[Generalized infantile neuroaxonal dystrophies with pigmentation and lipophanerosis of the pallidum in concordant twins (author's transl)].

Monozygotic male twins died at the age of 6 1/2 and 7 1/2 years respectively after a progressive course of mental deterioration, hypotonia, spasticity, optic atrophy and seizures that had commenced at the age of 2 years. Both patients showed generalized neuroaxonal dystrophy (NAD), marked by numerous spheroids, iron-positive pigment and lipophanerosis of the pallidum. NAD can be classified as a generalized form without pigmentation of the pallidum (infantile type of Seitelberger), a juvenile type of Rozdilsky, a generalized form with pigmentation (cases described here), and localized forms (infantile, late infantile, juvenile = classic Hallervorden-Spatz disease, adult types).


Effect of reticuloendothelial stimulators on the tissue changes and evolution of experimental atheroma in rabbits.

Administration of histamine phosphate or glycerol trioleate (RE stimulators) to cholesterol-fed rabbits induced identical pattern of changes in cholesterol, phospholipid and triglyceride levels of the blood. However, the incidence of atheroma index in aorta and coronary arteries were significantly higher in histamine-treated and glycerol-trioleate-treated animals compared to cholesterol-fed controls. The rise in these indices appeared to be only partly related to increase in serum beta-lipoproteins but mostly due to increased permeability of the endothelium and internal elastic lamina probably caused by histamine phosphate and glycerol trioleate resulted in greater degree of atheromatous lesions in those groups.


Molecular biology and oral contraception.

Recent developments in knowledge of sex hormone receptors and steroid analogue metabolism allow a rational selection of oral contraceptive steroids from among the numerous available products. Dose related metabolic effects of synthetic estrogens have been demonstrated. Many of these estrogenic actions are antagonised by norgestrel but not by any other commercially available progestogen. Generalised activation of lysosomal enzymes can be demonstrated in oral contraceptive users and is shown to be related to the total steroid dose per cycle, rather than to particular products. These findings suggest that the lowest dose combination of ethynylestradiol and d-norgestrel is the product of choice. Clinical results with such a product are described.


Herpetiform ulceration.

The rationale for the clinical existence of a less commonly found form of recurrent oral ulceration, herpetiform ulceration (HFU), is presented, illustrated by six clinical cases. The clinical and laboratory features that separate it from recurrent herpetic ulceration (RHU) and recurrent minor aphthous ulceration (RHU) are discussed. Although a viral cause has been proposed for the condition, based on the finding of intranuclear bodies, electron microscopic and other laboratory investigations by the authors indicate that there is insufficient evidence at present to confirm this. Since HFU does have a significant number  of histologic and immunologic features in common with recurrent apthous ulceration, it is thought that it should be considered to be a variant of this condition until the true cause of it is revealed.


Clinical and ultrastructural study of Burkitt-like leukaemia.

Six patients, two with acute lymphoblastic leukaemia (A.L.L.) and four with lymphosarcoma with early transformation into A.L.L., have been studied. All blast-cells demonstrated with cytological, cytochemical and ultrastructural features of Burkitt's tumour. The clinical evolution was fulminant and there was no remission of long duration despite intensive chemotherapy. The cytoplasm of the blast-cells displayed a great number of lipid droplets. The level of the anticapsid Epstein-Barr virus antibodies was high in the case investigated.


Studies of anabolic steroids: v. effect of prolonged oxandrolone administration on growth in children and adolescents with uncomplicated short stature.

A total of 130 patients with uncomplicated short stature (4 to 17 years of age) were treated with oxandrolone, 0.25 mg/kg/day, for up to four years. Oxandrolone therapy resulted in a two-fold increase in mean growth velocity in the first six months of therapy and was an effective growth stimulant for the full four-year period. There was no overall adverse effect of oxandrolone on post-treatment mean growth velocity or on skeletal maturation relative to height gain. There were 37 patients with greater increase in height age than bone age and 22 patients with greater increase in bone age than height age. Assessment of the contribution of oxandrolone therapy to the latter group is difficult because of inadequate methodology and the wide variation in individual growth patterns. Taken in their entirety, the data suggest that oxandrolone is useful in the prolonged treatment of uncomplicated short stature and is not associated with undesirable acceleration of skeletal maturation.


Eye color and responsiveness to arousing stimuli.

The hypothesis was advanced that dark-eyed subjects are more responsive to arousing stimuli than light-eyed subjects. 40 subjects listened to neutral and arousing auditory stimuli and viewed scenes which were neutral, violent, or sexual in nature. The dependent measure of arousal was a score derived from a combination of physiological responses recorded on a polygraph. Scores were significantly higher for dark-eyed than light-eyed subjects. Significant sex differences were also found, females having higher scores than males. Implications for future research and application were discussed.


Disappearance of insulin response after enzymatic treatment of sodium-transporting amphibian epithelia.

Amphibian epithelia specialized in trans-cellular sodium transport lose their capacity to react to insulin by a stimulation of this process upon treatment with collagenase; baseline activity and responsiveness to other hormones (vasopressin, aldosterone) bringing about such a stimulation are preserved. This renders it likely that proteases contaminating most collagenase preparations exert a detrimental effect on the receptors held responsible for interaction between insulin and its target cells in the tissues examined.


Effects of glutamate, aspartate, and two-presumed antagonists on feline rubrospinal neurones.

The actions of dicarboxyl amino acids (GLUT, ASP, DLH) and of presumed amino acid antagonists (GDEE, HA 966) were studied in rubrospinal neurones with microelectrophoretic techniques. ASP and GLUT depolarized reversibly the cell membrane and increased its conductance. ASP had slightly stronger actions than GLUT. DLH had strong depolarizing actions without a clearcut change in membrane conductance; this may be due to the fact that DLH effects do not involve synaptic receptors. A specific action as antagonists for GLUT could not be shown for GDEE or HA 966. HA 966 effects were often accompanied by apparent postsynaptic actions. GDEE antagonized DLH effects sometimes even stronger than GLUT effects. The effects of GLUT and ASP are in principal agreement with a function as excitatory transmitters. The demonstration of a role as transmitter substances in excitatory (e.g. corticorubral or interpositorubral) pathways, however, still awaits the specific pharmacological antagonist.


Distribution of estrogen receptors in subfractions of hen oviduct chromatin.

Hen oviduct chromatin was digested with DNase II and separated into two fractions. The MgCl2 insoluble chromatin fraction (43% of the total DNA) was enriched in nucleosome-like particles, which sedimented at 11 S and contained 185 base pairs of DNA. The MgCl2 soluble chromatin fraction (5% of the total DNA) was characterized by 5 S and 14 S peaks in sucrose gradients; Estrogen receptors in the chromatin fractions were labelled with [3H] estradiol using the steroid exchange assay. The concentration of receptors in the  MgCl2 soluble chromatin was 4;5 times higher than that in the MgCl2 insoluble chromatinmin sucrose gradient analysis the 11 S particles displayed a negligible specific radioactivity suggesting that estrogen receptors mainly bind to extranucleosomal chromatin.


Effect of treatment in vivo with N,N-dimethylnitrosamine or methyl methanesulphonate on the cytoplasmic DNA polymerase of regenerating rat liver.

A 10-16 fold increase in rat liver cytoplasmic DNA polymerase (DNA polymerase-alpha) was observed by 24 hrs after two thirds partial hepatectomy. Injection of either N,N-dimethylnitrosamine (DMN) or methyl methanesulphonate (MMS) At 6 or 12 hrs after partial hepatectomy completely inhibited this increased production of polymerase, but when given at 20 hours they had less effect. Neither compound altered the molecular size distribution of the enzyme. These data indicate that the lowered levels of DNA polymerase-alpha could play a major role in the reduction in DNA synthesis which occurs after carcinogen treatment.


[The influence of infectious bronchitis virus on egg production, fertility, hatchability and mortality rate in chickens (author's transl)].

In 35 flocks comprising almost 100,000 White Plymouth Rock birds producing hatching eggs, infectious bronchitis (IB) caused a decline in production which appeared to be connected with the age of the birds, when the outbreak started (table I). In outbreaks of IB in pullets 3-4 weeks before they are ready to lay there is a considerable risk of delay of production and a generally too low yield (fig 1). Egg laying birds, 25-34 weeks of age, suffered a drop in production from 20-80% (on an average 40%) and normal yield was never regained. After 6-8 weeks the production rate usually stabilizes around 6-12% below normal production. IB outbreaks in the middle of the production period (35-45 weeks) resulted in a decline of egg production of 40-90% (on an average 55%). Recovery of production usually occurred after 6-8 weeks (fig. 2). Observations of clinically typical outbreaks without any laboratory verification indicate that IB outbreaks at the end of the egg production period resulted in irreparable decline of production. Marked alterations in exterior and interior quality of the egg have been observed. Both mishapen appearance, rough and thin shell, bleached shell color and watery albumen have occurred. These facts did sometimes cause transient increased "sorting out" of haching eggs. Also fertility rate was noticed to be affected temporarily during and after an attack of IB. In 17 flocks drops of 1.7-22.4% (on an average 7.4%) were registered (fig. 3). Also hatchability decreased 3.0-43.8% (on an average 13.7%) (fig. 4). In most of the registered outbreaks of IB the weekly mortality remained below 1%, but in single cases the figure could rise up to about 4% (fig. 5), most often in flocks where complicating factors such as secondary infections caused by E. coli or M. gallisepticum were present.


Joining of ribooligonucleotides with T4 RNA ligase and identification of the oligonucleotide-adenylate intermediate.

T4 RNA ligase was found to join A-A-A-A-A-A and 32pU-U-U-U in the presence of ATP as cofactor. In this reaction the pyrophosphate of pU-U-U-U and pA was isolated by chromatography on a RPC-5 column, besides the joined product and the starting materials. This pyrophosphate was shown to be an intermediate in the joining reaction because of the fact that coupling with A-A-A-A-A-A to give the decanucleotide could be performed in the absence of ATP. The structure of the oligonucleotide-adenylate was determined by enzymatic digestion with base-nonspecific nuclease and venom phosphodiesterase. Futher evidence for the proposed structure was obtained by isolation of the intermediate obtained  by using pU-U-U-U and [alpha-32p]ATP. This pyrophosphate gave pA and pU by treatment with venom phosphodiesterase. Several other joining reactions between various purine- and pyrimidine ribooligonucleotides to 5'-phosphorylated ribooligonucleotides are discussed.


