[Structure of Candida tropicalis K-41 thermotolerant yeasts at various growing temperatures on a mineral medium with hydrocarbons]. In the C. tropicalis K-41 cells fixed by glutaraldehyde and osmium most membranes consisted of two electron-transparent and one electron-dense layer. Morphologo-structural peculiarities of the cell fraction grown at 39 degrees testify to a certain disconnection of energetic and constructive metabolism, inhibition of synthetic processes. Cell division was more active at 29 degrees.


Structure of cultured fibroblasts from dermatosparaxic calves. Clonal cell lines from the dermis of a dermatosparaxic calf were grown in tissue culture. After fixation in a mixture of glutaraldehyde and osmium, they were prepared for electron microscopy. Most cells contained a well-developed Golgi region, lysosomes, mitochondria, and dilated cisternae of rough endoplasmic reticulum. They also contained numerous, large bundles of intracellular fialments, many lipid droplets and extensive arrays of vesicles. Cultures accumulated substantial amounts of extracellular fibrillar material. The fibrils were loosely packed and indistinctly cross-banded. Bundles of intracellular filaments were commonly parallel in adjacent cells and also parallel to extracellular fibrils. These cytoplasmic features may result from the inability of the secreted collagen to form normal fibrils.


Pancreatic cholera (W.D.H.A. syndrome). Histochemical and ultrastructural studies. Results of light and electron-microscopic studies of primary pancreatic tumor and of metastasis in a new case of Pancreatic Cholera (P.C.) are reported. The primary tumor but not the metastases, contained unusual, large cystic glandular formations, lined both by pancreatic-duct- and small-intestine-like epithelia and closely connected with the endocrine proliferation. A part from a few D-cells, the endocrine tumoral cells could not be identified by histochemical stainings. Their ultrastructural pattern, with small secretory granules (diameter less than 300 nm) and numerous cytoplasmic bunches of filaments, was very similar to that of gastric and duodenal D1-cells. Normal duodenal D1-cells have been said to produce gastric inhibitory peptide, a substance structurally and biologically similar to the vasoactive intestinal peptide actually secreted by the tumor. The normal histological appearance of gastric, gallbladder, jejunal, ileal, right and left colonic mucosae is consistent with the responsibility of the tumoral secretion in the impairment of gut functions in P.C.


Morphogenesis of intracytoplasmic dense (inclusion) bodies in a recurring digital fibrous tumor of childhood. Light- and electron-microscopic investigations. This study presents the results of light-microscopic, histochemical, and electron-microscopic investigations of dense (inclusion) bodies in a recurring digital fibrous tumor of childhood. At ultrastructural level it was possible to observe several stages of development correlated with changes of ergastoplasmic reticulum. The viral nature of these bodies was refuted and the conclusion was drawn that their formation is associated with a disturbed intracellular metabolism. The defective intracellular transport of collagen precursors followed by abnormal deposition of collagenous proteins, which are also to some extent abnormally aggregated, could be of special importance.


Changes in the fine structure and function of a hormone-secreting adrenocortical tumour investigated in tissue culture. Tissue cultures of a surgically removed adrenocortical tumour causing Cushing's syndrome, and tissue cultures from the attached, tumour-free adrenal were studied. There were two cell types characteristic of tumour tissue. The cell type occurring most frequently had pronounced hypertrophied agranular endoplasmic reticulum. A fewer number of lipid-rich cells containing many electron-dense granules could also be found. The ratio of cells changed during cultivation. In the 17 days tumour culture, a higher percentage of lipid-rich cells could be observed. In spite of continuous ACTH treatment, the initially high hydrocortisone level decreased, gradually. It may be assumed that the lipid-rich cells are of reduced ability as regards hydrocortisone production.


Cellular composition of the so-called dermatofibroma (histiocytoma cutis). 9 typical cases of dermatofibroma or histiocytoma cutis resp. were studied by the aid of histochemical, enzyme histochemical and electron microscopical methods to examine the cellular composition of these lesions. The results suggest an anabolic and katabolic function of cells. Electron microscopically a broad spectrum of patterns of mesenchymal cells was found. Besides defined fibroblast-like and histiocyte-like elements a cell type was detected which was characterized by particular traits, as irregular nuclear outline, abundant rough endoplasmic reticulum, free ribosomes, bundles of filaments with single dense zones, micropinocytotic vesicles and a basement membrane-like material on the outer cell surface. This cell type constitutes the majority of cells in dermatofibroma or histiocytoma cutis resp. In some cells an arrangement of filament bundles resembling that in smooth muscle could be seen. By reason of these findings a certain resemblance to the so-called myofibroblasts can be stated. The variegation of the morphological picture suggests a multipotent precursor cell; the possibility of an origin from pericytes is discussed.


Ruptured benign hepatoma associated with an oral contraceptive. A case report. A ruptured benign hepatoma is described in a woman at full-term pregnancy. The patient had used an oral contraceptive for eight years before she became pregnant. According to several recent reports it seems likely that there is a relationship between the use of oral contraceptive agents and the development of liver cell tumours. Twentythree such cases have been found in the literature. Fourteen of these were not diagnosed before rupture. The present tumour differed from previously described lesions by containing foci of haematopoietic cells. As there were no signs of blood or bone marrow disease, it is suggested that the extramedullary haematopoiesis is a constituent of the tumour tissue.


Distribution of cytoplasmic vacuoles in blood T and B lymphocytes in two lysosomal disorders. Distribution of cytoplasmic vacuoles in purified T and B lymphocytes was analyzed in four cases of aspartylglucosaminuria (AGU) and in one case of neuronal ceroid lipofuscinosis (Spielmeyer-Sjörgren type). In all cases T cells were significantly more vacuolized than B cells. The ultrastructure of the cytoplasmic vacuoles was consistent with the concept of storage lysosomes. The cytoplasmic vacuoles both in T and B cells similar to abnormal lysosomes seen in the visceral organs in these diseases.


Stimulation of cellular autophagy by parathyroid hormone and cyclic adenosine 3',5': monophosphate in isolated tubular fragments from the rat's kidney cortex. Tubular fragments isolated from the cortex of the rat's kidney were qualitatively and quantitatively investigated with the electron microscope. The tubules frequently burst open and became "inverted" in such a way that the rarefied brush border now formed the outer circumference. By morphometry a decrease of the average cell volume in the proximal tubular fragments was ascertained. This was mostly caused by a loss of cytoplasmic ground substance, endoplasmic reticulum and ribosomes. Cytoplasmic herniations of the basal surface, filled with free ribosomes, suggested a partial shedding of the protein synthesizing apparatus. The number of autophagic vacuoles (AV) per unit area of cytoplasm was determined in proximal tubular fragments. After isolation alone, without further incubation, the number of AV was as low as the number found in an earlier study in proximal tubular cells in situ during the diurnal minimum. After control incubation the number of AV increased to about the mean value of the AV found in cells in situ during the whole diurnal cycle. By comparison with the control incubation the number of AV increased by a factor of 1.6 to 1.7, if cyclic adenosine 3',5': monophosphate (cyclic AMP) or parathyroid hormone (PTH) were added to the incubation-medium; it now reached about the number of AV found in situ during the diurnal maximum. The increase in the number of AV paralleled that of the production of ammonia and glucose from endogenous sources under the influence of cyclic AMP and PTH. This suggests that the breakdown of cytoplasmic components by cellular autophagy could be functionally related to gluconeogenesis. A quantitative comparison between the measured production of ammonia and glucose indicates, however, that in the system of isolated tubular fragments there may exist other mechanisms of degradation, and of the provision of substrates for gluconeogenesis, than cellular autophagy only.


[Treatment of patients with lung cancer with a combination of nitrosomethylurea and cyclophosphane]. Eighty five patients with pulmonary cancer, stage III-IV, were treated with a combination of nitrosomethyl urea and cyclophosphan. In squamous cell cancer a positive objective effect was gained in 35% of patients.


[Intrauterine transmission of induced hemoblastosis in monkeys, associated with type-C oncornavirus]. The possibility of intrauterine transmission of hemoblastosis was investigated in a group of 118 M. arctoides females with induced viral hemoblastosis. In the course of observations pregnancy occurred in 9 cases. Four of seven babies, delivered at term have developed hemoblastosis. The main signs of the disease were revealed in babies from the first days of their life. Hemoblastosis was accompanied with the appearance of a specific surface antigen and the presence of the "C" type oncornavirus in blood and organs of the babies, and also in cells of one embryo. Viral hemoblastosis was successfully passaged from one of the babies to three juvenile monkeys of the same species.


Altered immunologic specificity of cells infected with Herpes simplex virus: recognition of human antiserum. Human serum having complement fixation anti-herpex simplex virus activity was reacted with herpes simplex virus infected cells in tissue culture. By tagging the antibody to ferritin and examining the cells in the electron microscope, it was found that 1. the entire surface of the infected cell is antigenically altered and reacts with hyperimmune serum. The antigenic cell surface change is not limited to structurally altered sites, nor is it limited to sites where virus particles are present, and 2. cells in the early stages of infection react more strongly with hyperimmune serum than do cells in later stages. The possible clinical significance of the infected cell surface - antibody reaction is discussed.


Respiratory electron flow and ATPase system in photosynthetically grown Rhodopseudomonas palustris. Rhodopseudomonas palustris is grown photosynthetically on thiosulfate. As pointed out earlier, the chromatophore deficient cell-free fraction S-144,000 catalyzes the thiosulfate-linked ATP-dependent reversal of electron transfer in anaerobiosis, thus providing reducing equivalents in the form of NADH. Under aerobic conditions, this fraction also catalyzes the oxidation of NADH, ferro-cytochrome c, or ascorbate. ATP, ADP, and PPi are active in  retarding the aerobic electron flow. The electron retardation is stimulated by the addition of Mg2+ due to a Mg2+-stimulated ATPase present. The ATPase system in S-144,000 hydrolyzes ATP, ADP, and PPi. Similarly, ATP or ADP, or even PPi can function as energy sources in order to achieve the reduction of pyridine nucleotide. The ATPase turnover is diminished by NADH or NAD+. Admixture of ascorbate results in an increased ATPase activity. Exactly the enhanced amount of adenine nucleotide hydrolysis caused by the addition of ascorbate is inhibited by cyanide.


Ultrastructure of Trypanosoma duttoni.

