconi's anemia. There abnormalities involved in two stages: firstly the presence of a clone with 47 chromosomes + 21, which was not found during later examinations. One and a half years later, following a decline in the hematological condition, there appeared duplication of certain chromosome segments of the long arm of the 3 chromosome and of the intermediate segment of the long arm of the 12 chromosome. This latter type of abnormality affected differently the bone marrow and the blood in the bone marrow, we found 2 clones, one bore 2 markers obtained from 3 and 12, the other and marker obtained from the 12 chromosome. In the blood, there was simply a minority clone with only the marker originating in the 3 chromosome. This observation should be compared with the descriptions made by other authors. In all cases abnormal clones present an apparently unbalanced karyotype, characterised by excess material.


[Pitfalls of the normal electrocardiogram]. The authors report the cases of 7 patients with a normal basal electrocardiogram, whereas they were all affected with a high risk cardiovascular condition: coronary insufficiency in 3 cases, paroxysmal arrhythmia in 4 cases. They recall the limits of the conventional ECG and emphasise interest of dynamic recordings, with effort tests, and/on continuous ECG recording in the identification of certain transient heart manifestations.


[Obliterating parietal hemodissection or vertebro-basilar dissecting aneurysm]. The authors report the pathological and clinical findings of a dissecting aneursym of the basilar artery in a 32 year old man up till then in good health, who died two months later. The pathological study showed bilateral lesions of osteo-malacia in the neighborhood of the pons due to hemo-dissection affecting the right vertebral artery just before it enters the dura-mater, then its intra-cranial portion, the basilar trunk and the first part of the right posterior cerebral artery. The originality of this case resides in the finding of segmental stenosing panarteritis of the same right vertebral artery in the segment which precedes dissection. On this occasion, the authors carried out a review of the literature and considered a few comments on the etiology, the pathology, clinical findings and classification of this unusual disease.


[Löfgren's syndrome, sarcoidosis and Bouillaud's disease]. The authors report two cases of Löfgren's syndrome, preceded by febrile polyarthritis with rise in antistreptolysin titer. The relationship between sarcoidosis and rheumatic fever is discussed. A review of the literature concerning Löfgren's syndrome with joint pain, permitted the authors to follow the course of present pathogenic concepts which haveled to the present opinion of the sarcoidosis nature of Löfgren's syndrome, when the latter is accompanied by erythema nodosum. The prolonged rise in antistreptolysin 0 titer which might suggest rheumatic fever, was not explained, but as the streptococcus was never found in throat swabs, it is probable that this was a non-specific phenomenon. However, certain authors believe that streptococcal infection, where it exists, may play a role, if not in the etiology of the sarcoidosis, at least in the Löfgren's syndrome which may lead to its discovery.


[Study of insulin secretion in chronic pancreatitis]. 17 oral glucose tolerance tests with simultaneous estimation of plasma insulin, were carried out in 15 patients with chronic pancreatitis of which 7 were of calcific type. Among these patients, 10 had obvious diabetes and 3 chemical diabetes. The disorders of glucose regulation were more common in the calcific form of the disease. Serum insulin was then lower and not stimulant. The curves of plasma insulin obtained in non-calcific pancreatitis were variable. In hyperinsulinism, the oral glucose tolerance test showed flat or normal curves. In hypoinsulinism, the glucose tolerance tests were either normal or strongly pathological. This insulinism, as shown by this study of chronic pancreatitis, seems to be linked to an imbalance in the cell distribution of the islets of Langerhans. The role of glucagon appears preponderant.


The effect of long-term oestrogen replacement therapy on glucose and lipid metabolism in postmenopausal women. A prospective study was undertaken to determine the effect on carbohydrate and lipid metabolism of long-term oestrogen replacement therapy in an unselected group of 34 postmenopausal women. Treatment was with cyclically-administered conjugated oestrogen (1,25 mg daily) for 24-43 months. Each patient served as her own control. The mean 2-hour postglucose level for the group at the end of the study was greater than the original baseline values, but the difference was not statistically significant. The mean serum cholesterol pre-beta-lipoprotein and beta-lipoprotein levels for the group were significantly reduced. Triglycerides were unaffected. It is suggested that treatment with conjugated oestrogens can maintain a normal lipid profile, provided that the original levels are within normal limits and that therapy is instituted early and is maintained. Carbohydrate and lipid metabolism in the majority of postmenopausal women on long-term conjugated oestrogen therapy will not be adversely affected.


Topographical anatomy of human cerebral and cerebellar astrocytomas in vitro. This study further characterizes the morphological and in vitro properties of human neoplastic cells derived from one Grade IV cerebral astrocytoma and one Grade III cerebellar astrocytoma. Light microscopic observations performed weekly over a four month period revealed two morphologically indistinguishable cell populations in each of the tumor cultures. Scanning electron microscopy demonstrated the presence of microvilli, blegs, and ruffles on the cell surfaces of both tumors; however, these topographical features were more prominent in the cultures derived from the Grade III cerebellar astrocytoma. Scanning electron microscopy may provide a useful tool for the further morphologic classification of human astrocytomas.


Fibrous dysplasia of the skull with progressive cranial nerve involvement. The purpose of this report is twofold. First, to discuss fibrous dysplasia of bone as it relates to the neurosurgeon, and second to present a case of fibrous dysplasia of the skull with progressive involvement of the optic and trigeminal nerves. Of special interest in this case is the progression of the disease after puberty and the technical problems of decompression of the involved nerves. A combined approach to the lesion with otolaryngological assistance was undertaken.


Pulmonary blastoma.

Pulmonary blastoma. A primary pulmonary tumour in a four year old boy arising from the subpleural zone of the lung is described. It contains both stromal and epithelial elements at the primary site and in the bony metastases. The combination of the age of the patient, the site of the tumour, the stromal and epithelial elements present in the tumour suggest that this is a true pulmonary blastoma. Electronmicroscopy showed the presence of intranuclear viral particles.


Myocardial degeneration in mice treated with dibutyryl cyclic AMP and/or theophylline. Fibrinoid degeneration of myocardial fibrils was induced in BALB/c mice treated from 2 months of age with weekly injection of dibutyryl cyclic DAMP and/or theophylline. No evidence of cellular reaction or vascular occlusion was found.


Effect of storage and in vitro ischemia on the ultrasture of microsomal membranes and on microsomal enzymes. Pieces of liver (in vitro ischemia) and isolated microsomes were subjected to incubation at 4 degrees C and 37 degrees C for various time intervals. The effects on microsomal protein, phospholipids, and cholesterol and on microsomal phosphatases and electron transport enzymes were followed as a functional of time and temperature. NADH-cytochrome c reductase was very labile and was completely inactivated by 1 h, whereas G6Pase lost 50% of its activity after 2 h at 37 degrees C. IDPase and NADPH-cyt. c red. were of intermediate susceptibility whereas cytochromes b5 and P-450 were the most stable enzymes assayed. After 24 h of incubation of isolated microsomes at 37 degrees C there was no significant detachment of membrane components (protein, PLP or cholesterol), indicating that the inactivation of the enzymes was not primarily attributable to their solubilization. Instead, experiments with 14C-leucine and 14C-glycerol prelabeled microsomes demonstrated that the proteins detached from microsomes during incubation originated mainly from the intravesicular space due to repture of the microsomal membranes. The addition of a lysosomal extract during incubation did not alter either the rate of inactivation of the enzymes or the proportion of solubilized membrane components indicating that attack from the outside by proteolytic enzymes is not the mechanism for enzyme inactivation. There was no apparent correlation between the rates of inactivation of enzymes in vitro and their calculated half-lives in vivo or their postulated intramembranous localization. Ultrastructurally, enzyme inactivation was initially associated with alterations of the microsomal membranes, such as vesicle aggregation, membrane rupture, loss of unit membrane structure, and subsequently, thickening of membranes and transformation of the microsomes into nonrecognizable amorphous material.


Electron probe x-ray analysis of siderosomes in the rabbit haemarthrotic synovial membrane. Electron probe x-ray analysis of siderosomes produced in the rabbit synovial membrane by repeated injections of autologous blood revealed two kinds of siderosomes; (1) those containing a small amount of phosphorus and, (2) those in which no phosphorus was detectable. On the basis of these findings and past studies it is concluded that haemosiderin is an inorganic compound of iron, probably a hydrated ferric oxide and that a variable amount of organic material (proteins, lipids, phospholipids, etc.,) probably occurs in company with the haemosiderin in the siderosome, but these variable components which decrease in amount with the passage of time cannot be considered as an integral part of haemosiderin.


Lipid droplets of interstitial medullary cells of intact rat kidney with two-kidney Goldblatt hypertension. Electron microscopic studies have been carried out of the interstitial cells (IC) of the renal medulla in rats with Goldblatt hypertension. Analysis of variance has not revealed any differences in the number of droplets of "unclamped" kidney in the hypertensive rats as compared to the normotensive rats ("resistant" rats, rats with unilateral nephrectomy, and intact rats) at periods from 3 weeks to 1 year. The total volume of the droplets in the IC cytoplasm in hypertensive and intact animals also revealed no difference 3 weeks after the beginning of the experiment. A positive correlation has been found between the number of the droplets and their volume but the low value of the correlation coefficient (r = +0.28) suggests that the number of the droplets cannot be a reliable indicator of the variation of the amount (volume) of thelipid material contained in them. Since it is just the latter parameter that carries the most information for evaluating the content of the droplet material in the IC, preference should be given to calculating the droplet volume rather than counting the number of droplets. The IC in the animals of the experimental groups revealed hypertrophy and hyperlasia of the endoplasmic reticulum and the Golgi complex, which were especially marked at the earlier stages of the experiments.