Comprehensive care of the ileostomy patient.

Comprehensive care of the person with an ileostomy is an integral part of professional nursing. It is the responsibility of professional nurses to be knowledgeable and skilled in ileostomy patient care. This article has presented basic issues to be considered in facilitating the rehabilitation of the person with an ileostomy. Perhaps the most important factor to be considered is that the process of rehabilitation must begin at the first encounter with the person undergoing ileostomy surgery, must extend beyond the period of hospitalization, and must reach into the person's home and community.


[Necrotizing enteritis and geophagia].

Two cases of intestinal perforation due to necrotising enteritis in patients with pica are presented. The aetiopathogenesis of pica is discussed as well as its role in the development of necrotising enteritis.


Effect of dehydration of the cornea with experimentally induced ulcer on collagenase activity.

In the course of healing of experimental ulcer one could observe a distinct difference between a cornea, subjected to the action of glycerol and a control one. The damage to the chemical structure of collagenous fibers was much smaller than in the control. On the basis of the investigations performed one may conclude that glycerol, through dehydration of the corneal tissue and stimulation of mucopolysaccharide synthesis, suppresses the activity of collagenase. In polarized light this process was manifested by the double refraction phenomenon and in clinical observation--by an accelerated healing of ulcer.


Histiocytoma; histiocytoma proliferans; histiocytoma malignum: (clinical and morphological observations).

In a group of 112 cases of histiocytic neoplasms treated 1960--1973 103 benign tumors (histiocytoma), 3 semimalignant tumors (histiocytoma proliferans), and 6 malignant ones (histiocytoma malignum) were diagnosed. Clinical and morphological examinations indicate that under the influence of stimuli histiocytoma may undergo a biological transformation developing into less mature forms such as histiocytoma proliferans and histiocytoma malignum. The treatment of malignant tumors consisted in their removal together with a wide margin or adjacent tissues. In 2 cases enlarged lymph nodes were removed but no metastases were found. In one case death occurred 3 years after operation as a result of distant metastases.


Regulation of active alpha-aminoisobutyric acid transport expressed in membrane vesicles from mouse fibroblasts.

Membrane vesicles isolated from untransformed Balb/c and Swiss mouse fibroblasts and from those transformed by simian virus 40 catalyzed carrier-mediated uptake of L-alpha-aminoisobutyric acid. Concentrative uptake required the presence of a Na+ gradient (external Na+ greater than internal Na+) and occurred independently of endogenous (Na+ + K+) ATPase activity. This process is electrogenic, since uptake was stimulated by a K+ diffusion gradient (internal greater external) in the presence of valinomycin or by the addition of the Na+ salt of a permeant ion, conditions expected to create an interior-negative membrane potential. Both the initial rate of concentrative uptake of L-alpha-aminoisobutyric acid and its maximal accumulation, driven by a standard Na+ gradient, were decreased in vesicles from density-inhibited, untransformed cells and increased in those from cells transformed by simian virus 40 compared with vesicles from proliferating untransformed cells. An increased maximal velocity (Vmax) of uptake stimulated by Na+ gradient was observed in vesicles from transformed cells compared with those from untransformed cells, suggesting an increase in the number of carriers or in their mobility. Since the relative extent of accumulation of this model amino acid driven by a standard Na+ gradient also differed with growth or transformed status, an additional possibility for cellular regulation of this process could be alteration of membrane Na+ permeability or carrier response to Na+.


Handedness of crossover connections in beta sheets.

In a crossover connection, the polypeptide chain leaves one end of a beta sheet, forms a loop of any length and any conformation, and reenters the same beta sheet from the opposite end. Of the 85 examples of crossover connections which occur in the known protein structures, 83 are righthanded and only two are lefthanded. It is proposed that consistent handedness, even in long irregular loops, could be produced by the preferred twist direction of extended chain and the righthandedness of alpha-helices, provided certain conditions hold during the protein folding process.


Appearance in vivo of single-stranded complementary ends on parental herpesvirus DNA.

Intracellular forms of pseudorabies virus parental DNA were examined before and after the onset of viral DNA synthesis. Before initiation of synthesis, parental viral DNA acquires single-stranded ends. Circular and concatemeric molecules are also observed, indicating that the single-stranded ends are complementary. Viral DNA replication is initiated at an internal site within the DNA molecule, giving rise to characteristic replicative loops with single-stranded regions in the trans position. Such replicative loops were seen in unit-size (and smaller than unit-size) linear molecules as well as in circular and concatemeric molecules. These results show that the parental viral DNA molecules that acquire single-stranded ends, and consequently are able to form circles and concatemers, proceed to replicate.


Calcium-dependent regulatory protein of cyclic nucleotide metabolism in normal and transformed chicken embryo fibroblasts.

The concentration of a calcium-binding protein modulator of 3':5'-cyclic-nucleotide phosphodiesterase (EC 3.1.4.17; 3':5'-cyclic-nucleotide 5'-nucleotidohydrolase) activity is increased in chicken embryo fibroblasts upon transformation by Rous sarcoma virus. This modulator protein from fibroblasts, which has roughly the same molecular size, charge, and functional properties as that isolated from chicken brain, comprises approximately 1.32% of the soluble protein in homogenates of fibroblasts infected and transformed by Rous sarcoma virus. In comparison, the modulator comprises approximately 0.30% of the soluble protein in homogenates of normal fibroblasts from confluent cultures and 0.36% of the soluble protein in homogenates of fibroblasts infected with a transformation-defective mutant of Rous sarcoma virus. Modulator levels in normal fibroblasts at subconfluent cell densities are 0.42-0.76% of the homogenate soluble protein, i.e., between that found in confluent normal fibroblasts and in fibroblasts transformed by Rous sarcoma virus. These observations suggest that the levels of the modulator protein are elevated under conditions in which chicken embryo fibroblasts are undergoing rapid growth and have decreased adenosine 3':5'-cyclic monophosphate levels.


Comparison of regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in hepatoma cells grown in vivo and in vitro.

Unlike the normal liver, numerous transplantable rodent and human hepatomas are unable to alter their rate of sterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-GoA) reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34] activity in response to a dietary cholesterol challenge. It has been suggested that this metabolic defect is linked to the process of malignant transformation. Hepatoma 7288C "lacks" feedback regulation of cholesterol synthesis when grown in vivo but expresses this regulatory property when grown in vitro (then called HTC). Therefore, it was used as a model system to answer whether an established hepatoma cell line that modulates its rate of cholesterol synthesis in vitro can express this property when grown in vivo, and whether cells reisolated from the tumor mass have the same regulatory phenotype as before transplantation. Our results show that long-term growth of hepatoma 7288C in tissue culture has not caused a biotransformation that permits feedback regulation of HMG-CoA reductase when the cells are transplanted back into host animals. In addition, HTC cells reisolated from the tumor mass and established in tissue culture continue to have the ability to regulate HMG-CoA reductase activity. Therefore, malignant transformation is not categorically linked to the loss of the cellular components necessary to regulate sterol synthesis and HMG-CoA reductase activity.


Direct biochemical mapping of eukaryotic viral DNA by means of a linked transcription-translation cell-free system.

A method is described for mapping regions of eukaryotic viral DNA coding for specific proteins, utilizing a linked transcription-translation cell-free system primed with DNA fragments generated by restriction endonucleases. Three simian virus 40 (SV40) DNA fragments derived from that region of the DNA expressed late in lytic infection were purified. They were: Hpa I-A (0.76-0.175 map units), Bgl I-EcoRI-B (0.672-0), and Hpa II-EcoRI-B (0.735-0). (Fragments are named from the cleaving restriction endonuclease and electrophoretic mobility. End positions on the conventional map are in clockwise order.) These fragments efficiently stimulated the incorporation of [3H]UTP and [35S]methionine into trichloroacetic-acid-insoluble material in the linkec system. The location of the region of DNA coding for the viral structural proteins VPI, VP2 and VP3 was determined from the spectrum of polypeptide synthesis directed by the individual intact fragments and their specific endonucleolytic digests. The polypeptides synthesized in the cell-free system were characterized on urea-sodium dodecyl sulfate polyacrylamide gradient gels and by two-dimensional tryptic peptide analysis. ..


Hormonal control of pyruvate kinase activity and of gluconeogenesis in isolated hepatocytes.

Treatment of isolated rat hepatocytes with saturating concentrations of glucagon caused several modifications properties of pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40): S0.5 (substrate concentration at half maximum velocity) for phosphoenolpyruvate was about doubled, whereas Vmax was not changed; the activity measured at 0.15 mM phosphoenolpyruvate (physiological concentration) was reduced 65-80%; and there was also an increase in the Hill coefficient and in the affinity of the enzyme for the inhibitors Mg-ATP and alanine. Glucagon, 3':5'-cyclic AMP, and epinephrine caused an inactivation of pyruvate kinase together with a sitmulation of gluconeogenesis. Insulin (10 nM) antagonized the effect of suboptimal doses of glucagon or cyclic AMP and of even maximal doses of epinephrine, on both pyruvate kinase activity and on gluconeogenesis. These observations can be explained by a phosphorylation of pyruvate kinase by cyclic-AMP-dependent protein kinase, as described by Ljungström et al. [(1974) Biochim. Biophys. Acta 358, 289-298] in a reconstructed system. They offer a molecular explanation for the hormonal control of gluconeogenesis. Glucose caused an inhibition of gluconeogenesis with no corresponding change in pyruvate kinase activity.


The endoplasmic reticulum: a cytochemist's view (a review).

Enzyme cytochemistry has been used, at the light and electron microscope levels, to "mark" cytoplasmic organelles of mammalian cells. Catalase cytochemistry permitted identification of microperoxisomes, apparently ubiquitous organelles that are attached by numerous slender connections to the endoplasmic reticulum. Thiamine pyrophosphatase and acid phosphatase cytochemistry can be used to distinguish between the Golgi apparatus and a specialized acid-phosphatase-rich region of smooth endoplasmic reticulum (ER) that appears to be involved in: (a) the formation of lysosomes and melanin granules: (b) the processing and packaging of secretory materials in endocrine and exocrine cells; and (c) the metabolism of lipid. The acronym GERL has been given to this region of smooth ER because it is located at the inner or "trans" aspect of the Golgi apparatus and because it appears to produce various types of Lysosomes.


