[Studies of the regulation potential of glucose metabolism in the calf following infusion of fructose solution and using various hormones (ACTH, prednisolone, adrenaline and noradrenaline)]. Infusion of fructose solution (25 g in 100 ml) in sugar rations of 0.5 g or 1.0 g per kilogram of body weight usually induced in calf temporary drop of glucose in the blood plasma. This was attributable to rise in insulin secretion and glucose conversion or insufficiently fast effectiveness of insulin antagonists (adrenaline, glucagon, glucocorticosteroids). Such glucose drop could not be prevented by administration of 50 mg of prednisolone four hours before fructose infusion and 25 IU of ACTH five hours before infusion. Glucose as well as free fatty acids in the blood plasma went up in response to injection of 2.5 microgram/kg body weight during hypoglycaemia. The action of adrenaline was found to depend on the insulin dose given before in cases of insulin-induced hypoglycaemia. Doses of 0.5 g fructose per kilogram of body weight were administered in nine experimental infusions. Average half-life recorded from the blood plasma was 21.3 +/- 3.4 minutes.


Purification and characterization of bovine leukemia virus DNA polymerase. An RNA-directed DNA polymerase was purified from bovine leukemia virus (BLV) by successive glycerol gradient centrifugation, column chromatography on phosphocellulose and gel filtration on Sephadex G-200. The purified DNA polymerase transcribes heteropolymeric regions of 30--40 S RNA isolated from avian myeloblastosis virus. The enzyme differs from other known DNA polymerases of mammalian type-C RNA tumor viruses by the following properties: 1. Its apparent molecular weight as estimated by velocity sedimentation data is 58,000 at 0.12 M KCl and 43,000 in the presence of 0.50 M KCl. 2. It has a Mg2+ optimum of 10 mM, and a Mn2+ optimum of 0.25 mM with (rA)n-(dT)10 as template. 3. At 50 mM KCl it is inhibited more than 70%, but it is not inhibited by phosphate ions at 2 mM. These properties confirm the peculiar position of BLV within the family Retraviridae.


Metabolism of cyclic nucleotides in allergic rhinitis: studies on lymphocytes, granulocytes, and plasma level. The effect of isoproterenol on the cyclic nucleotide level in peripheral lymphocytes and granulocytes with allergic rhinitis patients and normal subjects has been studied. Responsiveness to 10(-5) M isoproterenol of lymphocytes decreased in the case of allergic rhinitis patients. When asthma was complicated to perennial rhinitis, a more significant depression was noted. In granulocytes the same tendency as with lymphocytes was noted although the difference was not significant. Basal level and responsiveness to 5 X 10(-3) M theophylline of both lymphocytes and granulocytes were similar in allergic rhinitis patients to normal subjects. The ratio of plasma cAMP to cGMP concentration was lower in the allergic rhinitis patients although the difference was not significant.


[Behavior of serum 25-hydroxycholecalciferol in humans after administration of vitamin D and 25-OHD3]. Serum levels of 25 hydroxycholecalciferol were evaluated following i.m. and p.o. vit. D2 and D3 and p.o. 25OHD3 administration. While no increment in 25OHD3 serum levels were observed after i. m. administration of non-hydroxylated calciferols, a marked increment of the metabolite was found following the oral administration. However the peak values were largely impredictable. Acute and chronic p.o. administration of 25OHD3 determines a rapid and dose-dependent increase of the serum levels of the metabolite. In addition considering that a lower dosage is required of 25OHD3 compared to vit. D, this metabolite is preferable in the therapeutic use.


Interference of MHV3 virus on ascites tumor growth. In this experimental study the Authors have evaluated the interference of MHV3 hepatitis virus on Ascites Tumor's growth, using 4 groups of mice, the first one considered as control, the others inoculated with the virus 48 hours before, at the same time and 48 hours after tumor's inoculation. In each group labeling index, mitotic index and ascites volume were assessed a week after tumor's inoculation. The results seem to reveal an inhibition of tumor's growth in the second group. For this reason on the base of these encouraging observation, the Authors will continue researches to further confirm these preliminary results.


The development and significance of transaminases and 5(1)-nucleotidase (5(1)-ribonucleotide phosphohydrolase) in chick testis. The development of testicular glutamate oxaloacetate (GOT) and glutamate pyruvate (GPT) transaminases and of 5'-Nucleotidase was monitored in the male Nigerian fowl. The findings indicated triphasic and monophasic oscillations of GOT and GPT respectively with age. 5(1)-Nucleotidase was found to decrease with increase in the chronological age of the chicks. Furthermore, while GOT and GPT exhibited cubic and quadratic relationships respectively with age and testicular weights, 5(1)-Nucleotidase was related to both variables in a quadratic manner. The results are discussed in terms of spermatogenesis which may bear profoundly on the overall reproductive performance traits of the Nigerian cockerel.


Hepatitis, cardiomyopathy and hemodynamics in furazolidone-induced round heart disease of turkeys. Twenty-five large broad-breasted white turkeys were fed a 22% protein diet supplemented with 500 ppm furazolidone from day 1 to 3.5 weeks of age and the same diet supplemented with 700 ppm furazolidone until 9.5 weeks of age. Following the development of round heart disease as indicated by altered electrocardiograms the 25 turkeys were sacrificed. In the livers of turkeys with biventricular dilatation (72% of cases) there was bile duct hyperlasia, portal fibrosis and intracytoplasmic globules in the hepatocytes. Globules stained pink with hematoxylin-eosin, deep red with PAS and variable with Massons trichrome stains in paraffin-embedded liver sections. Clear intracytoplasmic vacuoles demonstrable in hepatocytes of PAS stained liver sections embedded in paraffin did not stain as lipid in frozen sections but did contain sparse flocculent material in 1 micrometer sections of liver embedded in epoxy resin and stained with toluidine blue. At the subcellular level, the intracytoplasmic globules in hepatocytes were surrounded by a single membrane, contained flocculent material and had enzymatic properties characteristic of lysosomes. Blood pressure, heart rate, dp/dt max, total plasma proteins and plasma trypsin inhibitory capacity of turkeys with round heart disease were lower than corresponding values for control turkeys. Control turkeys did not exhibit the characteristic gross or microscopic lesions of round heart disease.


Dolphin pox: a skin disease of cetaceans. Poxvirus has been identified morphologically from skin lesions in captive and free-ranging bottlenosed dolphins, Tursiops truncatus and a stranded Atlantic white-sided dolphin, Lagenorhynchus acutus. The lesions, commonly referred to as ring or pinhole lesions, appear as solitary or coalesced circular grey blemishes. Advanced ring lesions may take the form of black punctiform stippled patterns known as "tattoo". Histologically, the stratum externum is thickened, and there is ballooning degeneration and eosinophilic intractyoplasmic inclusions in the stratum intermedium. These includions contain virus particles which exhibit typical poxvirus morphology. Stress, environmental conditions and general health appear to play a major role in the clinical manifestation of dolphin pox.


Bovine fetal inoculations with calf rotavirus. The serological and histopathological responses of bovine fetuses to in utero inoculation with virulent and attenuated strains of the calf rotavirus (reovirus-like agent of neonatal calf diarrhea) are described. Thirteen bovine fetuses, 63 to 190 days of gestation, were inoculated in utero with attenuated (three fetuses) or field strain virus (nine fetuses) or both (one fetus).Serum-neutralizing antibody titers ranging from 1:16 to > 1:256 were detected in six of eight fetuses tested, demonstrating the ability of the bovine fetus to respond immunologically to this agent. The youngest fetus in the series was inoculated at 63 days of gestation and developed a titer of 128 in 64 days. This represents the earliest stage of gestation at which a bovine fetus has been inoculated with a bovine virus and found to produce antibody to it. Serum neutralizing titers in six of the eight dams tested increased significantly following the inoculations of their fetuses in utero. Histological changes associated with viral replication and antigenic stimulation of the lymphoreticular system were observed. Pneumonic lesions consisting of both local and diffuse lymphoreticular proliferation were present in five of the nine fetuses that were alive at slaughter. Gliosis and perivascular cuffing were noted in the brains of two of these fetuses and meningitis was seen in one. No evidence of teratogenic change was found.


[Renal transplantation in the child. Medical and surgical aspects (author's transl)]. The authors report the experience of the Children's Hospital of Marseille about ten renal transplantations in nine children. Indications, immunosuppressive treatment, surgical techniques employed are detailed. The results study show two mains complications : rejection and arterial hypertension. A better recipient selection, as in adults, would increase good results.


[Benign synovialoma of knee in children (author's transl)]. The authors report 2 cases of benign synovialoma of knee in children. After studying the clinical and radiological symptomatology, they insist on the anatomical pathological criteria which are the only specific ones. However, this benign affection takes on a serious complexion, in the diffuse forms, on account of the incomplete and impairing nature of an exclusively surgical treatment.


[Undifferentiated renal sarcoma or Wilm's tumor (author's transl)]. About a case in a six year old Negro boy, the existence of a special pattern among the malignant renal tumors in children is emphasized; this tumor is marked from the Wilms' tumor by its peculiar behaviour (frequently poor evolution, high incidence of osseous metastasis in contrast with the rate occurrence of pulmonary involvement) and by a sarcomatous appearance at the pathologic examination. The classification and the suitable therapeutic management are discussed.


[Cyto-immunochemical detection of gamma endorphin in swine adenohypophysis]. An immunserum was prepared from gamma endorphin and its specifity was checked by the indirect method. It was tested on hypophysis which were taken from Pigs since birth till 3 months old. The anterior lobe as well as the intermediate lobe have reacted. The same cells were positive in the anterior lobe and recognized the anti-ACTH, anti-beta MSH and anti-beta LPH immunserums. However, the reaction was more labile than with these last immunserums and it was varying with the delay of fixation after the death and the penetration in the gland by the fixator.


[Persistence of paradoxical sleep in the cat after destruction of the pontine gagantocellular tegmental field with kainic acid]. The pontine gigantocellular tegmental field (FTG) does not play any role in paradoxical sleep (PS) since the destruction of the cell bodies of the FTG with kaïnic acid does not alter PS in the Cat. Elimination of PS following electrolytic destruction of the ventrolateral pontine reticular formation can be explained by lesions of fibers connecting the region of the locus caeruleus and the bulbar reticular formation.


[Fragments of linear unintegrated Rous sarcoma virus DNA, resulting from digestion with SmaI restriction endonuclease]. Linear unintegrated DNA of Schmidt-Ruppin Rous sarcoma virus, subgroup D (SR-RSV-D), was digested with SmaI restriction endonuclease, analyzed by agarose gel electrophoresis, "blotted" by Southern's method and hybridized with a viral 32P cDNA. SmaI cleaves this DNA at five sites, two of which are localized at the ends of the provirus. Src and env genes seem not to be restrictied by SmaI cleavage.