Ultrastructure of Trypanosoma duttoni. Trypanosoma duttoni exhibits the typical trypanosome morphology in that it is bounded by a unit membrane which included its anterior flagellum; it is surrounded by a framework of suppellicular fibrils, and it contains a nucleus and the posteriorly located kinetoplast-blepharoplast structures along with cytoplasmic organelles (mitochondria, Golgi, and enoplasmic reticulum). Very prominently displayed in T. duttoni is the contractile vacuole, which has not previously received wide-spread recognition. The kinetoplast is clearly continuous with mitochondria in some cases. Inclusion bodies are categorized into three distinct types, none of which can be conclusively designated as the very popular volutin granules, without cytochemical evidence. The existence of a third tubule among peripheral tubule doublets of the flagellum is observed.


A study of the neurohumoral control of glycolysis in the mouse brain in vivo: role of noradrenaline and dopamine. Intraventricularly injected noradrenaline, dopamine and isoprenaline increased glycolysis as shown by the decrease in the concentration of "free" glycogen and increase in the concentration of lactate. The effects of noradrenaline and isoprenaline were reduced in mice which had been pretreated with alpha-methyl-p-tyrosin. DL-Propranolol blocked the increase in glycolysis caused by noradrenaline, isoprenaline, sodium fluoride and analogues of 3,5-cyclic adenosine monophosphate. It is suggested that the results of this investigation can be explained by the various drugs and neurohormones acting on the adenyl cyclase system in vivo, either by blocking the action of the neurohormone on the membrane bound enzyme or by antagonizing the effect of 3,5-cyclic adenosine monophosphate on glycolysis.


[The anatomic and radiologic picture of the acetabulum (author's transl)]. The basic shape of the facies lunata shows at the inner margin of each of the three participating bones a dell into which the floor of the acetabulum progresses. These dells originate in nutritive vessels which enter the bone and claim this place. There always are groups of vessels and wide channels which may be visible on radiographs. The so far unexplained picture of a vascular canal in the roof of the acetabulum corresponds to the canal leading into the body of the ilium. Due to its position there is often restructuring leading to filling or covering of the canal. The entrance to this canal is shown as a gap in the arc of the acetabular cavity which would have to be added to that of the "tear figure" known so far. The closed arc, as always drawn, reults only when this entry has been filled up.


[Postsurgical management of cutaneous syndactyly (author's transl)]. The success of syndactyly operations depends to a considerable extent on the appropriate bandage-technique which according to the author's experience has proved to be highly effective.


In vitro translation of natural mRNAs in a cell-free system containing components from interferon-treated chicken fibroblasts and factor preparations from mouse ascites cells or rabbit reticulocytes. The effect of interferon has been studied in a mixed cell-free protein synthesizing system. Hemoglobin (Hb) and Encephalomyocarditis virus (EMC)-RNA can be efficiently translated in vitro in a system containing S-30 lysates or run-off ribosomes from primary chick embryo fibroblasts (CEF) and a postmicrosomal supernatant from mouse ascites cells or a ribosomal-wash preparation from rabbit reticulocytes. Ribosomes prepared from CEF pretreated with high doses of homologous interferon (500 units/ml) were able to translate Hb-RNA in the presence of heterologous factors with the same efficiency as ribosomes prepared from control cells. Translation of EMC-RNAP WAS SLIGHTLY Reduced if ribosomes from interferon-treated cells were used in the mixed cell-free system, confirming previous reports. No inhibitory effect caused by interferon treatment of CEF cells could be detected on in vitro translation of natural mRNAs if the cells had, in addition to interferon treatment, been infected with vaccinia virus. Possible reasons for the different observations made with out cell-free protein synthesizing system from CEF and with cell-free systems prepared from mouse cells are discussed.


On the phospholipase activity in bovine seminal vesicles and its possible role in the regulation of the prostaglandin biosynthesis. A phospholipid mixture was isolated from bovine vesicle tissue. This phospholipid preparation contained the following prostaglandin precursor fatty acids: 4.7 percent 5,8,11-eicosatrienoic acid, 9.1 percent 5,8,11,14-eicosatetraenoic acid and 0.9% 5,8,11,14,17-eicosapentaenoic acid. With this phospholipid preparation as substrate phospholipase activity could be detected in different fractions of bovine seminal vesicle cells. The highest phospholipase activity was found in the microsomal fraction, less in the mitochondria and essentially no activity in the cytosol. With a microsome preparation (acetone powder) of bovine seminal vesicles the influence of certain effectors on the phospholipase activity was investigated. Prostaglandins E2 and F2alpha (10(-5) M) showed 19 and 41 percent inhibition, DB-c-AMP (2 times 10(-9) M) 54%, c-AMP (10(-9) M) 22%, epinephrine (10(-4) M) 60%, testosterone (10(-5) M) 25% inhibition of the phospholipase activity. Whereas ethanol exhibits also a strong inhibition on the phospholipase activity, it shows a pronounced activation of the prostaglandin synthetase.


Virological studies on gynaecological patients. Endometrial epithelial cells and blood samples taken simultaneously with the curettage (first serum) of 138 patients suffering from menstrual bleeding disorders as well as materials obtained from 16 induced abortions, were studied for the presence of virus. Fourteen adenovirus 2 strains were isolated from samples of the patients. Endometrial epithelial cells of 35 patients were examined with immunofluorescence method and 23 of them displayed specific fluorescence referring to the presence of viral antigens, with adenovirus and herpesvirus antisera. Studying withserological reactions the first and second (convalescent) sera of patients, high titers were found against type 2 herpesvirus in both sera, and titer rise against the latent adenovirus types in the second sera. Neither infective virus nor the presence of viral antigens were demonstrable in materials obtained from induced abortions.


[Early bacteriological diagnosis of infections after osteosynthesis (author's transl)]. Postoperative infections after osteosynthesis belong to the most serious complications in traumatology. Efforts to prevent this danger by routine antibiotic prophylaxis are mainly rejected nowadays. Instead, it is studies whether infections can be diagnosed by bacteriological culture of secretions from Redon drains in patients with osteosynthesis for the purpose of starting an early specific antibiotic therapy. Bacteria were cultured from secretions of wounds in 11.3% of samples from 177 patients. Staph. aureus was found most frequently and was responsible for most of the postoperative infections (Tab. 1).


[Uremic polyneuropathies].

[Uremic polyneuropathies]. The report is concerned with the results of a study of polyneuropathy in 75 patients with acute and chronic renal insufficiency. The authors described the clinical characteristics of the different forms of neuropathy. In acute renal insufficiency the first signs of polyneuropathy appear during the stage of polyuria and are reversible. In chronic renal insufficiency and hemodialysis treatment of subclinical an sensory forms of neuropathy are mainly seen (2/3 of the patients). It was demonstrated that there was a retardation in the velocity of excitative conductivity through the nerves depending upon the severity of polyneuropathy. A longterm adequate hemodialysis may prevent the further development of polyneuropathy.


[State of the cerebral and peripheral blood circulation in chronic neurotoxoplasmosis]. In 124 patients with different forms of chronic neurotoxoplasmosis there was an increased tone of brain vessels without signs of a drop in the pulse blood repletion in the arteries of carotid and vertebro-basillar basins. There was also a decrease of the pulse blood repletion in the extremities (mainly in the lower) with a normal or insigficant increase of the tone in the vascular wall. A normalization of the rheographic curves in pharmacological tests and during treatment indicate a functional character of these changes in most of the cases.


[Destruction of cartilage in the adjuvants disease of the rat]. The structure of cartilage in rats with adjuvant disease was investigated lightmicroscopically and by scanning electron microscopy. Severe destruction of the cartilage with formation of lacunae only was observed in areas previously covered by pannus. However, outside the pannus differences between normal animals and animals with arthritis also were observed. In adjuvant treated animals a more fibrillar structure of the surface was seen as compared with untreated rats. This more fibrillar structure may be due to a loss of mucopolysaccharides. The severe destruction of cartilage must be related to the action of collagenase which only acts in areas with a close contact between cartilage and pannus.


Isolation, purification and properties of a factor from rheumatoid synovial fluid activating the latent forms of collagenolytic enzymes. 1. An activator catalysing specifically conversion of latent forms of human leucocyte collagenase and gelatin-specific protease into the active forms, has been isolated from rheumatoid synovial fluid and purified 55-fold with a yield of 16%. 2. Molecular weight of the activator is about 35 000. 3. The activator is thermolabile, and is irreversibly inactivated at pH below 5.5 or in the presence of low concentrations of trypsin or papain; it is resistant to the action  of lysozyme, hyaluronidase, diisopropylfluorophosphate, soybean trypsin inhibitor, p-chloromercuribenzoate, iodoacetamide and dithiothreitol. 4. The activator did not show any activity towards collagen, gelatin, casein, haemoglobin, histones, elastin or p-phenylazobenzyloxycarbonyl-peptide.


Steroid oxidoreductase activity of alcohol dehydrogenases from horse, rat, and human liver. Alcohol dehydrogenase from horse (isoenzyme SS and ES, but not EE), rat and human liver were found to catalyze the NAD-dependent oxidation of 3beta-hydroxy groups in 5alpha- and 5beta-steroids of the C19, C21, and C24 series. The enzymes from horse and rat liver were more active on 5beta-than on 5alpha-steroids. This difference was most marked with the enzyme from rat liver, especially with 3beta-hydroxyandrostan-17-ones and 3beta-hydroxypregnan-20-ones as substrates. The Km of isoenzyme ES from horse liver was lower for 3beta-hydroxy-5alpha-cholanoic acid (0.4 muM) than for 3beta-hydroxy-5beta-cholanoic acid (0.9 muM). 3alpha-Hydroxysteroids were not substrates for the enzymes from horse and rat liver. Human liver alcohol dehydrogenase had low affinity for 3beta-hydroxy-5alpha (and 5beta)-cholanoic acids, but oxidation could be clearly demonstrated by gas chromatographic analysis of the products.


Spontaneous rupture of the liver.

Spontaneous rupture of the liver. Four cases of spontaneous rupture of the liver are reported. In all these cases, pathological processes in the liver caused the rupture, i.e. primary hepatoma in 3 cases and a benign angiomatous tumour in one case. In one case, the diagnosis was not established until autopsy and in 3 cases at operation. In one of these latter cases, however, the bleeding source was not found until at a secondary surgical exploration. In none of the patients was the diagnosis suspected preoperatively. Four-quadrant puncture is highly recommended even in patients with only a slight suspicion of intra-abdominal hemorrhage. In cases with a ruptured solitary primary liver tumour, an acute liver resection might be performed. If there are multiple tumours--primary or secondary--simple hemostasis seems to be the treatment of choice. In patients with intra-abdominal hemorrhage, thorough palpation of the whole liver is an obligatory manovre during surgery.