Transfer of tRNAs to somatic cells mediated by Sendai-virus-induced fusion.

tRNAs from yeast (tRNAPhe and 4S RNA) and Escherichia coli (suIII+ tRNAITyr) have been transferred to mouse cells by means of a two-step transfer procedure [Loyter, Zakai, and Kulka (1975) J. Cell Biol. 66, 292-304; Schlegel and Rechsteiner (1975) Cell 5, 371-379]. In the first stage of the transfer tRNAs were incorporated into rabbit red blood cells (RBCs). Thereafter, the loaded erythrocytes were fused with recipient mouse cells by means of Sendai virus. At least 0.3-0.4% of the total input of tRNA used to load the RBCs could be transferred to mouse cells. Of the tRNA incorporated in the mouse cells, at least 50% could be recovered in the form of intact tRNA molecules when yeast 4S RNA was used. With E. coli suIII+ tRNAITyr a rather smaller proportion of the tRNA remained intact (33%). Although the loading of tRNA into RBCs is not essential for its uptake, we find that the transfer is four times more efficient with RBCs as a vehicle for the injection. Significantly, a fraction (2%) of the recipient cells possessed much more incorporated tRNA than the average cell when Sendai virus and loaded RBCs were used. Such cells were not found in control experiments in which tRNA uptake was induced by Sendai virus alone.


Vitamin K-dependent synthesis and modification of precursor prothrombin in cultured H-35 hepatoma cells.

The ability of confluent monolayers of H-35 cells, originally obtained from a rat hepatoma, to synthesize prothrombin in response to vitamin K1 (phylloquinone) was studied. As demonstrated by radioimmunoassay, selective barium salt adsorption, and two coagulation assays which discriminate between precursor- and mature-prothrombin, these cells retained their ability to synthesize precursor prothrombin (preprothrombin) in the absence of exogenous phylloquinone (vitamin K). When phylloquinone was added to the medium (100 ng/ml), the existing intracellular concentration of preprothrombin was reduced to 50% within 1 hr after exposure to the vitamin and slowly declined thereafter to approximately 30% of control levels by 36 hr. Concomitant with the rapid loss of intracellular preprothrombin was the appearance of mature prothrombin in the medium. The appearance of prothrombin was biphasic: occurring during the initial 0-6 hr interval, and again at an increased rate during the next 18-24 hr interval. The amount of prothrombin appearing in the medium exceeded by severalfold the amount of precursor mobilized. These data demonstrate that monolayer cultures of H-35 hepatoma cells retain their ability to synthesize preprothrombin and other enzymes, responsible for post-translational modification of prothrombin and its subsequent secretion, under the influence of vitamin K.


Freeze-fracture study of mast cell secretion.

Within seconds after exposure of rat peritoneal mast cells to polymyxin B, bulges appear on the surface of the cells. Freeze-fracture electron microscopy reveals that each bulge overlies a mast cell granule. In contrast to the even distribution of intramembranous particles in the plasma membrane of unstimulated cells, the intramembranous particles in the stimulated cells are unevenly distributed in the membrane of the bulges with large patches of membrane lacking intramembranous particles. The membranes over the most prominent bulges are entirely free of intramembranous particles, and in some instances there is an increased concentration of intramembranous particles at the margins of the bulges. Perigranule membranes exhibit the same changes in distribution of intramembranous particles. Electron microscopy of thin sections of rapidly fixed, stimulated mast cells shows a peculiar structure of the membrane overlying some bulges; instead of the pentalaminar membranes previously demonstrated, the membrane at these sites of presumptive fusion of perigranule and plasma membrane assumes the form of a single dense lamina with a fine fuzzy coating on either side. It seems possible that membrane fusion and subsequent pore formation proceed in the stimulated mast cell through a stage of flight of intramembranous particles and molecular rearrangement of the other membrane components.


Abnormal levels of 3':5'-cyclic AMP in isoproterenol-stimulated fibroblasts from patients with cystic fibrosis.

To determine if the abnormalities of exocrine secretion characteristic of cystic fibrosis could be investigated in vitro, I studied the synthesis of 3':5'-cyclic AMP after isoproterenol stimulation in skin fibroblasts derived from patients with cystic fibrosis and from normal individuals. Comparison of normal and cystic fibrosis cells showed that the latter had 2- to 5-fold greater levels of intracellular cyclic AMP after stimulation with isoproterenol. The difference between the strains was observed at every stage of the culture cycle and was specific to stimulation by beta-adrenergic agonists. It could not be accounted for by different dose- or time-response curves nor by leakage of cyclic AMP into the medium. The increased sensitivity to catecholamines may reflect an intrinsic genetic property of cystic fibrosis cells, and it may be feasible to use this system to study the biochemical basis of the genetic defect in cystic fibrosis.


Presynaptic calcium currents and their relation to synaptic transmission: voltage clamp study in squid giant synapse and theoretical model for the calcium gate.

A voltage clamp study of the presynaptic terminal in squid stellate ganglion has given quantitative results relating inward Ca2+ current to presynaptic membrane potential and postsynaptic response to inward Ca2+ current. The results indicate an S-shaped curve for the relationship between presynaptic potential and Ca2+ current and a linear relationship between Ca2+ current and postsynaptic potential. A similar S-shaped curve was found for the time-dependent properties of the Ca2+ conductance. Based on these results a mathematical model was developed which accounts for the experimental results in this and previously published papers by other authors. The model suggests that five subunits are involved in the Ca2+ gate and that the subunits change noncooperatively from an inactive to an active form upon membrane depolarization.


Localization and specificity of binding of subprimate placental lactogen in rabbit tissues.

A search for specific placental lactogen binding was undertaken in tissues obtained from late pregnant rabbits using the placental lactogens from sheep, cows, and human beings. 125I-labeled ovine lactogen exhibited highest specific binding to the adrenal gland (57.8%), followed by liver (21.5%), ovary (19.9%), mammary gland (15.9%), uterus (12.2%), kidney (8.8%), brain (8.5%), and adipose tissue (7.9%). In liver and mammary gland, the displacement curves for ovine and human lactogen were identical to that for bovine prolactin, indicating that they share the same receptor site. Although the displacement curve for bovine lactogen was parallel to that of the other lactogens the bovine hormone is less active in the radioreceptor assay.


The effect of some additives on the adsorption of tetracycline hydrochloride on magnesium trisilicate and milk.

The effect of various additives on the adsorption of tetracycline hydrochloride on magnesium trisilicate or milk was investigated. Adsorption-elution, dialysis and sedimentation volume measurements were used in the present investigation. Citric acid was found to exert the highest adsorption suppressing effect of the antibiotic on both antacids. The nonionic surfactants, polyoxyethylene-23-lauryl ether (Brij 35) and polysorbate 80, had an intermediate action, while polyethylene glycol 6000 (PEG-6000), polyvinylpyrrolidone (PVP), sodium carboxymethylcellulose (CMC) and urea had only a slight effect. On the other hand, the effect of sodium benzoate and sodium salicylate varied with concentration. Results of the elution study showed that the efficiency of the additives, as eluting agents, was more or less parallel with their influence on adsorption. The presence of citrate or Brij 35, having the highest adsorption-suppressing effect, was found to have a negligible effect on the chemical stability or microbiological activity of tetracycline. Conclusions were made that the incorporation of some of these additives may possibly reduce tetracycline-antacids interactions and consequently improve the antibiotic availability when co-administered with antacids.


Serum sialic acid levels in lung cancer patients.

The levels of N-acetyl neuraminic acid (sialic acid) in normal men and pre-and post-menopausal women were determined. Smoking post-menopausal estrogen therapy, oral contraceptives, and refreezing had no effects on sialic acid levels. Pre-treatment values from patients with lung carcinoma showed markedly elevated levels of sialic acid (0.697 +/- 0.149 muM/ml) as compared to those from normal controls (0.432 +/- 0.067 muM/ml). The potential usefulness of sialic acid as a biological marker is discussed.


Biochemical changes after hepatic injury from toxic doses of acetaminophen or furosemide.

The effects of hepatotoxic doses of acetaminophen and furosemide on the function and composition of hepatic endoplasmic reticulum were compared from 3 to 24 h after administration. Acetaminophen caused a significant decrease in microsomal protein concentration as early as 3 h after its administration, but furosemide did not affect the microsomal protein concentration until 24 h after the dose. Both acetaminophen and furosemide decreased the concentrations of cytochrome P-450 and cytochrome b5 in microsomes, and the activity of microsomal ethylmorphine N-demethylase and aniline hydroxylase. Glucose-6-phosphatase and UDP-glucuronyl transferase were not significantly affected by acetaminophen or furosemide administration, and neither diene conjugation nor hepatic triglycerides were increased. Incorporation of 3H-L-leucine into liver proteins was decreased by 50% after the administration of either acetaminophen or furosemide.


Quantitative analysis of the distribution of 3H-leucine in acid soluble chromatin proteins of Noviknoff hepatoma cells separated by two-dimensional polyacrylamide gel electrophoresis.

The acid soluble proteins of Novikoff hepatoma chromatin were labeled linearly with 3H-leucine for 16 minutes. Analysis on two-dimensional polyacrylamide gels showed that 13 of the 18 stained proteins were detected by autoradiography after a 16-minute in vitro incubation. The labeled molecules include the histones H2A, H2B, H3, and H4; and proteins A3, Aj, A8, A8', A15, A16, A24, B7, and B13. Relatively large amounts of isotope were incorporated into two other proteins, A3 and Aj, in addition to the histones. Some proteins, notably Aj, A8, A8' and A16 were labeled to a greater extent than would be expected on the basis of uptake of Coomassie Brilliant Blue R. None of the labeling patterns were characteristic of a precursor-product relationship either the histones or the nonhistone proteins.


Influence of size, protein concentration, protein synthesis inhibitors,and carbon on clearance of enzymes and proteins from blood.

In order to (1) clarify the mechanism(s) for clearance and maintenance of protein levels from and in extracellular fluids, and (2) explore the possibility of interconnections between enzyme plasma levels and those of tissues, rats were injected with glutamate dehydrogenase, phosphoglycerate, encolase, carbamyl phosphate synthetase, serine dehydratase, deoxyribonuclease I, ribonuclease A, hemoglobin, and human serum albumin. A close relationship between the molecular weights of enzymes and the rates of clearance was found.


[Determination of the variation in conduction speed of motor fibers and the effects of diphenylhydantoin (Phenytoin) and diazepam (Faustan)].

