Stability of nucleosomes in native and reconstituted chromatins. The stability of nucleosomes of SV40 minichromosomes extracted from infected cells or reconstituted by association of SV40 DNA and the four histones H2A, H2B, H3 and H4 was studied as a function of the ionic strength. As a measure of the stability of the nucleosome, we followed the disappearance of the nucleosomes from the original chromatin and their appearance on a "competing" DNA. We show here that the DNA and the histone components of the nucleosomes do not apprecially dissociate below 800 mM NaCl. At 800 mM and above, the histone moiety of the nucleosomes can dissociate from the DNA and efficiently participate to the formation of nucleosomes on a "competing" DNA.


Excision in vitro of the DNA bound carcinogen, 4-nitroquinoline 1-oxide. It has been shown that 4-hydroxyaminoquinoline 1-oxide, the proximate form of the carcinogen 4-nitroquinoline 1-oxide, binds covalently to the purine bases of DNA. Here we report that carcinogen-bound nucleotides can be excised from DNA by a 5' leads to 3' exonuclease associated with DNA polymerase I of E. coli in the forms of either mononucleotides or oligonucleotides. Beef spleen phosphodiesterase II (5' leads to 3') also split carcinogen-bound nucleotides, while a 3' leads to 5' exonuclease of DNA polymerase I and E. coli exonuclease III (3' leads to 5') could not excise the modified nucleotide.


Variation in DNA swivel enzyme activity during the mammalian cell cycle. Synchronized cells of a normal human lymphocytic cell line contain little swiven enzyme activity in G0 and G1 and high activity in Sphase. The level of activity in different growth phase appears to be related to the fraction of the population engaged in DNA replication. No endogenous inhibitor or activator of swiven activity could be demonstrated. The evidence implies that the enzyme may be present only during S phase; it is therefore a possible control factor for replication.


Nucleotide sequence of the restriction fragments hind L and hind M of SV40 DNA. The nucleotide sequence of the two minor SV40 DNA restriction fragments Hind L and Hind M is here reported. For this purpose we used 5'-32p-labeled DNA fragments either partially digested with snake venom diesterase for analysis by the wandering spot method or partially degraded with the base specific reagents dimethylsulphate or hydrazine for direct sequence analysis on gel. In the former procedure the strands were separated before degradation, while in the latter the strands were separated after modification but before the degradation. Due to the presence of several termination codons, the region Hind L - Hind M cannot be translated in a polypeptide. Also, no initiation codons for protein synthesis are present in this region.


[Bone scintigraphy in renal osteopathy]. 25 Patients with chronic renal disease are investigated. In 16 cases with conservative treatment the bone scintigram showed pathological uptake according to the creatinine level, mainly in the joints of iliosacrum, hip, knee and ankles. In three patients increased uptake in the skull was found. The bone uptake found by scintigraphy was highly pronounced in the patients treated by dialysis. The most frequently involved regions were the joints of iliosacrum and hip, facial cranium, skull, pelvis and metatarsus. The count-rate ratio of cranium to chest was significantly increased in 6 patients. The investigations 6 months later showed in 4 cases a further increase compared with the first values. Count-rates of the skull were found to be comparable to the highly increased uptake in Paget's disease. Bone scintigraphy is a suitable method to estimate semiquantitatively the bone turnover in renal disease.


Bone scintigraphy in children.

Bone scintigraphy in children. Bone scintigraphy with 99mTc-polyphosphate or 99mTc-pyrophosphate was carried out in 54 children suspected of bone disease. Signs of skeletal metastases were recognized in 13 children by scintigraphy whereas X-ray examination showed lesions in only 10 of these. In 5 children with primary osteosarcoma, three cases of fibrous dysplasia, and 4 cases of osteomyelitis, the lesions were clearly demonstrated by scintigraphy. Abnormal accumulation of radioactivity in soft tissue lesions was observed in primary adrenal neuroblastoma, Hodgkin's granuloma, and metastatic Burkitt's lymphoma. Several cases are reported, and the value of bone scintigraphy in children is discussed.


[Pleuresies in chronic pancreatitis and in pancreatic pseudocysts. A study apropos of 20 cases]. The pleurisies rich in amylase of the chronic pancreatitis and of pancreatic pseudo-cysts, studied in 20 cases, are quite unfrequent (0.5% of pleurisies of all kinds in the medical milieu). A pseudo-cyst was found 12 times out of 20 and a chronic pancreatitis without pseudocyst was found 8 times out of 20. Pleural effusion has a definite diagnostic valve, because in 70% of cases pancreatopathy cannot be recognized before it happens. The pleural liquid is rich in proteins and haemorrhagic in 2/3 of cases and its amylasic activity is either high or very high. Amylase level in pleural liquid is usually superior to amylasemia. The injection of lipiodol in the pleural cavity enables the visualization of a transdiaphragmatic fistula but this examination is not always well tolerated. The preoperatory cystography can opacify the pleura. In the absence of pseudo-cyst, medical treatment can dry the pleurisy in 70% of cases but does not modify the evolution of the pancreatic affection which will require surgery. Where a pseudo-cyst is concerned, surgery will often and quickly be the remedy.


Formaldehyde treated gelatin as a gel exclusion agent. A high molecular weight fraction of gelatin precipitated from a solution of Difco gelatin with polyethylene glycol has several favourable properties in gel exclusion chromatography. To manufacture the gel exclusion agent, the gelatin was dissolved in hot water, allowed to set in the cold and rendered insoluble by reaction with formaldehyde. When finely disrupted and used as bed material in columns this gel is capable of separating protein components from mixtures of proteins of widely different molecular weights. Favourable properties include elasticity at relatively low concentration, its availability and its inexpensive nature.


A large product of cell-free translation of messenger RNA coding for corticotropin. Polyadenylate-containing RNA prepared from the membrane fraction of bovine anterior pituitary gland was shown to direct the synthesis of a large translation product related to corticotropin (adrenocorticotropic hormone) in a cell-free system derived from wheat germ. This product was identified by immunoprecipitation with specific antibody against corticotropin, followed by electrophoretic analysis of the dissociated immunoprecipitate on sodium dodecyl sulfate-polyacrylamide gel. Further evidence for the identity of the translation product was provided by the presence of a common peptide in the chymotryptic digest of [35S]methionine-labeled cell-free product and in that of authentic corticotropin. The molecular weight of the translation product was estimated to be approximately 35,000, based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results indicate that corticotropin messenger RNA directs the cell-free synthesis of a product that contains the amino acid sequence of corticotropin but is much larger than this hormone.


Adrenal cholesterol uptake from plasma lipoproteins: regulation by corticotropin. The transfer of lipoprotein-bound cholesterol into adrenal cells was examined. Adrenal glands from unstimulated or corticotropin stimulated hypophysectomized rats were incubated with high density lipoprotein (HDL) or low density lipoprotein LDL containing radiolabeled cholesterol. The rate of transfer of labeled cholesterol from HDL into the glands was two to three times greater than from LDL. Corticotropin stimulation increased the transfer of cholesterol from HDL but not LDL. The effects of corticotropin were not dependent on subsequent cholesterol utilization for steroidogenesis. The process of cholesterol transfer from HDL was linear with time over 2 hr at 37 degrees and greatly reduced at 4 degrees. In addition, the transfer process became saturated above an HDL cholesterol concentration of 900 mug/ml. About 25% of the labeled adrenal cholesterol arising from HDL was recovered within the mitochondria. The labeled cholesterol within isolated mitochondria could undergo mitochondrial conversion to pregnenolone. Finally, the delipidated HDL apolipoproteins, apoA-I and apoA-II, when added to incubations containing less than saturating concentrations of HDL, stimulated transfer of labeled cholesterol from HDL to adrenal cells. These studies suggest that rat adrenal tissue possesses an HDL specific hormonally-responsive mechanism for accumulating extracellular cholesterol and that apoA-I and apoA-II have a significant function in the uptake process.


Interaction of integral and peripheral membrane proteins: affinity labeling of yeast cytochrome oxidase by modified yeast cytochrome c. To identify possible substrate-binding subunit(s) of yeast cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1-9-3-1), the purified enzyme was reacted with yeast iso-1-cytochrome c whose single free sulfhydryl group at position 107 had been activated with 5,5'-dithiobis(2-nitrobenzoate). The resulting cytochrome c derivative appeared to function as an "affinity-label" of cytochrome oxidase, since it rapidly inactivated the enzyme. Inactivation was competitively prevented by underivatized cytochrome c. When the "affinity-labeled" oxidase was analyzed by two-dimensional polyacrylamide electrophoresis in dodecyl sulfate (separation in the second dimension being carried out in the presence of excess sulfhydryl compound), it was found that the derivatized cytochrome c had specifically formed a mixed disulfide with the mitochondrially made subunit III (apparent molecular weight 24,000) of the oxidase. Similar results were obtained when underivatized iso-I-cytochrome c was crosslinked to the oxidase by oxidative disulfide bridge formation in the presence of ortho-phenanthroline and Cu++. These data indicate that the hydrophobic mitochondrially made subunit III of yeast cytochrome c oxidase is in close proximity to the cytochrome c binding site on the enzyme. Since cytochrome c and the mitochondrially made cytochrome oxidase subunit III are typical peripheral and integral membrane proteins, respectively, the present study suggests a useful approach for analyzing specific interactions between these different classes of membrane proteins.


Alterations in cell surface glycosphingolipids and other lipid classes of fibroblasts in familial hypercholesterolemia. The glycosphingolipids (GSL) and other major lipid classes were studied in cultured fibroblasts from a family with familial hypercholesterolemia. The GSL content in cells grown in medium containing fetal calf serum was increased 5-fold in the homozygote and 2- to 3-fold in both heterozygous parents. Cell surface labeling experiments, using the membrane probe galactose oxidase followed by reduction with KB3H4, showed an increased incorporation of 3H by the homozygous cells into GL4 (4-fold), GM3 (2- to 3-fold), and GL3a and GD3 (1- to 2-fold); the amount of 3H incorporated by the heterozygous cells was in between that of the homozygous and normal fibroblasts. The specific radioactivity of each of the GSL, except GL2a, was lower in the mutant cells. This unlabeled pool of GSL may be buried in the membrane matrix (less exposure), or located intracellularly, or both. The phospholipids were most markedly elevated (3-fold) in homozygous cells, with a disproportionate increase in phosphatidic acid and sphingomyelin (5- to 6-fold). The content of the GSL, except GL2a, and of the phospholipids was reduced about one-half in the homozygous fibroblasts grown in lipoprotein-deficient medium for 24 hr; by 5 days the GSL content was reduced to only 1.3 times normal and phospholipids to below normal. Incubation of normal fibroblasts in lipoprotein-dificient medium 24 hr had no effect on the GSL or phospholipid content; at 5 days, there was a 50% increase in both GL3a and GL4 with a 25% increase in GM3; there was no change in the phospholipid content. These data suggest that the defective regulation of lipid metabolism in this syndrome may be more extensive than previously realized.