[Purification of a membrane protein modifying the sensitivity of Na+/K+ ATPase to ouabain from a supernatant of plasma membrane treated with EDTA]. A membrane protein of M. W. 32,000 D and pI 5 has been purified from EDTA-treated plasma membrane supernatants by Page without detergents. These membranes are purified from the MF2S cell line issued from the murine plasmacytoma MOPC 173. The purified protein was able to induce a 300 fold increase in the Na+/K+ ATPase resistance to ouabaïn thus mimicking the original resistance of the enzyme to the drug.


[Purification from a total cellular lysate of a protein modifying the sensitivity of Na+/K+ ATPase to ouabain]. A protein (32,000 dalton) has been purified from M2FS cells derived from the murine plasmocytoma MOPC 173. Like tropomyosin, this protein when added with Ca++ to EDTA-treated plasma membranes prepared from the same cell, induced a drastic increase in the Na+/K+ atpase resistance to ouabain.


[Glucagon-producing endocrine pancreas tumors. Symptoms, diagnosis, localization, therapy and follow-up]. Three cases of glucagonoma syndrome caused by glucagon producing pancreatic islet cell tumors are reported. Modern procedures for diagnosis, localization, and classification are presented and advocated.


Impaired immune function and identification of polybrominated biphenyls (PBB) in blood compartments of exposed Michigan dairy farmers and chemical workers. In 1973 PBB's were accidentally mixed into animal feed, resulting in marked toxic effects. Meat and dairy products were widely consumed in Michigan. To determine the impact of PBB's, 55 exposed Michigan farm residents, 11 Michigan chemical workers and 46 non-exposed Wisconsin farmers were examined. Abnormalities included decreased number of T-lymphocytes with concomitant increase of lymphocytes with no detectable surface markers, "null cells", and altered lymphocyte function. Data obtained from skin testing using standard recall antigens, showed no consistent correlation between the delayed cutaneous hypersensitivity response and the impaired lymphocyte function. PBB (hexa) in separated white blood cells and red cells was positively identified and quantified by gas chromatography-mass spectrometry. PBB and immunological abnormalities were not detected in non-exposed Wisconsin dairy farm residents.


The emotion of pain and its chemistry.

The emotion of pain and its chemistry. Pain is not an electrical impulse derived from tissue injury but an emotional experience arising when a nervous input is interpreted in the light of experience and emotional context as being 'painful'. Pain may thus signify tissue damage, vivid sensory experience or inner turmoil. Pain may be distressing but it can also be pleasurable. Whether a given stimulus provokes pain and whether that emotional feeling causes distress varies from individual to individual and from moment to moment. The brain possesses chemically mediated mechanisms that can exert control over the experience of 'pain'. An understanding of such mechanisms suggests new approaches to the relief of distressing pain (and to the artificial production of pleasurable pain).


[Dopa and dopamine agonists in depression (author's transl)]. Following a summary of the functional organisation of the ascending dopamine systems, the pharmacology of the dopamine synaptic receptors is considered. The stress is placed upon the differences induced by dopamine agonists during short-term and long-term treatment. In this connection, recent ideas on the heterogeneous nature of the dopamine receptors, on their specificity and on their functional role will be discussed. The dopaminergic action of certain antidepressants will be studied by analysing the different types of activity: presynaptic release, direct pre- or post-synaptic agonism. The role of dopaminergic transmission in depression of mood is considered finally on the basis of clinico-biochemical correlations. Finally, dopaminergic activity is linked with the other possible changes in cerebral monoamines by drafting a table of the interactions between the neurotransmitters.


Relative rates at which dominant-lethal mutations and heritable translocations are induced by alkylating chemicals in postmeiotic male germ cells of mice. There is a close relationship between the rates at which dominant lethal mutations and heritable translocations are induced by ethyl methanesulfonate (EMS) or triethylenemelamine (TEM) in male postmeiotic germ cells. This relationship does not hold for isopropyl methanesulfonate (IMS), which induced only negligible frequencies of heritable translocations at doses that induced high levels of dominant lethal mutations. Nor does IMS behave like EMS and TEM in the degree to which eggs of different stocks of females repair premutational lesions that are carried in the sperm-large differences between stocks for IMS treatment and small differences for EMS or TEM treatment. These dissimilarities between IMS and the other two alkylating chemicals are postulated to be attributable to differences in the types of lesions present at the time of repair activity and to whether or not chromosomal aberrations are already fixed prior to postfertilization pronuclear DNA synthesis.


Separation of some polypeptide hormones by high-performance liquid chromatography. Twenty-one analogues of ACTH, three analogues of LH-RH and four insulins have been successfully separated on a commercial reversed-phase material with tartrate buffer--acetonitrile systems containing sodium 1-butanesulphonate and sodium sulphate as the mobile phase. The effect of the constituent amino acid residues on the order of elution has been studied in detail by using a variety of closely related peptides; the order of elution of a series of peptides, which differ by only one amino acid residue, can in most instances be explained in terms of the difference in the hydrophobicities of the amino acid residues concerned, but in some instances, such as in diastereoisomers or positional isomers, the order of elution must be interpreted in terms of the hydrophobicity of the whole peptide molecule. This chromatographic method has been proved to be very useful for the rapid examination of the purity of these peptide hormones and for the separation of closely related peptides with molecular weights up to ca. 6000.


Spectrodensitometric determination of trichothecene mycotoxins with 4-(p-nitrobenzyl)pyridine on silica gel thin-layer chromatograms. A simple method for the detection and spectrodensitometric determination of a number of trichothecene mycotoxins on silica gel layers based on a colour reaction between 4-(p-nitrobenzyl)pyridine and the 12,13-epoxy group in the trichothecene nucleus is described. The detection limits for the twelve trichothecenes examined were 0.025--0.2 micrograms per spot. Further, six of the twelve trichothecenes could be determined spectrodensitometrically in the range from ca. 0.05--0.2 to 10 micrograms per spot with a coefficient of variation of ca. 5%.


Effect of vasopressin and serosal hypertonicity on toad urinary bladder. The mucosal surface of toad urinary bladder was examined with scanning electron microscopy following its exposure to 20 mU/ml of vasopressin (VP), 10(-4) M 8-bromo-cAMP, 1 mM acetylcholine chloride, serosal hypertonicity, or a hypotonic bathing medium. After a 30-min exposure to VP, the arborizing ridge-like surface pattern typical of granular cells was transformed into microvilli, a response that was not dependent on transepithelial osmotic water movement. An identical response occurred following a 30-min exposure of the bladder to 8-bromo-cAMP, again in the absence of an osmotic gradient. Microvillus formation was not observed when cell volume was increased by incubation of tissue in half-normal amphibian Ringer's solution for 30 min, or with exposure to acetylcholine, which caused accentuation of the convexity of the apical surface of the granular cell similar to that observed with VP-induced osmotic water flow. However, 60 min of incubation in a hypertonic serosal medium (mannitol, 240 mM) caused transformation of ridges to microvilli mimicking the picture obtained with VP. These findings establish that transepithelial osmotic water flow with cell swelling is not required for microvillus formation on the apical surface of granular cells following VP stimulation, and that the surface changes are not due to cell swelling alone or to changes in the configuration of the apical plasmalemma. The results also suggest that the response to VP is mediated via the generation of cAMP. Finally, this study demonstrates that serosal hypertonicity also causes transformation of ridges to microvilli by a mechanism that is yet to be defined.


Growth of kidney epithelial cells in hormone-supplemented, serum-free medium. Madin Darby canine kidney cells can grow in synthetic medium supplemented with 5 factors--insulin, transferrin, prostaglandin E1, hydrocortisone and triiodothyronine--as a serum substitute. These 5 factors permit growth for one month in the absence of serum, and a growth rate equivalent to that observed in serum-supplemented medium. Dibutyryl cAMP substitutes for prostaglandin E1 in the medium, suggesting that increased growth of Maden Darby canine kidney cells results from increased intracellular cAMP. Potential applications of the serum-free medium are discussed. The medium permits the selective growth of primary epithelial cell cultures in teh absence of fibroblast overgrowth, and a defined analysis of the mechanisms by which hormones regulate hemicyst formation.


Isolation and characterization of a variant of B16-mouse melanoma resistant to MSH growth inhibition. A variant of B-16 F1 mouse melanoma was selected for its ability to survive and replicate in the presence of melanocyte-stimulating hormone (MSH). Although the variant (MR-4) was completely resistant to growth inhibition of MSH, cyclic AMP was still able to block cell replication. Tyrosinase activity in MR-4 cells was considerably lower than in B-16 F1 cells. MSH induced a two fold to three-fold increase in tyrosinase activity in both cell types, but the absolute activity in MR-4 remained significantly less than in the parental cells. MR-4 cells were also found to have a markedly depressed cyclic AMP-dependent protein kinase activity relative to B-16 F1 cells. The protein kinase from both cell types was stimulated by cyclic AMP, but the level of MR-4 kinase activity at maximal cyclic AMP concentrations remained considerably lower than B-16 F1 kinase activity under the same conditions. In both cell types adenylate cyclase activity was markedly stimulated by MSH. When equal numbers of viable F1 and MR-4 cells were injected subcutaneously into C57/B1 mice, the MR-4 cells formed tumors earlier and killed the host sooner than the parental F1 cells. We conclude that the biochemical alteration which allows MR-4 cells to replicate in the presence of MSH is a low level of tyrosinase activity, which in turn may be the result of low cyclic AMP-dependent protein kinase activity.


Cellular basis of prolactin action: involvement of cyclic nucleotides, polyamines, prostaglandins, steroids, thyroid hormones, Na/K ATPases and calcium: relevance to breast cancer and the menstrual cycle. The mechanisms of prolactin action are uncertain. Prolactin effects are characterised by great variability in the prolactin concentration required to produce a response and by the frequent occurrence of "bell-shaped" dose response curves. Relationships between prolactin and thyroid hormones and steroids are difficult to understand: both steroids and thyroid hormones may potentiate or inhibit prolactin effects in different situations. At the second messenger level, claims have been made that cyclic nucleotides, polyamines, Na/K ATPases and prostaglandins are involved. There is evidence that prostaglandin E1 may be an important second messenger and it is proposed that this is the clue to understanding the complexity. At low concentrations PGE1 enhances intracellular calcium release and at high concentrations PGE1 inhibits calcium release. The other second messengers proposed are all probably dependent upon calcium. Many prolactin effects may involve both PGE1 and another second messenger: at low prolactin concentrations PGE1 will potentiate the other messenger whereas at high concentrations the PGE1 effect will be inhibitory leading to a bell-shaped response. Thryoid hormones seem to enhance while glucocorticoids inhibit PGE1 synthesis. PGE1 dependent effects will thus be enhanced by thyroid hormone and blocked by cortisol. The reverse will be true of effects dependent on other second messengers.