The variation in the speed of conduction of motor fibers of the ulnar nerve was determined by Hopf's double-stimulus method and compared with values obtained from the duration of muscular response potentials for differently spaced points of stimulation. However, the values obtained from the difference of the duration of response potentials are inadequate since the duration of potentials cannot always be determined accurately. After a ten-day administration of faustan (15 mg per day) or phenytoin (300 mg per day) there was observed a decrease especially in the minimum rate of conduction of motor fibers of the ulnar nerve.


Plasma lipoproteins of lambs and sheep.

The major plasma lipoproteins of the adult sheep were high density lipoprotein (76%) having alpha-mobility on electrophoresis and low density lipoprotein (20%) having beta-mobility. Chylomicrons and very low density lipoproteins were minor constituents (less than 5%). The postabsorptive hyperlipidaemia in suckling lambs is mainly a result of increased concentration of low density and high density lipoproteins although the relative contribution of very low density lipoproteins was increased to 7-15% of the total lipoproteins. The hyperlipiaemia was markedly greater in an intact male lamb than in female or castrated male lambs. In suckling lambs a new lipoprotein (density 1-090 g/ml) appeared in the high density lipoprotein fraction but disappeared before weaning.


Photolysis of N-methyl and N-acetyl substituted amino acids.

Experiments on the production of free radicals in aqueous solutions of N-methyl and N-acetyl substituted amino acids by UV light are reported. The ESR spectra observed at 77 K show that the bond of the CH3- group of these substances is ruptured to a great deal compared with other bond ruptures producing paramagnetic centres. But in N-methyl substituted amino acids the methyl radical is less predominant than in N-acetyl substituted ones. At temperatures higher than 200 K the ESR spectra of all substances studied in our experiments are similar. It is supposed that a radical is formed with an unpaired spin near an oxygen atom.


The action of ionizing radiation on DNA in the presence of quinacrine. III. E.S.R. study: spin transfer in gamma-irradiated lyophilized DNA-quinacrine complexes.

E.S.R. spectra of different DNA-quinacrine complexes show as well at 77 K as at 293 K that there exists an electron transfer from the bases to quinacrine facilitated by the overlap of the theta-orbitals of the bases and the intercalated dye. The transfer range may extend over more than 25 or 50 nucleotides depending on the intercalation model considered.


Effect of Indomethacin on cyclic AMP phosphodiesterase activity in myometrium from pregnant rhesus monkeys.

Our results indicate that indomethacin inhibits cyclic AMP phosphodiesterase in the myometrium of the pregnant rhesus monkey under in vitro as well as in vivo conditions. Kinetic data on extracts of myometrium from pregnant rhesus monkeys indicated two cyclic AMP phosphodiesterase activities. The apparent Km value for the high affinity enzyme averaged 3.9 muM and for the low affinity enzyme 23 muM; the Vmax values averaged 0.56 and 1.4 nmoles cyclic AMP hydrolized per mg protein min-1 respectively. When indomethacin was added to the myometrial extracts, the activity of the high Km phosphodiesterase was competitively inhibited, with an average Ki of 200 muM; the low Km enzyme was noncompetitively inhibited with an average Ki of 110 muM. Experiments on myometrial slices demonstrated that 10 muM indomethsacin potentiated the effect of PGE1 and epinephrine on cyclic AMP levels, presumably by inhibiting the phophodiesterase activity. The uterine relaxing effect of indomethacin is generally attributed to the inhibition of prostaglandin synthetase activity. However, treatment of pregnant rhesus monkeys with therapeutic doses of indomethacin resulted in a significant inhibition of myometrial cyclic AMP phosphodiesterase activity in association with uterine relaxation and prolongation of gestation.


Radioimmunoassay measurement of ACTH-facilitated PGE2 and PGF2alpha release from isolated cat adrenocortical cells.

Prostaglandin (PG) biosynthesis by trypsin-dispersed cat adrenocortical cells was studied by radioimmunoassay (RIA). Parallel assays of incubation media using PGF2alpha and PGF1alpha antisera established that PGF2alpha is the primary PGF released by feline cortical cells. Following the reduction of PGE to PGF with sodium borohydride (NaBH4) these same two antisera were also used to identify PGE2 as the primary PGE released. RIA using a PGE antiserum confirmed the presence of PGE in the incubation medium. Steroidogenic concentrations of ACTH (50-250muU) enhanced PGE and PGF release, and indomethacin suppressed the ACTH-facilitated release. These studies provide additional evidence for ACTH-induced PG synthesis by feline cortical cells, and support the hypothesis that PGs play some role in the steroidogenic action of ACTH.


Phospholipase A activity in human and ovine uterine tissues.

Phospholipase A was assayed in crude lysosomal fractions of human decidua, amnion, chorion and myometrium. Activity was present in all the tissues and was highest in decidua and amnion which contained enzymes with pH optima of 6.5-8.0 and 7.2 respectively. Comparison of the activities in tissues obtained before labor with others obtained during labor showed no differences. In sheep, the fetal membranes contained a greater activity of phospholipase A than placenta and myometrium. Stimulation of the fetal adrenals with corticotrophin caused a marked increase in activity in both amnion and chorioallantois. It is concluded that the human amnion and the ovine amnion and chorioallantois could participate in the biosynthesis of prostaglandins by releasing stored arachidonic acid.


The role of prostaglandins in the development of refractoriness to LH stimulation by Graafian follicles.

The possibility that prostaglandins might be responsible for the development of the pre-ovulatory refractoriness to the stimulation by LH of cyclic AMP accumulation in vitro in the Graafian follicle was examined. Isolated rabbit Graafian follicles were obtained at estrus and at 0.5, 5 and 9 hours after an ovulatory dose of LH. The follicles were incubated in vitro in the presence of (8-3H)adenine and the accumulation of (8-3H)cyclic AMP measured. Follicles from estrous animals responded to the in vitro addition of LH with a marked increase of cyclic AMP accumulation and lost this response as the time of ovulation approached. Animals pretreated with indomethacin, which inhibits the usual pre-ovulatory rise of follicular prostaglandin levels, showed essentially the same loss of responsiveness. Indomethacin alone was without effect. It is concluded that prostaglandins are not the major factor in the development of refractoriness to LH stimulation in vitro which has been observed in pre-ovulatory follicles.


On the absence of "endogenous" acetaldehyde in rat and mouse blood.

Acetaldehyde was not detected in whole blood or plasma of control Sprague-Dawley rats or rats treated with Antabuse, or in whole blood of control Swiss-Webster mice or mice treated with diethyldithiocarbamate.


Isolation of an SV40 induced sarcoma transformation associated antigen.

A transformation associated antigen was isolated from an SV40 induced hamster sarcoma by sequential silica gel column chromatography and preparative silica gel 60 thin layer chromatography after tissue extraction with chloroform:methanol (2:1, v/v). It migrated with an rf of 0.21 on silica gel 60 thin layer chromatography plates predeveloped and developed in chloroform:methanol:water:glacial acetic acid (10:10:1.5:0.5, v/v) and an rf of 0.27 on cellulose F254 thin layer chromatography plates developed in the same solvent system. Antigenicity was determined using a fluorescence probe cytotoxicity assay to measure inhibition of antibody mediated complement dependent damage to homologous cultured transformed cells. Although compositional analysis of this substance is not complete, it appears to be a polar lipid and would support the concept that transformation associated antigens may be gene plus substrate specific rather than strictly gene specific.


Detection of estrogen binding in human mammary carcinoma by immunofluorescence: a new technic utilizing the binding hormone in a polymerized state.

Detection of neoplastic cells with the ability to bind estrogen has been accomplished utilizing the immunofluorescence technic and polymerized estradiol phosphate. Biopsies from 10 patients with the more common varieties of breast cancer have been studied and show excellent correlation with independently performed tritiated estradiol receptor assays. Preliminary results show that many mammary carcinomas are composed of heterogenous cell populations which vary in their estrogen binding capacities. To some extent, such variations are dependent upon the anatomical location of the malignant cells.


[Production and characterization of some mouse embryo cellular substrates in vitro].

Cell cultures with a different multiplication potential in vitro, depending upon the strain source used, were obtained from mouse embryos belonging to the CVA, C57 Black A2G and Swiss strains. Only the Swiss 12 culture underwent spontaneous transformation and was carried through more than 50 passages in vitro. The Swiss-12 substrate proved not to be contaminated either by viruses or micoplasma. It is less sensitive than other elective cell substrates to infection with attenuated polioviruses, cytopathogenic Coxsackie A9 virus and vaccinia virus, but its sensitivity to infection with Herpes simplex type 1 virus is similar to that of human embryo fibroblasts. After a high number of passages the Swiss-12 substrate permits, in comparison to other cell substrates (human heteroploid Hep-2 line, human embryo fibroblasts), a highly efficient qualitative differentiation between the growth media and calf serum.


Localization of apolipoprotein B in intestinal epithelial cells.

Indirect immunofluorescence techniques were employed to determine the distribution within intestinal epithelial cells of apolipoprotein B, a protein essential for the normal transport of fat. Isolated intestinal cells were prepared from rats either during active lipid absorption or after biliary diversion. Specific immunofluorescence from an antiserum to apolipoprotein B was detected in the apical portion of epithelial cells from bile-diverted animals, demonstrating that a pool of apolipoprotein B is present in the nonabsorptive epithelial cell and may be a component of intestinal cell membranes. During lipid absorption in normal rats, an early and sustained increase in immunofluorescence was demonstrated, consistent with an increase synthesis of apolipoprotein B during lipid absorption. This study demonstrates the presence of apolipoprotein B within intestinal epithelium and provides evidence for the participation of this apoprotein in intestinal lipid transport.


Spontaneous mutation of RNA tumour viruses.