Adrenal mediation of the effect of excess ACTH on testosterone levels in male: a study of a patient with probable ACTH secreting medullary thyroid carcinoma. An adult male patient with probable ectopic ACTH production by a medullary carcinoma of the thyroid, was studied before and after bilateral adrenalectomy. Pre-operatively, the patient had low plasma testosterone levels that returned to normal after surgery. The clinical course and study of the patient showed that, 1) chronic excess of ACTH may lower plasma testosterone levels in man, and 2) that this may be mediated through its effect on the adrenals.


Application of immunofluorescent technique in the cytologic diagnosis of human herpes simplex keratitis. In cases of keratitis it is often desirable for a correct treatment that a rapid etiologic diagnosis is established. This can easily be accomplished by using the immunofluorescent tecnique for the demonstration of herpes simplex viral antigen in corneal epithelium cells.


Oestrogen-inducible uterine progesterone receptors. characteristics in the ovariectomized immature and adult hamster. In order to characterize the uterine progesterone-binding proteins of oestrogen-primed and unprimed, ovariectomized immature and adult golden hamsters, cytosols were incubated with [3H]progesterone and/or other steroids and analyzed by sucrose-glycerol density gradient ultracentrifugation. Progesterone-binding components with sedimentation coefficients of 7S and 4.5S were found in the uterine cytosols, but not in the cytosols from the hypothalamus, pituitary, diaphragm, or small intestine. Oestradiol-17beta markedly elevated the level of 7S uterine receptor and this increase appeared to be due to new receptor synthesis, since actinomycin D and cycloheximide blocked this response. Fifty to 100 mug of oestradiol-17beta per kg body weight was found to promote a maximum increase in the 7S macromolecular component. The 7S receptor showed a tendency to saturate at 1 X 10(-7) M [1,2-3H]progesterone, indicating limited capacity. At a molar ratio of 100:1, unlabeled progesterone competed effectively for 7S and 4,5S [3H]progesterone binding, whereas 5alpha-pregnane-3,20-dione, oestradiol-17beta and testosterone did not. Moreover, [1,2-3H]cortisol and [1,2-3H]corticosterone did not bind to the 7S receptor, implying steroid specificity. CI-628, a non-steroid oestrogen antagonist, completely prevented [6,7-3H]oestradiol-17beta binding to its 8.5S uterine cytosol receptor, but was entirely without effect on 7S and 4.5S [3H]progesterone binding. Pronase, but not DNase or RNase, abolished 7S and 4.5S progesterone binding, suggesting that the binders are at least in part protein. Protamine sulphate and p-hydroxymercuribenzoate also obliterated 7S binding, implying that this receptor may be an acidic protein which contains sulfhydryl groups that are necessary for progesterone binding.


Exfoliative cytopathologic studies in organ transplantation IV. The cytologic diagnosis of herpesvirus in the urine of renal allograft recipients. Cellular changes of herpesvirus infection were found in 12 urine specimens from 4 renal allograft recipients. The cytologic diagnosis of herpes infection in the urine of renal allograft recipients has not been reported previously and is significant because of recent suggestions that viral infection contribute to allograft rejections. We were unable to find a consistent correlation between the cytologic diagnosis of herpesvirus and transplant rejection in the patients we studied.


An attempt to influence by drugs recovery sleep after sleep deprivation. Rats were deprived of sleep by placing them for 36 hours in a slowly moving drum. After this procedure, during recovery sleep, the latency of onset of the first rhombencephalic - paradoxical sleep period decreased and the proportion of telencephalic/rhombencephalic - slow wave sleep reversed (during the first hour of recovery sleep). Repeated administration during the deprivation period of physostigmine (0,5 mg/kg i. p. in 30 min intervals 20-30 times) inducing in waking animals in EEG pattern close to that of rhombencephalic sleep, or atropine (1 mg/kg i. p. in 60 min intervals 10-15 times) evoking an activity resembling telencephalic sleep, did not change the above measures of recovery sleep. Pharmacologically induced sleep-like patterns did not substitute for the sleep the rats were deprived off.


Cytopathogenicity of cytomegalovirus to human ecto- and endocervical epithelial cells in vitro. The effect of cytomegalovirus on cell cultures initiated from human uterine endo- and ectocervix was studied. Pure epithelial cultures were obtained which differed in morphology depending on the source. The ectocervical cells grew in mosaic-like regular epithelial patterns, whereas endocervical cultures had a poorer intercellular cohesion, irregular polygonal cell form and curved cytoplasmic processes. Occasional fibroblastic colonies grew in three out of 32 ectocervical cultures and in none of the endocervical cultures. In the latter no cells with fibroblast-specific surface antigens could be seen. Ectocervical cells were resistant to cytomegalovirus infection; only in three out of 20 cultures could individual altered cells be detected. In contrast, endocervical cultures supported the growth of cytomegalovirus and at best 30 per cent of the explanted colonies showed cytologic alterations as well as virus-specific immunofluorescence. The various types of altered cells are described and it si concluded that endocervical epithelial cells may be the site of replication of human cytomegalovirus so commonly found in cervical secretions.


Some new observations in an intracranial germinoma. A case of an intracranial germinoma from the suprasellar region of a 9-year-old girl was examined in the electron microscope. The tumor consists, for the most part, of both large polygonal and small lymphocyte-like elements. Annulate lamellae are common in the epithelial cells. The small blood vessels are fenestrated, and the endothelial cells contain tubular bodies, membrane-bounded vacuoles containing dense fluid and occasional tubules, arrays of tubules within the nuclear envelope and rough endoplasmic reticulum, and a markedly irregular luminal surface. Dense, lamellated structures are present in the widened, collagen-containing perivascular spaces.


Ultrastructural alterations of tissue cultures from human fetal brain infected with the E variant of EMC virus. Explant outgrowths from human fetal brain were infected with 104 plaque forming units of the E variant of the encephalomyocarditis virus. Ultrastructurally, the majority of the cultured cells were astrocytes containing a moderate amount of glial fibrils. The earliest alterations at 44 hrs after infection of the culture consisted of dilatation of the rough endoplasmic reticulum (ER) and moderate enlargement of the mitochondria with increased density of their matrix. Twenty hours thereafter, increased amounts of the rough ER and of free ribosomes were observed in the infected cells. This was followed by aggregates of larger dense particles which developed into a parallel lattice-like pattern within the cytoplasm, presumably presenting viral particles, without obvious cytonecrosis. The present observations of the continuous development of the crystalloid formation of the virus within the cytoplasmic matrix as well as the mode of formation of the free ribosomes adjacent to the ER support the previous hypothesis that, after the uptake of the virus into the cytoplasmic matrix, it associates with the ER, where production of viral RNA polymerase and of viral RNA is initiated.


Chick muscle in tissue culture: the ubiquity of viral infection. In chick skeletal muscle fibers cultured from embryos of commercially obtained "normal" eggs we have demonstrated numerous C-particles and large amounts of avian leucosis/sarcoma envelope antigen, especially when cultured in the presence of dinitrophenol. C-particles were present in t-tubules, which were possible intracellular viaducts of infection or dissemination and perhaps were the loci of receptors of viral invasion of the cytoplasm and sites of egress. The abundant lace-like membraneous proliferations, probably of t-tubules, usually had C-particles adjacent to or within them and perhaps were virus-provoked. Questioned is the validity of using cultured muscle, or extract, of embryos from ordinary chicken eggs for analysing normal biological phenomena--or conversely, is viral influence "normal" in chick development?


[Cerebral granular cell tumor in the rat after intraperitoneal application of aflatoxin b1 during pregnancy (author's transl)]. On a rat, which has spontaneous died 12 months after 4 times i.p. application of aflatoxin during pregnancy, there has been found a frontal tumor barely of the size of a pepper-corn which came out from the leptomeninx. A comparison to the Abrikossoff tumor concerning the light- and electron-microscope as well as the nucleic-acid concentration is justified. The protein content of the granula of the tumor cells is higher than the values known in the granular-cell myoblastoma of man.


Hematogenous cells in experimental Japanese encephalitis. Four adult mice were injected with 3H-thymidine repeatedly so that in their brains only circulating blood cells were labelled with 3H-thymidine. They then received an intracerebral injection of Japanese encephalitis virus, were sacrified on the 3rd, 4th and 5th day after inoculation: the brains were examined by light and electron microscopic autoradiography. Inflammatory cells appearing in the brain parenchyma and perivascularly in the acute stage of the experimental Japanese encephalitis are derived from circulating mononuclear leukocytes. They assume the shape of "rod cells" and are the main constituents of the "glial nodule" in the brain parenchyma. Their fine structural characteristics are discussed.


Vascular and neuroglial changes in experimental herpes simplex encephalitis enzyme histochemical study. An enzyme histochemical study of experimental herpes simplex encephalitis of the mouse has revealed a decrease in the number of capillaries displaying alkaline phosphatase activity. Glial cells showed increased Inosine 5 diphosphatase and ATPase activity. These enzyme histochemical changes were distributed throughout the nervous parenchyma while the lesions, seen by light microscopy, are localized to well defined areas. Mice inoculated with a pure culture of irradiated HSV failed to show the above mentioned modifications.


Fine structure of intercellular junctions and blood vessels in medulloblastomas. Six medulloblastomas were studied by electron microscopy. Two features were found which seem to be constant and essential characteristics of medulloblastoma. First, cell junctions are abundant between tumor cells. These are mostly desmosome-like but other, closer junctions, were also seen. Second, the capillary endothelia contain frequent tubular bodies and other inclusions which may be related to them.


Phagocytosis in the choroidal endothelium of the ischaemic rabbit eye. Phagosomes containing membranous debris were found in the choroidal endothelium of rabbits following periods of acute pressure ischaemia and also accompanying periods of post-ischaemic recovery. The membranous debris may be of visual cell origin and pass into the choroid by a transpigment epithelial route. Ischaemia may be a sufficient stimulus to induce the vascular endothelium to engulf this material. The phagosomes were found only in ischaemic or post-ischaemic tissue.


Development of osteopenia in the fourth lumbar vertebra during prolonged bed rest after operation for scoliosis. The fourth lumbar vertebra was studied with dual photon absorptiometry in a group of young women immobilized in bed for 21 to 46 days after operation for scoliosis. Twelve out of 13 showed loss of bone content. The monthly loss in most patients highly exceeded earlier reported losses from other bones and significantly exceeded the methodological error.