A family with massive acute vitamin D intoxication. Acute massive vitamin D overdosage occurred in a family after eating food cooked in a nut oil containing 5 million units of vitamin D3/ml. The plasma vitamin D was 55 and 60 i.u./ml in the father and mother respectively, and 9.6 i.u./ml in their 11-month-old infant (normal range, 0--1.6 i.u/ml). All the family presented with symptoms of hypercalcaemia and the infant responded quickly to prednisone. After steroids had failed to control the hypercalcaemia in the parents, neutral phosphate was successful, although necessary for 9 months. Before phosphate therapy it was shown that both parents were in strongly negative calcium balance, indicating that the vitamin D was mobilizing calcium from bone. Eleven years later all 3 patients are well but a renal biopsy in one of them shows persistent nephrocalcinosis.


Treatment of moderate to severe hypertensive patients with an orally active converting-enzyme inhibitor. Seventeen hypertensive patients were treated with captopril, an orally active inhibitor of converting-enzyme. All patients showed a fall in blood pressure (BP), although in some patients only after the addition of diuretics. In 2 patients a skin rash developed. One patient developed proteinuria. A renal biopsy revealed membranous glomerulopathy. Correlations were found between pretreatment plasma renin activity (PRA) and the decrease in BP, and between pretreatment PRA and the decrease in plasma aldosterone concentration (PAC). Filtration fraction (FF) fell, indicating a decrease in renal vascular resistance. Captopril decreased the sensitivity to exogenous angiotensin I (AI), dependent on the captopril dose used. The sensitivity to exogenous bradykinin increased impressively even on the lowest dose of the drug. These observations suggest extrapulmonary conversion of AI to angiotensin II (AII).


Captopril and salt subtraction to treat "uncontrollable" hypertension in haemodialysis patients. Eight patients on chronic haemodialysis for six months to 7 years with hypertension resistant to ultrafiltration and antihypertensive therapy, received Captopril (SQ 14, 225) an orally active inhibitor of converting enzyme. With this therapy, blood pressure was controlled in the 4 patients with the highest plasma renin activity. In the other 4, this treatment had to be supplemented with "isovolumetric salt subtraction", i.e. following conventional dialysis, 1-2 litres of ultrafiltrate were replaced by an equal volume of 5% glucose. The slight hyponatraemia induced by this procedure (plasma sodium 128mmol/L) was well tolerated. This procedure allows the removal of an excess of body sodium and seems to be effective even when conventional ultrafiltration during dialysis has failed. Administration of Captopril either alone or combined with "isovolumetric salt subtraction" induced good control of blood pressure in all 8 patients.


Renal osteopenia - an assessment of long-term therapy with vitamin D analogues. Renal bone disease was assessed for an average of 5.5 years in 9 patients on maintenance haemodialysis. The investigative methods included serial biochemical estimations, radiographic skeletal surveys and quantitative bone histology. Repeated bone mineral analyses and neutron activation analyses of a hand were also performed in order to monitor changes in skeletal calcium content. Before treatment, progressive osteodystrophy was demonstrated by all techniques. Following therapy with the vitamin D analogues, all patients noted symptomatic improvement; serum alkaline phosphatase reverted to normal and serum parathyroid hormone concentrations decreased. Radiographically, subperiosteal erosions healed while the histological features of osteomalacia and osteitis fibrosa were abolished. Both bone mineral and neutron activation analyses indicated that progressive skeletal demineralisation had been halted. However, a sustained increase in the overall mineral content of bone was not demonstrated. Thus, vitamin D therapy although improving the biochemical, radiological, and histological features of renal osteodystrophy may not restore bone mass to osteopenic bone.


Renal bone disorders in children: therapy with vitamin D3 or 1,25-dihydroxycholecalciferol. Twelve children with chronic renal failure (CRF) and sixteen children receiving regular dialysis therapy (RDT) were treated with between 10,000 and 50,000 IU of vitamin D daily. This was associated with an increase in serum calcium levels and reduction in PTH levels. In the children with CRF, secondary hyperparathyroidism was improved with treatment but its development was not completely prevented nor was healing complete. In the patients receiving RDT, treatment with vitamin D improved the changes associated with secondary hyperparathyroidism in 50% of cases but these features sometimes reappeared despite continuing treatment. Hypercalcaemia or metastatic calcification was not seen. Subsequently, 1,25(OH)2D3 was administered to 14 children receiving RDT. This was associated with the return of serum calcium levels to normal, inhibition of PTH synthesis and an improvement in intestinal calcium absorption. Fibro-osteoclasia was cured and there was improvement in actual bone resorption. There was also improvement in osteoidosis in those children who showed disturbances of mineralisation. Calcification in the limbus area of the eyes may occur and hypercalcaemia was seen commonly. Treatment with 1,25(OH)2D3 should only be offered to children with severe renal bone disease. Neither vitamin D3 nor 1,25(OH)2D3 can guarantee complete recovery of osteodystrophy and of growth arrest in uraemic children.


Circadian rhythm of cyclic nucleotide and GABA levels in the rat brain. Daily variation in the levels of cyclic nucleotides and GABA was examined in seven brain regions of male Sprague-Dawley rats. Significant daily rhythm of cyclic AMP levels was found in the cerebellum and pons medulla oblongata. Circadian variation of cyclic GMP levels was found in the cerebellum, cerebral cortex, striatum, and hypothalamus. Daily variation of GABA levels was found in the pons medulla oblongata and striatum. Cyclic GMP in the pons medulla oblongata and GABA in the hypothalamus were found to exhibit ultradian variation of levels. These observed daily fluctuations of baseline levels should be considered when examining the duration of action of various drugs upon these substances.


Action of various drugs with anti-inflammatory or anti-rheumatic properties on pleurisy due to Bordetella pertussis hypersensitivity in the rat. The authors studied various drugs with anti-inflammatory or antirheumatic properties on pleurisy due to Bordetella pertussis hypersensitivity in the rat. The following compounds were studies according to various methods of treatment: indomethacin, phenylbutazone, cyclophosphamide, desonide, chloroquine, levamisole, D-penicillamine and sodium aurothiopropanol sulphonate. The action on the volume of pleural exudate and on cell events depended on the compounds and the conditions of treatment. Only gold salt produced no reduction in the pleural volume under all methods of treatment. All the compounds studied produced various degrees of significant modifications at the level of the cell events.


Oxidation of NADH by melanin: effect of UV light and copper ions. The oxidation reaction of NADH with synthetic melanin from L-dopa was investigated under various physicochemical conditions both by spectrophotometric measurements and ESR spectroscopy. The different amounts of NADH oxidized and the effects on the formation and decay of melanin free radicals were compared. Some hypotheses on a common physical mechanism involved in electron transfer reaction and in electron excitation through a liquid-solid interface are presented.


[Radiologic diagnosis of the retroperitoneal masses (author's transl)]. A series of 75 patients with retroperitoneal masses (60 malignant and 15 benign tumours) have been studied. Urography and angiography were employed. The results of the two methods are correlated. The following criteria are taken into consideration: a) site; b) nature; c) extension of the mass. The importance of a precise definition of the extension of the tumour is stressed. In fact this can greatly influence the choice of the therapy.


[Multiple cutaneous neoplasms following repeated fluoroscopic examinations. (A case of clear-cell malignant hidradenoma associated with intra-epidermal epitheliomas of the Bowen type)]. A case of some neoplastic lesions of the skin of the back, arisen on undamaged skin, in a patient who underwent therapeutic pneumothorax and was submitted to several fluoroscopic examinations for pulmonary tuberculosis many years ago, is reported and discussed. An attempt of evaluation of the exposure to the ionizing radiations received by the interscapular region of the patient is made. The malignant clear-cell hidradenoma is a very rarely observed carcinoma: nine cases have been so far described.


Ligandin subunits and hepatocellular carcinoma in man and rat. Covalent binding of activated azo dye and methyl cholanthrene carcinogens preferentially occurs to subunit B of ligandin. This subunit contains 7 of ligandin's 9 cysteine residues which, according to Ketterer et al, are the site of covalent carcinogen binding. Subunit B appears to be cytoplasmic and intranuclear. We postulate that binding of activated carcinogens to subunit B may facilitate their transfer from cytoplasm to nucleus. Rat and human primary liver cell cancers often contain ligandin which is released into the circulation. In patients at risk for, or suspected of having primary liver cell cancer, increased serum ligandin concentrations may have diagnostic value.


Superoxide, hydrogen peroxide, and oxygen tolerance of oxygen-sensitive mutants of Escherichia coli. Oxygen-intolerant mutants of Escherichia coli K12 were selected by a replica plating technique after treatment with the mutagen, N-methyl-N'-nitro-N-nitrosoguanidine, to a lethality of 99.5%. One group of mutants had lost the ability to induce both peroxidase and catalase when exposed to oxygen but retained the ability to induce the manganese-superoxide dismutase. The second group of mutants had lost the ability to induce the activity of all these enzymes. Failure to induce peroxidase and catalase was associated with enhanced susceptibility of the bacteria to the lethal effect of oxygen. When a member of the first group of mutants was prevented from producing the manganese-superoxide dismutase by the presence of puromycin, its susceptibility to the lethal effects of oxygen was greatly increased. Two types of revertants were seen. In one group the ability to induce enzyme activity was recovered and was accompanied by the return of oxygen tolerance. Members of the other group lost the ability to respire and, therefore, no longer produced O2- AND H2O2. These results indicated that enzymic scavenging of both H2O2 and O2- provides an important defense against oxygen toxicity. The parallel loss of peroxidase and catalase, which was seen in all mutants, suggests that these enzymes constitute a precursor-product pair in E. coli. The parallel loss in two of these mutants of peroxidase, catalase, and the manganese-superoxide dismutase suggests a control linkage for these enzymes, the basis of which remains  to be explored.


Characterization of an angiotensin binding site in rabbit renomedullary interstitial cells in tissue culture: correlation with prostaglandin biosynthesis. High affinity binding sites for angiotensin II have been identified and characterized in rabbit renomedullary interstitial cells in tissue culture. Binding studies were performed using monoiodinated angiotensin II of high specific activity; the angiotensinase inhibitors dithiothreitol and phenylmethylsulfonylfluoride were added to the incubation medium to retard degradation of the labeled hormone. Uptake of 125I angiotensin II was maximal at pH 7.4 and Scatchard analysis indicated a single binding site with a KD of 3.1 nM. Binding to a particulate preparation of the cells was rapid and reversible. Competition for binding by angiotensin II analogs correlated with their biologic potencies: (Sar1Ala8) AII greater than AII greater than (desAsp1) AII greater than greater than 3-8 hexapeptide. The 1-7 heptapeptide was completely ineffective in displacing the labeled angiotensin II from its binding sites. Angiotensin II directly stimulated prostaglandin (PG) biosynthesis by the renomedullary cells in tissue culture; the concentration of angiotensin II that resulted in half maximal stimulation of PG biosynthesis (6.5 nM) was similar to the concentration of angiotensin II that resulted in half maximal occupancy of binding sites (3.1 nM). These results suggest that the renomedullary cells may provide a model homogeneous tissue for the study of the angiotensin receptor and the hormonal regulation of prostaglandin biosynthesis.


