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Biomedical subjects

R Linder

Publications and source records attributed to R Linder.

At least 73 records · Page 4Linked to original sources

[Cold struma nodule--enucleation or resection].

During 1969-1984 2,408 patients underwent thyroid surgery at the Dept. of General Surgery, Giessen University. In 72.5% cold nodules have been diagnosed. However, a cold nodule has been in less than 50% of all cases with cold nodules the causal indication for operation. Inspecting closely the whole thyroid gland, the operating surgeon removes the nodule with a segmental resection if there are no further regressions or suspicion of malignancy. This technique facilitates the histological detection of a possible highly differentiated carcinoma because of its invasion into the capsule.

Diagnosis, Differential↗

Isoelectric analysis of some Australian elapid snake venoms with special reference to phospholipase B and hemolysis.

Venoms of the Australian elapid snakes Austrelaps superbus and Pseudechis colletti were analyzed in an electrofocusing column. A. superbus venom, little studied in the past, was found to have a mouse i.p. lethal potency of 0.48 mg/kg and to contain at least four lethal components. Venoms of both species had relatively high direct hemolytic activity for washed rabbit erythrocytes, as contrasted with venoms from 23 other species of snakes that were not hemolytic under the conditions used. Among venoms of the same 25 species, those of A. superbus and P. colletti produced turbidity in diluted egg yolk, those of Bungarus caeruleus and Bungarus multicinctus were quantitatively less active on egg yolk, whereas venoms of the 21 remaining species were negative. The component of the venoms responsible for egg yolk reactivity was partially purified and the preparations obtained were strongly active when tested with diluted egg yolk or with erythrocytes. Thin layer and paper chromatographic studies showed that these preparations possessed phospholipase B activity for phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine and phosphatidylserine, but sphingomyelin was not degraded. The results suggest that hydrolysis of phosphatidylcholine is responsible for both egg yolk reactivity and hemolysis.

Animals↗

Action of bacterial cytotoxins on normal mammalian cells and cells with altered membrane lipid composition.

Cytotoxic proteins produced by a number of bacteria, as well as one from a marine invertebrate, were tested for their ability to disrupt the permeability barrier of mammalian cells. Agents were tested individually and in combination shown to have synergistic disruptive actions on erythrocytes. Toxins included the lipid-hydrolyzing enzymes sphingomyelinases C and D and cholesterol oxidase, as well as the non-enzymatic agents, helianthus toxin, streptolysin O and saponin. Cells treated included cultured human skin fibroblasts, normal human erythrocytes and erythrocytes enhanced and depleted in membrane cholesterol. Fibroblasts were disrupted by helianthus toxin and by the combination of sphingomyelinase C and cholesterol oxidase. Thin layer chromatographic analysis of the treated cells confirmed the enzymatic alteration of membrane lipids by the lipid hydroxylases. Human erythrocytes having an increased content of membrane cholesterol were more sensitive than normal cells to agents which interact with membrane sterol. Conversely, cholesterol-depleted cells were more resistant to these as well as other agents. Results are discussed in relation to biochemical mechanisms of action of the agents tested, and to their possible significance in bacterial pathogenesis.

Bacterial Toxins↗

[Abnormalities of the upper gastrointestinal tract diagnosed prenatally by ultrasound].

A hydramnion occurring during the second half of pregnancy may be due to atresias in the upper intestinal tract. Generally, one case of oesophageal atresia is likely to occur in every 2,500 births, often together with other malformations. Prenatal diagnosis of such atresias substantially improves prognosis for these children via optimal cooperation between the obstetrician and the paediatric surgeon. Characteristic features of oesophageal atresia in the sonographic image are, besides the hydramnion, the absence of visualisation of the stomach. Sonographic diagnosis of duodenal atresias is based on visualisation of the stomach, which is excessively filled with fluid, and of the portion of the small intestine located cranially of the stenosis. The patients treated by the author and presented here were successfully operated on via termination of birth and immediate surgery by the paediatric surgeon.

Adult↗

[Treatment of a prenatally diagnosed chylothorax].

A case of bilateral fetal chylothorax was diagnosed by ultra-second at 34 weeks gestation. The pregnancy had shown marked hydramnios. The ultrasound examination showed massive pleural effusions with marked compression of the both lungs a low diaphragm and a normal sized heart. After administration of Dexamethasone for pulmonary maturation a primary Caesarean section was done at 37 weeks pregnancy, the newborn was immediately intubated and the pleural effusions suctioned by bilateral pleural drainage. The lungs expanded satisfactorily, the drainage was removed 2 weeks later and the infant developed normally.