Studies on the pathophysiology of acute renal failure. II. A histochemical study of the proximal tubule of the rat following administration of mercuric chloride. Acute renal failure was induced in male rats by the subcutaneous injectioon of 4 mg HgC12 per kg body weight. Enzyme activities of the proximal tubule were studied histochemically at six time intervals from 15 min to 24 h. The enzyme studied were alkaline phosphatase, 5'-nucleotidase, acid phosphatase, alpha-glycerophosphate dehydrogenase (NAD-independent), malic dehydrogenase, succinic dehydrogenase, latic dehydrogenase, glucose-6-phosphate dehydrogenase and glucose-6-phosphatase. Decreases in activity were observed for alkaline phosphatase and 5'-nucleotidase after 15 min. Acid phosphatase was decreased after 30 min. These three enzymes returned to control levels after 3 h, but malic dehydrogenase and alpha-glycerophosphate dehydrogenase were decreased at this time interval. Succinic dehydrogenase was first decreased after 6 h. The earliest morphological changes detectable by light microscopy were observed in pars recta tubules in the medullary rays after 6 h, a time when all enzymes studied showed widespread decreased activity throughout the proximal tubule. After 24 h, the pars convoluta appeared morphologically normal but the pars recta was necrotic and exhibited calcification, whereas enzyme activity was decreased (absent in some cases) in both pars convoluta and pars recta. These results support the hypothesis that Hg++, when given in a sublethal dose, is associated with early histochemical changes in the brush border of the proximal tubule, which may be related to early changes in sodium reabsorption and to the subsequent development of acute renal failure. The observation that changes in plasma membrane-associated enzymes occur early and prior to alterations in enzymes of mitochondria and the endoplasmic reticulum suggests that Hg++ interacts initially with the plasma membrane.


The immunolocalization of ACTH and alpha MSH in human and rat pituitaries. Human and rat pituitaries were investigated immunohistochemically for ACTH and alpha MSH activity by means of the enzyme-labeling technique. In rat pituitaries cells present in both the anterior and intermediate lobes were reactive with the anti-ACTH antibodies, the cells from the intermediate lobe were also reactive with anti-alpha MSH antibodies. In human pituitaries, ACTH-immunoreactivity was found in cells from the anterior lobe and cells invading the posterior lobe. In 5 out of 15 pituitaries ACTH-immunoreactive cells located at or invading the posterior lobe were also reactive with the anti-alpha MSH antibodies. It is concluded that the human pituitary cells that invade the posterior lobe represent a population which is at least immunohistochemically identical with the intermediate lobe cells of the rat. The ACTH-immunoreactivity of intermediate lobe cells may be explained by the presence of a corticotropin-like intermediate lobe peptide (CLIP) which has been suggested to be a prohormonal fragment of alpha MSH.


Ionophore A23187 and dibutyryl cyclic AMP effects on cell shape and morphology of B-16 melanoma. Melanoma cells treated with dibutyryl cyclic AMP (db cAMP) for 24 h resulted in dendritic cells possessing parallel assembled microtubules. A23187 treatments resulted in a biphasic response: Long term effects of the ionophore were characterized by small epitheloid cells while the immediate response produced elongated cells with parallel arranged 10 nm microgilaments, characteristic of dispersive melanocytes.


Cell surface antigens induced by herpes simplex virus (HSV). Among the antigens induced by HSV on the surface of infected cells there are antigens binding anti-HSV antibodies by their combining (Fab) site (HSV-Ag), and others binding antibodies of various specificities, probably through their Fc fragment (IgR). HSV-Ag were demonstrated by cytotoxicity and mixed agglutination tests; IgR were made evident by passive hemadsorption. The ability to induce IgR is especially characteristic of HSV-1 strains, being absent or limited with HSV-2 strains. IgR were not detected on the surface of cells infected by other viruses, such as poliovirus 1, adenovirus 3, measles or vaccinia virus or by viruses belonging to the herpes group (e.g. cytomegalovirus and pseudorabies virus). The ability of bovine infectious rhinotracheitis virus to induce IgR was only slightly expressed. The practical implications of both HSV-Ag and IgR for the techniques aimed at detecting antigens induced by HSV on the surface of infected cells are further discussed.


Interaction between ceruloplasmin and Sendai virus envelope components. Note III. Separation of Sendai virus envelope components by affinity chromatography. Sendai virus envelopes solubilized by Triton X-100 at an alkaline pH were submitted to affinity chromatography on fetuin-Sepharose 4B. In the absence of Triton three groups of envelope fragments were eluted, while in the presence of detergent only two groups were separated. In both cases, envelope fragment populations eluted at low temperature contained hemagglutinin (HA), neuraminidase (N-ase) and HI-antibody blocking (HIb) activity. The populations eluted at 37 degrees C contained N-ase and HIb activity, but no HA. The populations isolated show various ratios of HA, N-ase and HIb, and have different affinities for the coupled fetuin and formolated RBC. Our data strongly suggest that binding to coupled fetuin takes place via enzymatic centres, while binding to RBC occurs via hemagglutinating centres.


Photodynamic effect of toluidine blue on MM virus. The photodynamic effect of toluidine blue (TB) was studied on MM virus cultivated in L cells and on the RNA extracted form MM virus inoculated to mice by intracerebral route. MM virus infectivity is completely inhibited by the photodynamic action of TB, due to lesions at the molecular level of the viral RNA.


Further immunological evidence for the presence of Fc receptors on the surface of HSV-infected cells. By coupling passive hemadsorption (PHads) reaction with a complement-mediated cytotoxicity test (CT) it is possible to detect the presence on the surface of hamster embryo fibroblasts of Forssman antigens, hindering the demonstration by PHads of the receptors for the Fc-fragment of immunoglobulins (FcR), possibly induced by herpes simplex virus (HSV). These antigens are acetone- and formol-resistant, but they are destroyed by treatment with methanol or ethanol. However, CT with anti-sheep RBC serum performed in HSV-infected monkey kidney cells is always negative, which proves that the attachment of immunoglobulins to these cells occurs exclusively through their Fc-fragments.


Immunoelectrophoretic characterization of Sendai virus antigens. Antigens extracted from Sendai virus by solubilization with Triton X-100 (Tx). Tween-20 (Tw) or Triton X-100 and SDS (Tx-SDS) were analysed by rocket, crossed and tandem immunoelectrophoresis. The migration of these antigens through 1% agarose supplemented with guinea pig anti-viral envelope protein anti-serum shows that Tx and Tw antigens consist of three fractions differing in their quantitative ratios, while Tx-SDS exhibits five different fractions. The method proved to be useful for the identification of anti-host antibodies in immune antisera by means of an antigen extracted from the chorio-allantoic membrane of embryonated hen eggs.


[Epithelial tumors of the liver (histology, histogenesis, classification)]. Under study were 120 epithelial hepatic tumors. The problems of histology, histogenesis, classification, morphogenesis of hepatic tumors are being under consideration from the point of view of modern oncology with due account of tumor progression and its development in tumor field. Various trends of differentiation with isolation of histologic variants of epithelial tumors of the liver have been shown. The histological classification is suggested.


[Polyadenylic acid rich RNA fractions in primary hepatomas induced with diethylnitrosamine]. The column chromatography with unmodified cellulose revealed a polyadenilic acid rich fraction of total RNA from diethylnitrosamine induced primary hepatomas and normal rat liver. It was shown that the quantity of this fraction was increased to 3.15 per cent. The 2.5% polyacrylamide gel electrophoresis of the polyadenylic acid rich fraction indicated its different spectra in tumors and normal rat liver, the main change being in bipolymer fractions with sedimentation coefficient 28 S and higher.


[Synthesis of virus-specific RNA under conditions of homologous and heterologous interference by Newcastle disease virus]. Homologous and heterologous interference by Newcastle disease virus (NDV) was manifested in a marked inhibition of virus-specific RNA synthesis of both the interacting viruses. Inactivation of the interfering NDV by irradiation reduced its capacity to inhibit the synthesis of virus-specific RNA of the homologous virus, leaving its effect on the synthesis of RNA of the heterologous virus unchanged. In contrast, treatment of cell cultures with heparin leading to reduced interferon production eliminated the heterologous interference but did not affect the homologous interference.


[Abortive myxovirus infection in Ehrlich ascites carcinoma cells. Production of heterokaryons in permissive cells and analysis of virus-specific structures]. Hybridization of Ehrlich ascitic carcinoma cells and chicken fibroblasts using UV-inactivated Sendai virus produced the following variants of homo- and heterokaryons: (a) uninfected Ehrlich cells, (b) fowl plague virus-infected chicken fibroblasts, (c) uninfected Ehrlich cells and uninfected chicken fibroblasts; (d) infected Ehrlich cells and infected chicken fibroblasts, (e) infected Ehrlich cells and uninfected chicken fibroblasts. The analysis of the material produced by heterokaryons gave the following results: when Ehrlich ascitic carcinoma cells infected with classical fowl plaque virus and labeled with 3H-uridine fused with uninfected unlabeled chicken fibroblasts, the heterokaryons, in addition to structures with the buoyant density of 1.29 g/ml typical for infected cells, also produced virus structures with a density of 1.25 g/ml and had a higher infectious activity (5.2 X 10(7) PFU/ml) than the structures produced by infected Ehrlich cells (5.8 X 10(6) PFU/ml); after fusion of Ehrlich ascitic carcinoma cells infected with fowl plague virus and labelled with 3H-uridine with unlabelled chicken fibroblasts infected with fowl plague virus heterokaryons produced virus structures with densities of 1.29 g/ml and 1.22 g/ml which had even higher infectious activity (8.6 X 10(8) PFU/ml) than the structures produced by infected Ehlrich ascitic cells.


[Study of LPV oncornavirus reproduction in mixed cell culture]. Electron microscopy and mathematical analysis were used to determine the intensity of LPV oncornavirus production by a single cell in co-cultivated human diploid cells and cells of the continuous T-9 line. Maximum production of intracytoplasmic particles of A type was observed at 48 hours of cultivation, and extracellular virions at 96 hours. Mature virions of B type were more numerous than mature virions of C type in the mixed culture. On the whole the amolnt of mature virions was greater than that of immature ones, and the amount of intracytoplasmic A type particles was considerably greater than that of extracellular particles. By the total amount of production of all virus-specific structures and the two-wave pattern of virus production this mixed culture passaged at a ratio of HDC to T-9 cells 2000 : 1 resembled a culture of T-9 line. Thus, this study indicates that the infected HDC culture at later intervals of cultivation (96 hours) is a more active "producer" of LPV oncornavirus than the main line of T-9 cells or mixed HDC--T-9 culture.