Virulence factors of Clostridium perfringens. Clostridium perfringens produces a variety of virulence factors. The mechanism of action of these factors usually falls into one of three groups. Some of these virulence factors, such as the alpha toxin, which is phospholipase C, and the kappa toxin, which is a collagenase, are enzymes that hydrolyze substances essential to the integrity of membranes or other body structures. Other virulence factors, such as the beta, episolon, and iota toxins, act primarily on the vascular endothelium, causing increased capillary permeability, especially in the brain. Still others, such as the delta and theta toxins, are essentially hemolysins. Theta toxin is similar in action and serologically related to streptolysin O.


Experimental animal models for anaerobic infections. An experimental animal model that stimulates the mixed aerobic-anaerobic microflora of intraabdominal sepsis was used to study antimicrobial efficacy in vivo. Treatment of infected rats with chloramphenicol resulted in only a modest reduction in the percentage of animals surviving infection with abscesses at necropsy. This unanticipated observation led to further exploration of the predominant anaerobes associated with the experimental infection. In vitro cultures of Bacteroides fragilis, susceptible to chloramphenicol in traditional tests, were capable of reducing chloramphenicol to its aryl amine derivative, which is biologically inactive. In contrast, metronidazole, an antimicrobial agent active against anaerobes, reduced the coli-metronidazole, an antimicrobial agent active against anaerobes, reduced the coli-form-associated mortality in this animal model. Subsequent studies showed that this reduction in mortality is dependent on the presence of an anaerobe and that the levels of Escherichia coli in mixed continuous culture with B. fragilis are reduced by addition of metronidazole. This reduction following addition of metronidazole was not observed either in a pure culture of E. coli or when clindamycin was added to a mixed culture. In a modification of the previously described model, infective material was placed subcutaneously into Wistar rats. Studies with this model suggested that the host's response to bacterial challenge is dependent on the site of infection and that organotropism of the implanted bacterial species is an important determinant of infection.


A new function for ceruloplasmin as an acute-phase reactant in inflammation: a scavenger of superoxide anion radicals. In summary, purified human ceruloplasmin inhibits several reactions mediated by superoxide anion in a fashion consistent with an ability to scavenge this free radical. It must be pointed out, however, that on a weight basis, the superoxide-scavenging activity of ceruloplasmin is substantially less than that of purified human erythrocyte superoxide dismutase. Nevertheless, since superoxide dismutase is almost exclusively an intracellular enzyme, ceruloplasmin probably represents the major circulating scavenger of superoxide anion radicals. The level of superoxide dismutase in human plasma has been reported to be 0.7 microgram/ml. It is not clear, however, how this was measured. We have found that concentrations of plasma exceeding 10% (v/v) interfere significantly with the assays routinely employed for detecting superoxide-scavenging activity. Consequently, we have not yet been able to quantify the superoxide-scavenging activity of either ceruloplasmin or superoxide dismutase in whole human plasma. Thus, we can only speculate that under conditions where levels of ceruloplasmin are markedly elevated, as during pregnancy, during acute infections, or in association with inflammatory diseases (such as rheumatoid arthritis), this acute-phase reactant may play a major role as a circulating scavenger of oxygen-derived free radicals.


[Experiments to obtain and test a cell-culture rotavirus-precipitating antigen]. The location of the rotaviral precipitating antigen and the possibility for its production from cattle rotaviral strains adapted on cell cultures of calf kidney were investigated. Highest titer antigen was produced by concentration with ammonium sulfate simultaneously from the maintaining medium and from the cell monolayer. Comparative studies on the antigenic and physico-chemical properties of the cell-cultural and the faeces rotaviral precipitating antigen were made. The identity of both antigens was proven by the immunodiffuse reaction and by their resistance to ether and tripsine. A considerably higher temperature sensitivity was established of the cell-cultural precipitating antigen as compared to that from faeces. The precipitating antigen was used for confirming the presence of antirotaviral antibodies in the serums of cattle, man and sheep.


[Neurologic syndromes affecting the shoulder (author's transl)]. A number of locally defined as well as generalised diseases of the peripheral nervous system is manifested in the shoulderarm region besides lesions of individual nerves through traumas or as a result of pressure. Radicular syndromes are particularly frequent. These are based on prolapsed disks or degenerative changes of the cervical vertebral column. We must differentiate between these syndromes and the often rather unknown neuralgic amytrophy of the shoulder. Our experience has shown that in too many cases, paralysis of the plexus cervico-brachialis is assumed, although this occurs almost exclusively on the basis of traumatic violence, much rarer due to pressure. In such cases, the physician should look for the scalenus syndrome, the costoclavicular syndrome, and the hyperabduction syndrome. As a rule, pain is the most prominent symptom in plexus pareses through new growths, eg Pancoast's tumour. In such cases, a clear distinction must be made against bursitis of the shoulder (periarthritis humeroscapularis), in which there are no neurogenic changes, but only myogenic changes manifested in the electromyogram. If the sudden pain is accompanied by swelling and weakness of the arm, there is every likelihood of the existence of Paget-von Schrötter's syndrome. A remarkably painless deformation of the shoulder joint should also suggest neurogenic arthropathy in syringomyelia. The physician should also consider disturbances of distant origin, for example in the region of the carpal tunnel, with pain radiating to the shoulder in the manner of brachialgia paraesthetica. Finally, any noticeable weakness or muscular atrophy in the shoulder region should suggest a disease of the neuromuscular system, mainly progressive muscular dystrophy or the rare shoulder girdle type of amyotrophic lateral sclerosis.


[Influence of straw manuring on the biological activity of a lessivé chernozem (author's transl)]. In a long-term experiment, the influence of straw manuring in spring and autumn on the biological activity of a lessive chernozem soil was examined. The quantity of carbon dioxide, evolved by the plots during May and June, showed an increase in soil respiration by straw manuring. Increasing amounts of nitrogen, given together with straw, had no significant influence on the quantity of carbon dioxide evolved. The base respiration, however, showed increasing rates proportional to increasing amounts of nitrogen. The variants manured with straw in autumn were superior to those manured in spring. For covering the efficiency of soil respiration, the field method applied noes not seem suitable. With high N-supply (200 kg/ka), the relative respiration rates show good stability of the organic substance, present in soil. This stability is higher with straw manuring in spring than in autumn. Straw supply in autumn influences the yield more favourably. Direct relation between the quantity of carbon dioxide evolved and yield cannot be inferred.


Biological oxidation of ammoniacal fertilizers as affected by the physical properties of soil. The study was made on the nitrification of ammonium sulphate and ammonium nitrate in nine soils, widely different in their texture and calcium carbonate content. Fertilizers were added to the soils in amounts to represent a cross section of a fertilizer band, ranging from 100 to 1000 ppm ammoniacal nitrogen. Results indicate the high capacity of all soils for nitrifying appreciable amounts of ammonium nitrogen during a short time. Both fertilizers nitrified rapidly and at about the same rate when applied in amounts less than 500 ppm NH4-N, but nitrification was rather rapid in soils rich in clay mineral and harbouring a denser population of nitrifying bacteria. At higher levels of NH4-N additions, ammonium as sulphate nitrified faster than as nitrate, especially in the high concentrations of NH4-N. Nitrite was detected in small amounts of less than 10 ppm in some soils, particularly in the coarse-textured ones, regardless of the type and amount of the fertilizer applied. Considerable amounts of nitrite accumulated in other soils and persisted for long time as a result of addition of high levels of NH4-N, especially in the form of ammonium nitrate.


[Postovulatory and post-implantation inhibition of fertility--general account (author's transl)]. Latest knowledge about interception and induced menstruation is discussed. Interception (postovulatory inhibition of fertility) can be undertaken by using oestrogens, anti-oestrogens and gestagens as well as non-steroid compounds. Induced menstruation is discussed as a method of post-implantation inhibition of fertility. Induction of menstruation, that is post-implantation contraception, will be feasible by means of anti-gestagens or inhibitors ov ovarian steroid biosynthesis. While most various research efforts have been undertaken, no practicable procedure has become available as yet.


The influence of growth temperature on the heat stability of inorganic pyrophosphatase from crude extracts of Bacillus stearothermophilus. Inorganic pyrophosphatase activity of crude extracts from Bacillus stearothermophilus adapts its thermostability to the growth temperature of the cells. Magnesium ions increase the stability of the enzyme in all cases. Depending on the growth temperature of the cells two pyrophosphatase species differing in their molecular weights and heat stabilities have been detected.


An ouabain-insensitive Na-ATPase of the arterial vascular muscle cell and its relation to ouabain-sensitive Na,K-ATPase. A Na+-stimulated, Mg++-requiring ATPase (Na-ATPase), which is insensitive to ouabain, has been demonstrated in the carotis and coronary arteries of different species. In dependence on the sodium concentration half-maximal activities of Na-ATPase are found in the range from 16 to 24 mM Na+. A replacement of Mg++ by Ca++ leads to a partial loss of activity. It does not, however, change its sensitivity to sodium. Compared to Na,K-ATPase, the Na-ATPase shows a considerably lower sensitivity to calcium. p-Chloro-mercuribenzoate, N-ethylmaleinimide, chloropromazine, sodium fluoride, ethanol and sodium azide influence the activity of the Na-ATPase in a characteristic way corresponding to the reactivity of Na,K-ATPase. Noradrenaline and isoprenaline do not lead to any significant change of its activity. The possible separate existence of a Na-ATPase independent of Na,K-ATPase, as well as its potential importance for cellular metabolism are discussed.


Basal, cAMP- and cGMP-dependent protein kinases in human brain tumors. Since the effects of cyclic nucleotides are mediated via protein kinases activation, we have studied the properties and regulation of these enzymes in cytosol and particulate fraction of normal cerebral tissues and of some human brain tumors. We found that distribution and activity of cyclic nucleotide-dependent protein kinases are regulated differently among various brain tumors and in comparison to normal gray and white matter. Pathological tissues show an higher cGMP-dependent protein kinase and this biochemical pattern is particularly evident in tumors with more pronounced malignancy. These data further confirm the hypothesis of a correlation between the increase of cGMP function and cellular growth and malignancy.