Mechanism of the formation of megamitochondria induced by copper-chelating agents. III. Formation and some biochemical properties of megamitochondria induced by diethyldithiocarbamate (DDC). Sodium diethyldithiocarbamate (DDC), a copper-chelating agent, has induced megamitochondria in mouse hepatocytes simply by feeding the animal with a diet containing the noxious agent. Megamitochondria have been isolated from the liver, specified above, in a medium containing albumin. Phosphorylating capacities of such megamitochondria have revealed that they are tightly coupled. Biochemical properties of megamitochondria, such as cytochrome contents, activities of copper-containing enzymes. and contents of Cu2+, strongly suggest that copper-chelating action of the agent may not be related to the formation of megamitochondria just as in the case of cuprizone-induced megamitochondria. Moreover, contents of divalent metals such as Ca2+ and Mg2+ were drastically decreased in the mitochondrial preparation specified above. Similarities in biochemical aspects of DDC-induced megamitochondria to those of cuprizone-induced megamitochondria together with ultrastructural changes in the liver and clinical appearances of the mouse treated with the agent would strongly suggest that the mechanism of the formation of megamitochondria induced either by DDC or by cuprizone may be the same.


The relationship of gastrointestinal endocrine cells to gastric epithelial changes with special reference to gastric cancer. Using advanced gastric adenocarcinoma and carcinoid as human material and gastric adenocarcinoma in rats induced by MNNG and in mice by localized X-irradiation of the stomach as experimental material, a pathological study was made on the relationship of gastric endocrine cells to gastric cancer. The results of the present study suggest that most of the endocrine cells in the cancer tissue are derived from the differentiation of cancer cells. Therefore, the following three may be given as the aformentioned relationship, that is, 1) carcinoid of endocrine cell origin, 2) endocrine cell carcinoma showing undifferentiated adenocarcinoma, and 3) endocrine cell cloning developed from the differentiation of cancer cell of adenocarcinoma. There is the possibility that most of 2) are of 3) origin and thus 2) and 3) should be discriminated from 1), having a functioning tumor in rare cases. The significance of reactive hyperplasia of endocrine cells in the non-metaplastic mucosa of the stomach around cancer and atypical epithelium is not yet determined, but that of EC cell seems at least to be related with the development of intestinal metaplasia in the gastric mucosa.


The formation of enlarged and giant mitochondria in the aging process of human hepatic cells. Measurement of area, circumference and total length of membrane profile of mitochondria of hepatic cells in 61 human biopsy materials (age range 21 to 81 years) have been ultramicrometrically performed on electron micrographs, supplemented by electroncytochemical examination of cytochrome c oxidase activity in some cases. The mitochondria decreased in number after 60 years of age. The first stage of compensation for the numerical loss of mitochondria was achieved by an increase of cristae in each mitochondrion, followed with a five year lag by an increase in their size. Formation of enlarged and giant mitochondria in aging process following the significant decrease in their number, may be considered to be of similar mechanism to polyploidization of the nucleus, whose division is interfered.


Damage to the stria vascularis in the guinea pig by acute atoxyl intoxication. The aim of the present study was to show the morphological degeneration at the ultrastructural level, after damaging the stria vascularis experimentally. The acute lesions, after acute atoxyl intoxication, occur after about 12 hours, and begin as a degeneration of both the marginal and the intermediate cells, whereas the basal cells remain mainly unaffected. The severely damaged marginal or intermediate cells may become loosened from the stria vascularis and rejected from it into the endolymphatic space. Under such conditions the basal cells may line the surface facing the endolymph, although this occurs very rarely. Intially, there may be a slight bulging of Reissner's membrane, but soon the membrane becomes depressed, and sometimes a total collapse occurs, with Reissner's membrane flattened over the tectorial membrane against the organ of Corti. It is only seldom that Reissner's membrane touches the strial surface. Mitochondrial degeneration with formation of intramitochondrial inclusion bodies is an interesting early finding in the damage pattern.


Induction of metastasizing carcinoma in rats and their biological characteristics. Induction of a spontaneously metastasizing carcinoma in rats was attempted. Four-week-old Sprague-Dawley female rats were thymectomized or/and splenectomized and fed 200 mg (20 mg times 10) of 3-methylcholanthrene from 7 weeks of age. In addition to these treatments, the early-appearing tumors were excised in order to select by isoimmunity the late-appearing ones that were less antigenic. The latter were easily transplanted into normal syngeneic female rats with metastasis to remote organs. This metastasizing capacity of the tumor became an inherent character in syngeneic normal rats from generation to generation of transplantation. With one of these tumors (MRMT-1) many cancer cells were histologically detected in circulating blood 3 days after tumor transplantation and arrested in capillary beds of lungs. The spontaneous metastasis to lymph nodes and lungs was macroscopically found within several weeks after tumor transplantation.


Time course of changes in plasma renin after blockade of the renin-system. Studies of conscious and anaesthetized, normal, adrenalectomized and spontaneously hypertensive rats. Inhibition of the angiotensin I converting enzyme with SQ 20.881 results in a 2 to 35 fold increase in plasma renin concentration in normal rats and in spontaneously hypertensive rats. The effect is transient, lasting for 1 to 3 hours even in the presence of prolonged blockade. The relative increase is independent of the pretreatment plasma renin concentration. The blood pressure is unchanged in conscious rats in which the effect of SQ 20.881 on plasma renin is believed to be due to a blockade of the negative feedback of angiotensin II on renin release. In anaesthetized rats, SQ 20.88) has an additional hypotensive effect which augments the increase in plasma renin. Saralasin is without effect on blood pressure and plasma renin in conscious normal rats and in spontaneously hypertensive rats, while it causes a transient 3 to 27 fold increase in plasma renin concentration in anaesthetized rats. It is suggested that this increase is hardly due to an interception of the feedback, but to the concomitant fall in blood pressure, as a similar hypotension and increase in plasma renin is produced by dihydralazine. It is furthermore found that Saralasin blocks renin release induced by SQ 20.881. This demonstrates that Saralasin is bound to the receptors in the juxtaglomerular cells and has slight, agonistic properties there. Both in conscious rats and in anaesthetized adrenalectomized rats substituted with DOCA and salt, SQ 20.881 as well Saralasin causes transient increases in plasma renin concentration. If such rats are only substituted with salt and not with DOCA, the effects of both blockers are in the form of severe hypotension and a permanent elevation of plasma renin.


The possible utilization of nuclear pockets of lymphocytes in the diagnosis of enzootic bovine leucosis. A comparative study of the presence of lymphocytosis and nuclear pockets in lymphocytes was carried out using blood samples from animals belonging to herds with bovine enzootic leucosis and from herds free from leucosis. It was found that there was a correlation between the presence of such nuclear projections in a certain percentage of the lymphocytes and a state of lymphocytosis. As this correlation seemed to be independent of the aetiology of the lymphocytosis, it was not considered possible to employ the demonstration of nuclear pockets as a more specific tool in the diagnosis of bovine enzootic leucosis than the lymphocyte counts in themselves.


Canine mycoplasmas: cultural and biochemical studies of type and reference strains. Media and conditions for cultivation of type and reference strains of the mycoplasmas presently known (except M. bovigenitalium, A. laidlawii and Ureaplasma strains) to occur in dogs are described. The colonial morphology, ultrastructure, filterability and absence of reversion confirmed that the strains belong to the order of Mycoplasmatales. All strains were cholesterol dependent and therefore of the family Mycoplasmataceae, genus Mycoplasma. Finally the most useful biochemical characteristics are specified.


Subtyping of herpes simplex virus.

Subtyping of herpes simplex virus. A number of different techniques to be used for the subtyping of herpes simplex virus (HSV) strains were studied. The strains were inoculated on chorio-allantoic membranes of embryonated eggs and on green monkey kidney (GMK) cells in order that the morphology of plaques produced might be observed. They were classified serologically by determination of K-values and inoculated intracerebrally in mice in order that their pathogenicity for mice might be observed. The inhibitory effect of high concentrations of thymidine on the multiplication of the strains in GMK cells cultures and the heat-stability of the virus-induced thymidine kinases were investigated. Rates of inactivation of the strains in the presence of AgNO3 were compared and, finally, the association of focal liver necrosis in intraperitoneally inoculated mice with the results of the serological typing was observed. The results suggested that the liver necrosis test was simple as well as accurate and useful as a screening typing-test. Reliable results were also obtained serologically and by the method demonstrating differences in the heat-stability of viral thymidine kinase. Using the other methods studied, difficulties to obtain clear-cut or reproducible typing results were encountered.


Enzyme activities and muscle strength after "sprint training" in man. Sprint type strength training was performed 3-4 times a week for 8 weeks by 4 healthy male students (16-18 yrs). The training was carried out on a treadmill at high speed and with high inclination. Muscle biopsies were obtained from vastus lateralis before and after the training period for histochemical classification of slow and fast twitch muscle fibres and for biochemical determination of metabolites and enzyme activities. Muscle fibre type distribution was unchanged, whereas fibre area indicated an increase for both fibre types in 3 subjects after training. The muscle enzyme activities of Mg2+ stimulated ATPase, myokinase and creatine phosphokinase increased 30, 20, and 36 percent, respectively. Muscle concentration of ATP and creatine phosphate (CP) did not change with training. Sargent's jump increased with on average 4 cm (from 47 to 51 cm), maximal voluntary contraction (MVC) with 19 kp (from 165 to 184 kp), and endurance at 50 percent of MVC with 9 s (from 47 to 56 s), respectively. After training all subjects showed a gain in body weight (mean 1.4 kg) and in thigh circumference (mean 1.5 cm) indicating a larger leg muscle volume and consequently also an increase in total ATP and CP.


Characterization of the metabolism of exogenous cyclic AMP by perfused rat heart and incubated prepubertal rat ovary. In order to study the metabolism of extracellular 3',5'-adenosine monophosphate (cAMP), rat hearts were perfused and prepubertal rat ovaries incubated with 3H- and 32P-labelled cAMP (0.025-1 muM). The rate of disappearance of cAMP from the medium was determined by "Ba-Zn-precipitation" and degradation products of 3H- and 32P-CAMP by paper chromatography. Both tissues degraded cAMP to 5'-adenosine monophosphate (AMP), but the enzyme kinetic for this phosphodiesterase activity was different (apparent Km value for the heart 3.95 muM and for the ovary 0.2 muM). AMP was further degraded, since also other labelled substances were found in the medium. An uptake of both 3H- and 32P-labelled substance(s) into the heart and the ovary was noticed. Tissue extracts contained several labelled purines, but the amounts of labelled cAMP did not exceed expected amounts in the extracellular space. In the ovary the uptake of cAMP and AMP seemed to be low, since the uptake of labelled substances was inhibited by high concentrations of unlabelled AMP or adenosine. The degradation of 32P-cAMP was unchanged when AMP was present, strongly suggesting that the phosphodiesterase enzyme was acting extracellularly. In the heart added AMP was very rapidly degraded making it impossible to elucidate whether cAMP was degraded extracellularly or not. It is concluded that elimination of extracellular cAMP under physiological conditions can be due to degradation of cAMP by various tissues. At least for the ovary this phosphodiesterase enzyme is extracellularly active.