There are 2 categories of spontaneously occurring avian and mammalian RNA tumour virus mutants: conditional and non-conditional. 1) Conditional mutants are able to replicate in or transform cells only under certain physiological conditions or in certain cells. RNA tumour virus temperature-sensitive mutants, focus-morphology mutants, and host range mutants are spontaneously formed. Some of these conditional mutants probably arise by point mutations in the viral genome. 2) Non-conditional mutants have genetic lesions that render them inactive under all conditions. There are non-conditional spontaneous RNA tumour virus mutants that are missing either the virion envelope glycoprotein or both the envelope glycoprotein and the virion DNA polymerase. These mutants cannot replicate or transform cells. Other spontaneous non-conditional mutants can replicate but are defective in their ability to transform fibroblastoid cells. These spontaneous transformation-defective mutants can have deletions in 10-20% of the genomic RNA. Conditional mutants with an altered host range occur at a high rate of approximately 1 mutation/50 infected cell generations during DNA-to-DNA information transfer. This type of conditional mutation requires cell replication but does not occur frequently either during the original synthesis of viral DNA (RNA-to-DNA information transfer) or during the transcription of progeny viral RNA from the (RNA-to-DNA information transfer) or during the transcription of progeny viral RNA from the DNA (DNA-to-RNA information transfer). Temperature-sensitive and focus-morphology mutants also have a high rate of spontaneous formation. Non-conditional mutants missing the viral envelope glycoprotein, DNA polymerase, or transformation gene, also appear to be spontaneously formed at a high rate. Normal avian and mammalian cells contain RNA tumour virus-related genes in their DNA. It is hypothesized that these endogenous RNA tumour virus-related genes in normal cells also have a high rate of spontaneous mutation and are involved in neoplastic processes.


Cytokine inhibition of DNA synthesis: effect on cyclic adenosine monophosphate in lymphocytes.

A greater than twofold increase in intracellular adenosine 3',5'-monophosphate (cyclic AMP) inhibited DNA synthesis, in stimulated rat lymphocytes. A two- to fourfold rise of intracellular cyclic AMP, starting at 16 hours, was produced by purified inhibitor od DNA synthesis added to such cells either at 0 or 16 hours, in close association with the initiation of DNA synthesis.


[The chemotherapy of tumors of the central nervous system (author's transl)].

The rational application of chemotherapy in tumors of the central nervous system is discussed in particular the use of the new derivatives of nitrosourea: BCNU (1-3 bis-(2-cloroetil) 1-nitrosourea) and CCNU (cloroetil-cicloesil-nitrosourea). The results of therapy with antimetabolites, alkylating agents, antibiotics, and plant alcaloids, are reported as well as those obtained with radio - sensitizing substances (containing B10 or BUdR, IUdR, FUdR). The results obtained in the United States and in Japan with BCNU and CCNU are considered as well as the personal data of 43 cases treated with BCNU and 10 cases treated with CCNU (including intracranial glial tumors, spinal glial tumors and metastatic tumors of the central nervous system).


Progesterone binding to hen oviduct genome: specific versus nonspecific binding.

Data are presented to explain discrepancies in the literature involving the in vitro binding of steroid receptor complexes to isolated nuclei and chromatin. The type of binding in vitro of the progesterone-receptor complex to nuclei, chromatin, or DNA of hen organs is largely determined by the ionic strength of the medium. Low ionic conditions (0.01 to 0.05 molar potassium chloride) result in a nonspecific, nonsaturable binding, while high ionic conditions (0.15 to 0.20 molar potassium chloride) create a tissue-specific, saturable binding. Pure DNA binds the steroid receptor complex extensively in low salt but very little in the higher salt conditions.


Thyroid hormones: effect of physiological concentrations on cultured cardiac cells.

Cultured cardiac cells prepared from newborn rat heart will respond in vitro to physiological concentrations of L-triiodothyronine. The cells are grown in a culture medium that contains hypothyroid calf serum. A dose response relationship of L-triiodothyronine indicates that this system may be a useful model for elucidation of the mechanism of thyroid hormone effects on the heart.


[Prevention of infections in patients subjected to immunosuppressive drugs. Experience of a nephrologist].

Infective complications favoured by non-specific immuno-depression are common after renal transplantation. Often severe, they represent the main cause of mortality. Their prophylaxis is necessary at all stages of treatment. Before transplantation, the eradication of curable infective foci is essential, and certain patients must be excluded from the programme. The operation is simplified to a maximum. The conditioning is such that one does no longer expose to the risk of aplasia. These facts render useless the isolation of the patient on a sterile unit. In cases of poor tolerance of the transplant, with repeated rejection, the reduction and eventually the stopping of immunosuppression is necessary. This attitude implies often early return to treatment by repeated hemodialysis, but it preserves to a maximum the chances of a new transplantation.


[Rejections and cytomegalovirus infections after renal transplantation].

Immunosuppressed patients are known to be susceptible to infectious agents. Association of allograft rejection and herpes virus infection (high incidence of cytomegalovirus) was yet reported after renal transplantation. Authors studied 19 rejection episodes on 24 renal transplantation performed for 17 months, cytomegalovirus infection being associated in 7. Because of the therapeutic difficulties observed in these cases, a preventive attitude is necessary.


[Infectious problems posed by patients with a renal graft and submitted to an immunosuppressive treatment].

Infective complications are analysed in 100 transplanted patients all receiving corticosteroid and azathioprine. 170 infective episodes were noted, only 13 patients never had infection during the period of observation. Two complications were dominated by their gravity : pneumopathies (n equals 29) fatal in 20.6% of cases, and septicemia (n equals 21) fatal in 28.5% of cases. Alone they represented 75% of the overall mortality in this series. More than 50% of failures due to death or detransplantation, were directly due to infection. The results show that this type of complication represents the main limiting factor to renal grafts in patients submitted to immunosuppressor treatment which depresses non-specifically, the whole immune response.


[Infections and immunosuppressive agents in rheumatology].

The authors review the problem of infection occurring in patients with chronic inflammatory rheumatism, e.g. rheumatoid arthritis, and lupus erythematosus, treated with cytolytic drugs for immunodepressive reasons. From their investigation, it seems that there is a high frequency of bacterial and mycotic and viral infections in these patients, but controlled investigations seem to show quite definitely that the frequency of these infections depends on the disease itself. The risk does not seem to be increased by cytolytic drugs. The only exception is herpes which appears in 10 to 20% of patients treated with immunosuppressive agents, as against 2% in a controll series. The other virus diseases did not have an abnormally high frequency. The conclusions are, of course, only of value for the types of treatment used in rheumatology.


[Fatal hyperparathyroidism].

Hyperparathyroidism is able to determine suddenly after a very poor clinical history a deep coma : in such a condition, the diagnosis with the paraneoplastic hypercalcemia may be a difficult one : cervicotomy can be the heroïc way to lead to diagnosis and in the same time to perform treatment. To avoid such a dramatic situation, the authors propose cervicotomy for every patient suspected of P.T.H. adenoma, when calcemia is higher than 115 mg c/l, even if the symptoms are very slight or nil.


[Congenital type II dyserythropoiesis].

The authors report a case of congenital dyserythropoieses, type II, the diagnosis of which was made in a young 15 year old girl with anemia, sub-clinical jaundice and splenomegaly. The following three criteria were found: erythroblastic hyperplasia with a high percentage of binuclear cells, a double peripheral red cell membrane under the electron microscope and a positive Ham-Dacle test. An isotopic study showed a double process or erythropoiesis which was inefficacious and peripheral hemolysis. In connection with this case, the authors then recall the main characteristics of the three types of congenital dyserythropoiesis. The origin and consequences of the peripheral membrane excess of the erythroblasts characteristic of type II are then discussed.


[Patient compliance with drug prescriptions. General problem and the special case of rheumatology].

In all branches of medicine, a large percentage of patients do not take the drugs which are prescribed for them. This percentage is situated at about 40%. The authors study this phenomenon in connection with data in the literature drawn from studies with objective controls. Rheumatology does not escape from this problem, whether one considers inflammatory rheumatism or degenerative rheumatism. The authors provide data from a personal series observed in arthrosic patients with an anti-inflammatory drug under trial. The various implications of this phenomenon are briefly discussed.


[Thoracic and abdominal actinomycoses. Anatomo-pathologic study of 5 cases].

The authors report 5 cases and study the thoracic and abdominal lesions of actinomycosis. This is a rare bacterial disease but not exceptional, discovered usually by chance on operative specimen on autopsy. The clinical and bacteriological diagnosis is very difficult although the lesions are characteristic. Thus it is always necessary to carry out biopsy and seek sulphur granules in the actinomycotic follicle. The differential diagnosis is usually easy with granulomycoses, but it is sometimes more difficult to distinguish the disease from nocardioses.


[Hematologic manifestations of thymomas].

The hematologic manifestations during thymomas are dominated by erythroblastopenia. Though, the other series can be affected and red series can present other troubles. The authors report two cases, one with erythroblasto-penia-hypogammaglobulinemia, the other with polycythemia, and a review of the literature attempt to make the point on the subject.


[Study of the action of sultopride on psychomotor agitation. Apropos of 31 cases].

A study of sultopride, a new derivative of the substituted anisamides, has shown that this neuroleptic drug reduces markedly and rapidly psychomotor agitation, especially its aggressive component. It also has an action on hallucinations. Its indications, in order of efficacy, are states of acute agitation, psychotic states during the active phase, acute manifestations of alcoholism and behaviour disorders such as expansivity, impulsivity and agressivity. Its tolerance is good considering its strong activity.


[The plateau of the apex cardiogram].

The apex cardiogram should normally include a flat part, but when one looks carefully, one may note that this flat part normally includes a flat wave between the descending part from the first summit and the part rising towards the second summit. This is therefore something which occurs in the middle of systole. Now, quite different curves, such as those of ventricular volume collected by rheography or cineangiography, also show a mesodiastolic occurence. As far as clinical medicine is concerned, it is expressed more frequently during proto or telesystole, rather than during mesosystole, which may be totally free of abnormal waves. What thus occurs in mesosystole? This is the question which is raised by these findings]


[Contribution of cytochemistry and delayed hypersensitivity skin tests in the diagnosis and prognosis of chronic lymphoproliferative syndromes].

Cytochemistry is disappointing in lymphoproliferative syndromes for it does not permit one to classify the various diseases with certainty. In the early stages, if the three indices are lowered, the prognosis seems poorer. A study of glucuronidase permits, in hyperlymphocytosis, one to differentiate benign from malignant lymphocytes, but does not permit one to differentiate from one another, the other chronic lymphoproliferative syndromes. The acid phosphatase is interesting in the study of hairy cell leukemia. Finally, it was not possible to distinguish chronic lymphoid leukemia from leukemia with lymphosarcomatous cells, nor from the cytochemical point of view nor using tests for delayed hypersensitivity.


[Multiple lipomas of the colon and rectum].

The authors report a case of multiple circumscribed colonic lipomas and undertake a review of the literature. Since the end of the 18th century, 45 clinical and autopsy cases have been reported. These exceptional lesions are sometimes strictly latent and discovered by chance, sometimes they may give rise to a picture of chronic intestinal obstruction and, more rarely, that of intussusception. Comparison of radiology and colonoscopy permits one to better suspect the diagnosis for there are unusual signs concerning both lesions. The treatment is mainly surgical but sometimes lipomectomy by the endoscopic route may be carried out when the lesions are not numerous.