Mechanism of the cerebrocortical vasodilatation during anoxia. The possible role of cerebrocortical ion homeostasis, NAD/NADH redox state and of cortical oxygen tension was investigated in the initiation of hypoxic cortical vasodilatation. In addition, changes in cerebrocortical extracellular concentrations of Na+, K+, and Cl- during anoxia were studied. The results were as follows. a) The cerebrocortical reflectance decrease, e.g. cerebral vasodilatation, lagged behind the cortical pO2 decrease by 1-2 sec, but preceded the decrease of arterial blood pressure and ECoG as well as the extracellular Na+, K+, Cl- increases by 20-30 sec. Since the cortical pO2 decreased first and the ion changes lagged behind the onset of vasodilatation by 20-30 sec, it is suggested that the CBF increase in hypoxia is mediated via the cortical pO2 decrease. b) A significant NAD reduction was already present after 20 sec. of nitrogen breathing. Since the ECoG and MABP decreased, and K+ activity increased much later than this, it is presumed that the NAD reduction during the first 30-40 sec of anoxia indicates an increased rate of glycolysis, but not mitochondrial hypoxia. c) In the predepolarization phase a 17% K+, 4% Na+, 5% Cl- increase is probably the result of a reduction of the extracellular spaces caused by water movement and by the migration of Na+ and Cl- from the extracellular to the intracellular space. The large K+, Na+, Cl- changes during terminal depolarization can be interpreted as a result of the failure of the membrane bound Na+ -K+ pump and of the altered ion permeability of the cell membranes.


[Neurotoxicity of formyl leurosine. An experimental and clinical study (author's transl)]. Leg paralysis and wallerian degeneration of sciatic nerve fibres have been produced in rats by intraneural injection of 0.5, 1 or 5 microgram of vincristine (VCR) or formyl leurosine (FLR) dissolved in 5 microliter of saline. Nerve lesions were dose-related, and were similar for equal concentrations of the two drugs. Six patients received one to three 5-day courses of FLR. The total dose of FLR administered ranged from 15 to 131 mg (mean 83 mg). Clinical signs of peripheral neuropathy were absent in four patients, and limited to orthostatic hypotension in one case and transient depression of reflexes in another. Motor conduction velocities measured in four peripheral nerves, and muscle evoked potentials remained unchanged throughout the treatment in all patients.


Effect of arterial hypoxia on the cerebrocortical redox state, vascular volume, oxygen tension, electrical activity and potassium ion concentration. The effect of different degrees of arterial hypoxia on cerebrocortical NAD/NADH redox state, reflectance, oxygen tension, extracellular potassium ion concentration, ECoG and arterial blood pressure was investigated in rats. The results may be summarized as follows. a) The decrease of cortical pO2 preceded the dilatation of cortical vessels by 15-20 sec but the changes in cortical extracellular potassium ion concentration, ECoG and arterial blood pressure started later than the vasodilatation. These results give further support to the regulatory role of cortical pO2 decrease in the initiation of cerebrocortical vasodilatation during arterial hypoxia. b) Since the K+ concentration of the brain cortex and the ECoG did not change in mild arterial hypoxia, the significant NAD reduction obtained in this experimental group is likely to be of cytoplasmic origin. The same conclusion applies to the initial periods of severe arterial hypoxia. On the basis of the extent of NAD reduction during various degrees of arterial hypoxia it is concluded that about 30% of the NAD reduction occurring in anoxia is of cytoplasmic origin. c) When the animals were ventilated with a gas mixture containing 4-7% oxygen, the brain cortex became nearly anoxic, partly because of the gradual decrease of arterial blood pressure. Finally, the mechanism of potassium leakage is identical under prolonged severe arterial hypoxaemia and on anoxic terminal depolarization.


[Multicentric gliomas. Report of a case (author's transl)]. The criteria of culticentric gliomas, based upon histological data, were recently defined (Bartzdorf et al. 1963) and permits us to distinguish them clearly from multiple gliomas. The authors report an atypical case of glioma for which the diagnosis of multicentric gliomas has been established after anatomical and histological studies. Physiopathological hypotheses are discussed. Emphasis is placed on the clinical pictures, diagnostic techniques as well as evolution and therapeutic aspects.


Intracellular oxygen tension and energy metabolism in the cat brain cortex during haemorrhagic shock. The changes in intracellular oxygen tension and energy metabolism of the cat brain cortex were studied by surface fluororeflectometry during haemorrhagic shock. The results may be summarized as follows. (a) Intracellular oxygen tension, i.e. the maximum cortical NAD reduction obtained during nitrogen gas inhalation decreased gradually during the hypovolaemic phase of shock and finally, the brain cortex became ischaemic. (b) Partial uncoupling of the cerebrocortical mitochondrial respiration and oxidative phosphorylation appeared in the very early period of bleeding, as indicated by the overshot of the cortical NAD/NADH redox state towards oxidation subsequent to the cessation of nitrogen gas inhalation. Partial uncoupling of mitochondrial respiration and oxidative phosphorylation became more pronounced during the later phases of bleeding, finally, the mitochondrial electron transport stopped. In line with these changes the frequency and the amplitude of ECoG decreased gradually and markedly during the hypovolaemic phase of shock. (c) Microcirculation and energy metabolism of the cat brain cortex were severely and irreversibly damaged during the hypovolaemic phase of shock. This was clearly shown by the fact that in the majority of experiments the nitrogen anoxia after reinfusion failed to bring about changes in the cortical NAD/NADH redox state and the ECoG changes occurred during bleeding did not improve after reinfusion. It is concluded that the early disturbances of cerebrocortical energy metabolism play an important role in the development of neural and vascular lesions of the brain that occur during haemorrhagic shock.


Reactivity of the cerebrocortical vasculature and energy metabolism to direct cortical stimulation in haemorrhagic shock. Direct electrical stimulation of the cerebral cortex was used to determine the changes of cortical carbohydrate and oxidative metabolism and of vascular reactivity during haemorrhagic shock. The results were as follows. 1. Electrical stimulation of the brain cortex applied in the control period led to a marked vasodilation and NAD reduction that was preceded in part of the experiments by a transient NADH oxidation. It is suggested that the increase in cortical NADH fluorescence observed during direct stimulation is due to the fact that the rate of cytoplasmic NADH production exceeded the rate of mitochondrial NADH oxidation and of the rate of H+-transport from the cytoplasm into the mitochondria. 2. The cerebrocortical vascular and NAD/NADH redox state responses induced by electrical stimulation changed in the early hypovolaemic phase of shock. At this time, electrical stimulation of the brain cortex led to NADH oxidation in the majority of the experiments or in some experiments, the stimulation did not bring about changes in the redox state of the cortex. The total loss of the reactivity to direct stimulation of the cerebrocortical vessels and of energy metabolism preceded the occurrence of cortical ischaemia during the hypovolaemic phase of shock. 3. Since after reinfusion of the shed blood, redox state and vasculature remained unresponsive to stimulation even in those experiments in which the cortical ischaemia improved, it is concluded that the carbohydrate and oxidative metabolism of the brain cortex were already irreversibly damaged in the early phase of hypovolaemic shock.


Extramammary Paget's disease. A critical reexamination. Fifty-five patients with extramammary Paget's disease were the source of material for this study. Step-sections were done through most of the specimens. Clinical information, including follow-up, was obtained on 45 of the 55 patients. Extramammary Paget's disease could be divided histologically according to where Paget cells were found, namely: 1) wholly within the epidermis and the epithelial structures of adnexa, and the dermis; 3) within the epidermis, the epithelial structures of adnexa, and contiguous epithelia of other organs such as the genitourinary and gastrointestinal tracts. Our conclusions are that extramammary Paget's disease is more than one disease and in most instances begins in the epidermis as an adenocardinoma and extends from there into contiguous epithelium of hair follicles and eccrine sweat ducts. Uncommonly, Paget cells extend from the epidermis into the dermis and from there may metastasize. Rarely, extramammary Paget's disease results from direct extension into the skin of an adenocarcinoma in a contiguous organ such as the genitourinary or gastrointestinal tract.


[The use of bone scintigraphy with technetium 99 m pyrophosphates in the diagnosis of algodystrophies. A report on 74 observations (author's transl)]. Bone scintigraphy with technetium 99m pyrophosphates was used to study a series of 74 cases of algodystrophies. Though non-specific, this investigation was the determining factor for confirming the diagnosis in more than 48% of cases, by demonstrating early bone hyperfixation, its topographical characteristics, and the return to normal conditions after 3 to 12 months. Bone hyperfixation has to be exaluated together with clinical, biological, and radiological signs when considering the diagnosis, and though in half the cases it is not indispensable for diagnosis, it is always of value for determining the amount of extension of the algodystrophic process.


Deficiency in the ability of serum from pigs on an atherogenic diet to stimulate the migration of 3T3 cells in culture. The serum of pigs developing atherosclerosis is deficient in the ability to stimulate the migration of Balb/c-3T3-A31 cells in culture. This deficiency appears to be due to the presence of an inhibitor located in lipoprotein-free serum. The migration assay was used to follow the changing migration activity of the serum of pigs on a changing diet.


Size of lipoproteins in intestinal lympho of sheep and suckling lambs. The relative importance of chylomicrons (Sf greater than 400) and very low density lipoproteins (Sf 20--400) in transporting lipids in lymph was investigated in surgically prepared adult sheep and pre-ruminant lambs fed low fat diets or infused intraduodenally with corn oil. The concentration of triacylglycerol in the intestinal lymph of sheep and lambs was increased from 520 and 925 mg/100 ml to 2326 and 2367 mg/100 ml respectively when corn oil was infused into the duodenum and the ratio of triacylglycerol to phospholipid changed from 3.7 and 5.5 to 9.5 and 9.7 respectively. The flow of lymph also increased. Electron microscopy and analytical and preparative ultracentrifugation showed that lymph lipoproteins from sheep and lambs fed low fat diets consisted mainly of lipoproteins 50 nm in diameter and that very low density lipoproteins (Sf 20--400) contirbuted up to 75% of the Sf greater than 20 lipoproteins. There were no lipoproteins with diameters above 150 nm. Infusion of corn oil into the duodenum of sheep and lambs increased the diameters of lymph lipoproteins. Most were 80--100 nm in diameter but substantial numbers above 150 and up to 400 mn were observed. The maximum contribution of very low density lipoproteins (Sf 20--400) to lipoproteins of Sf greater than 20 was 27--30%. The above findings demonstrate that the size of intestinal lymph lipoprotein particles increases with the amount of lipid absorbed from the small intestines and that the transport of lymph lipids, in ruminants, is similar to that previously found in rats, rabbits and man.