Imitation of glucagon effects on splanchnic hemodynamics and liver function by N6,2'-O-dibutyryl 3',5'-cyclic AMP (DBcAMP) in cats. Fasting cats anesthetized with chloralose were used for the experiments. DBcAMP infused at a rate of 340 nmol/kg/min increased the gastrointestinal and intrahepatic portal conductances whereas the hepatic arterial conductance was decreased. The hemodynamic responses to portal and systemic venous administration of DBcAMP were identical. In  half of the experiments DBcAMP increased the splanchnic ethanol elimination rate and oxygen consumption and in all experiments there was a decrease in the plasma clearance and extraction ratio of Indocyanine Green. No change in bile flow was observed. DBcAMP infused at a rate of 85 nmol/kg/min was without significant effects on either splanchnic hemodynamics or liver metabolism. DBcAMP infused at a rate of 850 nmol/kg/min accentuated the decrease in hepatic arterial conductanc- but was found to decrease the splanchnic ethanol elimination rate and oxygen cownsumption. Infusion of cAMP, AMP and adenosine at a rate of 340 nmol/kg/min were without measurable effects. Based on these results it is concluded that like the metabolic effects also the vascular effects of glucagon are caused by stimulation of specific glucagon receptors which results in an intracellular release of cAMP.


Rat liver mitochondrial enzyme activities in hypoxia. Rat liver mitochondrial enzyme activities were measured after exposing the animals to the atmospheric pressure of 380 mm Hg for 5 h and 14 days. Succinate dehydrogenase and succinate oxidase activities increased significantly during the hypoxic period of 14 days. No change was observed in cytochrome oxidase activity. Malate dehydrogenase and glutamate dehydrogenase activities increased somewhat, but not significantly. The efficiency of oxidative phosphorylation (the ADP:O ratio) in the isolated mitochondria remained unchanged. The exact mitochondrial protein values showed a 15% decrease as compared with the control group. The concentrations of cytochromes did not change significantly in the hypoxic group. During the short hypoxic period succinate dehydrogenase, succinate oxidase and cytochrome oxidase activities increased as compared with those in the control group.


Studies in asymptomatic primary hyperlipidaemia. V. Peripheral circulation. The occurrence of early signs of peripheral vascular disease (PVD) of the lower limbs has been studied with digital pulse plethysmography in 160 men and 123 women above the age of 35, who were all subjectively healthy but were found to have primary hyperlipoproteinaemia (HLP) at a health control centre. Quantitative analysis of serum lipoproteins with cholesterol and triglyceride (TG) determination of each of the very low (VLDL), low (LDL) and high (HDL) density lipoprotein clases together with lipoprotein paper electrophoresis was performed. Identical investigations were performed on control subjects with non-elevated serum lipids. Inclination time (IT) was substantially prolonged in 12% of HLP males and 7% of HLP females. The frequency of male subjects with prolonged IT was lower when only LDL was elevated (type IIA) than in the other types of HLP. The subjects with prolonged IT had three characteristic features. 1) Moderate elevations of both serum cholesterol and TG. These elevations occurred often in both VLDL and LDL lipoprotein classes. IT prolongations were not seen when VLDL or LDL lipoproteins were singly maredly elevated. 2) High frequency of smokers. 3) Most of the subjects were above the age of 50. The results suggest that the most atherogenic lipoprotein abnormalities to the arteries of the lower limb are on the one hand the relatively TG-rich part of the LDL (LDL1) fraction and on the other hand the relatively cholesterol-rich part of the VLDL fraction. Furthermore the results stress the deleterious influence of smoking even in the preclinical stage of PVD.


Studies on the serum lipid and lipoproteins in steatosis of the liver. In a medical department, specialized in liver diseases, 45 patients (33 men and 12 women) suffering from steatosis of the liver have been examined with reference to serum lipid abnormalities. Twenty-eight of the patients were chronic alcoholics. Annual check-ups, including biopsy of the liver, were made to evaluate the development of the steatosis. The patients did not receive treatment with drugs or diet. Thirteen patients showed hypercholesterolemia, 16 increased serum triglyceride and 8 increased serum phosphorus lipid. Two showed a type I lipoprotein anomaly and 33 a type II-like pattern, defined as increased beta-lipoprotein associated with increase of serum cholesterol, was found in four cases. Three had a type III and three a type IV abnormal pattern, with increased pre-beta-lipoprotein and serum triglyceride levels. Correlation analysis revealed correlations between pre-beta-lipoprotein and serum triglyceride as well as between serum triglyceride and serum free fatty acid levels.


Studies in asymptomatic primary hyperlipidaemia. I. Types of hyperlipoproteinaemias and serum lipoprotein concentrations, compositions and interrelations. 1. In order to study lipoprotein (LP) abnormalities in asymptomatic subjects with hyperlipidaemia, serum cholesterol and triglycerides (TG) were determined in about 20 000 active professional men and women attending a health control linked to their employment. 2. Quantitative LP analysis with preparative ultracentrifugation, separating very low (VLDL), low (LDL) and high (HDL) density LP was subsequently performed on the sera of 314 asymptomatic subjects, who at the screening had serum cholesterol larger than or equal to 350 mg/100 ml and/or TG larger than or equal to 3.5 mmol/l. Cholesterol and TG concentrations were serum and on the top and bottom fractions after separation in the ultracentrifuge at d=1.006. Typing of hyperlipoproteinaemia (HLP) was based on the concentration of VLDL TG and LDL cholesterol and in addition, in the case of type III and V HLP, the presence of a "floating beta" LP and fasting chylomicronaemia, respectively. 3. To illustrate the lipid values in the screened total population distributions of serum cholesterol and TG are given in the age range 41-45 years. In this age range mean serum cholesterol in fasting/non-fasting state was 239+/-2/238+/-1 mg/100 ml in males and 232+/-2/239+/-2 mg/100 ml in females.


Studies in asymptomatic primary hyperlipidaemia. Clinical, biochemical and physiological investigations. 1. To determine lipoprotein (LP) abnormalities, clinical characteristics and preclinical signs of atherosclerosis in asymptomatic subjects with hyperlipidaemia serum cholesterol and triglyceride (TG) concentrations were determined in 20,000 subjects attending a health control centre linked to their employment. 2. Three hundred and fourteen asymptomatic subjects with serum cholesterol larger than or equal to 350 mg/100 ml and/or TG larger than or equal to 3.50 mmol/l in the screening test but without signs or symptoms of secondary hyperlipideaemia or history of cardiovascular disease were examined further. 3. LP analysis with preparative ultracentrifugation separating very lof cholestrol and TG concentrations in each fraction was performed. LP paper electrophoresis was run on while serum and on top and bottom fractions after separation in the ultracentrifuge at d=1.006. Typing of hyperlipoproteinaemia (HLP) was performed according to WO based upon the values of for VLDL and LDL. Exercise ECG was performed on a heart rate controlled bicycle ergometer. The subjects worked at constant predetermined heart rates. ECG at rest and furing exercise was interpreted without knowledge of whether or not the subject has HLP and coded according to the Minnesota criteria. Digital pulse plethysmography was performed on the lower limbs....


Studies in asymptomatic primary hyperlipidaemia. IV. ECG at rest and during exercise and its relation to various lipoprotein classes. Among approximately 20,000 apparently healthy subjects whose serum cholesterol and triglyceride (TG) values were screened at a health examination, those with the most pronounced hyperlipidaemia have been selected for further studies. Thus, 188 males and 126 females, aged 30-65 years, with asymptomatic primary hyperlipoproteinaemia (HLP) and 59 male and 69 female controls with non-elevated serum lipids were studied with regard to frequency of ST segment depressions during exercise to near maximal heart rate. Furthermore, the concentrations of cholesterol and TG were determined in the lipoprotein (LP) classes very low (VLDL), low (LDL) and high (HDL) density LP, separated by preparative ultracentrifugation. From the LP analysis each subject's HLP was classified according to the typing system of HLP recommended by the WHO. The frequency of ST depressions (Minnesota code 4.1-4.3 as well as 4.1-4.4) increased with age, was higher in females than in males and was increased in all types of HLP in males. The percentage frequencies of ST depressions 4.1-4.4 in the various types of HLP were (male/female, p against controls): controls 16/36, type IIA 50 (p less than 0.01)/56, type IIB 64 (p less than 0.01)/75 (p less than 0.01)/75 (p less than 0.05), type III 67 (p less than 0.01)/33 and type IV HLP 40 (p less than 0.01/53. There was no significant difference in the frequencies of ST depressions in subjects with "high" and "low" BP (hypertensives were excluded from the study) or in subjects with "high" and "low" k-value for the i.v. glucose tolerance. Non-smokers had a tendency to higher frequencies of ST depressions than smokers. The association between different LPs and other "risk factors" and the occurrence of ST depressions in HLP were studied further with multiple regression analysis. Invariably age was the best predictor of ST depressions. The LP fraction giving the highest correlation coefficient was LDL cholesterol in both sexes. VLDL TG and LDL TG were also positively and significantly associated with ST depressions. HDL cholesterol was negatively but insignificantly correlated to ST depressions. When age and LDL cholesterol had been entered into the multiple regression, the only factor giving further significance was VLDL TG in males. Probability tables for the occurrence of ST depressions considering age and different levels of LDL cholesterol and VLDL TG were given. The importance of simultaneous consideration of both VLDL TG and LDL cholesterol in ST segment depression was evident from the tables. Of other "risk factors" (BP, glucose tollerance, smoking, ESR) entered into the regression together with only age and the LPs, only ESR contributed with borderline significance to ST depressions.


Differential inhibition of phosphodiesterase according to the organ origin of the enzyme. Essential differences in the degree of papaverine [5 x 10(-5) M]- and theophylline [1 x 10(-3) M]-induced inhibition of cyclic nucleotide phosphodiesterase (PDE) were found in homogenates from different structures of the CNS as well as from different organs of male albino rats. Both inhibitors of PDE showed a mosaic pattern of their inhibitory effects on the enzyme activity of the brain structures tested. Papaverine inhibited PDE by 36 percent in the spinal cord, 53 percent in the cerebellum, 56 percent in the cortex, and 75 percent in the brain stem. Theophylline inhibited PDE least in the cerebellum (26 percent ) and most markedly in the brain stem (68 percent). Still larger differences were observed in the inhibitory action of papaverine and theophylline on PDE of the organs tested (e.g., papaverine inhibited PDE by 6 percent in the heart and 73 percent in the spleen; theophylline inhibited PDE by 26 percent in the adrenals and by 72 percent in the heart. The mosaic sensitivity of PDE in different organs and brain structures to papaverine and theophylline was considered as an expression of isoenzyme heterogeneity.