Focal glomerular sclerosis.

Focal glomerular sclerosis was diagnosed in nine patients by renal biopsy. Proteinuria, hematuria, hypertension, and slowly progressive renal insufficiency unresponsive to corticosteroid and immunosuppressive therapy were consistent clinical findings. Focal, segmental, and global glomerular sclerosis with intraluminal deposits of hypereosinophilic and strongly PAS-positive material, intracapillary foam cells, and moderate interstitial involvement were consistent morphologic findings. The importance of this clinicopathologic entity in the spectrum of renal diseases has only recently been appreciated.


Virus peneumonia following measles: a virological and histological study of autopsy material.

Adenovirus, measles virus and herpesvirus were found to be responsible for the serious non-bacterial bronchiolar and interstitial necrosis in post-measles pneumonia in underprivlieged non-White children less than 4 years of age in Cape Town. Secondary bacterial bronchopneumonia, possibly antibiotically suppressed, proved to be less important in accounting for the extensive lung damage in 18 fatal cases that were examined virologically and histologically.


[Synovial sarcoma in the region of the head and neck].

A young woman with primary cervical synovial sarcoma above the collar-bone is described. Synovial sarcomas of the head and neck are infrequently reported. The pathology, treatment and progress appear to be very similar to that of synovial sarcomas situated elsewhere. It appears that primary lesions occur in younger people and that the survival rate is better than that for synovial sarcoma elsewhere.


Involvement of the nipple and areola in carcinoma of the breast.

The records of all patients in whom a mastectomy was performed for carcinoma of the breast at this clinic during a recent two year period were reviewed, and the gross specimens were re-examined to study the incidence of cancerous involvement of the nipple and areola and related local clinical findings. Cancer was present in the nipple or areola, or both, in 12.2 per cent of the specimens. When the nipple and areola were clinically normal, involvement of the nipple and areola by carcinoma was rare if the primary tumor was less than 2 centimeters in diameter and was not situated behind the areola.


The use of radioactive cesium chloride for imaging of malignant and benign pulmonary lesions.

129CsCl was investigated as an agent for imaging tumors of the lung, and based on the results of 56 patients studied, it has proved to be highly sensitive in detecting primary malignant tumors of the lung. The differentiation between pulmonary malignant lesions and tuberculosis appears to be feasible. However, false-positive images in patients with benign conditions are inevitable.


Primary carcinoma of the liver.

Since 1947, 173 patients have been seen with primary carcinoma of the liver; 68 percent had hepatomas, 26 percent cholangiocarcinomas, and 6 percent mixed-cell carcinomas. Of these patients, 9 percent were Stage I or unstaged, whereas 28 percent were Stage III and had short lengths of survival. The 108 patients with Stage II carcinoma of the liver were analyzed according to treatment regimens. Thirty-one patients were observed but untreated; 47 patients were treated by systemic chemotherapy and 25 patients were treated by surgical resection. Three patients were treated by infusion chemotherapy and two by dearterialization. When primary carcinoma of the liver is resectable, approximately 20 percent of patients may be expected to become long-term survivors. If not resectable, short-term improvement in length of survival (8 to 13 months) may be obtained by systemic or infusion chemotherapy and by hepatic dearterialization. Earlier diagnosis and an aggressive surgical approach lends hope for some cures for patients with this difficult disease.


The protective role of intraperitoneal antibiotic irrigation in contaminated penetrating wounds of the cecum.

Neomycin (500 mg.), polymyxin (500,000 U.), and bacitracin (50,000 U.) in one liter of saline, used as an abdominal irrigation solution, protects dogs against intraperitoneal infection and wound infections and markedly curtails adhesion formation after peritoneal contamination with cecal contents. Dogs treated with topical antibiotics after cecal puncture and local contamination were almost identical to control dogs without contamination. Equal volumes of saline irrigation offered no therapeutic advantage despite the theoretical benefit of diluting the bacterial and chemical challenge. Reported results are statistically significant (rho less than or equal to 0.05).


Comparison of two types of endothelial cells in long term culture.

Bovine aortic endothelial cells have been serially subcultured and maintained for ten months (24 passages) without any apparent loss of endothelial-like properties. There appear to be two endothelial cell types; one type is mononucleated, 40-60 mu in diameter, and the other (giant) cell type, multinucleate and 300-600 mu in diameter. Both cell types were identified as endothelial cells by established criteria; 1. ultrastructurally, by the presence of Weibel-Palade bodies, microfilaments and pinocytotic vesicles and 2. immunologically, by the presence of factor VIII antigen and thrombosthenin.


Studies of the thromboplastic effect of human plasma lipoproteins.

Human plasma lipoprotein fractions were prepared by flotation in the ultracentrifuge. Addition of these fractions to platelet-rich, platelet-poor and platelet-free plasma affected the partial thromboplastin and Stypven clotting times to various degrees. Addtion of high density lipoprotein (HDL) to platelet-poor and platelet-free plasma shortened both the partial thromboplastin and the Stypven time, whereas addition of low density lipoprotein and very low density lipoprotein (LDL + VLDL) fractions only shortened the Stypven time. The additions had little or no effect in platelet-rich plasma. Experiments involving the addition of anti-HDL antibodies to plasmas with different platelet contents and measuring of clotting times produced results that were in good agreement with those noted when lipoprotein was added. The relation between structure and the clot-promoting activity of various phospholipid components is discussed.


Intracytoplasmic uncoated capsids of human cytomegalovirus.

It has been generally accepted that capsids found in the cytoplasm of infected fibroblasts by adapted strain human cytomegalovirus (CMV) have bristle-like surface coating on them. This coating was said to be one of the important differences of CMV from herpes simplex virus. As well known, capsids of CMV increased in their over-all diameter through the process of moving from the nucleus to the cytoplasm. In some instances, however, uncoated capsids were detected in the cytoplasmic portions especially in the vicinity of tubular structures in the cytoplasm. It seemed that these uncoated capsids might be formed in the cytoplasm but had not emigrated from the nucleus.


Leukocyte adenosine triphosphatase activity in human bronchial asthma.

Changes in adenosine triphosphatase (ATPase) activity of the peripheral blood leukocytes were investigated in patients with bronchial asthma. Estimation of the leukocyte Mg++- and Ca++- dependent ATPases was carried out according to Hadden's method, incubating ATP with the membrane fraction of the leukocyte. The leukocyte ATPase activity was significantly elevated among asthmatic patients compared with control subjects. This elevated ATPase was seen in all asthmatics irrespective of acute attacks or the drug treatment. There was no clear correlation between the activity of ATPase and the percentage of leukocytes, neutrophils and eosinophils. There was no relationship between ATPase activity and adenyl cyclase activity of the same leukocytes from asthmatic patients.


Further study on the turnover calculation of lung lecithins.

Using the data reported previously by Moriya and Kanoh, the metabolic turnover of rat lung lecithins was calculated on the basis of the new assumption that the formation rate (Va) of lecithins from diacylglycerols did not equal the disappearance rate (Vb) of lecithins because of the presence of precursors other than diacylglycerols. The ratio of Va/Vb was almost the same in dienoic lecithin as that for total lecithins, whereas a very low ratio was found in saturated and hexaenoic species. The turnover time of lung lecithins estimated was markedly shorter than those determined in much later experimental periods after administration of labeled precursors. The reason for this discrepancy was discussed.


Further study on the effects of LH-RH in rat anterior pituitary.

As to the mechanism of the action of LH-RH on rat anterior pituitary, the participation of the adenylate cyclase system in gonadotropin release has been clarified. The authors previously reported that LH-RH increased the RNA synthesis in the rat anterior pituitary. In this study, the significance of the increase of RNA synthesis by LH-RH and the relationship between the adenylate cyclase system and the RNA synthesis system were investigated and the following results were obtained. (1) LH-RH induces not only the release of LH but also its synthesis in the rat anterior pituitary, and furthermore, RNA synthesis participates in LH synthesis. (2) The effects of LH-RH on RNA synthesis appeared to be independent from the effects on the adenylate cyclase system.


The specificity of the 3beta-hydroxysteroid dehydrogenase activity of bovine ovaries toward dehydroepiandrosterone and pregnenolone: evidence for multiple enzymes.

The 3beta-hydroxysteroid dehydrogenase activity in whole bovine ovaries was systematically studied using dehydroepiandrosterone (3beta-hydroxy-5-androsten-17-one) and pregnenolone (3 beta-hydroxy-5-pregnen-20-one) as substrates, in order to determine whether, in this tissue, the same or different 3beta-hydroxysteroid dehydrogenases metabolize these steroids. The majority of the activity, with both substrates was found in the microsomes. Detergent extraction of the microsomes indicated that more than one enzyme was present in this fraction. A number of experiments on the Triton X-100 extract of the microsomes (the stability of the activity, its nucleotide specificity and kinetic analyses) were most simply explained by a single enzyme metabolizing both steroids. However, the stereospecificity of hydride-ion transfer from pregnenolone to NAD+ (B transfer) was different than that from dehydroepiandrosterone to NAD+ (A and B transfer). Thus, as no single enzyme is known to catalyze the transfer of hydride-ion to both sides of NAD+, it is proposed that there are at least two 3beta-hydroxysteroid dehydrogenases in the Triton X-100 extract.


Identification of conjugated estrogen metabolites in dog plasma following administration of estriol-2,4,6,7-3H.

Following the constant infusion of 2,4,6,7-3H-estriol in male dogs for a period of 90 minutes, the radioactive metabolites present in arterial plasma were separated by solvent partition, DEAE-Sephadex, Celite partition and thin layer chromatography. The identities of the individual estrogens and estrogen conjugates were confirmed by specific activity determinations after chromatography in several different solvent systems, enzyme hydrolysis and chromatography of the unconjugated steroids and their derivatives.


Ribonucleases and neoplasia.