Effect of intravenously infused dexamethasone on collagen metabolism in skin of merino sheep. The effects of an 8-day intravenous infusion of dexamethasone (7.6 mg kg-0.75 body weight) on collagen biosynthesis and wool growth in skin were examined in four Merino wethers. Plasma dexamethasone concentrations reached their peaks during the first 24 h infusion, which were followed by relatively stable levels (c. 1 X 10(-7) M) for the next 4--5 days. Minor increases in plasma dexamethasone levels were recorded during the final 2 days of treatment. Dexamethasone concentrations quickly fell below the level of detection once infusion ceased. Marked decreases in the wet weight, thickness and protein content of skin were observed at the end of infusion. DNA content was reduced to 42.4 +/- 4.9% s.e.m. during the first 2 days of treatment, but in the next 4 days of infusion gradually increased to 85.0 +/0 12.5% of controls. The level of collagen (expressed as hydroxyproline content of its acid hydrolysate) was elevated throughout the infusion and then gradually declined in 3 weeks to about 60% of controls. The biosynthesis of collagen measured by the rate of [14C]hydroxyproline formation and the activity of proline, 2-oxoglutarate dioxygenase (EC 1.14.11.2. formerly prolyl hydroxylase) was reduced during the first half of treatment to a greater extent than the rate of [14C]proline incorporation into proteins. Wool growth was reduced by 80.4 +/- 11.6% in the post-infusion period which allowed three sheep out of four to be defleeced. Inhibition of collagen biosynthesis in sheep skin was due initially to a decrease in the activity of proline, 2-oxoglutarate dioxygenase and later to the reduced rate of proline incorporation into proteins. It was also evident that changes in biosynthetic rate of collagen were not reflected in the total level of skin collagen. The extent of wool growth depression in individual animals paralleled the changes in DNA content and the extent of collagen biosynthesis inhibition.


[Effect of silica on the anti-tumour activity of "Corynebacterium parvum" (author's transl)]. Silica, a specifically toxic substance for macrophages, has been used to study the role of these cells in the Corynebacterium parvum-induced anti-tumour protection. In the two experimental tumours studied, silica, C. parvum and tumour cells were injected by the same route: the intravenous route in the case of lymphosarcoma in XVII mice and the intraperitoneal in that of mammary carcinoma in C3H mice. The inhibition of the anti-tumour effect of C. parvum by the administration of silica was more pronounced in C3H than in XVII mice. Silica administration has only a weak and transient depressive effect on the stimulation of macrophage phagocytic activity induced by C. parvum. In addition, silica injection increased the adjuvant effect of C. parvum on the sheep red blood cell antibody response. These results suggest that the silica induced abrogation of the anti-tumour effect of C. parvum could be due to a local inhibition of macrophage stimulation at the tumour inoculation site.


Gel electrophoresis of rotavirus RNA derived from six different animal species. Rotavirus RNA prepared from calf, pig, mouse, deer, foal and dog-adapted human isolates was compared using polyacrylamide gel electrophoresis. Reproducible differences in the RNA migration patterns were found between all isolates. There were 11 clearly resolved segments in the pig, mouse and foal samples. The calf rotavirus RNA and deer rotavirus RNA separated into 9 bands and 10 bands, respectively. The dog-adapted human virus migrated in 12 bands, and this probably results from the complex passage history of the original human rotavirus isolate.


[Entero-uterine fistual as the first symptom of intestinal neoplasms. Description of a case]. Vaginal elimination of stool due to sigmoid-uterine fistula was the first symptom in a case of neoplasia of the sigma. Few instances of a similar fistula appear in the literature. Bouskela, Chérisié, Yourde and Taieb observed one case starting from the uterus. McGregor & Bacon have described a fistula starting from the colon due to diverticulitis, as have Colceck & Staumann, Smalley et al., and Johnston & Stubbs. No previous example of tumour of the large intestine as the cause of a fistula with the corpus uteri could be found. On examination, the patient presented losss of stool via the vagina and a sigmoid-uterine fistula. Her condition was poor. Blood glucose was high, the protein picture was altered with a los of albumin, and infection was present. Radical management was impossible. Left colostomy reduce the causes of infection and permitted devitalisation of the fistula. Subjective and objective improvement followed, though further enlargement of the tumour engulfing the sigma and uterus led to death some months later due to the onset of renal block.


Progressive muscular dystrophy type Duchenne. I. Spin label studies on the physico-chemical state of erythrocyte membranes. Electron spin resonance studies of erythrocyte membranes from patients with Duchenne muscular dystrophy exhibit changes in the physical state of lipids and proteins in membranes when compared to membranes from normal subjects. The results suggest that the alterations in membrane lipid-protein organization are present in this disease.


[Correlations between plasmatic alpha-tocopherol and lipids in male adults]. Plasma levels of alpha-tocopherol, beta-carotene, total lipid, total cholesterol, beta-lipoproteins, and triglyceride were measured in healthy italian male adults of various age groups. Alpha-tocopherol mean values varied from 0.96 mg/100 ml in the subjects of 18-24 years to 1,14 mg/100 ml in the subjects of 25-64 years and to 1,08 mg/100 ml in those above 55 years. No value lower than the generally accepted minimum of 0,5 mg/100 ml was found. Correlation coefficients of all the variables were also studied. Alpha-tocopherol was shown to be significantly related to age and plasma cholesterol. These data agree with other authors' results.


Interactions of neomycin with monomolecular films of polyphosphoinositides and other lipids. The interactions of calcium and the aminoglycosidic antibiotic, neomycin, with various lipids were investigated in monomolecular films. Lipids were spread over a subphase of 0.05 M N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, pH 7.0, and NaCl to give an ionic strength of 0.2. Measurements of surface pressure (pi) were taken with a Wilhelmy balance. In the absence of Ca2+, 1 muM--1 mM neomycin in the subphase decreased pi (i.e. condensed films) of all acidic lipids tested. In the presence of 1 mM Ca2+, neomycin did not change pi of films of phosphatidylserine, phosphatidylinositol and phosphatidic acid while it lowered pi of cardiolipin and cerebroside sulfate films. A unique pattern of interaction was observed with polyphosphoinositide monolayers. In the absence of Ca2+, 1 muM neomycin decreased pi followed by an increase of pi at higher neomycin concentrations. Ca2+ (1 mM) condensed the film significantly more than did neomycin. However, as little as 1 muM neomycin induced expansion of the calcium/lipid film which at 1 mM neomycin reached the same pi as in the absence of Ca2+. Such expansion was observed at all pressures of the film including the collapse pressure indicating a strong 'complex' between the drug and polyphosphoinositide not antagonized by Ca2+. In the absence of possible hydrophobic interactions, both the condensation and the expansion of the film should be mediated by ionic forces. Combined in vivo and in vitro evidence is discussed to suggest the polyphosphoinositides as the physiological receptors for aminoglycosides in the mammalian cell membrane.


Role of proteins and lipids in non-linear Arrhenius plots of Drosophila mitochondrial succinate-cytochrome c reductase studied by rebinding experiments. Abrupt changes in the Arrhenius activation energy of membrane-bound enzymes have often been correlated with changes in the physical state of membrane phospholipids. Similar changes in activation energy have also been found in soluble enzymes. The possibility exists, therefore, that in some of the membrane-bound enzymes the changes might reflect intrinsic changes of the proteins independent of changes in the membrane phospholipids. This hypothesis was investigated using Drosophila mitochondria isolated from wild type and the mutant Ocd ts-1. In this mutant it has been shown that succinate-cytochrome c reductase exhibits a change in Arrhenius activation energy at 18 degrees C which is not found in the wild type (Sondergaard, L., Nielsen, N.C. and Smillie, R.M. (1975) FEBS lett. 50, 126-129). A quantitative thin-layer chromatographic analysis of mitochondrial phospholipids showed sphingomyelin to be more abundant in the wild type than in the mutant (5.2% and 4.3% of the total phospholipids, respectively). Since it was shown that the succinate-cytochrome c reductase had a lipid requirement for full activity, reciprocal rebinding experiments were done. These experiments showed that the reconstituted membranes exhibited the change in activation energy at 18 degrees C only when the protein moiety came from mutant mitochondria, that is, the change was independent of the source of the phospholipids used.


Exchange of phospholipids between unilamellar vesicles of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine and plasma very low density lipoproteins. Purified phosphatidylcholine exchange protein from bovine liver was used to exchange [14C]dipalmitoyl phosphatidylcholine from sonicated vesicles to human plasma very low density lipoproteins (VLDL). The exchange of [14C]-dipalmitoyl phosphatidylcholine for VLDL phospholipids was temperature dependent and linear with respect to time and amount of exchange protein. In the absence of the exchange protein, less than 10% of the [14C]dipalmitoyl phosphatidylcholine was transferred. At an initial weight ratio of [14C]-dipalmitoyl phosphatidylcholine vesicles to VLDL phospholipid (1.2 mg) of 2.2, the exchange protein (14 microgram) replaced 55% of the VLDL phospholipids with [14C]dipalmitoyl phosphatidylcholine in 15 min; VLDL protein and cholesterol content were unaltered. From these studies we conclude that the exchange protein is a useful method to alter the phospholipid composition of VLDL under conditions such that there is minimal perturbation of the lipoprotein.


A cyclic GMP-dependent histone kinase bound to liver nucleoli. A method of steady-state electrophoresis in polyacrylamide gels was used to analyze the presence of cyclic nucleotide binding components in cell extracts. Multiple cyclic AMP and cyclic GMP binding components were detected in soluble cytoplasmic and nuclear extracts derived from avian liver, but only a single cyclic GMP binding protein was found in the 0.3 M NaCl extract of liver nucleoli. In the presence of cyclic GMP, this protein phosphorylated efficiently a calf thymus histone mixture and an endogenous nucleolar protein, which migrated identically with histone H4 in sodium dodecyl sulfate polyacrylamide gel electrophoresis. The isoelectric point of the cyclic GMP-binding protein was 4.8. Addition of cyclic GMP did not influence the activity of the endogenous nucleolar RNA polymerase.


Electron spin resonance study of human alpha 1-acid glycoprotein interaction with a spin labelled steroid. The interaction of human alpha 1-acid glycoprotein (AAG) with a corticosteroid was studied using nitroxide labeled deoxycorticosterone and electron spin resonance (ESR) spectroscopy. The ESR spectra of the spin labeled steroid in the presence of AAG could be used to characterize the ligand-protein interaction at equilibrium without the need of a separation between bound and free species. An association constant Ka of 6.10(5) M-1 at 20 degrees C and a binding capacity of one site per mole protein were found. ESR spectra recorded at equilibrium at various temperatures allowed the calculation of enthalpy and entropy variations for the steroid-protein interaction; these thermodynamic parameters exhibited a rapid change above 45 degrees C which may be related to a protein conformational modification above this temperature, as detected by circular dichroism study. The ESR spectra width could be used to define a polar character for the spin label environment in the steroid binding site of AAG and to calculate an apparent rotational correlation time of 2.8 x 10(-8) sec for the steroid-protein complex in aqueous solution at 20 degrees C. It can be concluded that spin labeling and ESR methodology is of value in the study of steroid-protein interactions of biological significance above all because it can provide direct physico-chemical information concerning the local environment of the ligand in its binding site at equilibrium.