Effect of 3':5'-cyclic AMP on glucose transport in rat adipocytes. An indirect method for obtaining a reliable measure of the rate of glucose transport into adipocytes is described. Evidence is presented that altered levels of 3':5'-cyclic AMP can influence the transport of glucose into adipocytes. When cyclic AMP levels were lowered with antilipolytic agents (insulin, nicotinic acid, or clofibrate), rates of glucose transport were increased. In contrast, when adipose tissue levels of cyclic AMP were elevated by lipolytic hormones or theophylline, glucose transport when cyclic AMP levels were elevated by lipolytic agents. Agents that can raise cyclic AMP but inhibit lipolytic (procaine, amitryptyline, and phenylethylbiguanide) reduced the rate of glucose transport. Other data are presented that are consistent with the conclusion that cyclic AMP inhibits glucose transport into adipocytes.


Subnuclear systems for synthesis of simian virus 40 DNA in vitro. We have developed two subnuclear systems for synthesis of DNA of simian virus 40 in vitro. We prepare chromatin from infected cells by the method of Hancock [(1974) J. Mol. Biol. 86, 649-663]; these "chromatin bodies" can be disrupted and large debris can be pelleted, leaving a supernatant ("soluble system"). Both chromatin bodies and the soluble system incorporate deoxyribonucleoside triphosphates into nucleoprotein complexes that contain simian virus 40 DNA. The DNA labeled in short pulses sediments in neutral sucrose gradients slightly faster than mature simian virus 40 DNA, as expected for replicating intermediate. When rebanded in alkaline sucrose gradients, about half of the radioactivity is found in short strands (200-300 nucleotides) and half in longer strands (up to full viral size). When these systems are supplemented with a cytoplasmic preparation from HeLa cells, synthesis is stimulated about 5-fold, and the short strands are converted into strands of up to full viral length as well as into covalently closed circles. These subnuclear DNA-replicating systems should be useful for biochemical fractionation and characterization of some of the proteins required for DNA replication.


Hydrolysis of nicotinamide adenine dinucleotide by choleragen and its A protomer: possible role in the activation of adenylate cyclase. Choleragen and the isolated A protomer catalyzed the hydrolysis of NAD to ADP-ribose and nicotinamide. The protein with NADase activity (NAD nucleosidase; NAD glycohydrolase, EC 3-2-2-5) migrated on polyacrylamide gels with choleragen, and chromatographed on Bio-Gel P-60 columns with the A protomer. The NADase activity of choleragen and of the A protomer was increased markedly in acetate and phosphate buffers, and enhanced over 10-fold by dithiothreitol in high concentration. NAD hydrolysis was proportional to choleragen concentration; the Michaelis constant for NAD was about 4 mM with both choleragen and the A protomer. The demonstration that the A protomer of choleragen catalyzes an enzymatic reaction involving activation of the ribosyl-nicotinamide bond of NAD, a reaction analogols to those catalyzed by diphtheria toxin, supports the hypothesis that activation of adenylate cyclase by choleragen involves the ADP-ribosylation of an appropriate acceptor protein.


Distribution of 3':5'-cyclic AMP and 3':5'-cyclic GMP in rabbit retina in vivo: selective effects of dark and light adaptation and ischemia. By use of highly sensitive radioimmunoassays, 3':5'-cyclic AMP (cAMP) and 3':5'-cyclic GMP (cGMP) were measured in individual layers of light- and dark-adapted rabbit retinas, and the effects of ischemia were determined. In light-adapted retinas, cGMP levels ranged 50-fold, with over 90% of the total concentrated in the photoreceptor cells. The layer of outer segments contained 95 mumol/kg of dry weight, or three times the concentration present in the remainder of the photoreceptor cell layers. By contrast, levels of cAMP varied only 4-fold; the lowest level (6 mumol/kg of dry weight) was found in the outer segment layer and the highest level (22 mumol/kg of dry weight) in the inner segment layer of the photoreceptor cells. Dark adaptation elevated cGMP levels only in retinal layers containing photoreceptor cells, and the greatest proportional increase was observed in the synaptic layer of photoreceptor cells. Dark adaptation also caused increases of cAMP that were restricted to the outer plexiform and outer nuclear layers. Ischemia lowered cGMP levels, but only in retinal layers containing photoreceptor cells, and elevated cAMP levels, primarily in the inner layers of the retina. The effects of ischemia were greater in the dark-adapted than in light-adapted retinas. These results indicate that cGMP and cAMP levels in retina are influenced by the light adaptational state, that ischemia markedly modifies these processes, and that the effects of both light exposure and ischemia are regionally selective.


Inhibition and stimulation of the development of the bioluminescent system in Beneckea harveyi by cyclic GMP. The development of the luminescence system in Beneckea harveyi is controlled by cyclic nucleotides at the level of transcription. In the wild type, it is repressed by exogenously added guanosine 3':5'-cyclic monophosphate and this repression is overcome by the addition of adenosine 3':5'-cyclic monophosphate. These observations alone support a model in which these nucleotides act antagonistically. On the other hand, in a mutant requiring adenosine 3':5'-cyclic monophosphate for maximum luminescence, guanosine 3':5'-cyclic monophosphate stimulates the synthesis of the luminescence system at low concentrations and inhibits it at higher concentrations. These results are apparently not consistent with a model involving a simple antagonistic effect of guanosine 3':5'-cyclic monophosphate on the action of adenosine 3':5'-cyclic monophosphate.


Determination of molecular weight of the protein moiety in protein-detergent complexes without direct knowledge of detergent binding. Sedimentation equilibrium measurements can be used to determine the molecular weight of the protein moiety of a protein-detergent complex without prior knowledge of detergent binding. The procedure is to adjust the solvent density by addition of D2O so as to blank out the contribution of bound detergent to the sedimentation potential. An approximate measure of detergent binding can be obtained from the effect of solvent density on the sedimentation result. The procedure is also applicable to protein-lipid complexes. It can be used for complexes containing both lipid and detergent if the lipid content is known. The use of the method is demonstrated by experimental data for the AI polypeptide of serum high density lipoprotein, in separate complexes with nonionic detergents and with a phospholipid.


Induction and decay of glucagon-induced amino acid transport in primary cultures of adult rat liver cells: paradoxical effects of cycloheximide and puromycin. Liver parenchymal cells were isolated from adult rats and cultured in collagen-coated plastic petri dishes in serum-free medium. Glucagon induced 4- to 5-fold increases in alpha-aminoisobutyric acid (AIB) transport within 6 hr. Dexaemthasone had no direct effect on AIB transport but greatly potentiated the induction by glucagon ("permissive effect"). Levels of 3':5'-cyclic AMP increased 30- to 100-fold within 30 min after glucagon addition to cultures that had been treated with dexamethasone, and dibutyryl cyclic AMP mimicked the glucagon induction of AIB transport. Additionally, dexamethasone exerted a "permissive" effect on induction of AIB transport by dibutyryl cyclic AMP, whereas the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine induced AIB transport only in cultures that had been treated with dexamethasone. Induction of AIB transport was not dependent upon the continued presence of glucagon, but induced AIB transport activity decayed to uninduced levels within 3-4 hr after glucagon removal. The protein syntesis inhibitors puromycin and cycloheximide inhibited both induction and decay of glucagon induced AIB transport, but had a stabilizing effect if added once induction or decay had commenced. Unlike cycloheximide, the inhibitory effect of puromycin on the glucagon induction of AIB transport was reversible.


Conversion of 3T3 fibroblasts into adipose cells: triggering of differentiation by prostaglandin F2alpha and 1-methyl-3-isobutyl xanthine. Green and Kehinde [(1974) cell 1, 113-116] have isolated clones of Swiss 3T3 fibriblasts that are able to convert to adipose cells. In this paper we report on two chemicals (prostaglandin F2alpha, 0.1 mug ml, and 1-methyl-3-isobutyl xanthine, 0.5 mM) that are able to rapidly and irreversibly program the fibroblasts to differentiate into adipose cells. Confluent cultures treated with prostaglandin F2alpha and insulin for 3-5 days, followed by insulin alone for 7-48 hr, yield numerous adipocyte colonies compared to control dishes and dishes treated with insulin alone. Cells treated with prostaglandin F2alpha or 1-methyl-3-isobutyl xanthine alone, rinsed, and then exposed to insulin gave similar results, indicating that the continuous presence of the triggering agent is not required to elicit the conversion of the fibroblasts to adipocytes. Agents that raise intracellular levels of 3':5'-cyclic AMP. 1.0 mM; 8-bromo-cyclic AMP,0.5 mM; and prostaglandin E1, 0.1 mug/ml) do not trigger the conversion process, suggesting that cyclic AMP may not be the mediator of differentiation in these cells. 8-Bromo-cyclic AMP, however, does induce thase; 3':5'-nucleotidohydrolase; EC 3.1.4.17) in these cells; the induction appears to be mediated by increases in intracellular cyclic AMP levels. These results indicate that this cell line might offer a system for studying the regulation of a type of cellular differentiation.


Induction of mouse type-C virus by translational inhibitors: evidence for transcriptional derepression of a specific class of endogenous virus. Several biologically distinguishable type-C RNA viruses are genetically transmitted in mouse cells. In the present report, chemicals that inhibit several different steps in protein synthesis are shown to cause marked increases in the cellular concentration of virus-specific RNA and the subsequent induction of virus. Analysis of the effect of translational inhibitors on mouse embryo cells of different genotypes indicates that activation of viral RNA is specific for one endogenous virus class and is a dominant genetic characteristic. Two lines of evidence favor the hypothesis that the induction of viral RNA involves transcriptional derepression rather than an alteration in its post-transcriptional processing. First, nuclear and cytoplasmic fractions of induced cells are shown to demonstrate similar increases in their concentrations of virus-specific RNA. Second, the decay of induced viral RNA following inhibition of further RNA synthesis by actinomycin D is not prevented by continued exposure to the inducer. These findings weigh heavily against the possibility that translational inhibitors act to stabilize viral RNA post-transcriptionally. The results are consistent with a model in which the expression of one class of endogenous virus is regulated by a labile repressor protein acting at a transcriptional level.