[Production of J-96 cell culture chronically infected with herpes simplex virus and study of some of its properties]. Comparative effectiveness of various methods for production of chronic infection with herpes simplex virus (HSV) in J-96 cell culture: inclusion into the culture fluid of the infected cultures of immune serum to herpes virus, immune serum to HSV-infected J-96 cells and frequent changes of the medium, is described. The advantage of the second method has been found. The chronically infected culture was resistant to superinfection with the homologous virus. In passages, when the chronically infected culture produced no active infectious virus, the portion of cells containing the virus antigen was 0.8%. In this culture interferon was found in a low titer. Morphological and histochemical studies also indicated some changes in chronically infected cultures as compared with the controls, namely, an increase in the number of spindle-shaped elements, thickening of the nuclear membrane, an increase in the DNA concentration. The culture has been designated JH and is in the 220th passage now.


[Study of experimental chronic infection in mice caused by herpes simplex virus]. A chronic herpetic infection was produced in white random-bred mice by intradermal inoculation with the L2, 333 and K strains. The virus was regularly detected in the blood of the animals by the method of co-cultivation of leukocytes and human embryo fibroblasts for 70 days (the observation period). The virus was isolated from the brain, the spinal cord and viscera from the 3rd till the 30th postinoculation day. The virus antigen was found in leukocytes, and erythrocytes of the blood, the spinal cord and the brain from the 7th till the 70th day, and in the liver and spleen from the 7th to the 30th day. The titer of interferon in the viscera and serum of mice in the first 2-3 days after inoculation was 8 units, and subsequently 2 units. The interferon-producing activity of the blood leukocytes in mice was reduced (16-32 units) as compared to that in uninfected animals (64-128 units). The antibody titer at 7 days after incoulation was 1 : 32 in the blood serum of mice, at later intervals no antibody was found. Inflammatory and dengerative changes in the central nervous system and viscera of mice were detected throughout the observation period starting from the 7th day postinoculation.


[Clinical picture and prognosis of insulinoma]. A case of insulinoma is reported, with initial malignant degeneration, diagnosed and operated 16 years ago. Six years later hypoglycemic attacks appeared again and lymph metastasis from malignant degenerated insulinoma were found near to the pancreas. After a period of eight years, in good health state, a third surgical operation was performed because of repeated hypoglycemic attacks and a new metastasis from the insulinoma was found in the pancreas tail. The patient has no hypoglycemic phenomena 18 months after the last operation. Besides that long-period of progress of the malignant degenerated insulinoma, not observed so far, certain peculiarities of the carbohydrate metabolism of the patient are stressed upon, as well as the necessity of early diagnosis and timely surgical treatment of insulinoma.


[Expression of individual proteins of mouse mammary gland cancer virus in tumors in mice of various strains]. Expression of the main structural proteins of mammary gland cancer virus, gp52 and p27, was studied with the immune sera to these proteins in homogenates of tumors from mice of low and high cancer lines. Protein gp52 was found only in tumors of mice-carriers of MTV-S. In a fraction of purified type A particles from the cytoplasm of mammary gland cancer no gp52 was found, but with the antiserum to p27 this fraction reacted by a line identical to that with the antigen from C2HF mouse tumor.


[Several functional changes in the  livers of patients with diabetes mellitus]. The authors have studied the functional liver state in 107 patients with diabetes mellitus. Various stages of functional liver disturbances were found in a considerable part of them. With a few exceptions, the latter have the highest incidence and severity among the patients with decompensated, with mixed type diabetes and with remote vascular degenerative manifestations. Radioisotope investigations with 131J-Bengal pink, reveals the earliest developed changes in some of the liver functions, as compared with rest of the tests. The functional liver state is recommended to be determined in all diabetics with a view to an early detection of the developed functional disturbances and their timely treatment.


[Development and study of an experimental herpesvirus vaccine]. The strains suitable for the development of herpesvirus vaccine were selected as a result of studies on numerous herpes virus strains isolated from patients with relapsing herpes infection of various localizations. Infectious tissue culture antigens were obtained by roller cultivation of chick embryo fibroblast cultures infected with herpesvirus in the presence of 0.2% human serum albumin. A high immunogenic and antigenic activity of the experimental vaccines prepared from these antigens was established. Animal experiments demonstrated the possibility of control of the specific activity of herpesvirus vaccines.


[Isolation and study of biophysical properties of oncornaviruses type A and C minimal forms]. The method of differential centrifugation was used for concentration and purification of the minimal form of oncornaviruses type A and C. The structures showed heterogeneous distribution in sucrose density gradient and formed a peak in the zone of 1.135 g/ml. Electron microscope examinations of negatively stained preparations showed that the size of the minimal forms of oncornaviruses type A and C was 25-60 nm, the diameter of nucleoids 10-30 nm.


[Determination of free and protein bound cortisol, transcortin binding capacity and adrenocorticotropic hormone in the plasma of patients with hypertension]. The total non-conjugated plasma cortisol in 60 patients with hypertension disease (HD)is 17.5 mkg/ml. The free non-conjugated cortisol represents 8.45 per cent of the total - 1,5 mkg%, considerably (p less than 0.0001) higher than that in healthy subjects. Protein conjugated cortisol is 16.0 mkg%. The bounding capacity of transcortin the plasma of hypertonics is considerably decreased (p less than 0.0001) - 15.8 mkg (in healthy - 18.5 mkg) per 100 ml. ACTH level in the plasma of patients with HD is 32.0 pg/ml, considerably higher than that in healthy (25.8 pg/ml, p less than 0.0001). The elevation of the biologically active cortisol fraction in plasma of hypertonics is a function both of hypothalamo-hypopheseal stimulation and of transcortin level. That latent hypercortisolism is admitted to be manifestation of hypothalamo - hypopheseal superstimulation by increased ACTH secretion, in case of confirmed cerebro-hypothalamic disturbances in patients with hypertension disease.


[Determination of viremia in patients with para-influenza by immunofluorescence technic]. Viremia in parainfluenza was studied in 80 patients (35 children and 45 adults) in the time course of the disease during the springautumn period of 1969-1974. For the detection of viremia, the immunofluorescence procedure, namely, the detection of early stages of virus replication in the tissue culture cells infected with the blood from the patients, was used. The tests were performed with 204 blood specimens. The blood clot was diluted 1 : 1 with distilled water and followed the conventional method. Commercial FITZ-globulins with high antibody titres to parainfluenza virus type 1, 2, and 3, influenza A2 and B and adenovirus types 3 and 7, were used. The clinical manifestations of parainfluenza in the observed patients were typical of the disease. Complications developed in 60% of the cases. As a result of clinical and laboratory examinations, viremed early and late (up to 22 days) in the disease in patients of different age groups both at high and low fever; for longer periods and later in the disease it was observed in patients with complications (pneumonia, maxillary simusitis), but always in the presence of clinical manifestations of parainfluenza.


[Results of serologic surveys of children with acute stenosing laryngotracheobronchitis]. The materials of serologic surveys of 269 children with acute stenosing laryngotracheobronchitis hospitalized in Children's Infectious Hospital No. 3, Leningrad, are presented. Acute stenosing laryngotracheobronchitis developed most frequently against the background of low titres of antibody to viruses of the respiratory group. Severe cases of the disease were caused by influenza A2 virus, milder cases by influenza B, parainfluenza, respiratory syncytial and adenoviruses.


[Bacteriological, virological, and mycological check-up in patients on regular dialysis treatment and after renal transplantation (author's transl)]. Regular bacteriological control examinations of the dialysate may contribue to the elimination of pyrogenic and even septic reactions. Regular checks of HBS-Ag and HBS-Ab are an effective measure in the early diagnosis of hepatitis B, which is characteristically anicteric and follows a prolonged course in patients on regular dialysis treatment (RDT). Virological examinations can be helpful in the diagnosis of cytomegalovirus (CMV) disease in certain cases of unexplained fever. Regular bacteriological examination of the urine is important in the detection of a urinary tract infection possibly necessitating binephrectomy prior to transplantation. After renal transplantation bacteriological control examinations of the urine, determinations of HBS-Ag and HBS-Ab, complement-binding reactions to CMV and mycotic cultures from the throat, sputum and urine should be regularly performed. Urinary tract infections may be found in up to 88% of the transplanted patients. Hepatits-B infection was noted in 62.8% of this case material. Positive Candida albicans cultures from samples of the uurine usually indicate systemic Candida albicans infection. The described diagnostic measures contribute to an effective prophylaxis and therapy of infective complications in patients on RDT and after renal transplantation.


[Thymic carcinoid. Case report and review of the literature (author's transl)]. A case of a primary thymic carcinoid tumour of a 32 year old male is reported, and the previously published 25 cases are reviewed. The neoplasms occur in adults, predominantly in males: they are located in the anterior or antero-superior mediastinum. The only sufficient treatment is the surgical excision; through radiotherapy may be indicated in some cases, too. The tumour is characterized by the formation of rosettes, ribbons and garlands; sheet-like or medullary areas, and large clusters with central necrosis. The tumour is positive for the Grimelius argyrophil silver stain. Ultrastructurally numerous dense-core "neurosecretory" granules are observed. The formal pathogenesis is similar to that of carcinoid tumours of other locations; particularly of those arriving from derivates of the foregut, respectively from the APUD cell system. At present it cannot be decided whether this particular tumour of the thymus represents an autochthonic thymic carcinoid or simply a teratoma with a differentiation in one direction in the sence of a simplified teratoma.


Hepatitis B virus, cirrhosis and primary carcinoma of the liver. An electron microscopic study. The core and coat of hepatitis B virus were found by electron microscopy in parenchymal cells of a liver biopsy from a 61 year old man with chronic active hepatitis and cirrhosis of the liver. Laparoscopy, 35 days after liver biopsy, and autopsy 42 days later confirmed the cirrhosis and showed in addition a well differentiated hepatoma. The possibility of a viral aetiology for the cirrhosis and primary carcinoma of the liver is considered.