Influence of light on activity of adenylate kinase and pterin-protein complexes from pea chloroplasts. The activity of adenylate kinase (AK) and of pterin-protein complexes (PPC), whose proteins have adenylate kinase activity comparable to that of the enzyme was studied. It was established that light inhibits adenylate kinase activity and that this effect is partially eliminated by phosphate ions. The forward and reverse reactions catalyzed by AK and PPC were studied and it was found that the activity of native protein complexes is different in the forward and reverse reactions. The thermostable protein both of adenylate kinase and of the pterin-protein complexes had identical activity in the ADP dismutation and the reverse reaction.


Kinetic and chemical properties of ATP sulphurylase from Penicillin chrysogenum. Adenosine triphosphate sulphurylase (ATP: sulfate adenylyltransferase, EC 2.7.7.4.) has been purified from the filamentous fungus. Penicillium chrysogenum, and characterized physically, kinetically, and chemically. The P. Chrysogenum enzyme is an octomer (mol. wt. 440 000) composed of eight identical subunits (mol. wt. 55 000). Some physical constants are S20,w = 13.0 X 10(-13)s, D20,w = 2.94 X 10(-7) cm2 X s-1, v = 0.733 cm3 X g-1, A1%1cm = 8.71 at 278 nm. The enzyme catalyses (a) the synthesis of adenosine 5'-phosphosulphate (APS) and MgPPi from MgATP and SO2-4, (b) the hydrolysis of MgATP to AMP and MgPPi in the absence of SO2-4, (c) Mg32PPi-MgATP exchange in the absence of SO2-4, (d) molybdolysis of MgATP to AMP and MgPPi, (e) synthesis of MgATP and SO2-4 from APS and MgPPi, and (f) Mg32PPi-MgATP exchange in the presence of SO2-4. The Vmax values of reactions (a)-(c) are about 0.10-0.35 mumole X min-1 X mg enzyme-1. The Vmax values of reactions (d)-(f) are about 12-19 mumole X min-1 X mg enzyme-1. The catalytic activity of the enzyme in the direction of APS synthesis is rather low (0.13 unit X mg protein-1, corresponding to an active site turnover number of 7.15 min-1). However, the ATP sulphurylase content of mycelium growing on excess SO2-4 is 0.22 unit X g dry wt.-1, which is sufficient to account for the maximum in vivo rate of SO2-4 assimilation. The normal catalytic reaction is Ordered Bi Bi with A = MgATP, B = SO2-4, P = MgPPi, and Q = APS. Several lines of kinetic evidence suggest that the E.MgATP and E.APS complexes isomerize (to E approximately AMP.MgPPi and E approximately AMP.SO4, respectively) before the second substrate binds. Chemical modification studies have disclosed the presence of essential arginine, histidine, carboxyl, and tryosine residues. The latter is rather acidic (pKa = 7 or less). Nitration of the tyrosine increases the Km for MgATP without significantly affecting Kia for MgATP or Vmaxf. This result, and the fact that MgATP plus nitrate protects the enzyme against inactivation by tetranitromethane while MgATP alone does not, suggests that the essential tyrosine plays a role in nucleotide isomerization (perhaps as an adenylyl acceptor).


Oxidative phosphorylation linked to the dissimilatory reduction of elemental sulphur by Desulfovibrio. Hydrogenase and cytochrome c3 purified from Desulfovibrio gigas and D. desulfuricans strain Norway form a soluble complex which is capable of transferring electrons from molecular hydrogen to colloidal sulphur (S0). In this reaction, sulphur is reduced to hydrogen sulphide. Since both strains are capable of growth using elemental sulphur as terminal electron acceptor, it was of interest to check for oxidative phosphorylation in this sulphur reduction sytem. Membranes isolated from D. gigas or D. desulfuricans strain Norway contain hydrogenase and c-type cytochromes and catalyse the H2 leads to S0 reaction. With D. gigas, esterification of orthophosphate is coupled to the membrane-mediated transfer of electrons from H2 to S0. A P/2e ratio of 0.1 was observed and this value could be reduced by the addition of colloidal sulphur with c2 may be more than a purely chemical reaction. Since whole cells can use sulphur flower while cell-free extracts react only with colloidal sulphur, it is evident that cells handle sulphur in a way which is not yet fully understood.


Inhibition of adenine nucleotide transport in mitochondria of winter rye seedlings. Inhibition of adenine nucleotide transport was studied in mitochondria of winter rye (Secale cereale) seedlings. It has been shown that plant mitochondria have a translocase similar to the adenine-nucleotide translocase of animal mitochondria, since atractyloside, at a concentration of 40 micro M, inhibits Chance's State 3 respiration 100%. It has been demonstrated that palmitoyl-CoA--formed by a mitochondrial system for activation of fatty acids--lowers the rate of State 3 respiration during succinate oxidation, if palmitate, CoA and ATP are introduced into the incubation medium simultaneously. This can be explained by an inhibition of transport of adenine nucleotides through the internal mitochondrial membrane. The inhibition in question is counteracted by addition of carnitine.


Effect of dietary supplementation of vitamin E on serum lipids and lipoproteins in rabbits fed a cholesterolemic diet. The effect of dietary supplementation of vitamin E on serum cholsterol, triglycerides, lipoproteins and lipoprotein composition was studied in rabbits fed a one per cent cholesterol diet for a period of twelve weeks. Vitamin E supplemented animals were found to maintain significantly lower concentrations of serum cholesterol, triglycerides and very low density lipoproteins (d less than 1.006). The difference in the serum lipid content was mainly in the very low density lipoproteins of d less than 1.006. The possibility of an increased clearance of chylomicron remnants and decreased inhibition of extrahepatic lipoprotein lipase in hypercholesterolemic rabbits as a result of vitamin E supplementation is discussed in the light of the results obtained.


Effect of dietary excess leucine on nicotinamide nucleotide level in rat liver. 1. Six groups of rats were freely fed diets containing casein at 5, 10 and 20% levels with and without nicotinic acid. After 2 weeks on these diets, hepatic nicotinamide nucleotide and free nicotinic acid concentrations were studied. 2. Hepatic nicotinamide nucleotide level was kept in the normal range in rats fed the 10 and 20% casein diets with and without nicotinic acid. 3. L-leucine supplemented at the 5% level to the 10 and 20% casein diets caused significant decrease in hepatic nicotinamide nucleotide level only in rats fed nicotinic acid devoid diet. 4. Hepatic nicotinamide nucleotide in rats fed the diet in which casein was replaced by zein increased significantly by adding nicotinic acid. This increase in the hepatic nicotinamide nucleotide caused by dietary supplemented nicotinic acid was not reduced by the addition of L-leucine. 5. The hepatic free nicotinic acid level did not change even in rats of which hepatic nicotinamide nucleotide was significantly reduced. 6. Urinary excretion of nicotinic acid and N-methylnicotinamide was increased significantly by adding nicotinic acid to the diet but was not affected by adding L-leucine at the 5% level. 7. From the above results, a possible mechanism of L-leucine action was discussed.


Natural hypocholesterolemic agent: pectin plus ascorbic acid. An addition of 5% citrus pectin and 0.5% ascorbic acid to high-fat diet of guinea pigs prevented total cholesterol accumulation in blood serum and the liver. Two groups of persons were given a preparation containing a daily dose of 15 g pectin and 450 mg ascorbic acid for 6 weeks. In 21 healthy persons with mild hypercholesterolemia total serum cholesterol dropped significantly by 24 mg/100 ml (8.6%), while the concentration of high density lipoprotein cholesterol remained unchanged. In 11 hyperlipemic outpatients (type IIa, IIb and IV) total serum cholesterol dropped by 68 mg/100 ml (18.7%). The changes in triglyceridemia proved inconsistent.


Serum lipids in swine fed large quantities of whey. The causal relationship between hyperlipidemia and atherosclerotic diseases is undoubted. But studies of the last years have shown that this relationship is quite complex and may be even controversial. A food which has recently been placed in the foreground in lipid metabolism research is milk and its products. By accidental findings it was shown that the more milk was drunk, the lower the serum cholesterol concentration became. This brought about some controlled feeding studies on animals and humans. We chose swine for our feeding study because of their resemblance to human lipid metabolism. 57% of the whole energy consumed consisted of whey powder fed in a crossover study lasting 112 days. The results show that total cholesterol was significantly lower during whey feeding. The lipid decrease also included the HDL-fraction and, to a lesser degree, triglycerides. It seems well enough proved to be an accepted fact that the relative high content of saturated fatty aids in milk is cancelled by a substance present in milk and some of its products such as whey. Further investigations to study this milk factor in more detail including the application of high fat diets will be done.


Possibly electrotonically-mediated synaptic transmission: time-intensity trades in neurons in the superior olivary complex of cat. Microelectrode studies were conducted on the probability of firing of neurons in the superior olivary complex of 11 anesthetized cats. Time-intensity trades were established for dichotic clicks. Inhibition was observed for interaural time differences in the region .05--4 msec. The authors point out that these extremely brief times render explanation difficult in terms of chemically-mediate synaptic transmission, and speculate that these results, while of an indirect nature, may be an expression of electrical synaptic transmission.


Studies on aminoglycoside antibiotics: enzymic mechanism of resistance and genetics. The kanamycin inactivating enzyme, 3'-phosphotransferase and 6'-acetyltransferase were first found in 1967 and on the basis of the enzymic mechanism of resistance a new research approach to the development of active useful derivatives was explored. The enzymic mechanism of resistance was conclusively confirmed by the synthesis of 3'-deoxykanamycin A and 3',4'-dideoxykanamycin B which did not undergo inactivation by 3'-phosphotransferase and inhibited the growth of resistant strains. Besides APH(3') and AAC(6') described above, the following enzymes were found to be involved in the mechanism of resistance to aminoglycosides: APH(3''), APH(5''), APH(6), APH(2''), AAC(3), AAC(2'), AAD(3''), AAD(2''), AAD(4'), AAD(6). Not only the removal of the group which undergoes the enzyme reaction but also the modification of the group binding to the enzyme has also given active derivatives such as amikacin etc. The substrate specificity of the enzymes, enzymes in the immobilized state, and the application of proton and 13C nmr for structure determination of reaction products are reviewed. It was noticed that all enzymes involved in resistance contain adenosine- and aminoglycoside-binding sites. These enzymes were thus suggested to be mainly different primarily in the positional relationships between these binding sites. It suggests a close evolutionary relationships of these enzymes. The role of these enzymes in the biosynthesis of aminoglycoside antibiotics is discussed and a general mode of the biosynthesis of aminoglycosides is proposed: a gene or gene set involved in biosynthesis of 2-deoxystreptamine which has no cytotoxicity is widely distributed and the deoxystreptamine produced is transformed to the final products.