DNA-relaxing activity and endonuclease activity in Xenopus laevis oocytes. Complex simian virus 40 DNA produced by a soluble cell-free extract derived from stage 6 oocytes of Xenopus laevis consists of fully relaxed circles (i.e., with no superhelical turns). An endonuclease and a DNA-relaxing protein, either or both of which could be responsible for the relaxation of the complex DNA, have been purified from the extract. The endonuclease(s) produces nicked circles (having a single-strand scission) and linear full-size molecules. The DNA-relaxing protein is in the nucleus, has a molecular weight of apporximately 70,000, and is able to remove both negative and positive superhelical turns.


An 18,000 molecular weight polypeptide induces early events and stimulates DNA synthesis in cultured cells. Extracts of serum-free medium, conditioned by contact with SV40-transformed BHK cells, stimulate DNA synthesis in cultured fibroblasts. From this source, we have purified a homogenous basic protein of 18,000 molecular weight, termed fibroblast derived growth factor. In submicrogram quantities, fibroblast derived growth factor stimulates DNA synthesis in mouse 3T3 cells, in the absence of added serum. Prior to the onset of DNA synthesis, both serum and fibroblast derived growth factor induce an array of nearly simultaneous biochemical changes in the membrane to 3T3 cells that include stimulation of the uptake of nucleosides, 2-deoxyglucose, and 86Rb+. These results strongly suggest that the early events are integral components of the proliferative response, rather than coincidental effects of nonmitogenic molecules present in serum.


Prevention of spontaneous leukemia in AKR mice by type-specific immunosuppression of endogenous ecotropic virogenes. AKR/J mice, 80-90% of which ordinarily die of spontaneous lymphocytic leukemias by 12 months of age, were significantly protected from developing leukemia in the initial experiment by a single course of treatment with AKR serotype-specific antibodies mad in goats and processed as immune gamma globulin (IgG). In experiment 1, IgG was given on the day of birth and on four additional days, and finished on day 14. This schedule resulted in suppression of over 4 logarithms of normal virogene expressions up to 25 days of age and led to partial viral suppression for over 200 days of age. At 365 days of age, 20 of 24 (83.3%) control animals were dead of leukemia whereas six of 30 (20%) treated animals had died of leukemia. In a second experiment, only four inoculations of IgG were given from birth to 20 days, after which they were given three inoculations of radiation-killed vaccine specific for AKR-Gross leukemia virus and one injection of murine sarcoma virus-Gross leukemia virus 10 days later. This combined immunization procedure provided significant virus suppression up to 288 days of age. At 300 days of age, 30 of the 50 (60%) controls had died of leukemia while only 1 of 24 (4.2%) of the immunized mice developed fatal leukemia; the significance of protection for each of the experiments was P LESS THAN 0.001. We conclude that these data establish in classical fashion with type-specific immunosuppression the determining role of type-C endogenous virogenes in leukemogenesis and, at the same time, also established the feasibility of nearly total prevention of leukemia in AKR mice.


Occurrence of BK virus DNA in DNA obtained from certain human tumors. DNA sequences from BK virus have been detected by measurements of reassociation kinetics in DNA preparations isolated from five of 12 human tumor tissues and three of four human tumor cell lines; no DNA sequences from BK virus could be found using the same assay in DNA samples obtained from nontumor tissues removed from various patients. Whether or not this association is trivial, indicative of infection by BK virus, or correlative with the tumor state must await the testing of additional samples of normal and tumor tissues as well as a definition of the physical state of the genome of BK virus.


Hypophosphatemia: mouse model for human familial hypophosphatemic (vitamin D-resistant) rickets. A new dominant mutation in the laboratory mouse, hypophosphatemia (gene symbol Hyp), has been identified. The Hyp gene is located on the X-chromosome and maps at the distal end. Mutant mice are characterized by hypophosphatemia, bone changes resembling rickets, diminished bone ash, dwarfism, and high fractional excretion of phosphate anion (low net tubular reabsorption). Phosphate supplementation of the diet from wearning prevents the appearance of severe skeletal abnormalities. The hypophosphatemic male mouse resembles human males with X-linked hypophosphatemia and the Hyp gene is presemably homologous with the X-linked human gene. The mouse model should facilitate study of the defect in transport of plasma inorganic phosphate anion.


Biological and serological characterization of radiation leukemia virus. Radiation leukemia virus, isolated from radiation-induced lymphomas in C57BL/Ka mice and propagated in that strain, is thymotropic and leukemogenic in vivo but replicates poorly, if at all, in mouse and mink fibroblast cultures in vitro. Comparative studies indicate that this naturally occurring virus is distinct from the previously recognized classes of endogenous murine ecotropic and xenotropic C-type viruses which are capable of replication on fibroblasts (fibrotropic) but are neither thymotropic nor leukemogenic. These studies also demonstrate that a differentiation-specific restriction system governing the replication of the murine ecotropic C-type viruses operates in addition to the previously defined Fv-1 and SRV gene restriction systems.


Changes in expression of murine leukemia virus antigens and production of xenotropic virus in the late preleukemic period in AKR mice. We recently reported that thymocytes from 6-month-old preleukemic AKR mice express higher levels of murine leukemia virus (MuLV)-related antigens that thymocytes from 2-month-old mice. We have now found that the level of xenotropic MuLV (defined operationally as MuLV able to infect mink cell cultures) is also markedly increased in thymus of 6-month-old AKR mice and that this increase in virus correlates closely with increased MuLV-antigen expression. There is no increase of MuLV antigen or xenotropic virus in spleen or lymph nodes. Production of ecotropic MuLV remains unchanged with age in thymus, lymph nodes, and spleen. Thymic grafts from 6-month-old AKR mice, but not from 2-month-old mice, induce both amplified MuLV-antigen expression and xenotropic virus production in the thymus of young AKR recipients. Experiments with lethally irradiated AKR mice reconstituted with syngeneic bone marrow cells indicate that age-related changes in the thymus rather than in bone marrow precursor cells are responsible for MuLV-antigen amplification.


Intraneuronal guanylyl-imidodiphosphate injection mimics long-term synaptic hyperpolarization in Aplysia. The phosphodiesterase (3':5'-cyclic AMP 5'-nucleotidohydrolase, EC 3.1.4.17) inhibitor thepohylline enhances both the amplitude and duration of a long-lasting synaptic hyperpolarization in identified neuron R15 in Aplysia californica. Intraneuronal injection into R15 of glanylyl-imidodiphosphate, an adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activator, results in a deep and long-lasting hyperpolarization of the cell, similar to that produced by synaptic stimulation. Biochemical analysis confirms that guanylyl-imidodiphosphate activates adenylate cyclase in Aplysia californica nervous tissue, without affecting phosphodiesterase activity. These observations suggest that adenosine 3':5'-cyclic monophosphate plays a role in long-lasting synaptic inhibition and are consistent with a post-synaptic site of action for adenosine 3':5'-cyclic monophosphate.


Physical-chemical approach to the transient change in Na ion conductivity of excitable membranes. A new method is proposed for analyzing the rapid transient current component (Na ions) in voltage clamp experiments on excitable membranes. The method is based on only two very general assumptions: the Na ion conductivity of an excitable membrane is determined by some general membrane parameter, the kinetic behavior of which is consistently described by the sum of only two simple exponential terms. A least square computer analysis for the data by L. Goldman and C.L. Schauf on Myxicola axons is described [(1973) J. Gen. Physiol. 61, 361-384]. The method gives (as a result) the relationship between conductivity and membrane parameter. A physically plausible, chemical model (cycle of three states) is proposed for a dissipative control of the Na ion conductivity. The rate constants for the specific model are calculated from kinetic parameters derived only from the general analysis. These rate constants reproduce the original voltage clamp data in every feature which includes peak current ratios (h infinity)-shift with test potential. By allowing for differences in the experimental conditions, we derive essentially the same rate constants for the voltage clamp data of A.L. Hodgkin and A.F. Huxley on squid giant axons.


DDC-induced retrograde amnesias prevented by injections of dl-DOPS. Injection of a dopamine beta-hydroxylate inhibitor, diethyldithiocarbamate (DDC) in rats 30 min prior to training of a step-down passive avoidance task impaired performance of the task 24 hr later. Similarly, injection of DDC 30 min prior to testing blocked retrieval of a passive avoidance habit trained in normal rats the previous day. Injection of a direct norepinephrine (NE) precursor, dl-thero 3,4-dihydroxyphenylserine (DOPS) 60 min before DDC prevented both amnesias. These data support the hypothesis that reduced levels of NE are responsible for DDC-induced amnesias.


Subcutaneous mastectomy data: a preliminary report. This is a preliminary report on data accumulated in the first 12 months by the Subcutaneous Mastectomy Data Evaluation Center at Saint Francis Memorial Hospital in San Francisco, California. We present some statistics on 419 subcutaneous mastectomies performed by 105 plastic surgeons.


6-Hydroxydopamine and the aggressive behavior induced by marihuana in REM sleep-deprived rats. 6-Hydroxydopamine (6OH-DA) pretreatment increased the aggressive behavior induced by marihuana in REM sleep-deprived rats. Brain catecholamine assays revealed that 6OH-DA depleted popamine (DA) and norepinephrine (NE) to a different extent, increasing the DA/NE ratio. Intraventricular injection of NE significantly decreased the aggressive behavior of these animals, whereas control solution or DA injections had no effect. The possible role played by DA and NE in the aggressive behavior induced by marihuana in REM sleep-deprived rats is discussed.


Pre- and post-junctional supersensitivity: differentiation by intraventricular infusions of norepinephrine and methoxamine. Intraventricular infusions of methoxamine, an adrenergic agonist that has a relatively low affinity for the presynaptic uptake mechanism, produces a significant dose-dependent increase in locomotor activity comparable to the increase elicited by infusion of equimolar doses of norepinephrine (NE). The behavioral responsiveness to infusion of both NE and methoxamine was more than doubled 3 weeks after pretreatment with 6-hydroxydopamine (6-OHDA). These results indicate that the increased responsiveness to NE induced by 6-OHDA is due to enhanced postsynaptic receptor sensitivity rather than to a loss of presynaptic uptake inactivation.


Effect of desmethyldiazepam and chlordesmethyldiazepam on 3',5'-cyclic guanosine monophosphate levels in rat cerebellum. Three different ben,odia,epines (diazepam, its pharmacologically active metabolite desmethyldiazepam, and the derivative chlordesmethyldiazepam) have been compared in our study for their effects on 3',5'-guanosine monophosphate (cGMP) cerebellar levels. Desmethyldiazepam and chlordesmethyldiazepam are several-fold more potent than diazepam in decreasing rat cyclic cGMP cerebellar concentrations. None of the three drugs induces detectable changes of cerebellar cyclic 3',5'-adenosine monophosphate (cAMP). On the other hand, the three compounds did not modify the levels of cGMP in cerebellum of newborn rats, where Purkinje cell and dendrites lack synaptic contacts. However, injection of gamma aminobutyric acid (GABA) in the newborn is still able, as in the adult, to decrease cGMP concentration in cerebellum. Our data support the hypothesis that cGMP cerebellar concentrations may be reliable biochemical marker of the clinical activity of benzodiazepines.