Biochemical data provide good evidence of a lack of acid and alkaline RNase activities in ascites tumour cells. Analyses of whole solid tumours appear of doubtful value, but fractionation studies reveal RNase deficiencies in mitochondrial fractions whereas inconsistent results are reported for microsomal fractions. Nuclei, nucleoli, and ribosomes isolated from tumours show relatively weak activities. Large variations are noted in determinations on purified lysosomes. Histochemical analyses by two different approaches demonstrate a multifocal loss of RNase activities in preneoplastic tissues, a lack of activities in cancer cells, and the presence of appreciable activities in stromal tissue and necrotic areas of tumours. These results suggest that RNase activities found in homogenates and cellular fractions of heterogeneous tumours may derive mainly from stromal cells, phagocytes, and extracellular fluids of necrotic areas. A close correlation seems to exist between activation of RNases and tumour regression. A large variety of therapeutic agents induce increases in tumour RNase activities whereas ineffective agents do not. The activation of RNases precedes obvious regression and apparently represents de novo synthesis of RNases in cancer cells. It emerges from these studies that loss of RNase activities could represent a critical event in carcinogenesis, that RNase deficiencies would persist in cancer cells, and that RNase activation would be closely associated with tumour regression. Losses of RNase activities in preneoplastic tissues are followed by changes in the properties of cytoplasmic RNA probably due to alterations in ribosomes in areas of neoplastic transformation. Deficiencies in the RNase system could be the source of abnormalities in cellular RNA or RNA-containing particles that would lead to neoplasia.


Lipoprotein composition and lipoprotein interrelations in 50-year-old men with hyperlipoproteinaemia.

The serum lipoprotein (LP) composition and LP lipid interrelations were studied in 50-year-old men with different types of hyperlipoproteinaemia (HLP) and in randomly sampled health controls from the same population. The ratio cholesterol/triglycerides in very low density lipoproteins (VLDL)was high in HLP type III. The other types of HLP showed ratios not significantly different from the controls. The low density lipoprotein (LDL) cholesterol concentration was similar in controls, type III and type IV while, by definition, higher values were seen in type II A and II B. All types of HLP showed statistically significantly higher LDL triglycerides than the controls. HLP type II A and II B showed cholesterol/triglyceride ratios in LDL similar to the controls. The corresponding ratio in type IV was lower than in the control subjects but the lowest ratio was seen in type III with a mean value below the 5th percentile of healthy controls. The high density lipoprotein (HDL) cholesterol concentration was decreased in HLP type IV. Apparently elevated HDL triglyceride levels were seen in all types of HLP with the highest mean value in type III. The LP lipid interclass relationships were analysed in the random sample of health men and compared to corresponding relationships in the different types of HLP. Apart from HLP type III and HLP type IV with low LDL cholesterol levels all other types of LP interconversions. Intype IV a significant negative correlation between VLDL concentration and LDL cholesterol concentration and the cholesterol/triglyceride ratio in VLDL. There were no significant correlations between LDL cholesterol concentration and VLDL lipid variables in other types of HLP and normolipidaemia.


Dietary and drug treatment of hyperlipidaemia. A feasibility study in asymptomatic middle-aged men.

83 middle-aged men with different types of hyperlipoproteinaemia were recruited from a health examination survey. They were treated with diet for 3 months and with diet and drugs in combination over a 2-year period (63 men used drugs). The serum lipid reductions after the dietary period were 14% and 27% for serum cholesterol and triglycerides, respectively. After 2 years the corresponding reductions were 21% and 42%, indicating an additional effect of diet and drugs. There was an average body weight reduction of 4.3% during the first 3 months which was maintained over the 2-year period. Special considerations in treating asymptomatic individuals are discussed.


[Effect of thymosterin A on the immunological reaction of mice].

Proliferaiton of thymus-dependent lymphocytes and immunological reaction of the line CBA mice immunized with sheep erythrocytes was studied as affected by thymosterol A. The data obtained confirmed the authors' assumptions on a stimulation effect of thymosterol A on division of thymocytes. Introduction of the mentioned preparation against a background of the antigenic aciton of sheep erythrocytes causes an increase in the amount of cells synthesizing hemolysins more than by 60% as compared to the control. The preparation effect depends on the dose. The data are presented, which makes it possible to assume that the mentioned effects may be due to the action of thymosterol A on the content and activity of the intracellular cyclic AMP.


[Change in lipid metabolism in sports wrestlers under conditions of physical load and body dehydration].

Control of forty six sportsmen-wrestlers determined that the loss in weight accounting for 3.5% leads to a certain reduction of nonesterified fatty acids (NEFA) in venous blood and to a significant increase in the content of esterified fatty acids (EFA), beta-lipoproteids, phospholipids and cholesterol. Analogous as to the trend (excluding NEFA) but a little less pronounced changes these values occur after physical load on sportsmen who did not undergo dehydration. Under conditions of dehydration a 40-minute work on veloergograph caused additional changes in the values under study. An hour after finishing the physical work the total level of lipids as well as of their fractions such as beta-lipoproteids, EFA and cholesterol remains considerably higher than that in the control. Thus, the loss in weight itself as to the character of the changes arising in the lipid metabolism is to some extent similar to physical load suffered by a sportsman organism and therefore may exert unfavourable effect on the working capacity.


Antibiotic managment in renal failure.

This is a brief compilation of the work of many investigators. It includes facts about toxicity and recommendations about antibiotic management in patients with renal failure. As new data are accrued, changes in these recommendations will be necessary.


Interaction of ultrasound with neoplastic tissue: IV. alteration of biologic activity in cells derived from rat Wilms' tumor sonicated in vivo.

Paired Wistar-Furth male rats were implanted subcutaneously with the Furth-Columbia rat Wilms' tumor. Seven days after implantation the tumors were either subjected to therapeutic ultrasound irradiation or were left as untreated controls. On the ninth day after implantation the animals were sacrificed, and suspensions of cells were made from the excised tumors by trypsinization. The cells were counted using trypan blue dye as an indicator of viability. New rats were then implanted with cells either from sonicated tumors or cells from controls. In half the recipient animals the suspensions were matched by total cell count. In the other half of the rats cell counts were matches for viability by the dye exclusion test. Tumors developed in a total of 8 of 11 rats receiving control cells and they died. A palpable tumor did not develop in any rat receiving cells fromsonicated tumors during the ninety-day study period. Surviving rats were challenged with Wilms' tumor by trocar implant. Tumor developed in all recipients, and they died.


Radiolucent defects within renal pelvis.

Radiolucent filling defects within the renal pelvis are common findings in diagnositc urography, and because of their myriad causes the diagnostician is often faced with a challenging problem. Several of the more unusual causes of renal pelvis filling defects are described and their diagnosis, pathophysiology, and therapy discussed.


[Plasma prekallikrein activation by highly dispersed organic silica].

Human and animal blood plasm precallikrein was studied as activated by the high-dispersed preparations of silica (aerosils) which carry on their surface various chemically grafted organic radicals. It is shown that hydrophilic silica containing -COOH, -HN2, -OH groups, contrary to the hydrophobic ones, are efficient in activating human plasm precallikrein. Precallikrein activation is dependent on concentration of hydrophilic aerosil, temperature and specific surface of the activator.


[Study of certain components of the kinin system in acute purulent peritonitis].

Under study was the kinetics of changes in the kinin content, the activity of kininase and blood proteolytic activity in acute purulent peritonitis in 63 patients. The kinin activity was judged indirectly by the kinin level in blood. The results of the study indicated that in acute purulent peritonitis the kinin concentration in blood is decreased in proportion with the gravity of the disease course.


[Immunogenic properties of a polyvalent inactivated vaccine from respiratory viruses (IBR, Pi-3, Ad-1, Ad-3].

Studied was the authors' inactivated polyvalent vaccine having an adjuvant, prepared from the respiratory viruses IBR, Pi-3, Ad-1 and Ad-3. It was found that at the subcutaneous vaccination of calves and pregnant cows there were virus-neutralizing, hemagglutination-inhibition, and complement-fixing antibodies as established by the 14th day following treatment. Revaccination was carried out on the twenty-eighth day when the antibodies reached high titers. The latter showed peak values on the 14th day following revaccination. The prevaccinal and vaccinal antibodies did not interfere with the process of immunogenesis. The virus-neutralizing antibodies against IBR had a titer of 5 log on the 150th day, while the virus-neutralizing and hemagglutination-inhibition antibodies against Pi-3 showed the same titer even after the 180th day following vaccination. There were in the milk of the vaccinated cows, in the seventh month of pregnancy, specific lactoglobulins of the IgA and IgG classes which were contained in the 27-36, 45-48 and 51-54 fractions, distributed in three peaks by their protein content. The level of the virus-neutralizing, hemagglutination-inhibition, and complement-fixing antibodies against the inactivated vaccinal respiratory viruses showed that the subcutaneous treatment with the polyvalent vaccine leads to the production of antibodies that are secreted with milk


[Use of polyethylene glycol (PEG) in the isolation of the IBR virus].

Experiments were carried out to use polyethylene-glycol (PEG)--6000 in the isolation of the IBR virus from field material. The sedimentation with PEG proved easy, fast and selective. Large amounts of field material suspension could be treated which made it possible to attain volume concentration of such suspensions and to raise the relative concentration of the virus in them. Thus the virus could be isolated more quickly and in a more dependable way, avoiding the toxic effect of some of the initial materials on the cell culture.


[Study of Aujeszky's disease virus replication by using an immunofluorescent method].

Studied was the interrelationship between the Aujeszky's disease virus (the avirulent mutant strain MK and the virulent strain 2) and chick embryo cells during cultivation with and without 5-iod-2-desoxiuridine. In experiments with the virulent strain the presence of a granular antigen could be observed at the 4th hour following the infection of the nucleus. After the 10th hour the antigen showed migration from the nucleus toward the cytoplasm. After the 24th hour a complete destruction of the cellular monolayer was observed, along with the production of polynuclear cells. In the experiments with strain MK the antigen seemed to appear first in the cytoplasm after the 10th hour of infecting the cells, and after the 12th hour it was found in the nucleoplasm too. In this case full destruction of the cells set in after the 48th hour of infection. In the cultivation of strain MK in cell cultures containing 5-iod-2-desoxiuridine no disturbances in the normal cycle of reproduction was observed. The virus replicated equally well both with and without the antimetabolite. In the cultivation of the virulent strain 2 in cell cultures that contained 5-iod-2-desoxiuridine a coarse, granular antigen was noticed in the cytoplasm of single cells after the eighth hour of infection. After the 12th hour the nuclei of these cells manifested slight flourescence (hardly visible single granules). After the 48th hour the nuclei of the involved cells were swollen, and the cytoplasm presented slight, diffuse fluorescence, some of the cells being destroyed.