[Radiochemical investigations on the decomposition of (mono) methyl-mercury by means of acid with regard to the determination of total mercury in fish (author's transl)]. Considerable amonts of mercury in fish muscle tissue are organically bound i.e. appear as (mono)methylmercury-compounds. In order to make mercury of organic origin available for the determination of total mercury by the "cold vapour atomic absorption method", a splitting of the carbon-mercury bond by means of suitable chemical treatment must be maintained beforehand. The main subject of this article are investigations with special regard to the behaviour of (mono)methylmercurychloride during different wet digestion methods. The procedures under study involve wet digestion under reflux with HNO3, with mixtures of HNO3 and HC10(4) and HNO3 and  H2SO4, as well as wet digestion with HNO3 in a closed system (pressure decomposition). The course of the decomposition of (mono)methylmercury dependent on time, temperature and concentration of reagents are discussed in detail. All experiments were controlled by measurement of the radioactivity of Hg-203 which had been added in the chemical form of CH3-Hg-Cl. From the analytical results obtained two methods of sample preparation have been derived that permit a reliable determination of total mercury in fish.


[Resistance to chemotherapy of aerobic bacteria from nonspecific odontogenic infections]. Germs in patients suffering from nonspecific odontogenous infections described in a previous paper were analysed with regard to their resistance to chemotherapy (1964 to 1971). At the same time it was discovered that in the bacteria groups: staphyloccocus aureus, streptococci and pneumococci and enterobacteriaceae plus pseudomonas (344 strains) their sensitivity to penicillin, streptomycin, chloramphenicol, oxytetracyclin, erythromycin, polymyxin B and nifurantin varied in several and significant ways. Significant changes were established in the resistance of staphylococcus aureus to all the potentially effective antibiotics, while from 1969 to 1971 the strains with the least resistance appeared. In the 1970 to 1971 period strepto- and pneumococci showed insensitivity to penicillin and streptomycin more frequently than before. From 1969 to 1971 entero-bacteriaceae and pseudomonas also showed evidence of increasing loss of sensitivity to chloramphenicol and oxytetracyclin, whereas the frequency of strains resistant to polymyxin B and nifurantine diminished. The findings are being discussed.


[Isolation of various structural elements of gram-negative bacteria of the Bordetella genus and a study of their properties. II. Isolation of the cytoplasmic membrane fraction from the protoplasts of B. pertussis and a study of their chemical and enzymatic properties]. A possibility of obtaining a fraction of cytoplasmic membranes maximally purified of the cell wall material was for the first time shown on a model of Gram negative bacteria (B. pertussis). The results of electron microscopy, chemical analysis for the presence of the cell wall material--hexosamines, and of the activity of the respiratory chain enzymes served as control.


[A study of toxic substances in pertussis cultures]. For the purpose of studying the toxic properties of pertussis strains with different agglutination composition and to ascertain the interrelationship between the action of the toxic substances and the serological type of the strains the author used a test of the weight change in albino mice to which crude and heated (at 56 degrees C for 10 minutes) suspensions of the strains of various serological types were injected intraperitoneally. The toxic properties were checked in 17 strains. The test of the change of the animal body weight with the determination of the regression coefficient permitted to determine roughly the presence of the toxic substances in the strains; the action of the thermostable dermonecrotic toxin and thermostable endotoxin was expressed with greater constancy than that of the lymphocytosis stimulating factor. There was no interrelationship between the manifestation of the action of toxic substances in the pertussis strains and their serological type. The toxic activity peristed in the strains stored in dried condition.


[Study of leukotoxic activity of Cl. perfringens type A toxin and its fractions obtained by gel filtration and ion exchange chromatography]. In gel-filtration of Cl. perfringens type A toxin on Sephadex F-100 and F-50 there was revealed relationship between the leukotoxic activity and a high-molecular component. A method of ion-exchange chromatography on a column with DEAE-Sephadex A-25 from the Cl. perfringens toxin there were obtained 8 fractions 3 of which possessed a marked leukotoxic activity: the capacity to destroy neutrophils in the Svejcar and Vancurik test and to-depress the phagocytic activity of leukocytes. Lecithinase and lethal activity was revealed in one of these fractions only. Leukotoxic fractions differed by the capacity to destroy neutrophils and to decrease their phagocytic activity.


[Study of smallpox vaccine virus distribution in the body of rabbits following oral immunization]. Virological and immunofluorescent methods were applied to the study of the distribution of the smallpox vaccine virus in the organs and tissues of rabbits immunized orally. It appeared that the vaccinal process developed with a predominant localization of the antigen in the regional (in respect to the site of administration) lymph nodes; the virus was revealed in the cell cytoplasm.


Activities of prostaglandins and prostaglandin endoperoxides at adrenergic neuroeffector junctions. The results presented in this paper indicate that: 1. The prostaglandin synthesis inhibitor, indomethacin, increases noradrenaline turnover in a variety of rat organs. This observation increases the probability that prostaglandins are involved in the control of adrenergic neurotransmission in vivo. 2. Administration of endoperoxides inhibits the release of noradrenaline from adrenergic nerve terminals. The effect can be explained, however, at least in part, by formation of degradation products, presumably mainly prostaglandin E2. 3. Prostaglandin F2 alpha enhances smooth muscle responses to adrenergic nerve stimulation in rabbit heart and guinea pig vas deferens. These actions must be considered prostjunctional, since the release of noradrenaline is unchanged or depressed.


Influence of ethanol oxidation rate on the lactate/pyruvate ratio and phosphorylation state of the liver in fed rats. The effect of the ethanol oxidation rate on the interaction between the phosphorylation state (the [ATP]/[ADP] X [HPO4]2- ratio) and the redox state (the free [NAD+]/[NADH] ratio) of the liver cytosol was studied in intact fed rats. The rate of ethanol oxidation was inhibited to different degrees with pyrazole. The ethanol oxidation rate had no influence on the liver lactate level but correlated significantly with the pyruvate level. Accordingly, a significant correlation was also found between the ethanol oxidation rate and the lactate/pyruvate ratio. The rate of ethanol oxidation correlated significantly with the liver 3-phosphoglycerate level. No change in the glyceraldehyde-3-phosphate level was found. No correlation was found between the ethanol oxidation rate and the glyceraldehyde-3-phosphate/3-phosphoglycerate redox couple. Ethanol administration slightly increased the liver ATP level, but the simultaneous administration of pyrazole eliminated this effect. Other adenine nucleotides and HPO4 2- were not changed. The changes in the rate of ethanol oxidation had no effect on the phosphorylation state in the fed liver. It is assumed that in the fed liver the phosphorylation state is so well stabilized that the redox level has no influence.


Demonstration of corticotrophin-releasing activity in rat and human peripheral blood. Corticotrophin-releasing activity of rat or human peripheral blood was examined with a sensitive in vitro CRF bioassay, using cultured rat adenohypophyseal cells and ACTH measurement by radioimmunoassay. A dose-related ACTH secretion into the medium occurred in response to plasma or serum obtained from unstressed rats or humans. The minimum effective dose was 2.5 mul (0.1% of the medium concentration). No concomitant release of TSH occurred, indicating that cellular destruction was not the source of ACTH in the medium. As previously found with hypothalamic extract, 50% of the maximum ACTH secretion produced by a given quantity of plasma occurred within 1-5 min. Fifty per cent of CRF activity was retained after plasma was boiled for 5 min. CRF activity of serum was not different in intact, 1-10 min ether-stressed, adrenalectomized, hypophysectomized or dexamethasone-treated rats. There was no significant difference in CRF activity between serum from intact rats and those with complete forebrain removal and hypophysectomy, indicating that serum CRF originates from a source outside the forebrain or pituitary. Because of the lack of correlation of blood CRF activity with conditions in which there are marked differences in in vivo ACTH concentration, it is possible that the blood CRF activity we measure is non-specific.


Histochemical manifestations of early and late changes induced by Aflatoxin in rats. Wistar rats were intraperitoneally treated with different doses of Aflatoxin B1 (5 and 7 mg/kg body weight) and sacrificed after various periods (6, 24, 48, 72 h, 5, 6, 7, 8, 9, 10 days and 86, 96, 97 weeks) in an attempt to detect liver, lung, intestine, spleen, mesenteric lymph nodes alterations. There are histochemical indications to suggest early liver changes for both doses in carbohydrates metabolism (decreasing of: polysaccharides, acid and neutral mucopolysaccharides, LD activity diffusely distributed through the all lobule). After 86, 96, 97 weeks from Aflatoxin administration, hepatocytes alterations rendered evident by fat accumulations, depletion or loss of polysaccharides, acid and neutral mucopolysaccharides, loss of cytoplasmic enzymes activities, altered pattern of surface ATP-ase are associated with diffuse fibrosis. The findings are suggestive that liver alterations are depending on dose and duration of exposure and could be detected by histochemical methods before significant morphological changes appear.


Time course of proteolytic enzyme alterations in the motor end-plates after stimulation. Authors studied the proteolytic enzyme activity of motor end plates in the diaphragms and M. flexor digitorum brevis of rats after administration of cholinesterase inhibitors and after supramaximal electric stimulation, using the colour film digestion technique. Enhanced enzyme activity characterizing stimulated motor end plates persisted up to 12 h after stimulation. No proteolytic activity could be shown any more 24 h after stimulation, indicating restoration of the resting state. The role of metabolites (oligopeptides and amino-acids) released by the function-dependent axoterminal proteolysis is discussed in relation to neurochemical transmission processes.


Diagnostic significance of fasting serum bile acid in liver disease. Serum bile acid was extracted with Amberlite XAD-2 followed by determination with an enzymatic and fluorimetric technique. Normal value for fasting serum bile acid was found to be 3 +/- 2 muM. Serum bile acid level was raised markedly early in the course of acute viral hepatitis, subsequently fell rapidly before resolution of biochemical tests, and was elevated again in relapse. In chronic liver disease serum bile acid was elevated moderately and correlated roughly with disease severity. In comparison with routine biochemical tests, serum bile acid correlated significantly with serum bilirubin, BSP retention and other hepatic tests, except serum cholesterol. Thus fasting serum bile acid level is a reliable screening test for a variety of liver disease to assess functional and morphological impairment of the liver.