Long term results of venesection therapy in idiopathic haemochromatosis. Observations on the clinical effects of venesection therapy in 85 treated, as compared with 26 untreated, patients with idiopathic haemochromatosis showed decreased pigmentation and hepatomegaly together with a return to normal tests of liver function in half the patients who had abnormal tests at presentation. Control improved in 28 per cent of those patients with diabetes mellitus, although some patients developed it during the period of observation, despite venesection. Portal hypertension, testicular atrophy and arthropathy were not improved. In only 12 patients was there sufficient reaccumulation of iron after the initial course of venesection to merit further treatment. Rates of iron accumulation in these patients varied between 1-4 mg and 4-8 mg per day and chelatable iron levels were noted to be inappropriately high in relation to body iron stores during the early stages of the reaccumulation period. Life table data shows that the percentage survival five and ten years after diagnosis was 66 and 32 per cent respectively for the treated patients, and 18 and 6 per cent respectively for the untreated patients, both statistically highly significant differences (p less than 0-01). Possible clinical differences such as age of presentation, the presence of diabetes mellitus, cirrhosis, clinical hepatic failure and hepatoma between the treated and untreated groups that might otherwise have weighted survival in favour of the treated group were corrected by the use of covariant analysis. This gave mean log survival values of 4-15 and 2-88 for the treated and untreated patients respectively, equivalent to 63-4 months and 17-8 months, a highly significant difference (p less than 0-01). Ten patients, all of whom had cirrhosis at the time of diagnosis, died of malignant hepatoma between three and 15 years after completing venesection therapy. There was also a high rate of death from neoplasms in a variety of other sites--22 per cent in the venesected group, strikingly higher than that rate predicted for a similarly aged population using national cancer mortality rates.


Dysfibrinogenaemia and primary hepato-cellular carcinoma. The mechanisms of blood coagulation and fibrinolysis have been evaluated in 28 black adult Africans with primary hepato-cellular carcinoma (HCC). A characteristic pattern of abnormalities has been defined. Dysfibrinogenaemia appears to be a useful biological marker for the disease. The reptilase test (RT) is a simple, reliable and sensitive means of detection of this metabolic abnormality. It is suggested that the RT should be used to screen populations at high risk of developing HCC, such as cirrhotics, in conjunction with alpha fetoprotein determinations, which, alone, are inadequate for the purpose. The haemostatic defect may have relevance to the pathogenesis of HCC, and further suggests a potentially useful, additional, therapeutic modality.


The bile ducts.

The bile ducts. The common duct is a critical conduit. Hippocrates observed that to maintain health it is important to keep the yellow bile from the liver in balance. The present authors provide extensive descriptions of the structure, function, anomalies and disorders of the bile ducts, and make special note of the radiographic techniques available for use in diagnosis.


Computed body tomography.

Computed body tomography. Only the surface of the diagnostic possibilities inherent in CT imaging has been scratched. Solic organ pathology is readily visible in most instances by computed tomography. With further extension of present knowledge and development of newer contrast agents, the ability of computed body tomography to image a wide range of diseases appears almost limitless.


Phosphatidylethanolamide derivatives of prostaglandins E1 and E2. Prostaglandins E1 (PGE1) and E2 (PGE2) have been coupled with the amine group of phosphatidylethanolamine (PE) by means of dicyclohexylcarbodiimide. These complexes basically mimic the relaxant and contractile effects of the corresponding free prostaglandins (PGs) on various smooth muscle preparations, but exhibit a delayed onset of action and a lower affinity for the PG receptors. The complexes are comparable with the free, parent PGs, in their intrinsic activities. The same holds true for the effects on blood pressure and on the motility of the uterus in situ. The PGE2-PE complex is hydrolysed to release obviously free PGE2 by cell-free homogenates prepared from various tissues, but not by blood plasma. The PGE2-PE complex is immunologically indistinguishable from the free PGE2.


Correlation between cyclic AMP and LH release following prostaglandin E2 administration. Five min following a single iv injection of PGE2 into ovariectomized mature rats pretreated with estrogen and progesterone, plasma LH and plasma and pituitary cyclic AMP levels were raised significantly. A close correlation was observed between increased pituitary cyclic AMP contents and release of plasma LH. The average level of cyclic AMP in the anterior pituitary and plasma cyclic AMP increased significantly, while the circulating plasma LH level was not changed at 1 min after PGE2 injection. Plasma LH le-el increased at 2 min after PGE2 and reached a maximum level at the above-mentioned time. This is consistent with hypothesis that increased release of hormone is a consequence of increased pituitary cyclic AMP content.


Comparison of luteolytic effectiveness of several prostaglandin analogs in heifers and relative binding affinity for bovine luteal prostaglandin binding sites. The relative binding affinities for both the prostaglandin (PG)E1 and PGF2alpha specific bovine luteal binding sites were determined for five PGE and fourteen PGF derivatives and analogs. Relative binding affinity was determined in vitro using membranes prepared from bovine corpora luteal (CL) obtained from the slaughterhouse. The parent structure of the analog was a dominant feature in determining the affinity for the respective PG binding site. Luteolysis was determined in cattle following intramuscular injection of various doses of prostaglandin once between days 6 and 14 after estrus and measuring CL regression by ovarian palpation per rectum, interval between injection and return to estrus and duration of the subsequent estrous cycle. A dose which was luteolytic was established for each of eight PGF-type compounds, and a dose which was not luteolytic was also established. There appeared to be limited association between the relative affinity for the PGF2alpha specific site in vitro and the estimated luteolytic dose range of these PGF analogs when tested in cattle. Differences in in vivo luteolytic potency for the compounds tested could not be explained by differences in binding affinity. Differences in metabolism and absorption may also be important in the determination of in vivo potency.


[Interference associated with cell cultures chronical by infected with the Junin virus]. Supernatants from Vero cells persistently infected with Junin virus interfered with cytolitic and lethal activities of standard virus. Two Vero cell sublines, chronically infected with Junin virus named VRJ1 and VRJ3, were obtained after prolonged cultivation of cells which survived primary infection. VFJ1 was maintained over a period of 48 days, by biweekly serial transfers while VRJ3, similarly treated, was cultivated for 385 days. One of the characteristics of these cell lines was resistance against superinfection with homologous virus that ordinaily produced CPE and plaques in normal Vero cells; the cells were then considered chronically infected. Supernatants taken at different cell passage level were tested for its interference activity after centrifugation to eliminate floating cells and debris. The degree of CPE intensity caused by inoculation of Vero cells with 10(4), 10(5) or 10(6) TCID 50 of standard virus was markdely deppressed (Figure 1) by coinfection with supernatant from passage 3 of VRJ3 (VRJ1p1), VRJ1p1 supernatant also had interference activity as shown by coinfection with standard virus and expressed by plaque forming inhibition(Table 1). The plaque production of standard virus was inhibited by coinfection with VRJ1p1 supernatant which did not originate plaques when inoculated alone. The interference capacity of VRJ1p6 supernatant was reduced (Table 1) coincidentally with the formation of 55 PFU/ml. Interference activity was neutralized by Junin specific antiserum and inhibited by chloroform treatment. When Vero cells infected with VRJ1p6 supernatant were challenged with standard virus 72 hs later, an inhibition of 98% was achieved (Table 2) in contrast with value of 35% showed in Table 1.


Experimental challenge of pregnant gilts with swine influenza virus after vaccination. Inactivated swine influenza virus was concentrated by filtration. Two 5 ml doses given subcutaneously two to three weeks apart to SPF gilts of breeding age of bred gilts was antigenic as measured by the hemagglutination-inhibition (HI) test. Higher HI titers of longer duration were produced in unvaccinated gilts after experimental challenge. Vaccinated gilts reverted to negative (less than 1:20) HI tests after challenge. Pigs from vaccinated gilts were heavier when weaned at five weeks of age than pigs from unvaccinated gilts. No swine influenza virus was isolated after challenge from placentas or pigs born dead or that died after farrowing.


[The concept of risk in poliomyelitis (author's transl)]. In poliomyelitis the risk is of neurological accidents resulting either from the circulation of wild viruses (spontaneous risk) or from the introduction of virus-vaccine (vaccine risk). The spontaneous risk varies both according to the virus type and according to various factors which determine host resistance. Well known among these are: the intrinsic characteristics of the population at a given period (genetic factors and previous experiences of this population with poliomyelitis viruses); environmental factors (water supply, living conditions, rapid urbanization...) which are extremely variable among geographic zones, and cultural factors just as variable among populations. The vaccine risk involves two aspects: the risk of neurological accidents due to use of live vaccine, which has changed from the beginning of vaccination and risk of inefficacy due either to the vaccine itself, whether live or inactived or to temporary ill-understood unfitness of a vaccine to provoke an immunitary response. At the present time, spontaneous and vaccine risks are balanced only in the so called developed countries in which the vaccine risk is accepted as necessary to maintain the spontaneous risk at the lowest level.


[Facial paralysis with inverse autonomic-voluntary dissociation from a frontal lesion. Cortical origin. Relation to supplementary motor area]. As a result of 6 cases of frontal tumour presenting central facial paralysis with inverse dissociation this symptom was investigated in patients subjected to cortical excisions for intractable epielpsy. A study of 8 cases of frontal cortical excision, 6 of them affecting the internal and posterior portion, and two the prefrontal region, has provided evidence of a link between inverse automatic-voluntary dissociation facial paralysis and lesions affecting the Penfield supplementary motor area. In such cases, facial palsy is usually associated with motor disorders in the limbs, the most characteristic of which is unilateral motor under-utilisation. The possibility of inverse dissociated facial paralysis occurring as a result of a rostral premotor lesion cannot be ruled out in our present state of knowledge.


[Neurologic manifestations in Mycoplasma pneumoniae. Apropos of 12 cases]. Specific serological methods now enable us to demonstrate that Mycoplasma Pneumoniae is responsible for a variety of neurological symptoms. We describe 12 new cases: 2 encephalites, 8 diffuse polyradiculoneurites and 2 isolated lesions of the cranial nerves. These 12 cases, together with the 42 recorded in the literature, bring total number of published cases to 54. Analysis emphasizes the extreme polymorphism of the neurological manifestations and their favourable prognosis in most cases, however serious the initial symptoms. Although the pathogenesis of neurological symptoms produced by Mycoplasma Pneumoniae is still debatable, evidence supports an immunoallergic reaction.