[Effects of concanavalin A on the adsorption and penetration of paramyxoviruses into cells].

The lectin concavaline A, when added to cell cultures of chick embryos and calf kidney one hour prior to their injection with the virus of the Newcastle disease and that of parainfluenza-3 in cattle produces no adverse effect on the cell receptors of these viruses. On cells treated with concavaline 60 per cent and more virions are adsorbed as compared with the untreated cells. This is explained by the fact that concavaline binds to the cellular and viral glucoproteins. Virions bound to concavaline do not penetrate into the cells. The titers of the paramyxoviruses obtained from lectin-treated cells were by 2 log. lower than the virus titers obtained from untreated cells. Mono- and bivalent concavalines inhibit more slightly the reproduction of para myxoviruses.


[Glomus cell clusters of the lymph node].

Nine lymph nodes with so-called benign nevus cell nevi were studied by light microscopy. In three cases the lymph nodes were also examined by electron microscopy. The solitary or multiple cell clusters were 35-645 mu in diameter and were usually found in the lymph node capsule or cortex. They were more frequent in the older patients. There was no predisposition for either sex. Specific morphologic features allowing clear cytologic identification of the cells were not evidient. In particular, there was no indication that they represented nevus cells. However, they showed a great morphologic similarity to glomus cells. In addition, they were usually found near blood vessels. We assume that the cell clusters were hamartias related to glomangiomas. We call them glomus cell clusters.


Characterization of two different factors chemotactic for cancer cells from tumor tissue.

Two different factors chemotactic for cancer cells were extracted in pseudoglobulin fraction of rat ascites hepatoma transplanted tissue. After chromatography on Sephadex G-50 and CM-sephadex, these factors were separated by gel filtration on Sephadex G-100. The factor a was further fractionated by immunoadsorbent chromatography with goat antirat gamma-globulin antibody and then with rabbit antirat hemoglobin antibody; it was a protein with a molecular weight of about 78,000, resembling a chemotactic factor previously reported, and its activity was thermolabile. The previously undescribed factor b was also a protein with a molecular weight of about 14,000 and its activity was thermostable. Intradermal injection of these factors at low concentrations induced an extravascular migration of circulating tumor cells and formation of metastatic secondary tumors; and little difference in the in vivo effect between these factors was observed. It was thus assumed that the combined action of these two factors may be involved in malignant invasion.


A study of the Ag factors in a British (West Midland) population.

168 sera from a British (West Midlands) population of normal blood donors were typed for the factors Ag (x, y, a1, d, t, c, g and h). The results were compared with the published data from other populations. The 8 factors were found in 27 different phenotypic combinations including a single instance of the combination Ag (y-h+) not previously reported. The occurrence of this phenotype is discussed in relation to the theoretical models of the genetic control of the Ag system.


[Biochemistry of benign-symmetrical lipomatosis (adenolipomatosis Launois-Bensaude, Madelung's disease)].

1. Total lipids, total cholesterol, cholesterol esters, phospholipids, triglycerides and free fatty acids as well as the fatty acids profiles of the different lipid classes were determined in serum, lipomatous and normal adipose tissue. Triglycerides were elevated in patient L's serum. The distribution of serum lipoproteins in this patient's serum showed a type IV according to Fredrickson. All other lipid parameters were within the normal range. Palmitoleic acid was increased nearly in all lipid fractions of the patients' sera as well as in the lipids of lipomatous subcutaneous adipose tissue. 2. The lipomatous adipose tissues of the patients showing no histological abnormalities revealed higher levels of cyclic AMP than normal subcutaneous adipose tissue. 3. Serum uric acid was normal (patient E.), between the normal and pathological range (patient L.) and elevated (patient W.). Urinary uric acid excretion was increased in all three patients. 4. 14C-glycine was overincorporated into urinary uric acid in all three patients. 5. Adenine phosphoribosyltransferase activities in the hemolysates were within the normal range. A decrease of hypoxanthine-guanine phosphoribosyltransferase activities could be demonstrated in two patients' (e., w.) erythrocytes. Erythrocyte phosphoribosylpyrophate synthetase activity was slightly increased in patient L.'s and twice the normal value in patient W.'s erythrocytes.


[Further experimental investigations on the therapy of gas gangrene with ozone and oxygen (author's transl)].

In continuation of a recently-published investigation on the effect of intramuscular injections of an ozone-oxygen mixture on experimental gas gangrene in the guinea pig, 2 additional experiments were performed in order to establish the efficacy of the therapy when given twice daily instead of only once. Futhermore, the effect of an analogous therapy was investigated with the use of pure oxygen. The ozone-oxygen therapy reduced the death rate from 100% in untreated control animals to 73.6 and 70.0%, respectively, in the 2 series of experiments. The median survival times were prolonged from 0.56 and 1.33 days to 5.50 and 6.66 days. The use of oxygen twice daily reduced the death rates significantly even further to 57.0 and 47.9%. With this therapy the median survival time was increased to 8 and more than 12 days. The differences in therapeutic effect of the 2 gases were not, however, statistically significant. On account of its simple applicability previous experiments on animals it is proposed that this therapy be employed also in cases of human gas gangrene. In addition, the bactericidal effect of CaCl2, as used in this experimental study, on vegetative forms of Clostridia is demonstrated.


Cytomegalovirus replication and the host immune response.

Cytomegalovirus (CMV) is closely associated with host cellular structures, and this has a significant impact upon the immunologic response following infection. CMV may be recovered from a variety of body secretions and fluids during acute infection, and protracted shedding may supervene in some instances. The reasons for a variable host response to CMV infection remain unclear, and the mechanisms responsible for the establishment of persistence have not been worked out. CMV persistence and latency are discussed, and some recently derived relevant data are presented. An animal model has been developed consistent with clinical observations pertaining to CMV transmission with blood. Results obtained in the course of these and other studies support the concept of immunological activation of latent CMV. The timing of CMV infection relative to an unrelated antigenic challenge is probably critical in determining the emergence of immunodepression or enhancement. Some aspects of CMV sero-diagnosis are also reviewed.


Cytomegalovirus infection in children undergoing open-heart surgery.

A group of 124 children undergoing open-heart surgery was followed prospectively in order to estimate the risk of cytomegalovirus (CMV) infection due to transfused blood.Ninety-three patients (75%) had complement fixation (CF) titers of < 1:4 against CMV on admission. Of this seronegative subgroup, nine patients (9.7%) subsequently became infected with CMV. All nine showed seroconversion, and six were viruric 12-14 weeks after surgery. Comparative seroepidemiological studies of the hospital population showed that in the age ranges studied (3-16 yr), the infections seen in the study group represented a significant excess over expectation. This infection rate was consistent with a model of transmission by blood transfusion with a risk of 2.7% per unit but not proven.Thirty-one patients had CF antibody to CMV on admission. CMV was isolated from 14% of urines of seropositive children both before and after surgery, but only two patients showed CF antibody rises to CMV. Thus the frequency of CMV infection associated with open-heart surgery and transfusion could not be calculated in the seropositive subgroup.CMV infection was not related to the primary diagnosis or to Down's syndrome.


Hepatitis A.

Hepatitis A is a disease of worldwide distribution which occurs in endemic and epidemic form and is transmitted primarily by person-to-person contact through the fecal-oral route. Common source epidemics due to contamination of food are relatively common, and water-borne epidemics have been described less frequently. The presumed etiologic agent of hepatitis A has now been visualized by immune electron microscopic (IEM) techniques in early acute-illness-phase stools of humans with hepatitis A as well as in chimpanzees experimentally infected with material known to contain hepatitis A virus. In addition, several new serologic tests for the detection of antibody against hepatitis A virus have been described. These include complement fixation and immune adherence techniques. Current data suggest that hepatitis A is caused by a single viral agent lacking the morphologic heterogeneity of hepatitis B viral components and that there may be relative antigenic homogeneity between strains of virus recovered from various parts of the world. Serologic studies to date also indicate that hepatitis A virus is not a major contributing cause in post-transfusion hepatitis.


[Surface tension in rat lungs after quartz dust inhalation (author's transl)].

The influence of quartz dust (1000mg/m3) on surface tension in rat lungs was investigated. The exposure-times were 5, 15 and 30 hours. The animals were killed, 1, 7, 14, 28 and 90 days after quartz dust exposure and the surface tension was measured in a Wilhelmy balance. There was no significant difference between control animals and quartz dust animals in gammamax, gammamin and S. But there were significant differences in the same groups in hysteresis shape index and compressibility-coefficient.


Reduction of folate levels in the rat: Difference in depletion between the central and the peripheral nervous system.

1. Rats were deprived of dietary folate for 12 and 9.5 months in two experiments; one with and one without succinylsulfathiazole added to the diet. Folate levels decreased faster in the former experiment and the final blood values were lower. Tissue folate was examined in the latter experiment only. 2. The animals were repeatedly examined with neurological tests and compared with a control group supplemented with folic acid. Every test proved normal. Measurement of motor nerve conduction velocities after 12 months in the experiment where succinylsulfathiazole was given revealed lower velocities in the non-supplemented group. There was no difference between the groups in the experiment without succinylsulfathiazole. 3. In the latter experiment brain folate was reduced by only 16% in the non-supplemented animals compared with the controls, whereas whole blood folate fell by 60%, liver folate by 50% and sciatic nerve folate by 59%. 4. The central nervous system is resistant to systemic folate depletion, whereas the peripheral nerves are depleted to the same degree as the extra-neural tissues.


[Drug therapy of hyperthyroidism].

The possibilities of the treatment of hyperthyroidism are mentioned, in which cases the author especially deals with the medicamentous therapy, taking into consideration the different chemical groups (imidazol derivations, thiourazil derivations, perchlorates) and their therapeutic mechanisms. The indications and contraindications of this treatment and the possible side effects are compiled in form of a table. The in-vitro-parameters which are necessary for the observation of the course are estimated in their significance. The author deals with the problems of the additional treatment. Taking into consideration indications and contraindications as well as controls of the course of functional parameters the medicamentous therapy concerned is a treatment with a good prognosis. It is promising particularly in such cases, when suitable parameters are used for the solution of the question concerning the end of the therapy. For this purpose nowadays two tests are at our disposal: 1. modified Alexander's test (radioiodine-test and suppression test under thyreostatic therapy) and 2. TRH-test with radioimmunological determination of TSH. The treatment should be carried out in adequate endocrinological dispensaries, as there are certain risks in not optimal therapy.