Do sleep patterns relate to the desire for alcohol? A measure of disposition to drink in alcoholics was developed using a progressive ratio schedule for reduction of delay in receiving a drink of two ounces of 95 proof ethanol. This measure showed increased disposition to drink during early abstinence compared to lab abstinence (more than seven days) during experimental intoxication compared to lab abstinence and shortly after a low dose drink during late abstinence. A multiple regression analysis of this measure for four subjects after alcohol withdrawal, showed significant effects for days abstinent and EEG sleep variables, particularly stage REM%. Low REM% was associated with high values for the disposition to drink. REM sleep deprivation, however, failed to significantly alter the measure of disposition to drink. Results are interpreted as supporting the hypotheses that sleep disturbances relate indirectly to the disposition to drink.


Calcium pyrophosphate-induced pleurisy in rats: a new model of acute inflammation. A model is described of acute inflammation in the pleural cavity of rats using calcium pyrophosphate as the irritant. This model would seem to simulate the pseudogout syndrome. It has been shown to be acute in onset, dominated by polymorphonuclear cells, complement independent. The advantage of the model is that volume of exudate, numbers and types of cells may be quantitated. Prostaglandins and cyclic AMP have been measured in the migrating cells. The significance of these findings has been discussed.


A comparison of the relative rates of hemolysis induced by various fibrogenic and non-fibrogenic particles with washed rat erythrocytes in vitro. Correlations between in vitro hemolytic activity and the in vivo fibrogenic activity of a number of particulate materials are demonstrated. Fibrogenic particles are capable of inducing hemolysis, while non-fibrogenic particles are not. It is suggested that particulates inducing a rate of hemolysis greater than 1 X 10(-4) min-1 may be fibrogenic.


Free silica analysis of environmental samples-a critical literature review. The various analytical procedures for the analysis of free silica in environmental samples all suffer serious deficiencies, to the extent that there is no acceptable routine method. Each sample represents a minor research effort. Many of the uncertainties are related to an amorphous surface layer on quartz.


1975 Yant Memorial Lecture New aspects on dust and pneumoconiosis research. This lecture deals with pneumoconiosis, in particular with fibrotic tissue reactions caused by SiO2 and asbestos dusts in the lungs. The term "fine dusts" is defined in connection with the setting up of MAC-values. The aerodynamical diameter of particle shaped and fibrifom dust is set forth. Results of the fundamental research with SiO2, Coal mine and asbestos dusts in animal and cell experiments are explained.


Echocardiographic diagnosis of right atrial extension of Wilms' tumor. A fourth case is presented of propagation of Wilms' tumor to the right atrium through the inferior vena cava. Ultrasonic examination of the heart was diagnostic of the tumor and the diagnosis was confirmed by angiographic studies and surgical exploration. This report provides the first echocardiographic description of a right atrial tumor in a child.


Renewal of the epithelium in the descending colon of the mouse. IV. Cell population kinetics of vacuolated-columnar and mucous cells. Proliferation and migration of cells in the vacuolated-columnar and mucous cell lines were studied in the descending colon of adult female mice given a single injection or a continuous infusion of 3H-thymidine and killed at various intervals from one hour to 12 days. This investigation was carried out using one mum-thick Epon sections which were radioautographed after staining with the periodic acid-Schiff technique and iron-hematoxylin. In the normalized crypts with ten equal segments, labeled vacuolated cells at one hour after injection of 3H-thymidine were encountered in the lower four segments and in decreasing numbers in segments 5 through 7. From the percent labeled cells in segments of the crypt, the birth rate and fluxes of cells were computed. Moreover, it was found that a cell in the vacuolated-columnar cell line would undergo three mitotic cycles on the average from its birth at the cryptal base to its extrusion from the surface; of these three cycles, the last one which took place from segment 3 to segment 7 appeared to be a changeover from dividing cells to non-dividing cells, in accordance with the "slow cut-off" model of Cairnie et al. ('65b). Mucous cells located in segments 1 through 6 of the crypt were capable of incorporating 3H-thymidine and thus capable of undergoing mitosis. However, the rate of turnover of mucous cells based on proliferative rate was found to be much lower than the rate of turnover of mucous cells based on the transit time in the non-dividing segments of the crypt. Since there was a concomitant overproduction of cells in the vacuolated cells and newly formed mucous cells in the lower portion of the crypt, it was concluded that some vacuolated cells would give rise to mucous cells. This putative transformation occurred in the lower four segments of the crypt. Mucous cells which were formed by transformation would migrate upward along the cryptal wall and accumulate more mucus in the theca; in doing so, they would undergo two divisions, on the average, before they became non-dividing mucous cells. In ascending the cryptal walls, both vacuolated-columnar cells and mucous cells appeared to migrate at a similar speed; they moved much slower at the base of the crypt and accelerated toward the upper portion of the crypt, but they migrated at a constant speed in the non-dividing segments of the crypt.


Cytopathological effects of estradiol on the arcuate nucleus of the female rat. A possible mechanism for pituitary tumorigenesis. Large subcutaneous doses (2 mg/21 days) of estradiol valerate (EV) given over several months will induce a prolactin and growth hormone-secreting pituitary tumor in female rats. The medial basal hypothalami (MBHs) of such EV-treated animals were examined at different time intervals with light and electron microscopes to determine whether EV affects the MBH and to relate any observed effects to the process of tumorigenesis. The MBHs of extensively treated rats exhibited profound glial and neuronal changes. The filament content of astrocytes was greatly increased and large dense pleomorphic inclusions filled both astrocytic perikarya and processes. Degenerating neuronal elements have been observed in the neuropil of extensively treated animals. Dark cells identified as M cells were seen to engage in phagocytosis and were loaded with dense inclusions. Some neurons in MBH contained large quantities of lipofuscin that was different in appearance from that of normal females of the same age. The glial reaction developed gradually. At earlier stages of EV treatment there were fewer reactive glia and these contained fewer inclusions. Myelin figures often occurred in these early inclusions. Reactive glia in EV-treated rats did not appear in the preoptic area, dorsomedial nucleus or lateral hypothalamus but were found in ventromedial nucleus. Retired breeders and starvation-stressed rats resembled normal controls. These pathological changes in MBH may result from a direct effect of EV on the hypothalamus. It is possible that, in addition to its effects on the hypophysis, EV suppresses or injures hypophysiotropic cells in MBH, thus releasing pituitary chromophobes from inhibitory hypothalamic influences. This could result in hypersecretion and neoplasia.


Quantitative morphology and carbohydrate histochemistry of the mouse submandibular gland following prepubertal castration. The endocrinologic basis for morphological and biochemical sex differences in the mouse submandibular gland have not been clarified. Previous studies have emphasized the maintenance of glandular differences in adult animals, rather than considering the factors responsible for their developmental etiology. Male CD-1 mice were castrated at intervals between 10 and 50 days of age and killed at 100 days. The quantitative development of granular tubules and the carbohydrate histochemistry of the submandibular glands were compared to untreated males and females. The area of granular tubules increased with age at castration. Nested analysis of variance indicated significant differences among treatments and among sections within individual glands. No group of castrated males had a greater development of tubules than untreated females. Carbohydrate histochemistry demonstrated an increase in carboxylated mucosubstances in the acinar cells and granular tubule cells of castrated animals.


Comparison of the adaptive changes in disaccharidase, glycolytic enzyme and fructosediphosphatase activities after intravenous and oral glucose in normal men. Seven subjects were fed a 3,000 kcal defined formula diet daily for 19 days. Except for one 5-day period, 50% of the total caloric intake was provided as either oral or intravenous glucose. The study was divided into four periods as follows: period I lasted 5 days and provided 50% of calories as glucose; period II lasted 5 days and provided no carbohydrate (70% fat and 30% protein); period III lasted 4 days and provided 50% of calories as intravenous glucose and 50% of calories as oral fat plus protein; period IV lasted 5 days and provided 50% of calories as oral glucose. Intestinal biopsy specimens were taken on days 3 and 5 of each period, except period III when biopsies were done only on day 4. No change in intestinal morphology occurred during the study. The carbohydrate-free diet caused the alpha-glucosidase (maltase and sucrase) activities to decrease significantly from that seen with the glucose diet. Sucrase decreased from 14.4 +/- 1.0 to 7.1 +/- 0.9 mumoles/min per g tissue and maltase decreased from 56.1 +/- 3.4 to 30.0 +/- 2.1 mumoles/min per g tissue. Glycolytic enzyme activities decreased during the carbohydrate-free period (pyruvate kinase decreased from 236 +/- 12 to 78 +/- 8, fructose 1-phosphate aldolase decreased from 147 +/- 6 to 53 +/- 4, fructose-1,6-diphosphate aldolase decreased from 151 +/- 8 to 55 +/- 3, and hexokinase decreased from 21 +/- 3 to 7 +/- 1 nmoles/min per mg protein, respectively). Intravenous glucose caused no change in disaccharidase activities. The enzyme activities during periods I and IV were identical and significantly higher than during period II with the exception of fructose-1,6-diphosphatase which increased during period II as compared with periods I and IV. These findings provide an explanation for the transient period of decreased tolerance to dietary sugars when patients are weaned from total parenteral feedings to enteral feedings.


Fatal disseminated adenovirus infection in a renal transplant recipient. A 61 year old woman died of diffuse interstitial adenovirus pneumonia 55 days after receiving a cadaveric renal allograft. The adenovirus was serologically distinct from the 33 known human adenovirus serotypes and appears to represent a new human adenovirus. Pathologic and virological findings indicate that the pneumonia was only one manifestation of a disseminated infection, the source of which may have been a latent adenovirus infection preexisting in the donor kidney. The establishment of the etiologic diagnosis in this case, which was complicated by the presence of oculocutaneous and esophageal herpes simplex virus infection as well as focal pulmonary aspergillosis, required coordinated histopathologic and virological investigation. Our findings demonstrate that severe viral infections in transplant recipients are not caused exclusively by members of the herpesvirus group.