Conformational motility in D-glyceraldehyde-3-phosphate dehydrogenase influenced by subunit interactions. Binding of four molecules of NAD to pig muscle glyceraldehyde-3-phosphate dehydrogenase decreases the apparent reactivity of Cys-153 -- a residue exposed only temporarily -- towards PMB in all four subunits of the enzyme. However, the change of reactivity is not a linear function of the degree of saturation with coenzyme, inasmuch as the first two, tightly bound NAD's exert a much larger effect than do the other two. The apparent reactivity of Cys-153 was investigated in GAPD's produced by hybridization of enzymes modified on residue Cys-149 with different reagents. The homotetramer-NAD complexes of these modified species were shown to exhibit different dissociation constants: native GAPD less than (alkylated--Cys-149)-GAPD less than (mercaptidated--Cys-149)-GAPD. The tight binding of 2 NAD's on the hybrid tetramers decreases the reactivity to the same extent in liganded and non-liganded subunits. The decrease in the apparent reactivity of Cys-153 is due to the restriction of local conformational motility around thes residue. Binding of NAD shifts the equilibrium towards a more closed form of the protein, whereas the rate constant of mercaptide formation itself remains unaltered. These findings suggest that the NAD-induced conformational changes are also reflected in the local fluctuation of the protein around Cys-153. The subunit interactions still operate in the hybrids and mediate the NAD-induced conformational changes.


The modulation of the prostaglandin-induced (E1, E2, F2alpha) motility of the large intestine by the adrenergic system. The effect of adrenergic stimulating and inhibiting drugson the prostaglandin-dependent colonmotility in man was examined. By stimulating the adrenergic beta-receptors the prostaglandin-induced contractions were reduced and finally eliminated...


Some characteristics of phosphorylation and dephosphorylation of proteins of isolated rat liver nuclei. The phosphorylation and dephosphorylation reactions of the proteins of isolated rat liver nuclei were examined in the presence of ATP. It was shown that the plateau value of the phosphorus incorporation at high concentrations of ATP is the result of an equilibrium of phosphorylation and dephosphorylation. The data of 32P-labelling experiments and those of chemical determination of net change of phosphorus content were compared. The activity of an efficient protein phosphatase in rat liver nuclei is demonstrated. It was shown that the pool of protein-phosphorus in the nuclei is heterogeneous as regards its turnover rate. A protein-phosphorus fraction of high turnover dominates the picture of phosphorylation and dephosphorylation reactions when studied with [gamma-32P] ATP in vitro.


Effect of modification of SH-groups in D-glyceraldehyde-3-phosphate dehydrogenase on the properties of enzyme--coenzyme complex. The NAD-binding of pig muscle glyceraldehyde-3-phosphate dehydrogenase after modifying certain SH-groups of the enzyme was studied by spectrophotometric titration and gel-chromatography. The enzyme modified on residue Cys-149 with N-ethylmaleimide, iodoacetate or p-mercuribenzoate binds NAD less tightly than does the unmodified enzyme. However, the differences between the NAD-binding sites characteristic of the native tetrameric enzyme are largely retained in the modified enzyme. Residue Cys-153 is near to the surface of the enzyme and is temporarily exposed due to the fluctuation of the protein. It can be modified only after blocking Cys-149. Modification of residue Cys-153 with N-ethylmaleimide does not further influence NAD-binding. Reaction of Cys-153 with p-mercuribenzoate does not directly cause the release of NAD. In this case the enzyme-coenzyme complex decomposes due to secondary conformational changes. This followed from the finding that the disappearance of the absorption band characteristic of the enzyme-coenzyme charge transfer complex is a first order process is equal to that of the structural changes following mercaptide formation of Cys-153.


Improvement in peripheral nerve function immediately after haemodialysis. During haemodialysis there is a growth in the amplitude of muscle and nerve action potentials evoked by median nerve stimulation. It is therefore suggested that even a single period of haemodialysis causes some temporary improvement in the defective peripheral nerve function that accompanies uraemia.


Krabbe's disease. A light and electron microscopic study. Ultrastructural studies of brain and sural nerve biopsy specimens from a patient with Krabbe's disease disclosed periodically constricted or twisted tubules in addition to the more abundant and characteristic crystalloid and prismatic structures within macrophages. It is suggested that the twisted tubules may result from the intracellular accumulation of lactosyl ceramide. Familiarity with these unusual tubular structures is of practical as well as theoretical importance since they may be encountered in brain and peripheral nerve biopsy specimens obtained for the morphological diagnosis of Krabbe's disease.


Calcification of the perineurium. A case report. Necropsy of a patient who died of uremia complicating juvenile diabetes revealed selective calcification of the perineurial sheaths in the sciatic nerves. The calcium phosphate deposits were limited to the outer layers of the perineurium while the innermost lamellae were free. Structural analysis, including electron diffraction and X-ray microanalysis, showed electron-dense, spicular deposits, which were composed mainly of finely crystallized hydroxyapatite. The end-stage diabetic nephropathy of the patient was associated with an extremely high calcium phosphorus ion product known to favour metastatic calcification. The mechanism of the selective localization of the calcium phosphate deposits to the outer layers of the perineurial sheaths is discussed with reference to the structure and suggested barrier function of the perineurium in regard to phosphate ions.


Intramembrane particle distribution and lectin binding of glioblastoma cells after long term subculture. Human glioblastoma cells in long-term monolayer culture showed an even distribution of intramembrane particles (IMP) on all surfaces of the plasma membrane; junctional complexes were rarely observed and rectilinear arrays were not seen. Cells treated with Con A-ferritin and Ricin II-ferritin showed an even distribution of lectin receptors and under conditions used no capping occurred. Lectin-ferritin complexes were taken up into pinocytotic vesicles. Cleaved preparations of Ricin II-ferritin treated cells showed no change in the distribution of IMP.


Presenile dementia with Alzheimer-, Pick- and Lewy-body changes. An autopsy case of unclassifiable presenil dementia is reported. The outstanding pathological findings were as follows; 1. presence of senile plaques, neurofibrillary changes, Pick bodies, Hirano bodies, granulovacuolar degeneration of neurons, etc. 2. numerous Lewy bodies in the brain stem and diencephalon, 3. peculiar swollen neurons with intracytoplasmic, eosinophilic and argentophilic inclusions ("Lewy-like-bodies") in the cerebral cortices. Detailed study of the last mentioned inclusions indicates that they are almost identical to Lewy bodies, though there are some minor differences, in histochemical and electronmicroscopic findings. Nosologically, this case may represent either a combination of Alzheimer's disease, Pick's disease and idiopathic Parkinsonism with "Lewy-like-bodies" in the cerebral cortices, or a single disease. As far as we know, no similar case been reported.


High density lipoprotein concentrations in newborn infants. The lipoprotein pattern was analyzed by agarose gel electrophoresis in 19 new born infants of varying gestational age. The HDL concentration was determined by rocket immunoelectrophoresis in another 41 newborn infants. Infants with a gestational age of less than 33 weeks had very low HDL concentrations compared to preterm infants with a gestational age of less than or equal to 33 weeks and term ihfants. In the first 5-10 days after birth the HDL concentration increased markedly in preterm infants (gestational age less than 37 weeks) whereas it remained unchanged in term infants.


Telecobalt therapy for malignant lung tumours. The authors present the results of telecobalt therapy in 194 patients with malignant lung tumours treated between 1967 and 1971. The 3- and 5-year survivals were 9.7 and 5.4% respectively, with an average survival of 15 months. The results obtained depend on the microscopy, the clinical staging and on the irradiation techniques possible; several prognostic groups may be distinguished.


Changes in the activities of nucleoside triphosphatases and nucleoside kinases in Vero cells infected with Simian virus 40. Changes in the activities of three enzymes involved in nucleotide metabolism were studied following infection of Vero cells with SV40. The results showed that SV40 infection enhanced the activities of uridine phosphokinase and UMP phosphokinase involved in nucleotide synthesis and suppressed the activity of nucleoside triphosphatases involved in nulceotide degradation. These SV40-induced enzyme activity changes probably served to somehow increase the quantity of nucleotides for virus proliferation.


Spontaneous malignant transformation in two epithelial cell lines of rat liver cells. The cellular morphology, chromosomal structure, and tumorigenicity of two lines (B and J-13) of rat epithelial cells were examined serially during in vitro cultivation. The cells for such cultures were derived from the hepatic tissues of two 7-day-old male rats of the Donryu strain. The cultured cells were first inoculated into newborn syngenetic rats on the 641st day in vitro (80th subcultures) for line B, and on the 446th day (58 subcultures) for line J-13. The inoculated cells produced tumors with hemorrhagic ascites in rats after long latent periods, viz, 215-599 days in line B and 170-369 days in line J-13. All the tumors were undifferentiated hepatocarcinomas. The pleomorphism in shape and size of the cultured cells gradually became obvious with time of cultivation and was more pronounced in recultured tumor cells. Chromosomes of the culured cells were a normal diploid pattern until about the 200th day in vitro, but thereafter the modal chromsome number shifted to hypodiploid or hypotriploid via hypodiploid stages. The chromosome constitution of recultured tumor cells resembled that of inoculated cells in number distribution, but had changed to a more complicated karyotype. In experiments with line B, the same marker chromosome was detected in all tumor cells analyzed as had been present in inoculated cells.


The effect of ACTH on oxygen uptake by skeletal muscle, brain, liver, kidney and myocardium slices of the rat. Using Wartburg's method the effect of ACTH on oxygen uptake by slices of various tissues of the rat was investigated in relation to the duration of ACTH action in the organism. A reduction in oxygen uptake by tissue slices was found 1 hour after ACTH injection with a rise after 16 hours. It seems that in the first phase ACTH exerts an inhibitory effect on tissue respiration indirectly through the adrenal cortex, while in the second phase it may exert a stimulatory influence either directly or by some other mechanisms.