[Can radiophotographic detection be discontinued in rural areas at the current stage in Rumania?]. Considering the fact that in the rural environment the population groups at great risk are not sufficiently well known, in the case of tuberculosis, it is recommended that 1 or 2 more integral detection operations be carried out in this environment and to carry out a detailed investigation of the differentiated risk of various population groups.


[Epidemiological and statistical problems in tubercular meningitis in children. (Observations during 1955-1974 period in the Satu-Mare district)]. The progressive decrease of the frequency of tuberculous meningitis in children will lead in the near future to the elimination of this type of localization, as a result of elimination of chronic focuses, achieved by strictly supervised treatment. The rare cases observed in the last years are due either to well-established contacts (parents, grandparents, neighbours), or to sporadic or even unique contacts with chronic cases.


[Aspects of integral anti-tuberculosis chemotherapy in 15 rural medical stations of the Constanţa district]. The study of aspects of integration of chemotherapy during the initial stages of the anti-tuberculous treatment, carried out in 15 rural medical circumscriptions in the Constantza and mpedgidia anti-tuberculous dispensaries, has demonstrated the applicability of standardized chemotherapy schemes at the level of general practice network. The personnel working in the frame of this network showed considerable interest and preoccupation with the optimal achievement of the strictly supervised treatment. The results of bacteriological controls (direct BK examination and cultures), indicated that in 97,4% of the cases these results are maintained negative in patients that could be evaluated. An assessment of this action revealed that the indices showing the incorporation of patients in the strictly supervised treatment as well as the regularity of the administration have been very good.


[Investigation of some risk factors in tubercular infection in children]. A total of 2057 children, from a village with an isolated farm of tuberculous cattle have been classified in the following groups: A--1843 children from healthy families; B--140 children whose parents were working at the bovine farm; C--70 tb contacts, and D--4 children with parents working at the farm and relatives suffering with tuberculosis. All were skin tested simultaneously with 1 and 10 PPD units. Milk was brought home from the farm by those who worked there, that was used without boiling. A total of 14,5% of all the children had a reaction of more than 5 mm to one PPD unit. The percentages were of 8,4 in group A 52,1 in group B and 94,3 in group C (P less than 0,001). Incidence of more than 9 mm reactions was of 5% in group A, 45% in group B and 91,4% in group C (P less than 0,001). The mean diameter for one PPD unit was of 1,1 mm in group A, 7,58 mm in group B and 15,88 mm in group C (P less than 0,001). The major risk factor is represented by the tuberculous patients, but use of milk, or of milk derivatives from diseased cattle could also be incriminated. Synchronous neutralization of these two sources of contamination remains the primary action to be carried out for the prevention of the tuberculous infection dissemination.


[Obstructive syndrome in laryngotracheal stenosis]. Pulmonary function studies were carried out in 13 patients in whom the diagnosis of a central (laryngeal or tracheal) stenosis was confirmed by endoscopy. Following lung function tests were performed: static lung volumes (VC, RV, TLC), FEV1.0 and FIV1.0, flow-volume loops of forced expiratory and forced inspiratory vital capacity efforts from which PEFR and PIFR, maximal expiratory (VEmx50) and maximal inspiratory flow at 50 per cent of vital capacity (VLmx50) were measured, Raw, helium mixing time and pharmacological test with acethylcholine. FIV1.0 values and flow-volume loops permitted the classification of the patients into 3 groups: 1. fixed obstruction (6 cases): decrease in about equal proportions of maximal expiratory and inspiratory flows (FEV1.0 and FIV1.0); normal FEV1.0/FIV1.0 ratio; 2. extrathoracic variable obstruction (1 case): predominant decrease in maximal inspiratory flows (FIV1.0). FEV1.0/FIV1.0 ratio is twice as normal; 3. intrathoracic variable obstruction (5 cases): exclusive or predominant reduction in maximal expiratory flows, as in COPD but with the difference that the expiratory limb of the V:V loop showed an excessive reduction in PEFR, a plateau in the midzone of the VC and a terminal portion with normal configuration. Raw was almost always increased, RV sometimes, helium mixing time was prolonged only in presence of COPD or lobar stenosis; pharmacological tests were negative in 3 out of 4 cases. Pulmonary function abnormalities did not allow a prognosis of the nature of the underlying lesion. The severity of the obstruction as evaluated by endoscopic examination was not related to the functional disturbances. In one case no functional alterations were found despite a severe tracheal stenosis.


[Clinico-functional correlations in chronic obstructive bronchopneumopathy: dyspnea and arterial oxygenation]. The severity of dyspnoea was confronted to the value of the partial pressure of arterial oxygen at rest in a group of 51 patients with chronic non-specific pneumopathy associated to medium or severe ventilatory obstruction (VEMS under 1,5 I). The patients have been classified as "predominantly bronchitic" or "predominantly emphysematous" on the basis of clinical, radiological and biological criteria. In the group as a whole there was no relation between the partial pressure of arterial oxygen and the severity of the dyspnoea. The analysis of sub-groups evidenced a tendency to decrease of the oxygen pressure with accentuation of dyspnoea in the "bronchitis" group, although the coefficient value of this inverse correlation did not reach the treshold of statistical significance (r = -0,46; p greater than 0,05).


[Cured chronic pulmonary tuberculosis].

[Cured chronic pulmonary tuberculosis]. The application of RMP and EMB in the treatment of chronic tuberculosis results in massive and durable sputum conversion, objectivated by the decreased prevalence of chronic cases and increase in the number of cured chronic patients, which impose a differentiated type of dispensarization. The presence of the post-tuberculous syndrome requires qualified pneumological assistance; the authors suggest that cured chronic patients be maintained in a supervised group for the rest of their lives. The cured chronic patient with tuberculosis should remain the major preoccupation of the anti-tuberculous dispensary, in the frame of the ambulatory pneumological assistance.


[Comparative serum and secretory IgA studies in recurrent bronchial infections (preliminary note)]. In a group of 84 patients with recidivating bronchial infections IgA were evaluated with the aid of radial immunodiffusion according to Mancini. In all the patients IgA were determined from expectoration extractions and in 50 of them serum IgA were also determined. In 38 cases the determinations were simultaneous. Concentration of S IgA was low in most of the cases (65%). These results are probably influenced by the technical difficulties raised by detaching the connections existing between S IgA and mucus fibrils from the bronchial secretion. The results obtained in the dosage of serum IgA are comparable with those mentioned in the current literature. No correlations were possible between S IgA and serum IgA and there proteins can be considered as independent.


[Severe complications following intermittent administration of rifampicin]. In the last two years the authors have noted the cases of five patients with pulmonary tuberculosis to which intermittent treatment with Rifampicin was administered (twice weekly, 600-900 mg/day), in association with Ethambutol. Between 2 and 6 months after the treatment was started, 24-72 hours after the last administration of Rifampicin acute renal failure developed in all five cases. Two of the patients also had signs of liver failure (increased serum transaminase, lowered pseudo-cholinesterase, increased BSP retention), and in one of them there was also a hematological syndrome consisting in hemolytic anemia and thrombocytopenia. Four of the patients benefited from application of diuretics, hydroelectrolytic re-equilibration and/or hemodialysis. One of the subjects died 12 hours after being hospitalized, with acute pulmonary oedema, refractory to treatment. From the histopathological viewpoint glomerular lesions were found in the kidney (non-uniform thickening of the basal membranes by PAS-positive deposits). In two of the patients various immunological tests have been carried out (Coombs test, lymphocyte-migration inhibition, serum and urine immunelectrophoresis) that, by their alterations, provide some elements indicating the immunological origin of the phenomena.


[Current incidence of tubercular infection in children in the Dolj district]. A lot of 122459 children under the age of 14 were tested intradermally with 2 U PPD. Most of them had been vaccinated at birth and some revaccinated later during the 1966-1967 period, which does not represent interpretation of the prevalance of tuberculosis today, bearing in mind the low postvaccinal allergy of young children and the interval after the last vaccination, only the children with a reaction of more than 10 mm in diameter were taken into consideration as they represented the highest probability of the actual spread of the infection. In the age group up to 6 years 6.82% of the children were infected and 17.12% of the school children of grades II to VIII, i.e. less than the mean values recorded in the whole country. This was attributed to the intensive specific chemotherapy applied within the area. The prevalence gradually increased from 3.93% at the age of l year to 4.90% at 3 years, then sharply to 6.93% at 4 years (when the child's relations are extended) and 10.46% at 5 years. The proportion of infections was of 12--13% in grades II--IV (7-9 years), 16.63% in grade V, 20% in grade VI and 23.21% in grade VIII (13-14 years). The present values are much lower than those recorded in 1966. The present risk of infection is of 1%, with an annual decrease rate of 7%, starting in 1956. By comparison with the published data it is considered that neutralization by chemotherapy of all bacilli carriers will accelerate the rate of decrease of infection.


[Chemotherapy of the source and the risk of infection in home contacts]. An attack treatment with 3 drugs during 4-6 months and a consolidation treatment with 2 drugs then INH was applied in 595 cases detected between July 1, 1968 and June 30, 1972, i.e. 264 group A (positive), 200 group B (negative cultures) and 131 group C (pleuretics). The contacts had been in close contact with the source for at least three months before establishing the diagnosis; 549 had been vaccinated at birth with BCG and 209 revaccinated; 413 had undergone chemoprophylaxis with INH.  The control group comprised 1008 subjects, the mean age of the groups being very close; they were followed up for 2 years and 1 month and 2 years and 7 months.  Testing was done every year with 1 u PPD IC 65. The contacts were controlled annually by radiophotography and X-ray and the controls only in case of shifting of the test. Among the contacts there were 44 conversions in the subjects with an initial tuberculin reaction of 0-5 mm and 4 in those with an initial tuberculin reaction of 6-9 mm, representing 15.1% (group A 27.7%, group B 9,8%, group C 10.5%). Three months after the initiation of chemotherapy the proportion of conversions in the three groups (group A 12.3%, group B 5.9%, group C 10.5%) was equal to that of the controls (8.8%). The next year there were 11.2% conversions among the contracts (group A 11.4%, group B 9.6% and C 17.7%) as against 11.9% among the controls. In the first year 8.3% of the contacts contracted tuberculosis (A 15.6%, B 2.4%, C 4.0%) and 0.32% of the controls. The next year 2.8% of the  contacts fell ill (A 4.3%, B 2%, C 0%) and 0.5% of the controls. Among group A contacts aged 0 to 6 years there were 31.7% conversions and 30.7% cases of tuberculosis in the first year, and 7.1% and 1.8% respectively in the following year. Group B and C presented 10.9% conversions and 6% cases of disease in the first year, and no case of tuberculosis in the second year. Chemotherapy reduced conversions and sickness in this group three months after the diagnosis was established.