Placental insufficiency in relation to postterm pregnancy and fetal postmaturity. Evaluation of fetoplacental function; management of the postterm gravida. As pregnancy extends post term, incidence of placental insufficiency, fetal postmaturity (dysmaturity), and fetal perinatal death increases rapidly as a consequence of reduced respiratory and nutritive placental function. Despite a compensatory fetoplacental respiratory reserve capacity, fetal distress is observed in about one third of postterm pregnancies. On a biochemical level, placental pathophysiology in postterm-postmaturity pregnancies is not well understood. Postmaturity is correlated with increased incidence of placental lesions, fetal hypoxia-asphyxia, intrauterine growth retardation, increased perinatal death, and neonatal morbidity. Early diagnosis of fetal postmaturity is difficult because currently applied test methods allow recognition only when placental insufficiency is far progressed. Therefore, in postterm gravidas with a favorable cervix, induction of labor should be considered; in older primigravidas, in whom fetal losses may be sevenfold increased, or in multiparas with a history of obstetric complications, pregnancy may require termination by cesarean section. Pregnancy may be allowed to continue under close supervision in cases of uncertainty of duration of gestation, in gravidas carrying small babies, in young primigravidas, and in multigravidas in whom placentofetal function tests are normal. As long as fetal scalp blood sampling during labor does not show fetal acidosis, despite abnormal fetal heart rate pattern and meconium release, vaginal delivery may be attempted when deemed possible within a few hours. In parturients attention must be paid to the extent of uterine activity and type of medication; lateral positioning of the gravida and maternal oxygen breathing, facilitating fetal oxygen supply, are important features. Because during bearing-down efforts placentofetal respiratory reserves of postterm gravidas may become further compromised, immediate delivery by forceps or vacuum extraction may be considered. After delivery the umbilical cord should not be clamped immediately in order to allow increased fetal blood supply and to counteract fetal hypovolemia. Dysmature newborn infants require special care by the neonatologist.


The epidemiology and interrelationship of cervical dysplasia and type 2 herpesvirus in a low-income housing project. This report examines the association between cervical dysplasia and herpes simplex virus type 2 antibodies in a low-income housing project, Atlanta, Georgia. We established a clinic in this project at which women could receive a breast examination and Papanicolaou smear and have blood drawn to be tested for herpesvirus type 2 antibodies. Prevalence of herpesvirus rose sharply as age increased. There was a significant absence of antibodies in young, nulliparous women. Dysplasia showed a tendency to be related to age, age at first pregnancy, and total number of pregnancies. None of these associations was significant. The major finding of the study was that the 15- to 24-year-old women with herpesvirus had a relative risk of 5.44 of having cervical dysplasia compared to women without herpesvirus antibodies. these data are consistent with the concept that herpesvirus infections may be etiologically related to the initiation of cervical neoplasia. However, a cohort study is needed to determine whether herpes infection precedes or follows the earliest neoplastic changes.


Evaluation of serum progesterone during treatment of malignant trophoblastic disease. Serial assays of serum progesterone and serum human chorionic gonadotropin (HCG) were performed in eight cases of choriocarcinoma before and during treatment of the disease. Serum progesterone was measured by the competitive protein-binding technique and serum HCG was measured by the hemagglutination inhibition method. Serum HCG gives a better index of response of the tumor to treatment when compared to serum progesterone. In cases where the ovaries are still present serum progesterone does not disappear completely when the disease is eradicated and fluctuates cyclically, thus reflecting ovarian activity. However, in most cases with pulmonary secondaries, serum progesterone was elevated in spite of undetectable serum HCG. With widespread metastases serum progesterone rose to pregnancy levels and remained persistently high. Cerebrospinal fluid progesterone in a case of choriocarcinoma with cerebral metastasis was 5 ng. per milliliter, which was very much higher than in normal pregnant subjects. The findings of serum progesterone in comparison to serum HCG during therapy of choriocarcinoma are discussed.


Intrauterine pressure wave form characteristics in hypocontractile labor before and after oxytocin administration. The data demonstrate that the contractions of hypocontractile active labor and normal spontaneous labor are different in several measures in addition to maximal amplitude. Furthermore, when the pathophysiology is corrected by the use of oxytocin, the contractions resemble those of normal spontaneous labor except in the maximal rate of tension development. Our data tend to support the subcellular model of uterine contractility, although the incompleteness of these models limits interpretation.


Purification of human placental estradiol 17 beta-dehydrogenase study of the steroid-binding site. Human placental estradiol 17 beta-dehydrogenase has been purified by affinity chromatography. The purified enzyme is homogenous by polyacrylamide-gel electrophoresis. To study topography of the steroid-binding site, 16 alpha-bromoacetoxyestradiol 3-methyl ether was synthesized with estriol 3-methyl ether, bromoacetic acid, or [2-3H] bromoacetic acid and dicyclohexylcarbodiimide. The steroid alkylates cysteine, histidine, methionine, and tryptophan under physiologic conditions. Being a substrate of the enzyme, it must bind at the steroid-binding site. The steroid inactivates the enzyme in a time-dependent, irreversible manner. Inactivation of the enzyme by excess 16 alpha-bromoacetoxyestradiol 3-methyl ether follows pseudo--first-order kinetics with t1/2 = 1.5 hours. Amino acid analysis reveals that a histidyl residue is carboxymethylated. Estradiol-17 beta slows inactivation; 2-mercaptoethanol stops it. Previous studies have shown a histidyl residue also present at the catalytic region of the active site of 20 beta-hydroxysteroid dehydrogenase from Streptomyces hydrogenans. It is tempting to consider that these histidyl residues may be an essential component for the dehydrogenation of the steroid substrates.


Effects of estrogens on systemic and regional circulations in normal and renal hypertensive sheep. Effects of estrogen administration on systemic and regional circulation were studied in normotensive and renal hypertensive, chronically instrumented nonpregnant and pregnant ewes. Arterial pressure, cardiac output, and uterine, renal, superior mesenteric, and iliac blood flows, as well as uterine oxygen transfer, were monitored before and after intravenous administration of Premarin or estradiol-17 beta. The results show that: (1) estrogen administration produces a marked decrease in uterine vascular resistance and increase in uterine blood flow and oxygen transfer, lasting for about 2 hours; (2) arterial pressure, cardiac output, and other regional blood flows were not affected by estrogens; (3) the magnitude of uterine vasodilatation produced by estrogens was greater in the hypertensive than in the normotensive animals; it was also greater in the nonpregnant than in the pregnant state; these findings indicate that the magnitude of uterine vasodilatation depends on the status of the uterine vascular resistance in the resting state; (4) blockade of the autonomic nervous system at various levels, as well as administration of a mild antihistaminic agent, failed to alter the magnitude of the estrogen-induced uterine vasodilatation. These results indicate that estrogens act directly on the uterine vascular bed and produce a redistribution of flows and resistances in the body; the precise sites of this redistribution are not as yet determined.


Fibrous histiocytoma of the corneoscleral limbus. A 21-year-old white woman had an apparently benign fibrous histiocytoma at the corneoscleral limbus. By histopathologic and ultrastructural studies, the tumor consisted of lipid-containing histiocytes and fibrocytic cells arranged in a storiform configuration with a collagenous interstitium. After an excision, the lesion gradually decreased in size and did not recur in a five-month follow-up period.


Clinical and immunologic responses in patients with viral keratoconjunctivitis. Of 120 individuals suffering from follicular conjunctivitis, with or without keratitis, 56 had epidemic keratoconjunctivitis caused by adenovirus type 8. The remaining 64 patients had keratoconjunctivitis produced by several different viruses, including herpes simplex, adenoviruses types 3, 7, 8, 16, 21, and 29, and others. Positive viral cultures were difficult to obtain after the first week of illness in most viral infections. Serologic tests were far more successful in indetifying causative agents. Hemagglutination-inhibition tests in adenovirus infections proved to be fast, accurate, and more sensitive than other serologic tests. Among the epidemic and nonepidemic adenovirus groups, the degree of corneal involvement in the infections appeared to be correlated with the level antibody against the infectious agent. Patients with low antibody titers had more severe keratitis than those with high titers. This correlation was true for both the epidemic and non epidemic patients.


Intralysosomal formation of amyloid fibrils. Unusual inclusions, which occurred in the reticuloendothelial cells intimately associated with fresh amyloid deposits, were analyzed by electron microscopy. The inclusions were located in the areas rich in the primary lysosome type of dense bodies and the cytoplasmic invaginations containing well-oriented amyloid fibrils. They were single-membrane-bounded, measured 0.3 to 0.8 mu in width and 0.5 to several microns in length, and showed considerable variation in the electron density of their contents. The latter consisted of two different ultrastructural elements: fibrillar profiles and a homogeneous or finely granular electron-dense substance. The fibrillar profiles were virtually identical in ulstrastructure to the amyloid fibrils and were well-oriented parallel to the long axis of the inclusion. The homogeneous or finely granular electron-dense substance appeared to be comparable to that composing the dense body matrix. The inclusions were usually acid phosphatase positive, but did not take up intravenously injected Thorotrast particles. These data led us to conclude that these inclusions were transitional forms from the usual dense bodies to the deep cytoplasmic invaginations containing well-oriented amyloid fibrils (which are accepted by most investigators as the sites of amyloid formation) and thus constitute direct evidence for the involvement of lysosomes in amyloid fibril formation.


Mechanism of lymphoma cell death induced by cyclic AMP. A mouse lymphoma tissue culture line, S49, is killed by isoproterenol, choleratoxin, or prostaglandin E1, inducers of cyclic AMP (cAMP) in these cells, or by the analog dibutyryl (db) cAMP. Cell death follows arrest in the G1 phase of the cell cycle. Mutant subclones obtained by growing S49 with dbcAMP were resistant to killing. They were deficient in cAMP-dependent protein kinase. These results are discussed in relation to the possible physiologic role of cAMP-induced cell death in T-cell differentiation.


Intraperitoneal oxygen and carbon dioxide tensions in experimental adhesion disease and peritonitis. Intraperitoneal oxygen and carbon dioxide tensions were studied in rats during silica-induced adhesion formation or fecal peritonitis. Measurements of PO2 and PCO2 in the abdominal cavity were performed by means of an implanted Silastic tonometer. During active adhesion formation one to three weeks after administration of silica, the intra-abdominal PO2 decreased by 50 per cent from normal whereas the intra-abdominal PCO2 and the rate of oxygen consumption in the peritoneum were elevated. Progressing peritonitis also resulted in decreased intraperitoneal PO2 and increased accumulation of carbon dioxide in the peritoneal cavity. In rats with peritonitis the rate of oxygen consumption in the peritoneal exudate clearly exceeded that in the peritoneal membrane.


Ligation of a branch of the portal vein for carcinoma of the liver. Portal branch ligation, a new surgical treatment for unresectable carcinoma of the liver, was performed in twenty patients. All the patients tolerated the procedure, and morbidity and mortality were minimal, even in patients in poor general condition. The responses to ligation differed considerably, but significant palliation was attained in some patients and one survived six years. The effect of portal branch ligation on the tumor appears to be closely related to the degree of tumor vascularity, tumor malignancy, and portal circulatory disturbances such as cirrhosis, portal hypertension, or portal thrombosis. We believe that the present procedure can be recommended for clinical application in some patients with unresectable carcinoma of the liver.