Studies on cartilage formation. XX. Histochemical investigation of some enzymes of glycogen metabolsim in regenerative articular surfaces. In 28 dogs the distal articular cartilage of the femur was removed and the regenerating articular surface on the 70th postoperative day was studied histochemically for hexokinase, glucose-6-phosphatase, phosphohexose-isomerase, fructose-1, 6-diphosphatase, aldolase, glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, lactate dehydrogenase isoenzymes, phosphoglucomutase, phosphorylase, glycogen synthetase, UDP--glucose dehydrogenase, and UDP-glucuronic acid-4-epimerase. The articular surface consisted of fibrous tissue and of cartilage islets. The latter contained cells differentiating into cartilage and young chondrocytes. The glycolytic enzymes reacted positively in the regenerative articular surface. Enzyme activities were higher in the cells (particularly the chondroblasts and young chondrocytes) of the cartilage islets than in the connective tissue. In the cells differentiations into cartilage, beside the LDH isoenzymes characteristic of glycolysis, a significant LDH1 and LDH2 activity was observed. At the same site the presence of fructose-1, 6-diphosphatase-activity could be assumed, but there was no glucose-6-phosphatase activity. Glycogen synthesis proceeded in the cells of the cartilage islets and UDP-glucuronic acid-4-epimerase activity was observed in the differentiated cells. UDP-glucose dehydrogenase activity was positive in every section of the articular surface.


Cyclic nucleotides in bacteria.

Cyclic nucleotides in bacteria. The question of the ubiquity of cyclic AMP in bacteria is not yet closed. The recent introduction of more sensitive and reliable assays for cyclic AMP should settle the problem. My prediction is that although there may be some organisms that do not contain cyclic AMP, they probably have some yet undiscovered regulatory nucleotides that play similar roles. Although cyclic AMP has been shown to be unessential for growth of E. coli under optimal laboratory conditions in glucose-containing medium, it undoubtedly can play a role in survival. Cyclic AMP allows bacteria to adapt to a variety of new nutritional conditions. The significance of the observations that cyclic AMP shows a concentration-dependent stimulation or inhibition of growth rate in E. coli is not yet clear. The pathways regulated by cyclic AMP are, for the most part, those which involve carbon metabolism. On the other hand, pathways of nitrogen metabolism are not uniformly regulated by cyclic AMP. In several organisms, some nitrogen pathways are regulated by glutamine synthetase. Specialized processes such as the formation of flagella, fruiting bodies, and buds often appear to be controlled by cyclic AMP. This is similar to the situation in mammalian cells wherein many differentiated functions are regulated by cyclic AMP. Catabolite repression can be explained by an inhibition of the synthesis of cyclic AMP, which does not require an invocation of a primary effect of catabolite action on cyclic AMP phosphodiesterase or on a secretory process, although these two processes are probably of secondary importance. There are some fundamental similarities between the effects of catabolites in inhibiting E. coli adenylyl cyclase and the effects of hormones on mammalian adenylyl cyclase. Both processes require the interaction of the effector with a membrane-bound receptor and may transmit the inhibitory or stimulatory signal to adenylyl cyclase via some coupling factor. Cyclic GMP is clearly present in bacteria, although the features of its molecular biology are just beginning to be laid out. How many other regulatory nucleotides, whether cyclic or linear, remain to be found in bacteria is a problem for the future.


Cyclic AMP and gastric secretion: the illusive second messenger. We have surveyed the literature which bears upon the contention that accumulation of intracellular cyclic AMP is a necessary intermediate event between secretagogue and secretion of acid by the stomach. In our view, the evidence in favor of this hypothesis is wanting for these three reasons: (i) the evidence does not fit with better established information about regulation of gastric secretion and about hormonal actions on the cyclic AMP system; (ii) technological problems involved in the biological preparations employed and in the assay procedures used make the evidence nearly uninterpretable; and (iii) there exists a body of contradictory evidence at least as convincing as that which favors the thesis. These three arguments against acceptance of the theory are not definitive and are not intended to dissuade investigators interested in gastric mucosal metabolism from their quest. And, although we are not at this time adherents of the preceding hypothesis, we are also not unmindful of its basic appeal, which has attracted numerous scientists into a study of the metabolic correlates of gastric acid secretion. Unfortunately the general appeal of the second messenger hypothesis is such as to make it almost a paradigm of gastric secretory physiology in the seventies, in Kuhn's sense of that word (118). The disadvantages of paradigms are that they tend to obscure negative evidence among their adherents, and they arouse controversies more marked by heat than by light.


Estrogen biosynthesis in the ovaries and testes. This review has presented some of our recent data on estrogen biosynthesis and has drawn upon these, as well as numerous observations, to design the two-cell type, two-gonadotropin model, applicable to both sexes, for the biosynthesis of gonadal estrogens and its regulation. Some of the data upon which this model, depicted in Figure 15, are based are quite preliminary and in many cases have been derived from experiments with tissues from animals over a rather narrow age span. Consequently, in future years this model may appear too simplistic to explain gonadal estrogen synthesis at all stages of development. However, whatever the fate of the model, whether it be broken and rebuilt on firmer foundations or furnished more lavishly, it is hoped that it will result in some of the corners being "rounded." There has been an emphasis on some of the similarities between the two sexes with respect to enzyme capacities, hormone receptors, and control mechanisms for the various cell types in the ovaries as compared to the testes. In particular, the striking similarities both structurally and functionally between Sertoli cells and granulosa cells are now recognized. Vive la difference.


Characterization of an adenylate cyclase system sensitive to histamine H2-receptor excitation in cells from dog gastric mucosa. A method of preparing viable cells from dog gastric mucosa is described. Cyclic AMP in these cells is elevated by histamine and 4-methyl histamine but 2-methyl histamine is only a weak agonist. The effects on cyclic AMP levels are inhibited competitively by metiamide and burimamide which give apparent KBvalues of 3.5x10-7 M and 2.3x10-6 M, respectively. These values are similar to those reported for other histamine H2-receptor systems. The H1-receptor antagonists, mepyramine and chlorpheniramine, have no inhibitory effect on the histamine induced elevation of cyclic AMP: promethazine inhibits the system but not by a competitive mechanism. It is concluded that the histamine stimulated adenylate cyclase system is probably located in the parietal cell component.


The swollen leg.

The swollen leg. Systemic causes of leg edema include idiopathic cyclic edema, heart failure, cirrhosis, nephrosis and other hypoproteinemic states. Lymphedema may be primary, or secondary to neoplasm, lymphangitis, retroperitoneal fibrosis and, rarely (in the U.S.), filariasis. Thrombophlebitis and chronic venous insufficiency are not uncommon causes. Finally, infection, ischemia, lipedema, vascular anomalies, tumors and trauma can be responsible for the swollen leg.


Comparison of foundry dust evaluation by various methods. Matched sets of dust samples were collected in gray iron foundries for the purpose of comparing results obtained by four sampling techniques. Both respirable and total dust samples were collected. The results are compared on the basis of total concentration and on the basis of silica content. The problems in obtaining an adequate sample for silica analysis are considered. A proposal is made for using total respirable dust as an index of permissible dustiness in foundries.


Mechanisms contributing to myocardial accumulation of technetium-99m stannous pyrophosphate after coronary arterial occlusion. The relation between the accumulation of pyrophosphate and technetium-99m in myocardium with reversible and irreversible ischmic injury was studied in dogs subjected to transitory or persistent coronary arterial occlusion. Among four dogs with coronary occlusion maintained for less than 20 minutes, none had either increased MB creatine kinase (CK) (the "myocardial" CK isoenzyme) activity serum or a positive 99mTc stannous pyrophosphate image. Seven dogs with coronary occlusion maintained for 30 or more minutes had elevated serum MB CK activity, and five of the seven had positive (abnormal) images. Thus, although false negative images may occur occasionally despite myocardial damage, both increased serum MB CK and abnormal images generally accompanied prolonged coronary occlusion. In contrast, ischemia without infarction was not associated with abnormal images. Both 99mTc and 32P labeled pyrophosphate were accumulated extensively and proportionally in myocardium from zones of infarction, and uptake of both tracers was comparable although modest in isolated mitochondria. Similar results were obtained after myocardial infarction in animals with induced profound leukopenia. Thus, phagocytosis of the radiopharmaceutical agent by leukocytes migrating into the infarct is not an essential mechanism accounting for uptake. These results indicate that abnormal images reflect uptake of pyrophosphate, associated with 99mTc, by irreversibly injured myocardium rather than leukocytic infiltration involved in the inflammatory response in the heart.


Estrogen use in postmenopausal women.

Estrogen use in postmenopausal women. Fifteen per cent of postmenopausal women living in a retirement community used oral estrogens. Both use and new-use continued in the seventh, eighth and ninth decades of life, although use and age-specific use-prevalence declined after age 70. Mean duration of most recent continuous use was 105 months. Vaginal estrogenic preparations were used infrequently, briefly, and usually by women who also used oral estrogens in the same year. The most commonly used oral estrogenic preparation was conjugated equine estrogens (Premarin).


Acute hemorrhagic conjunctivitis: a mixed virus outbreak among Vietnamese refugees on Guam. In May 1975 the authors investigated an outbreak of acute hemorrhagic conjunctivitis that affected an estimated 29,000 refugees from South Vietnam who stayed on Guam while en route to the United States. Illness usually lasted6-10 days and was characterized by conjunctival injection (100%), lid edema (84%), eye irritation (81%) and subconjunctival  hemorrhages (45%). Conjunctival swabs and paired serum specimens on a limited number of patients implicated enterovirus 70 as a major etiologic agent and adenovirus 11 as a less frequent agent. Adenovirus 8 and herpes simplex virus caused concurrent, sporadic cases of keratoconjunctivitis. Forty-three per cent of the refugees in a sample of 604 refugees were affected, and the attack rate was highest on evacuation vessels where crowding and poor sanitation facilitated person-to-person spread of infection. Because the outbreak subsided on Guam, and because infection was transmitted there to only 13 of about 1300 Americans in frequent contact with affected refugees, the risk of secondary outbreaks inthe United States appeared small.