[Reducing the risk of tuberculosis in children vaccinated with BCG]. In 1973, of 1774192 children aged 18 months to 6 years, 82,2% had to be revaccinated with BCG, 10.7% presented tuberculin reactions larger than 10 mm and 7.1% were absentees. In 1974 a number of 485 children belonging to the respective age group contracted tuberculosis. Analysis of these cases showed that the risk of tuberculosis was of 10.9 per 100,000 revaccinated subjects and of 74.6 per 10,000 absentees.  BCG vaccination not only lowered the risk of the disease but also reduced the risk of a severe evolution and death.


[Intradermal BCG vaccination of the ,ewborn in the 1972-1975 period]. The study included 1015 children vaccinated BCG at birth in the "Gh. Marinescu" Maternity Hospital of Bucharest during the 1972-1975 period. The Romanian lyophilized BCG vaccine prepared in sodium glutamate in doses of 0.10 mg/0.1 ml was used. Of these children 543 were vaccinated in the Maternity Hospital and 472 by the vaccination teams of the Institute of Phthisiology, Bucharest. During the first two years 660 of these children were controlled at various intervals. Sensitivity to 2 U PPD was moderate during the first year, the mean diameter being of 4-5.3 mm in the children vaccinated before discharged from hospital and of 3.5-6.7 mm in diameter in the children vaccinated after discharge. At the age of 1 and 2 years the mean diameter did not exceed 3 mm. The vaccinal scar was present in more than 95% of the children in the first year, the mean diameter ranging between 3.6 and 4.8 mm. No postvaccinal complications were recorded. The authors consider that the results obtained can be taken as criteria for assessing the operational and technical effectiveness of BCG in neonates.


[Contribution of pulmonary scintiscanning to the diagnosis of chronic obstructive bronchopneumopathy]. In a lot of 32 cases of chronic obstructive bronchopneumopathy, a correlation was established between the extent and location of the regional perfusion deficiencies (studied by scintigraphy) and overall functional disturbances Vmax MEVS X 100VC, residual volume, R, PaO2, PaCO2). In 85% of the cases regional perfusion disturbances were detected and grouped into six scintigraphic types. A good correlation was found between these disturbances and the MEVS X 100/VC index and modified partial pressure of the gases (O2, CO2) in the arterial blood. Unexpected was the absence of a mathematical correlation between perfusion disturbances and the residual volume and R, suggesting the great variety of the disturbances grouped under the general denomination of chronic obstructive bronchopneumopathy.


Exclusion of pre-beta lipoproteins from agarose gel electrophoresis in the presence of chylomicrons. Chylomicrons present in the fasting serum of patients with type V hyperlipoproteinaemia have been found to exclude pre-beta lipoproteins from entering into agarose gel during lipoprotein electrophoresis. It is recommended that when chylomicrons are present they be removed prior to diagnostic and quantitative lipoprotein electrophoresis in agarose gel.


[Results of intermittent treatment with antitubercular agents in cavernous pulmonary tuberculosis in adults]. The effectiveness of the intermittent treatment (2/7) with Rifampicin + Etambutol, administered over periods of 3 to 24 months, was tested in a log of 229 out-patients suffering from tuberculosis (bacilli carriers). Negativation of the cultures was obtained in 88.4% of the cases, most of the failures being recorded in the aged patients from rural areas, suffering from various other associated diseases and in those who did not cooperate. As these patients raise particular problems concerning the therapeutical attitude, the authors consider they should be admitted to hospital, at least during the critical periods of the disease.


[Influence of tobacco smoking on the development of experimental pulmonary tuberculosis]. The present investigation was designed to the study, in rabbits, of morphologic and enzymatic pulmonary alterations produced by tobacco smoke and the course of tuberculosis under these conditions. The histologic examination revealed muciparous hyperplasia and pavementing metaplasia of the bronchic epithelium, accompanied by interstitial cellular reactions, reticulin, fibrilogenesis, atelectasis, emphysema and marked debility of the animals. In the animals treated with tobacco smoke the tuberculous lesions were very extensive and had an exudative-necrotic character. Under the influence of chemotherapy, applied during three months, reorganization of the lesions was reduced in comparison to the controls and an intense bacteriological activity persisted.


Virus-specific IgM antibodies in acute gastroenteritis due to a reovirus-like agent (rotavirus). 62 serum samples from 24 patients with rotavirus gastroenteritis were tested for IgM antibodies against a bovine rotavirus by an indirect fluorescent antibody technique. IgM antibodies were detected in one or more of the serum samples from all but one of the patients. IgM antibodies were not detected in samples obtained from 11 of the patients after the 5th week of illness. Absorption of sera for IgG with Staphylococcus aureus increased the sensitivity of the IgM antibody test. It is concluded that the presence of IgM antibodies against bovine rotavirus in a patient's serum, as measured by the present technique, does suggest a recent rotavirus infection. On the other hand, the lack of IgM antibodies in the serum of a child with acute gastroenteritis between the second and the 5th week of illness tends to exclude rotavirus as a cause of the disease.


[Clinical observations on 2 cases of congenital pulmonary malformation]. The present paper reports on two cases of congenital malformation of the lungs, in young adults, treated surgically. Each case had particular clinical features: left pulmonary aplasia with residual thymus and herniation of the right lung in the left pleural cavity in one case, and left pulmonary hypoplasia with aberrant pulmonary circulation, secondary cystic bronchiectasia, serofibrinous pleurisy. The necessity of an early diagnosis and surgical treatment is emphasized.


The clinical features of infantile gastroenteritis due to rotavirus. The symptoms of 100 hospitalised cases of rotavirus infantile gastroenteritis are described. Most patients presented with high fever between the 2nd and 5th day, having started with diarrhoea or vomiting or both. 42% of the infants had upper respiratory tract symptoms. Severe electrolyte disturbance did not occur, although there was a suggestion of a correlation between the higher blood ureas and the number of rotavirus particles in the stools. The mean duration of illness of uncomplicated cases was 13.4 days. Infants were more severely affected when enteropathic coliforms were also present, the total duration of illness being extended to 23 days. It is suggested that rotavirus or similar virus infection may be an essential precursor in the majority of coliform gastroenteritis.


Rotavirus-associated gastroenteritis in two adults probably caused by virus reinfection. Rotavirus infection was diagnosed by virus detection and by serological methods in 2 women with acute gastroenteritis, aged 22 and 29 years, respectively. Both patients had been in close contact with children with rotavirus gastroenteritis. Rotavirus-specific antibodies were detected in serum specimens obtained prior to the illness in one of the patients, and the serological response in both patients suggested a reinfection with rotavirus as cause of the disease.


[Ganglions a rare cause of isolated peripheral nerve lesions]. Extra- and intraneural ganglionic cysts rarely involved peripheral nerves. They are found in the neighbourhood of large joints. The ulnar nerve is affected most often by extraneural cysts at the wrist. Intraneural cysts prefer the peroneal nerve at the tibiofibular joint. Ganglionic cysts as a cause of peripheral nerve damage are often overlooked, mainly because they are not considered as a cause of pain, paresis or sensory changes. Surgical treatment is recommended.


[How do hormones act?].

[How do hormones act?]. Hormones act via receptors, i.e. structures which contain specific binding sites for any given hormone. The transmission of information is accomplished by reversible binding of the hormone to the receptor. Steroid hormones and triiodothyronine act via receptors which are located in the nucleus and regulate the biosynthesis of specific proteins. Peptide hormones and catecholamines combine with receptors within the cell membrane, thereby regulating the membrane-bound enzyme adenyle cyclase. The product of this enzyme, cyclic AMP, acts as a transmitter of the action of these hormones in the interior of the cell.


[Radioimmunological measurement methods in ambulatory endocrinology]. Measurements of plasma-hormone concentrations can be helpful for differential diagnosis in clinically suspect endocrine disorders. By means of radioimmunological methods a series of hormones can be estimated in small plasma volumes. The assay technique differs from chemical methods routinely used in a clinical laboratory. Reagents and details of immunoassay procedures vary between laboratories, and hence hormone estimations from different institutes cannot be directly compared. The plasma half-life of many hormones is 10-30 minutes. The regulation of hormone secretion is complex. Dynamic tests using a known stimulation or suppression provide a better estimate of the function of an endocrine axis than a single random measurement. Hormone assays should be required and interpreted in close collaboration with the endocrine laboratory, which should provide competent counseling with respect to methodologic and endocrinologic aspects.


[Adrenocortical diagnosis in ambulatory practice]. The determination of plasma cortisol concentrations is a valuable aid in the diagnosis of some important adrenocortical diseases. Since cortisol is secreted episodically, the diagnostic value of diurnal profiles of plasma cortisol is often limited. On the other hand, a simple ACTH test or an overnight dexamethasone suppression test permit, in most instances, definite diagnosis or exclusion of adrenocortical insufficiency and Cushing's syndrome respectively.


[Changes in serum lipids and lipoproteins in acute hepatitis]. In 50 patients with acute hepatitis serum lipide and lipoproteins were determined at regular intervals and the results were compared with the usual liver function tests. Australia-antigen was established in 26 patients. During the first three weeks of the disease the most striking finding was a significant increase in the triglycerides, which was most pronounced at the end of the second week. Triglyceride levels usually returned to normal during the fourth week. In the course of the disease, lipoprotein electrophoresis showed marked decrease or absence of alpha- and pre-beta-lipoproteins during the first two weeks. During the third week faint alpha and pre-beta bands recurred in most patients. By the end of the fourth week lipoprotein electrophoretic findings were back to normal. There was general correlation between routine tests of liver function and results of lipid analyses throughout the course of the disease. This typical pattern of serum lipid and lipoprotein changes was found with near-consistency in patients with HAA-positive hepatitis. It was also present in the majority of HAA-negative patients, though in these the characteristic discrepancy between hypertriglyceridemia and simultaneous decrease of the pre-beta-lipoprotein band in eletrophoresis was, on the average, absent.