Epstein-Barr Virus antibodies in patients with carcinoma of the nasopharynx and carcinoma of other sites in the head and neck. Serum antibody titers to Epstein-Barr virus were significantly elevated in a group of twenty-three patients with nasopharyngeal carcinoma as compared with eighty-six patients with cancer of other sites in the head and neck and 222 age-matched controls. Our findings in this group of patients support the suggestion of an association between the Epstein-Barr virus and nasopharyngeal carcinoma.


Sebaceous cell carcinoma of the parotid gland. Sebaceous cell carcinoma of the parotid gland is a rare lesion. A review of the English literature reveals nine previously reported cases. Two cases are presented in which the tumor was originally diagnosed as mucoepidermoid carcinoma. Aggressive treatment of the recurrence, which was subsequently recognized as sebaceous cell carcinoma has resulted in apparent cure. Histologic features and possible histogenesis are discussed.


Pre-operative neutralization of gastric acidity. The incidence of Mendelson's syndrome in the four major Auckland hospitals is reviewed. The frequency of this condition was reduced following the pre-operative administration of magnesium trisilicate mixture in two hospitals. A trial was conducted in a third hospital and this showed that a 52 per cent incidence of highly acid gastric juice (pH less than 2.5) in patients prepared for elective surgery was reduced by administration of magnesium trisilicate mixture at the time of premedication. When the magnesium trisilicate mixture was given within the 30 minutes prior to induction of anaesthesia, the number of patients with highly acid gastric content fell to one per cent.


Cytoplasmic inclusions of neurons in the monkey visual cortex (area 19). Several unusual neuronal inclusions were found in certain cells of the rhesus monkey visual cortex (Area 19): 1. Filamentous bodies, present in the small stellate cells of layer IV, globoid, 0.3-0.6 mum in diameter, consisting of fine 50 A filaments in a hexagonal meshwork. These are often associated with the labyrinthine bodies. 2. Labyrinthine bodies found exclusively in the small stellate cells of layer IV, including certain neurons with dispersed ribosomes. These are 0.4-0.7 mum in diameter and consist of 900 A wide tubes which interconnect with one another. The walls of these tubes are continuous and made up of a sheet or honeycomb lacework of small hexagonal 150 A subunits. 3. This inclusion, an aggregate 0.3-0.7 mum in size, consists of small membrane-bounded vesicles with a single dense granule associated with other non-membrane bound small dense droplets. The inclusions are always associated with the maturing face of the Golgi complex of certain layer IV pyramidal cells; as such, they may be an unusual product of the Golgi apparatus. These observations were confirmed by examination of stereo pairs of electron micrographs. Speculations are made with regard to possible functions for these inclusions.


Re-evaluation of dosage and duration of action of d-tubocurarine in the pediatric age group. A cumulative dose-response curve for d-tubocurarine based on body weight was determined for 44 infants and children 1 day to 7 years of age during halothane, nitrous oxide and oxygen anesthesia. Depression of thumb adduction was measured. Age difference did not affect the mean dose-effect response. Infants less than 10 days old, however, showed the wideest deviation of responses. When the effect of d-tubocurarine is determined by twitch response, infants and children are more resistant to d-tubocurarine and recover faster than adults from similar levels of neuromuscular depression. Monitoring of neuromuscular function by train-of-four stimulation proved as useful as it is in adults.


Clinical evaluation of the action of dexamethasone. The antioedematous action of dexamethasone was assessed in 28 patients with supratentorial and infratentorial intracranial tumours and craniocerebral trauma. The criteria of evaluation included the state of consciousness, signs of focal cerebral injury, autonomic disturbances and signs of raised intracranial pressure. The greatest improvement was obtained in patients having intracranial tumours with herniation of the brain stem. In cases of extensive craniocerebral trauma no evident improvement was achieved.


[The structure of biological membranes: localization of sulfoquinovosyldiglyceride in various membranes of chloroplasts using specific antibodies]. The sulfoquinovosyl pole of at least a part of the sulfolipid molecule, in the envelope and the thylakoids of chloroplasts, is accessible to the specific antibody. Agglutination of the chloroplasts is due to the sulfolipid which is located on the envelope and uniformly distributed on the external surface. Reactivity of the sulfolipid located on the membrane of thylakoids, when exposed to the corresponding antibody, appears to be different from the sulfolipid reactivity of the envelope: the antibody fails to agglutinate the thylakoids. Thylakoids altered by osmotic chock are sensitized to agglutination. Immunoenzymatic studies followed by electron microscopy  revealed the presence of the sulfolipid on the membrane of the various thylakoids. The local reactions did not appear to be continous.


Mechanism of action of neurotoxins.

Mechanism of action of neurotoxins. This paper is a summary of studies over the past few years that pertain to animal neurotoxins. These toxins are found throughout the animal kingdom. Homologies exist in the structures of these poisons within classes and point to conservation of active sites throughout evolution. In the case of the peptides, invariant amino acids may be involved in the active site, be essential for maintaining the shape and conformation of the molecule or serve as a fulcrum for folding of the peptide chain after synthesis. At the nuclear or DNA-level, a constant base sequence may regulate gene operation so that only a specific amino acid is coded. Physiologically, and with ultrastructural and biochemical correlation, the predominant mode of action of neurotoxins relate to one or the other of the major activities of the excitable cell,--on conductile activity affecting Na+ or K+ permeabilities, on output or secretory activities affecting the release of neurotransmitter or on in put generator activities affecting the receptor molecules for transmitter themselves. The future of these animal neurotoxins in neurobiological research is secure. The elucidation of molecular mechanisms, by which these various physiological activities of excitable tissue are expressed, will surely involve one or more of these fascinating, naturally-occurring compounds.


[Determination of the penicillin acylase activity of E. coli cultures using a method of gas-liquid chromatography]. Penicillinacylase activity was determined in E. coli by the product of benzylpenicillin destruction, i.e. phenylacetic acid formed under the effect of the enzyme. The determination was performed on a chromatograph. The immobile phase consisted of 10 per cent of ethylenglycol edipate on chromosorb A, modified with 2 per cent H3PO4. Nitrogen was used as the gaseous carrier. The method is rapid and handy for mass testing of the cultures with a purpose of detecting penicillinacylase-producing strains. It provided reliable determination of penicillinacylase in the cultures producing simultaneously beta-lactamase, another penicillin-destroying enzyme.


[Rifampicin effectiveness in experimental anaerobic gas infection]. The inhibitory effect of rifampicin against most of 82 strains of pathogenic Clostridia was evident at a concentration of less than 0.1 gamma/ml. The bactericidal concentrations were close to the bacteriostatic ones with respect to 74 strains. The protective effect of rifampicin in mice with experimental anaerobic gaseous infaction caused by different species of pathogenic Clostridia was evident at doses of 0.5 mg/kg. In infections caused by associations of Clostridia and Staph. aureus resistant to other antibiotics, rifampicin was effective, while ampicillin had no protective effect. Rifampicin administered 24 to 96 hours before the infection prevented the specific process. A number of other antibiotics, such as ampicillin, cephaloridin, morphocycline and 7-chlor-7-desoxylincomycin had no such a capacity. The prolonged prophylactic effect of rifampicin was associated with maintenance of low antibiotic levels in the blood and muscle tissues which were higher than the minimum inhibitory concentrations. The effect of rifampicin against the background of a rapidly developing process was less pronounced and limited in time.


Bactericidal activity of superoxide anion and of hydrogen peroxide: investigations employing dialuric acid, a superoxide-generating drug. The addition of dialuric acid (a superoxide-generating drug) to a suspension of resting human neutrophils resulted in a stimulation of cellular hexose monophosphate shunt activity. Measurement of oxygen consumption demonstrated a rapid rate of oxygen uptake by the drug alone in aqueous solution. The subsequent addition of catalase (but not of superoxide dismutase) resulted in a substantial release of oxygen, indicating that H(2)O(2) was accumulating in the media. The generation of O(2) (-) by the drug was verified by measuring the rate of reduction of cytochrome c by the drug in the presence and absence of authentic superoxide dismutase. The growth of Escherichia coli B and Staphylococcus aureus was inhibited in vitro by addition of the drug to a suitable culture media; the degree of inhibition was dose dependent. This inhibition of bacterial growth could be completely reversed by the addition of as little as 5 mug of purified catalase, but was not affected by concentrations of superoxide dismutase that were 2,000-fold higher. These results suggest that the dialuric acid-induced stimulation of hexose monophosphate shunt activity in neutrophils is due to accumulated H(2)O(2). Further, the contribution of superoxide to the bactericidal activity towards E. coli and S. aureus is probably minimal compared with that of H(2)O(2).


Mecillinam (FL 1060), a 6beta-amidinopenicillanic acid derivative: bactericidal action and synergy in vitro. A newly described 6beta-amidinopenicillanic acid derivative, mecillinam (formerly called FL 1060), showed a high in vitro activity against Enterobacteriaceae. The effect on Escherichia coli was bactericidal and was due to lysis of the cells. The longer the culture grew under the influence of mecillinam or the lower the inoculum, the greater the bactericidal effect. The morphology of the cells changed towards large spheric forms (2 to 5 mum) under the influence of mecillinam. Consequently a great discrepancy between the optical density and the viable count was seen. The morphologically abnormal cells could be protected against lysis in vitro by addition of ionized compounds such as sodium chloride. Abnormal cells were more sensitive to ampicillin than normal cells. As expected synergy could be demonstrated between mecillinam and ampicillin. This was marked under experimental conditions where the abnormal cells were protected against lysis.


Mode of action of polymyxin B: physiological studies with Bacillus subtilis-resistant mutant. Polymyxin B resistance in Bacillus subtilis can be suppressed by the synergistic action of lysozyme or of an analogous cell wall lytic activity released by B. subtilis spores during germination. Such a synergistic effect is probably due to partial cell-wall digestion by lysozyme that allows polymyxin to reach its site of action and is therefore distinct from the analogous synergistic effect described by other authors in Escherichia coli. In the latter case polymyxin B probably damaged the outer membrane, allowing lysozyme to reach and digest the cell wall.


Irreversible inhibition of herpes simplex virus replication in BSC-1 cells by zinc ions. Zinc sulfate added to the medium of herpes simplex virus-infected BSC-1 cells, at a concentration of 0.1 mM, inhibited the synthesis of infectious virus progeny by 95 to 96%. A concentration of 0.2 mM zinc sulfate inhibited herpes simplex virus synthesis by 99.8% as determined by centrifugation in sucrose gradients and by plaque assay on BSC-1 monolayers. The inhibition of herpes simplex virus replication in BSC-1 cells was found to be irreversible.