Stability of aqueous perchlorate formulations. The stability of three aqueous perchlorate formulations used in nuclear medicine was studied as a function of the formulation and storage temperature. The formulations were intravenous potassium perchlorate solution, oral sodium perchlorate-sorbitol solution and oral potassium perchlorate in cherry syrup solution. The assays were conducted gravimetrically by precipitation with tetra-n-pentylammonium bromide. All formulations were found to be stable at least nine months. It is recommended that any formulation containing potassium perchlorate be kept at room temperature since precipitation of the active ingredient may occur if refrigerated. Sodium perchlorate formulations, however, may be refrigerated if desired because of their greater solubility.


Benign hepatic tumors and oral contraceptive pills. In order to consider possible environmental factors related to the development of benign hepatic tumors, all reports of this disorder in the case records of five different hospitals in Rochester, New York, during the past 10 years were reviewed. Seven patients with benign hepatic tumors of the liver and two with peliosis hepatis were identified. Among the seven with a benign hepatic tumor, four were women currently receiving oral contraceptives; one had been receiving this medication in the past, and two had no history of exposure to any steroid whatsoever. The two patients with peliosis hepatis were receiving long-term androgenic anabolic steroids. Dilated, thin-walled vessels and vascular spaces were a more prominent feature of the tumor seen in four patients receiving oral contraceptive pills. It is emphasized in this report that benign hepatic tumors do occur in men and in patients with cirrhotic liver without the use of any kind of steroids.


Plasma human placental lactogen, oxytocinase, and placental phosphatase in normal and toxemic pregnancies. A total of 625 serum samples were drawn from 400 normal and 225 hypertensive toxemic pregnant women. Each sample was simultaneously assayed for its human placental lactogen (HPL), oxytocinase (O), and placental phosphatase (PP) concentration. In addition, accurate placental and infant birth weights were determined in those cases where the serum sample was obtained within 14 days of delivery. The results showed a significant rise and correlation of each of the three proteins with increasing weeks of gestation. Although the infant birth weight was unrelated to the serum level of the three proteins, both the HPL and O concentrations were significantly correlated with the placental weight in the normal pregnancies. In both types of pregnancies, the concentration of O was significantly related to that of PP and this was also true for HPL and O and HPL and PP. In all instances O was more strongly related than PP. In the toxemic pregnancies there was a higher O and lower PP level than in normal gestations. These data suggest that placental enzyme measurements, especially O, could be clinically helpful in monitoring high-risk pregnancies.


Etiologic factors in the pathogenesis of liver tumors associated with oral contraceptives. Within the last several years, previously rare liver tumors have been seen in young women using oral contraceptive steroids. The Registry for Liver Tumors Associated with Oral Contraceptives at the University of California, Irvine, has clearly identified 27 cases. The recent literature contains 44 case reports. Common to these 71 cases has been a histopathologic diagnosis of focal nodular hyperplasia, adenoma, hamartoma, and hepatoma. Significant statistical etiologic factors include prolonged uninterrupted usage of oral contraceptive steroids. Eight deaths and liver rupture in 18 patients attest to the seriousness of this new potentially lethal adverse phenomenon.


An insulinoma without fasting hypoglycemia. A patient with a 25-year history of episodic irritability, confusion, and unconsciousness was suspected of having organic hypoglycemia. He was fasted for a 72-hour period without developing symptoms. At the end of the fast his blood sugar was 85 mg/100 ml and the immunoreactive insulin (IRI) concentraion was elevated to 350 microunits/ml. Surgical exploration demonstrated a 4 x 3 centimeter insulinoma in the tail of the pancreas. Since proinsulin-like components (PLC) are known to be elevated in patients with islet cell tumors and have only 5 to 10 per cent of the biologic activity of insulin, it is suggested that a major portion of the IRI was PLC. This case demonstrates that the inability to withstand prolonged fasting does not exclude the diagnosis of an insulinoma and suggests a mechanism whereby such patients can tolerate fasting.


The influence of prostaglandin G2 on platelet ultrastructure and platelet secretion. Prostaglandin G2 (PGG2) is a labile endoperoxide produced physiologically following exposure of platelets to aggregating agents. We report here studies using isolated PGG2. This agent stimulates a concentration-dependent internal platelet contraction very similar to that produced by the calcium ionophore A23187. EDTA prevented platelet aggregation but did not prevent PGG2-stimulated internal contraction or secretion. In contrast, prostaglandin E1 and dibutyryl cyclic AMP inhich selectively labilizes platelet granules, was added to platelets together with PGG2 there was a superadditive effect on platelet secretion. Thus, granule labilization induced by PMA is a separable phenomenon and complementary to the effect of PGG2 on contraction. The ultimate degree of secretion is dependent on both processes. Studies using additional inhibitors supported the hypothesis that PGG2 activates platelets (either directly or following conversion to thromboxane A2) by transporting calcium from an intracellular store to the cytoplasmic site of the platelet contractile proteins.


Lithium-induced diuretic effect of antidiuretic hormone in rats. The effect of a low dose of lithium (1 meq/kg per day) on renal function and its response to antidiuretic hormone (ADH) was studied in unanesthetized rats. This dose of lithium itself had no influence on renal water and electrolyte excretion, but lithium-treated rats responded paradoxically to exogenous ADH by increases in urinary volume, excretion of total solutes, sodium, potassium, and phosphate. Administration of ADH in the presence of lithium led to a lowering of urine osmolality, but free water clearance was not significantly reduced. Adenylate cyclase from the renal medulla of animals treated with ADH and lithium had a lower response to synthetic vasopressin in vitro than in animals treated with lithium alone. The results suggest that exogenous ADHis diuretic in the presence of a low concentration of lithilm. The predominant mechanism for this diuresis is probably inhibition of electrolyte and isomotic water reabbsorption in various nephron segments, including those proximal to the collecting ducts. ADH also markedly increased urinary excretion of lithium and appears to promote accumulation of lithium in the renal medulla.


Central antihypertensive effects of inhibitors of the renin-angiotensin system in rats. The possibility that mean arterial pressure (MA) might be maintained by an effect of angiotensin II or its precursors on the central nervous system in rats made hypertensive by occluding the aorta between the renal arteries was investigated. Aortic coarctation produced severe hypertension (MAP greater than 150 mmHg) and plasma renin activity values (radioimmunoassay) at least 10 times normal within 2-6 days after surgery. [Sar1, IIe8]angiotensin II, an angiotensin II antagonist administered centrally via an intracerebroventricular (icv) injection (10-100 mug), lowered the MAP in a dose-dependent manner. Peripheral administration of [Sar1, IIe8]angiotensin II (bolus injection) at 100 mug intra-arterially was ineffective, but the antagonist did lower arterial pressure when infused intravenously for 1 h at 4 times this dose. Less than Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro, a converting enzyme inhibitor, and pepstatin, a renin inhibitor, were ineffective via an icv injection. These results suggest that angiotensin II is in part responsible for the elevation in blood pressure following aortic coarctation in rats. Both central and peripheral administration of [Sar1, Ile8]-angiotensin II lowered mean arterial pressure but the antagonist lowered arterial pressure at lower doses and produced a more rapid decline in arterial pressure when administered into the central nervous system then when administered intra-arterially or intravenously.


In vivo control of mitochondrial enzyme concentrations and activity by oxygen. Newborn and adult dog heart mitochondria were prepared from animals chronically adjusted to varying arterial oxygen tensions. Similarly, rat liver and heart mitochondria were isolated from animals acutely exposed to lowered inspired oxygen. After isolation, all mitochondrial samples were assayed under normoxic conditions. These experiments illustrated the following effects of oxygen on mitochondrial function: 1) respiratory activity in State 3 or in the uncoupled state increased after hypoxia and decreased after increased in vivo oxygenation; 2) similarly, the turnover of cytochrome oxidase increased in hypoxia and decreased after increased oxygenation; 3) after chronic hypoxia cytochrome oxidase, cytochrome c and b concentrations decreased per miligram of mitochondrial protein; 4) all mitochondrial preparations were well coupled and exhibited normal capabilities to perform oxidative phosphorylation. The data are interpreted to indicate sensitive control of mitochondrial respiratory capacities by oxygen in vivo.


A halfway house for mentally ill offenders. The authors describe the resocialization of recovering mentally ill male offenders through the halfway house program to which they were released. A number of guiding principles are discussed in connection with the care of this high-risk population. Partial residence for those about tp be discharged from the hospital was one feature of the program. Evaluation of the program after three years showed a lower than average rate of recidivism and relatively low operating costs; in addition, it appeared that predictions regarding possible dangerousness can be made with greater confidence when halfway house residence is part of the treatment plan for this type of population.


A progressive approach to the problem of foodborne infections. Qualitative and quantitative bacteriological examinations of 100 samples of perishable foods from 39 retail stores were performed to determine the presence of bacterial contaminants and to explore the feasibility of establishing and utilizing microbiological standards in enforcement. Forty-six per cent of the samples had standard plate counts in excess of 100,000 per gram, 17 per cent showed coliform organisms in excess of 100 per gram, 20 per cent revealed the presence of Staphylococcus aureus and 2 per cent Clostridium perfringens. None of the shell fish samples grew Vibrio parahaemolyticus. The bacteriological findings are discussed in relation to pertinent variables and the use of microbiological standards for potentially hazardous foods is explored. All 450 retail food establishments in a selected area of Western Suffolk County (New York) were subjected to comprehensive study, using a scoring system developed by the Food and Drug Administration. Initial inspections revealed 32 per cent as having one or more major violations. Follow-up inspections were performed to insure compliance and most violations were corrected within four weeks. Six months later all establishments were reinspected. The scoring system was found to have limited value. Half the establishments with major violations on initial inspection had major violations six months later as compared to less than a quarter of those with no initial major violation.


Renal cell carcinoma in a patient successfully treated for Wilms's tumor. A woman who had received successful therapy for Wilm's tumor of one kidney in childhood developed renal cell carcinoma in the opposite kidney 21 years later. Such an occurrence has not been reported previously. A discussion of the differential diagnosis of calcified renal mass lesions and the angiographic differentiation between Wilms's tumor and renal cell carcinoma is presented. The possible relationship between these two primary renal tumors is considered.