High-field 13C NMR Studies of certain normal and abnormal human plasma lipoproteins. High-field (63.4 kilogauss) Fourier transform nuclear magnetic resonance spectroscopy 13C in natural abundance has been used to study the structural organization and molecular dynamics of constituent lipids of normal human very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). The same method was used to study the abnormal beta-VLDL of two type III hyperlipoproteinemia patients having markedly differing ratios of VLDL cholesterol to triglyceride (0.3 and 0.6, respectively). Resolution obtained at 63.4 kilogauss has made possible the assignment of several additional resonances of cholesterol ring carbon atoms, not resolved in earlier studies at lower fields, in the VLDL spectra. The rotational reorientation of the ring portion of cholesteryl esters in VLDL (normal) and beta-VLDL (abnormal) is not highly anisotropic and is similar to that for cholesteryl esters disolved in excess triolein. The rotations of cholesteryl esters in LDL are more highly anisotropic and significantly more restricted. The results suggest that the structural organization of the lipid components in beta-VLDL resembles that found in normal VLDL but differs significantly from that for normal LDL.


Bovine lymphosarcoma: development of a radioimmunologic technique for detection of the etiologic agent. A highly sensitive and specific radioimmunoassay has been developed for the major structural protein of an oncornavirus etiologically associated with bovine lymphosarcoma. This test can be used to identify cattle which have been exposed to the bovine leukemia virus and may thus develop or transmit the disease. Analysis of randomly obtained serums indicates that infection that infection with this virus is widespread among cattle.


Hormonal release of programmed behavior in silk moths: probable mediation by cyclic AMP. The eclosion hormone triggers a stereotyped preprogrammed pattern of behavior in silk moths. The effects of the hormone were duplicated by the injection of dibutyryl adenosine 3', 5'-monophosphate, adenosine 3', 5'-monophosphate (cyclic AMP), or guanosine 3', 5'-monophosphate (cyclic GMP) into theophylline-treated pharate moths. Treatment with theophylline reduced the latency of the response to a low dose of hormone, presumably by blocking phosphodiesterase. Endogenous levels of cyclic AMP, but not cyclic GMP, increased significantly in the central nervous system within 10 minutes after hormone injection. We conclude that an early step leading to the release of the eclosion motor program is an increase in cyclic AMP in target neurons of the central nervous system.


Synaptic transmission: long-lasting potentiation by a postsynaptic mechanism. Slow decreases of ionic conductance across neuronal cell membranes, which generate slow synaptic potentials, can increase the effectiveness of synaptic transmission. Slow conductance decreases sufficient magnitude increase the amplitude of monosynaptic fast excitatory postsynaptic potentials in B cells of the bullfrog sympathetic ganglion. By this postsynaptic mechanism, activation of one synaptic pathway can cause an increase in transmission, lasting several minutes, across another synapse. This may provide an important mechanism for synaptic integration and control of neuronal interaction.


Analysis of living tissue by phosphorus-31 magnetic resonance. Nuclear magnetic resonance is a new method for assaying the content of phosphate metabolites in intact tissues. Its nondestructive nature allows simultaneous and repeated determinations of these compounds with a minimum perturbation of tissue. Changes in the concentrations of the phosphates as a function of time characterize the metabolic machinery of the tissue and reveal alterations in enzymic activity that result from drug treatment or disease. The entire phosphate profile shows differences between normal and diseased muscle which should be of diagnostic value. Further, by examining phosphate profiles we detected a family of chemical compounds that were not previously known to exist as major constituents in muscle. Of these, two have been isolated and one has been identified as glycerol 3-phosphorylcholine. Finally, shifts in the positions of resonances monitor the internal environment of the living system, its hydrogen ion concentration, the complexing of alkaline earth metals with ATP, and compartmentalization within the cell.


Slow persistent infection caused by visna virus: role of host restriction. Proviral DNA has been demonstrated by in situ hybridization in foci of cells of a lamb infected with the RNA slow virus visna. A few of these cells also contain the major virion structural antigen p30. This restriction in virus gene expression in the infected animal provides a mechanism for persistence of virus in this chronic infection.


Collagenase production by rheumatoid synovial cells: stimulation by a human lymphocyte factor. Human peripheral blood lymphocytes incubated in culture for 1 to 3 days at 37 degree C, but not at 4 degree C, release a soluble factor which can stimulate, up to 400-fold, collagenase production by isolated, adherent, rheumatoid synovial cells. Production of lymphocyte factor is enhanced by phytohemagglutinin or concanavalin A. By gel filtration the factor has an apparent molecular weight of about 12,000.


Localization of cyclic GMP and cyclic AMP in cardiac and skeletal muscle: immunocytochemical demonstration. When rat cardiac and skeletal muscle are explored by immunocytochemical procedures designed to show sites of localization of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP), distinct staining patterns for the two nucleotides are seen. Antibody to cyclic AMP is found in the area of the sarcoplasmic reticulum, while antibody to cyclic GMP is found with a periodic distribution corresponding to that of the A band. This suggests a role for cyclic GMP in the regulation of myosin.


Glia maturation factor: effect on chemical differentiation of glioblasts in culture. A protein factor from the adult brain increases the concentrations of adenosine 3',5'-monophosphate and S-100 protein in glioblasts in culture. Such changes are correlated with the outgrowth of cell processes.


Defined dimensional changes in enzyme cofactors: fluorescent "stretched-out" analogs of adenine nucleotides. A concept is presented for testing the dimensional restrictions of enzyme-active sites by stretching the substrate or cofactor by known magnitude. These restrictions of enzyme-active sites specific for purine cofactors were tested by the synthesis and evaluation of lin-benzoadenosine 5'-triphosphate, 5'-diphosphate, and 3',5'-monophosphate with respect to enzyme binding and activity. These "stretchedout" (by 2.4 angstroms) versions of the adenine ribonucleotides bind strongly, slow the enzymatic rates, and have useful fluorescence properties.


Endogenous opiate receptor ligand: electrically induced release in the guinea pig ileum. Opiate receptors mediate the electrically evoked inhibition of the myenteric plexus-longitudinal muscle preparation of the guinea pig ileum. The electrically induced activation of the opiate receptor was produced by a prolonged simulation at 10 hertz and provides the first evidence that an endogenous opiate receptor ligand is released by nerve stimulation. The specificity of the phenomenon was demonstrated by the reversal obtained with the narcotic antagonists naloxone, naltrexone, and GPA 1843; GPA 1847, the (+)-isomer of 1843, did not cause reversal. The model system described should be useful for the study of the storage, synthesis, and release of endorphins.


[Bronchial biopsy and fiberscopy].

[Bronchial biopsy and fiberscopy]. The authors report the results of bronchial biopsies carried out during fiber endoscopy in 165 patients, including 100 bronchial carcinomas, 17 cases of tuberculosis, 7 cases of sarcoidosis, and 41 patients with various forms of respiratory disease, out of a total of nearly 900 fiber endoscopies carried out directly under local anesthesia.  It appears that the tissue samples obtained by biopsy with forceps are interpretable in almost all cases, that the result of biopsy is nil in sarcoidosis, low or limited, in cases of granuloma budding into the bronchial lumen as in tuberculosis.  In bronchial carcinoma, the proof of malignancy was made in 65% of cases and the histological type determined in 52% of cases. These levels rose respectively to 75.7 and 62.2% in cases where the endoscopic appearance was that of a bud of vegetation.  These results make this method competitive in bronchial carcinoma, compared with other methods of sampling, biopsy carried out under bronchoscopy and bronchial brushing under fiber endoscopy in particular.


[Richettsial pericarditis and pleurisy]. The authors report two cases of rickettsial disease due to R. Conori with mainly pericarditis in one case, sero-fibrinous pleurisy in the other.  They then recall a few general data concerning this rickettsial disease and the very restricted place that it occupies in the etiology of pericarditis and, even more so, in the case of pleurisy.  The conditons of diagnosis, which are mainly serological, are discussed, in particular with regard to pericarditis and tuberculous pleurisy.


[Hepatic schistosomiasis and sarcoidosis with voluminous subdiaphragmatic adenopathies]. The authors report a case of a West-Indian with sarcoidosis and peripheral, mediastinal and, above all, sub-diaphragmatic lymph nodes. The latter were very large and palpable through the abdomen, confirmed by lymphography and found to be due to S. Mansomi schistosomiasis. Liver biopsy carried out under peritoneoscopy, showed schistosomal granulomatosis with sarcoidosic granulomatosis. The authors consider that the rareness of this association is only apparent and does not correspond to the frequency of bilharziasis nor that of sarcoidosis in these subjects. They emphasize the mistakes which may result in interpretation of liver biopsy. They recall a few special characteristics of sarcoidosis in West-Indians, in particular, the possibility of failure of corticosteroid therapy as in their case, due to the onset of miliary lung disease under treatment, and show the lymphographic appearances of sarcoidosis.


[Australia antigen and chronic hepatitis in blood donors]. A routine search for Australia antigen in 29,936 blood donors at the Orleans Hospital Blood Transfusion centre led to the discovery of 105 apparently healthy carriers. Liver function tests were carried out in 80 of the latter and revealed abnormalities in 34 of them. Out of 18 patients who had no other explanation such as alcohol or drugs and who had abnormal tests six months later, 11 accepted liver biopsy. Histology revealed 4 cases of post-hepatic cirrhosis, 2 cases of chronic aggressive hepatitis, 2 cases of chronic persistent hepatitis and 3 livers with non-specific changes.


[Clinical and statistical study of 100 patients with vitiligo. II. Associated lesions]. A study of 100 cases of vitiligo showed the frequency of associated skin and visceral lesions. A skin disease was associated in 24 cases: psoriasis 4 cases, alopecia 4 cases, eczema 3 cases, malignant melanoma 2 cases, dermatitis herpetiformis 1 case, lichen planus 9 cases. However, only one case of Sutton's naevus was noted. Among other associations noted in 28 cases, there were 7 cases of thyroid disease, 5 cases of diabetes, 1 case of chronic rheumatoid arthritis and 3 gastric disorders. The frequency of these various associations was discussed in the light of other authors' reports. If one compares the 21 cases associated with auto-immune disease and the other cases of vitiligo, there was no significant difference for the various parameters studied. Thus the significance of the various biological signs of autoimmunisation remains doubtful and even the precise definition of vitiligo remains uncertain.


[Meningoradiculitis after tick bites. Apropos of 9 cases]. The authors report a series of 9 cases of meningoradiculitis after tick bites and compare them with 56 other cases in the literature. Clinically, the bite is followed by a free interval, then more or less extensive local erythema, pain then paralysis is undoubtedly the most typical presentation. Uni- or bilateral paralysis of the 7th cranial nerve was found in more than 50% of cases. Erythema may exceptionally be absent. There may be forms with pain alone. Finally, there may sometimes be pyramidal signs or signs of brain irritation. As concerns the course, one should note the absence of respiratory complications, and although there are usually no or minimal sequelae, one should note the slowness of the recovery in certain paralytic cases. In the laboratory, pleocytosis is constantly found in the C.S.F. As concerns physiopathology, there are 3 theories, virus, allergic and toxic.