Hormone-induced modification of EGF receptor proteolysis in the induction of EGF action. A proposal that EGF action is mediated through enhanced internalization of EGF receptors is modified to account for more recent evidence. EGF receptors turn over at a rapid rate, and the maintenance of a steady state of EGF receptors on the cell surface is provided through a rapid synthesis of EGF receptors, balancing their removal. This rapid turnover of unoccupied receptors may arise through their internalization and proteolysis in the lysosomes, in much the same way as receptors are internalized and degraded when exposed to EGF, which enhances internalization. This provides a dilemmma for the endocytic activation concept, since slight enhancement of receptor internalization gives rise to a strong hormone response. This problem may be solved by the observation that EGF induces a change in its receptor, exposing an otherwise unavailable site for proteolytic cleavage. This hormone-dependent modification of receptors may be the critical step in the induction of responses to EGF and other hormones that are internalized with their receptors. Both platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) are shown to down-regulate EGF receptors, though transiently, placing still more stringent requirements on the specificity by which hormones might act through endocytic activation of their receptors.


[Keratodermic genodermatosis with hydrocystomas, miliary cysts, xanthelasmas, nail and dental dystrophies, and basal cell epitheliomas]. Two cases of a condition including palms and soles keratoderma, ectodermal dysplasias and basal cell epitheliomas are reported by the authors, with clinical, genetical and pathological data. The condition is called Keratodermal Genodermatose with hydrocystomas, milium cysts, xanthelasma, dental and nail dysplasias and basal cell epitheliomata (Borda's syndrome).


[Cadmium content of vegetable foods in the effective range of a lead smelting plant]. In the effective range of a lead smelting plant, the repercussions of cadmium emissions (mainly past) on vegetables, fruit, soil and drinking water as well as of immissions were investigated by means of atomic absorption spectrometry. As compared to the "normal" cadmium level, the cadmium contents in vegetables and fruit were some 2- to 85-fold higher; and those in soils, some 70- to 230-fold. The mean contents in vegetables ranged from 0.4 to 25.5 p.p.m. (on a dry-weight basis); those in fruit, from 0.09 to 1.17 p.p.m. Cadmium concentrations varying from 6.8 to 22.8 p.p.m. were found in soil samples. The drinking water contained 0.009 p.p.m. of cadmium. The mean cadmium contents in the atmosphere and the sedimentary dust were 0.007 mg/m3 and 0.550 mg/m2/30d, respectively. In the territory investigated, the total human uptake of cadmium supplied by vegetables, fruit, potatoes, drinking water and air is 3.3-32.6 microgram/d. The following cadmium levels were found in human organ samples obtained at necropsy: right and left renal cortex, 33.99 and 35.98 p.p.m., respectively; liver, 3.14 p.p.m.; lungs, 0.63 p.p.m.; pancreas, 1.47 p.p.m.; brain stem, 0.16 p.p.m.


On the molecular structure of some prostaglandin receptors. Hypotheses are presented of the detailed molecular structure of two prostaglandin receptors both concerned in tumor-promotion processes. These structures have been derived by the comparison  of the molecular structure of agents active at the site with (i) a simple theoretical protein structure and (ii) the known x-ray structure of phospholipase A2. The first model receptor is stimulatory to the tumor-promotion process and may be located on the control system for ornithine decarboxylase. The binding of PG here is cooperative with the binding of Ca++. Naturally-occurring agonists at this receptor may include members of the cathartic class of drugs such as colocynth, chrysarobin, etc. Naturally-occurring antagonists at this site may include a number of anti-tumor compounds such as datiscoside. The second model receptor (PGE1) is inhibitory to the tumor-promotion process and is located at a specific allosteric site on the x-ray-determined structure of phospholipase A2. This site overlaps for one for lysolecithin (excitatory), for which tumor-promoting phorbol esters such as TPA are agonists and some anti-tumor drugs such as maytansine may be antagonists.


Decreased myocardial and renal content of 3',5'-AMP in genetically hypertensive rats: effects of PGE2 and PGF2 alpha. Levels of c-AMP in heart and kidney of genetically hypertensive rats (SHR) were significantly lower than in normotensive Wistar animals. PGE2, 10 microgram/kg ip markedly increased the concentration of c-AMP in heart and kidney of SHR animals, but was without effect on this cyclic nucleotide content in normotensive controls. PGF2, in doses up to 100 microgram/kg, did not influence the concentrations of c-AMP in heart and kidney of SHR animals. Alterations in adenylate cyclase--c-AMP system in genetic hypertension are discussed.


9, 11-Azo-12-oxa-15-hydroxyprostanoic acid: a potent thromboxane synthetase inhibitor and a PGH2/TxA2 receptor antagonist. 9,11-Azo-13-oxa-15-hydroxyprostanoic acid (AOHP) is shown to be a potent inhibitor of thromboxane synthetase with an IC50 at about 10(-6)M. It also blocked the agonist actions of 9,11-epoxymethano-PGH2 (IC50 9 x 10(-7) M) and TxA2 (IC50 2.4 x 10(-6) M) on human platelet-rich plasma indicating that it also is a PGH2/TxA2 receptor blocker.


PGI2 and PGD2 effects on cyclic AMP and human T-cell mitogenesis. The effects of PGI2, PGD2, and PGF2 alpha on human peripheral blood lymphocytes (HPBL) cyclic AMP levels and their response to a T cell mitogen (PHA) were investigated. It was determined that although PGI2, PGD2, and PGE2 all elevate intracellular levels of cyclic AMP in HPBL, only PGD2 and PGE2 exert potent suppression of PHA-induced lymphocyte proliferation. It is suggested that the instability of PGI2 in aqueous solution is at least partially responsible for its relative inability to maintain elevated levels of cyclic AMP and concomitant suppression of mitogenesis. PGD2 was found to exert an effect very similar to PGE2, both in terms of cyclic AMP elevation and suppression of T cell mitogenesis.


Metabolism of cyclic 3',5'-AMP injected into the rat brain lateral ventricle. (14C)-cAMP was injected into the lateral ventricle of the rat brain and autoradiographic studies and assay of metabolism of this nucleotide were carried out. (14C)-cAMP rapidly penetrates into the cerebrospinal fluid in other brain ventricles and into the subarachnoidol cerebellar space. 14C was also present in the brain tissue adjacent to the lumen of the ventricles. Given intraventricularly (14C)-cAMP is rapidly metabolized and the presence of 14C in the brain tissue is probably the consequence of the incorporation of metabolites of (14C)-cAMP.


[Ochronotic arthropathy. A case report: radiographic and scintigraphic comparative  study (author's transl)]. After description of etiopathogenetic, anatomopathological and clinical aspects of the disease, the authors relate about a case of ochronotic arthropathy, lining on its typical radiological patterns. Scintigraphic study with 99mTc-pertechnetate and with 99mTc-pyrophosphate, excluding any phlogistic component, agree with dysmetabolic and degenerative nature of this arthropathy.


[Seroepidemiological study of Herpes simplex virus type 2 in adult women of Costa Rica]. The frequency of genital Herpes simplex type 2 infections in a group of twenty adult Costa Rican women was studied by isolation of the virus and the measurement of neutralizing antibody activity in sera. The virus could not be isolated in any of the vaginal secretions. Neutralizing antibody activity to herpes virus types 1 and 2 was found in sera from sixteen subjects. An antibody II/I index equal to or larger than 87, indicative of infection with Herpes simplex type 2 was found in fifty per cent of the population studied, a second segment was composed by the subjects with indices below 87. Evaluation of antibody activity to Herpes simplex type 2 revealed that: a) only a small percentage of the women lacked detectable antibody activity to the virus; b) there is a significant difference (p < 0.005) between the mean number of years of sexual experience among the two population segments; and c) there is a positive correlation (p < 0.05) between II/I index values and age among the women of the population segment with a II/I index equal to or larger than 87.


Histochemistry of the post-resuscitation changes in the brain. In 20 dogs, acid mucopolysaccharides, gangliosides, lysosomal enzymes and iontransport enzymes were investigated. Material was taken 2, 24 and 72 h after 15 min of clinical death due to electrotrauma. Changes in the post-resuscitation period indicated deterioration of transmembrane ion--metabolite transport in the brain. These changes had phasic variations that reflect the complexity of post-resuscitation processes.


Effects of ascorbate on leucocytes: Part I. Effects of ascorbate on neutrophil motility and intracellular cyclic nucleotide levels in vitro. A preliminary series of experiments indicated that ascorbic acid and calcium and sodium ascorbate in the absence of serum had no stimulatory effect on neutrophil motility. However, when neutrophils were pre-incubated with ascorbate at concentrations between 5 X 10(-2)M and 1 X 10(-1)M in the presence of fresh normal autologous serum (5% final concentration) considerable stimulation of random motility and migration towards the leuco-attractants C5a and casein was observed. The serum factor required for ascorbate-mediated enhanced locomotion was heat unstable and was probably not serum albumin since no stimulation of cell migration was observed when serum was replaced with varying amounts of human serum albumin. Calcium ascorbate was the most potent stimulant of neutrophil motility. Concentrations of calcium and sodium ascorbate which increased migration promoted elevation of intracellular cyclic guanosine monophosphate (cGMP) levels, but not of adenosine monophosphate (cAMP). These same concentrations also caused increased glyclytic activity. It is suggested that the enhanced neutrophil motility mediated by ascorbic acid and calcium and sodium ascorbate in the presence of serum may be due to increased cGMP and/or glycolysis.


Community participation in cardiac rehabilitation. Cardiac patients are not solely responsible for their own rehabilitation. The rehabilitative process is a prolonged one, and success lies in multidisciplinary management involving the patient, the immediate family and the community. The Health Act (Act No. 63 of 1977) has various implications for the future provision of rehabilitative services in South Africa. Each member of the health team and the community has a specific role to play, either within or outside the hospital setting, thus providing ongoing rehabilitative supervision of cardiac patients.


The heart in diabetes mellitus. Part I. Biochemical basis for myocardial dysfunction. The heart in acutely diabetic animals is subject to multiple inhibitions of glucose metabolism caused by enhanced metabolism of free fatty acids (FFA) and ketone bodies. Such metabolic changes may impair the reaction of the diabetic heart to oxygen lack. In chronically diabetic hearts the increased deposition of triglycerides in the heart and the formation of glycoproteins may underlie the newly recognized clinical entity of diabetic cardiomyopathy.


[A case of peripheral neuropathy in an acromegalic subject. Pathogenetic considerations]. A case of acromegaly with peripheral neuropathy characterized by acroparaesthesiae in the median nerve field of both sides is presented. Electrophysiological examination shows bilateral slowing of the motor conduction velocity of the median nerve through the carpal tunnel. The possible pathogenetic mechanisms of the peripheral neuropathy in acromegalic are discussed in the light of the most recent theories about the GH action. Suggestions are made that some associated hormonal disorders diabetes, hyperaldosteronism, hyperthyroidism) can play some part in the neuropathy pathogenesis.