Acrodysostosis coinciding with pseudohypoparathyroidism and pseudo-pseudohypoparathyroidism. The diagnosis of acrodysostosis has been differentiated from that of pseudohypoparathyroidism or pseudo-pseudohypoparathyroidism by the absence of endocrine abnormalities, more generalized osseous abnormalities, and a characteristic facial appearance. Two cases are presented which fulfill all of the major features of acrodysostosis: peripheral dysostosis, nasal hypoplasia (pug nose), and mental retardation. The first case had all the metabolic abnormalities of pseudohypoparathyroidism; the second case had urinary cyclic adenosine-3',5'-monophosphate findings suggestive of pseudo-pseudohypoparathyroidism. Therefore acrodysostosis cannot be differentiated from pseudohypoparathyroidism or pseudopseudohypoparathyroidism on clinical and radiologic features only.


Detection of pulmonary nodules by computed tomography. In 11 of 23 patients, computed tomography of the chest detected pulmonary nodules that were not detected by conventional chest radiography or whole lung tomography. CT is recommended for patients suspected of having pulmonary metastasis and those with a solitary pulmonary nodule.


Ecological associations of vesicular stomatitis virus in rural Central America and Panama. The principal objective of this study was to determine ecological associations of vesicular stomatitis virus (VSV)- New Jersey and VSV-Indiana in rural Central America and Panama. Two types of information were linked: the results of neutralizing antibody tests performed on sera from 3,232 lifetime residents of 189 rural study communitities of Central America and Panama, and ecological characteristics of the study communities as determined from natural resource atlases. The major finding was that neutralizing antibody acquistion to VSV-New Jersey was greatest for persons living at elevations between 350 and 649 meters, with relatively open, dry vegetation and distinct seasonal alternation of dry and moist (not wet) ground conditions. Similar ecological associations were found for VSV-Indiana, except that the risk of infection was also high in moist environments with dense tree cover. The results suggest that VSV-New Jersey and VSV-Indiana have similar but not identical maintenance and transmission cycles and that basic maintenance cycles for both viruses may exist in dry, open habitats rather than in tropicla rain forest habitats as was previously assumed for VSV-Indiana.


Biophysical mechanisms of anesthetic action: historical perspective and review of current concepts. The large number and diversity of anesthetic agents were evident to investigators 80 years ago, and suggested a physicochemical theory of anesthesia. Meyer and Overton were the first to offer a quantitative relationship between a physicochemical property and potency of anesthetic agents. They also focused attention on the lipid phase as the site of anesthetic action. Ferguson realized that the concentration of an agent at its site of action bears a generally unknown relation to the concentration in the external phase. However, at equilibrium the activity of an agent is the same in every phase, motivating Ferguson to suggest that activities rather than concentrations be used as indices of dosage. The critical-volume theory resulted from modification of the Meyer-Overton theory to include the molal volume of the anesthetic. The allowance for molal volume resulted initially from an attempt further to regularize the experimental data. The concept of a critical-volume fraction of anesthetic being necessary for narcosis was discussed in most detail by Mullins. Subsequently, the concept of the effect of the anesthetic has changed from filling of free space to expansion and fluidization of the membrane. The ability of pressure to cause excitant phenomena and antagonize anesthetics is predictable from the critical-volume theory and is therefore highly significant evidence. K. W. Miller and associates are perhaps most prominent in the recent quantification and formalization of the critical-volume theory and HPNS. The existence of a separate convulsant site(s) is suggested by the demonstration of significantly different compressibilities associated with anesthesia and convulsions. Work corroborating a separate convulsant site involved measurement of the partial molal volumes of a series of related convulsant and anesthetic ethers and calculation of each compound's solubility parameter. Multiple convulsant sites may exist, and these two methods may not have accessed the same site. Understanding the anesthetic-convulsant duality will have important practical application to deepwater diving, and may well offer important insight into the neurophysiologic and electrophysiologic effects of anesthetics. The application of ESR and NMR allows investigation at the molecular level of effects of anesthetics on biological and model membranes. Magnetic resonance techniques have generally supported the concept of membrane fluidization by anesthetics. Some investigators have recently attempted to displace the focus of attention from the lipid phase. However, the evidence is clearly against the aqueous-phase theory of Pauling and S.L. Miller. The microtubule theory of Allison and Nunn has not accumulated supporting evidence comparable to the lipid theories. Contradictory evidence makes any evaluation of this theory speculative. Additionally, the interspecies and intracellular variability of microtubules raises questions of the relevance of many studies...


Immunogenetic polymorphism of lipoproteins in swine. 1. Four additional serum beta-lipoprotein allotypes (Lpp2, Lpp4, Lpp5 and Lpp15) in the Lpp system. Four additional swine serum lipoprotein allotypes are described. Specific anti-allotype reagents were obtained from alloimmune precipitating sera produced in lipoprotein-defined-type recipients immunized with normal sera and subsequently with lipoprotein fractions. Identification studies indicate that the four serologically defined low-density lipoprotein (LDL) variants, designated Lpp2, Lpp4, Lpp5 and Lpp15, are members of a previously described Lpp system. The individual specificities, Lpp2, Lpp4 and Lpp5, are determined by three co-dominant autosomal genes, Lpp2, Lpp4 and Lpp5, respectively, whereas the common specificity, Lpp15, is controlled by a complex of genetic information of the Lpp2 and Lpp4 genes, and by the two previously described alleles, Lpp1 and Lpp3; Lpp15 occurs on the same molecule with respective individual specificity. The Lpp5 and Lpp15 antigens behave as a pair of alternative allotypic specificities. The double immunodiffusion test in agar was employed to demonstrate independent phenotypic expression of each allelic gene in the Lpp heterozygous animals, for the analysis of the immune sera, and for lipoprotein testing of 3305 sera. Marked differences in gene frequencies were found between the swine breeds tested. As a result of characteristic frequencies, only nine of 15 possible Lpp genotypes were found in the breeding herds tested; the remaining six genotypes were obtained from testcross matings.


[Lymphadenopathy caused by hemophagocytic sinus histiocytosis (Destombes-Rosai-Dorfman syndrome). Immunologic and histopathologic study of a new case]. The case reported is one of lymphadenopathy due to haemophagocytic sinusal histiocytosis which had progressed for more than 10 years before resulting in death at the age of 58 years. In this advanced form, all superficial and deep nodes were involved. In addition to histiocytic hyperplasia, with haemophagocytosis and lipid overload, there was plasmocytic hyperplasia, i.e. B-lymphocytes, with polyclonal hypergamma-globulinaemia and an increase in the levels of many antibodies, in particular against rubella and the Epstein-Barr virus. The aetiopathological significance is discussed, in particular the role of an infection due to the EB virus.


Role of triglyceride-rich lipoproteins in atherogenesis. The hypothesis that chylomicron cholesterol is a causal factor in the accumulation of cholesterol in atheromatous lesions is compatible with the finding reported here that hypercholesterokmia in the cholesterol-fed rabbit is due, at least, in part, to the accumulation of chylomicron remnants. The presence of lipoprotein lipase in aorta suggests the possibility that chylomicron remnants are formed on the arterial surface and that they may be deposited in the deeper layers of the arterial wall without prior release into the bloodstream. Consequently, the cholesterol-rich lipo-proteins in the plasma may be the product rather than the precursor of the atherogenic process.


The low-density lipoprotein pathway in human fibroblasts: relation between cell surface receptor binding and endocytosis of low-density lipoprotein. The studies reported here, coupled with our previous studies, indicate that LDL is ingested by cultured human fibroblasts in a process that resembles adsorptive endocytosis. The critical step is the binding of the lipoprotein to a high-affinity cell surface receptor. Uptake of LDL by this receptor-mediated process permits the cell to aquire cholesterol from the lipoprotein, and this acquisition, in turn, suppresses the cell's own cholesterol synthesis and activates the cell's system for reesterification and storage of the incoming cholesterol. In cells from patients with the receptor-negative form of homozygous FH, the cell surface receptor is functionally absent. The absence of high-affinity binding to this receptor produces a defective uptake of LDL and prevents the normal process of feedback regulation of cholesterol synthesis by the lipoprotein. The physiologic importance of the LDL pathway is indicated by the fact that patients who lack the LDL receptor (FH homozygotes) develop both profound hyper-cholesterolemia and fulminant atherosclerosis. It is likely that other defects in the LDL pathway account for other forms of hypercholesterolemia and atherosclerosis in man.


Hyperreactive arterial endothelial cells: a clue for the treatment of atherosclerosis. Arterial endothelial cells, which are capable of phagocytizing carbon particles of the same size as beta- and pre-beta-lipoprotein, were found only in endothelial cells of arterial segments susceptible to atheromatous changes in susceptible animal species, and the distribution closely corresponded to the susceptibility. The distribution of such endothelial cells is dense in large arteries, in the openings to their branches, especially in downstream portions, of rabbits, hens, and cocks; however, the distribution is relatively scanty in arteries of rhesus monkeys and is very scanty in dogs. Carbon particles were also rare in the suckling rabbit and tended to increase with age. They were not found in Wistar rats but were found in spontaneously hypertensive rats, which showed a characteristically diffuse distribution, even in relatively small arteries. The carbon particles, phagocytized, were released to the subendothelial space but were difficult to pass through the internal elastic lamina and tended to stagnate there for more than one month. The authors therefore call these cells hyperreactive endothelial cells. Various vasoactive substances, such as angiotensin II, histamine, and serotonin, significantly enhanced the phagocytic activities of arotic endothelial cells in rabbits; epinephrine and norepinephrine also slightly enhanced these activities. Various smooth muscle relaxants, such as ATP, pyridinol carbamate (ATP synthesis-enhancing substance), cycli-AMP, dibutyryl cycli-AMP, phthalazinol (cyclic-AMP phosphodiesterase inhibitor), iproveratril (calcium entry-inhibiting substance), colchicine, and vinblastine, with their different modes of action, commonly inhibited phagocytic activities, a finding that suggests a significant role for contractile protein in the permeability problem of atherogenesis. The atheromatous lesions of cholesterol-fed rabbits exhibited a striking increase in hyperreactive endothelial cells, accompanied by a marked rise in the activity of low-Km cyclic-AMP phosphodiesterase activity in atheromatous lesions and adjacent muscular layers, especially in rabbits with rapidly progressing atheroma.