[Changes in bone marrow cellularity close to cancer metastases. Cyto-histologic study]. Before starting any therapy, we systematically studied by biopsy the bone marrow of 66 patients suffering from various cancers and suspect of marrow metastasis. Metastatic cells were thus found in 45 patients. Bone marrow composition was examined on histologic sections by granulometric method, while relative proportions and morphology of the various hematopoietic series were examined on cytologic prints. It then appeared that any important metastatic invasion goes together with deep alterations of the surrounding hematopoietic tissue, with frequent peri-metastatic collagenic fibrosis and hypoplasia of the various cell-lines; when metastatic growth is still moderate, hematopoietic tissue is, on the contrary, often hyperplastic, "irritative". These marrow alterations are not to be found far from the metastasis, and thus seem to be directly linked to the actual presence of cancerous cells.


[Severe forms of so-called functional epigastric pain]. The authors report 17 severe cases of functional epigastric pain. There was a long history of severe pain with an effect on general health. It was resistant to usual symptomatic treatment. There were two special characteristics: fixity in time, and the ability to produce the pain on palpation of the region around the aorta. A psychological study showed an unusual form of neurotic decompensation occurring under special circumstances. Drug treatment in hospital gave favourable results which were maintained 2 to 5 years later on follow up.


[Epileptic seizure revealing a cerebral arterial accident during administration of oral contraceptives with platelet function disorders]. The authors observed the onset of an epileptic fit in a 27 year-old woman, ten months after starting treatment with the contraceptive pill. Carotid arteriography revealed the existence of non-obstructive lesions in the area supplied by the left anterior cerebral artery. Disorders of platelet aggregation and disaggregation were demonstrated 15 days after stopping the contraceptive treatment. The significance of these abnormalities is discussed in the light of data in the literature.


[Spontaneous septic arthritis in disseminated lupus erythematosus]. The authors report the case of a young 17 year-old girl with acute systemic lupus erythematosus who presented with purulent arthritis due to Group A hemolytic streptococcus in the knee, and perhaps other joints. She had not yet received any treatment. The purulent arthritis was cured by antibiotics. In spite of corticosteroids and immuno-suppressive agents (Chlorambucil), the patient died one year later. Spontaneous purulent arthritis is rare during systemic lupus erythematosus. We found only 8 other cases in the world literature. Contrary to our case, these were patients already treated with corticosteroid or immuno-suppressive agents. In our patient, the absence of previous treatment permitted us to incriminate the lupus itself in the onset of this infection. The conditions of onset of infection during lupus erythematosus are discussed.


[Circulatory disorders induced by amantidine]. Amantadine has been used since 1969 in the treatment of Parkinson's disease. In 1970, were described the special symptoms noted in the lower limbs due to this drug. The authors, after a review of the various disturbances, have studied 10 cases by Capillaroscopy. They emphasize the interest of the study of this abnormality of the micro-circulation, producing vaso-constriction of the arterioles and venules.


[Mixed hyperlipoproteinemias. Importance of diet]. The interest of diet is particularly clear in mixed hyperlipemia. In fact, the authors were only able to define the type of lipid abnormality after a test diet and prolonged supervision. One should never treat mixed hyperlipemia straightaway with hypocholesterolemic agents. The authors studied 22 patients with a form only demonstrable in the laboratory. There were no clinical signs of arteriosclerosis. In the group of dyslipemic subjects with minor hyperlipemia, they obtained normal figures for serum cholesterol and triglyceride. The results remained stable after 4 months supervision.


[Emergency surgical treatment of septal perforations in the acute phase of myocardial infarct. Apropos of 2 cases operated on successfully in the 48th hour and 5th day after development after the necrosis]. The authors report two personal cases of septal perforation during the acute phase of myocardial infarction which under medical treatment would have been rapidly fatal, and which were treated successfully by surgery on the second and fifth days respectively after the infarction, i.e. very early. After briefly recalling the main diagnostic and etiological factors of this serious complication, and the spontaneous prognosis which is usually catastrophic, they emphasise that in presence of poorly controlled heart failure and cardiogenic shock, uncontrollable by intensive medical treatment, only early surgical repair during the first few hours or days of the course of the coronary accident will permit one in certain cases to avoid a fatal issue as proved by their two cases and a review of recent publications. They emphasis the place of circulatory assistance by intraaortic balloon in the preparation of patients for operation and the methods of mycardial revascularisatin during the operation.


[Cerebromeningeal hemorrhages and their sequelae in congenital deficiencies of plasma hemostasis factors. Apropos of a case of Stuart factor deficiency with early cerebromengeal hemorrhage leading to hydrocephalus with considerable psychomotor retardation]. We have taken an interest in cerebro meningeal haemorrhages in congenital plasmatic coagulation Factor deficiency with out obvious traumatic origin. We have observed such accidents in a new born child with congenital Stuart factor deficiency and in four cases of haemophilia A. It seems from our experience and from the literature that such haemorragic accidents are not particularly frequent in congenital coagulation deficiency and contribute only for a few to creation of a psychomotor inadapted population.


[Effects of the nervous system on the kidney. Part I. Review of the literature]. The authors review the literature on the effects of the nervous system on the kidney in 3 stages: 1) Historical stage when the role of the renal nerve supply was overetimated by Claude Bernard. 2) Intermediate stage between the two wars with a clinical description of uremic encephalits or acute delirium. From the experimental point of view was demonstrated the inessential character of the nerve supply for the survival of the kidney. 3) Modern stage: from the clinical point of view one may distinguish functional nephropathies including those of nervous origin. The latter are due to metabolic or vascular mechanisms which are intricated to various degrees. Problems of regulation are raised in man by certain findings.


[Study of factors favoring infection in total hip prosthesis. Twenty-five observations]. The authors report 25 cases of infection following total hip replacement and individual factors are analysed. The role of immunological abnormalities is discussed. They distinguish early infection due to the operative conditions from late infection where individual factors are the most important. A few preventive measures are proposed, they emphasise the necessity of a large scale study of factors favouring late infection.


[Eosinophilic leukemia and disseminated intravascular coagulation]. Eosinophil leukemia is still an uncertain entity owing to the lack of specific markers for malignancy. The authors report a case with increased serum vitamin B12 and intravascular coagulation, and discuss the value of these two abnormalities as functional markers.


[Clostridium perfringens infection. Problems posed excluding resuscitation]. The authors report 18 cases of Clostridium perfringens infection and discuss the main clinical and etiological aspects apart from gynecological forms and those usually requiring intensive care. Pathological foci, digestive infection and the problem of bacteremia are discussed together with appropriate treatment.


[Alternating low calory diets (200 to 1000 calories), their value in the treatment of resistant obesity]. In obesity resistant to traditional low calory diets, the authors alternated short periods of moderate low calory intake (600 to 1,000 calories) with periods of very restrictive low calory intake (230 to 300 calories). The results of this method are analysed in 105 patients. This method permits loss of weight in difficult cases of obesity, both during intensely low calory diets and during less severe low calory diets. This technique is well accepted by the patients and is less monotonous than very unbalanced multi-fractionated diets or with prolonged courses of fasting. The results are all the more satisfactory when the patient is young, when the obesity is recent and marked, which does not, however, exclude its efficacy in long-standing cases of obesity.


[Mediastinopulmonary sarcoidosis; the indications for corticosteroid therapy]. The authors, following prolonged observation for from one to ten years, on average 5 years, of 60 cases of thoracic sarcoidosis, of lymph node or miliary type, propose a therapeutic attitude which, although not new, is frankly oriented towards therapeutic abstinence in the lymph node forms, and very restricted indications for hormone therapy in the miliary forms. In this respect, they agree with many authors, in particular English language authors, who consider that corticosteroid therapy is only justified in the acute forms, with a disturbance of general health and characteristic functional involvement. Such an attitude may appear shocking to those who tend to prescribe corticosteroids for their immediate efficacy, but in the long-term, it appears justified.


[Toxic thyroid adenoma and malignant hypercalcemia of parathyroid origin]. Malignant hypercalcemia due to the association of hyperthyroidism and hyperparathyroidism is rare. We report a case with a fatal course in spite of surgical treatment of both lesions. Death occurred seven days after the operation due to ventricular tachycardia, in spite of return to normal of the calcemia, the serum phosphorus, the serum electrolytes and relief of the thyro-toxicosis. There is a great deal of histopathological evidence for the association of a toxic parathyroid carcinoma and a thyroid adenoma.


[IgM myeloma].

[IgM myeloma]. The authors report the case of a 62 year old woman in whom bony pain led to the discovery of lacunar osteolytic appearances, in particular in the skull, abnormal medullary plasmacytosis and serum monoclonal immunoglobulin with Bence-Jones proteinuria. The case was unusual as the immunoglobulin observed was an IgM. This finding led the authors to a critical revision of the distinctive characteristics of multiple myeloma and Waldenström's macro-globulinemia, emphasizing the distinguishing value of the cytological criterion. The authors recall the various neoplastic proliferations of the B lymphocytes at the various stages of their maturation and emphasize the predominance of monoclonal IgM during proliferations affecting the early stages of maturation of the B lymphocytes and the rareness of these IgM during plasma cell neoplasms.


[Clinical aspects and course of drug-induced upper digestive hemorrhage]. In a series of 500 patients admitted to hospital for upper digestive hemorrhage, the authors studied the influence of taking drugs on the clinical characteristics and course of the original disease. Taking aspirin is exceptional before rupture of esophageal varices. One may isolate a homogenous group of elderly women consuming aspirin and another anti-inflammatory drug, and bleeding from a gastric ulcer. One may also isolate another group of men, bleeding from acute gastro-duodenal lesions after taking aspirin alone. If one considers apart portal hypertension, owing to its extreme gravity, one may note that the prognosis depends on the age. One patient out of five, dies of hemorrhage after the age of 60 years. Taking an anti-inflammatory drug at this age is thus not harmless.


[Preliminary psychological survey in the study of cardiac rehabilitation through controlled physical activity]. The authors carried out an enquiry in 32 patients as part of a more extensive study which permitted them to show the necessity of early physical rehabilitation after myocardial infarction which should be gradual and as prolonged as possible under permanent medical control. Subjects under training usually adhere enthusiastically to this program of progressively complete and rapid social reinsertion, by the development of new relationships, whether personal, familial or professional.