Cesarean Section↗

Species susceptibility to delayed toxic neuropathy in relation to in vivo inhibition of neurotoxic esterase by neurotoxic organophosphorus esters.

Tri-o-cresyl phosphate (TOCP) and O-ethyl O-(4-cyanophenyl) phenylphosphonothioate (cyanofenphos, Surecide) were found to be delayed neurotoxicants. They were administered to chickens by gavage at 100 and 30 mg/kg . d for 15 d, respectively. In CD-1 mice neither TOCP nor cyanophenphos induced any of the usually recognized clinical symptoms of neuropathy when administered daily by gavage at 262 or 31.25 mg/kg . d for 30 d, respectively. In the chickens, TOCP and cyanofenphos produced about 98 and 90% in vivo inhibition of brain neurotoxic esterase (NTE) activity. In the mice, 24 h after the last daily dose, TOCP and cyanofenphos produced only about 50 and 40% in vivo inhibition of the brain NTE activity. Parathion [O,O-diethyl O-(4-nitrophenyl) phosphorothioate], at 2 or 6.75 mg/kg . d for 15 or 30 d, did not induce neuropathy in either chicken or mice and produced no significant in vivo inhibition of brain NTE activity at the end of the dosing regimen. The specific activity of NTE in control chicken brain crude homogenate was much higher than that in mouse brain homogenate. These results suggest that the differences between chickens and mice in susceptibility to neurotoxic organophosphates may be attributed to (1) inhibitor specificity of NTE forms in the brain in these two different animal species and/or (2) inability of the active metabolites of these neurotoxic compounds to reach the site of action.

Animals↗

Histopathologic lens changes in mirex-exposed rats.

The early histologic lesions and sequential changes in the development of mirex-induced cataracts were studied in the offspring of lactating female Sherman rats given oral doses of mirex for 5 consecutive days post partum. The earliest histologic change, seen at neonatal day 7, was slight swelling of the individual cortical lens fibers. At day 9, many swollen but intact fibers were observed, and at days 11 and 13, extensive degeneration and necrosis appeared throughout the cortex of the affected lenses.

Animals↗

Phospholipase D activity of Corynebacterium pseudotuberculosis (Corynebacterium ovis) and Corynebacterium ulcerans, a distinctive marker within the genus Corynebacterium.

A search has been made for corynebacterial phospholipase D, "ovis toxin," a sphingomyelinase (phosphatidylcholine phosphohydrolase, EC 3.1.4.4), among a wide variety of corynebacteria. Phospholipase D activity has been found in strains exhibiting the biochemical properties characteristic of Corynebacterium pseudotuberculosis or of Corynebacterium ulcerans and in no other species of Corynebacterium. Methods for the assay of phospholipase D as a sphingomyelinase and methods for screening for phospholipase D in the presence of Corynebacterium equi on washed sheep blood agar are discussed.

Corynebacterium↗

[Neutralizing capacity, pepsin inactivation and binding to bile acids and lysolecithin of the antacid magaldrate (author's transl)].

The neutralizing capacity of pentaaluminum-decamagnesiumhentriacontahydroxide-bis(sulfate)-hydrate (magaldrate, Riopan), a stable Al-Mg-hydroxide mono-substance, determined by a modification of the method described in literature, surpasses the efficacy index (mval divided by g) of various commercial antacids. These results coincide with the findings of other workers. The intragastric pH is rapidly and consistently raised to a value between 3 and 5 which is not exceeded (no acid rebound). Due to this fact, pepsin is inactivated and finally adsorbed by magaldrate. Moreover, magaldrate binds a considerable amount of substances contained in duodeno-gastric reflux, such as bile acids and lysolecithin (aggressors in case of gastritis, peptic ulcer, stress ulcer, peptic esophagitis).

Aluminum Hydroxide↗

Stepwise degradation of membrane sphingomyelin by corynebacterial phospholipases.

The mechanism of in vitro synergistic lysis of sheep erythrocytes by Corynebacterium ovis and Corynebacterium equi was investigated. Hemolysis required (i) the action of phospholipase D from C. ovis, (ii) the action of an extracellular protein of C. equi, and (iii) Mg2+. Maximum lysis required imposition on the system of a fourth condition (step iv), such as chilling. Steps i, ii, and iv occur sequentially and in that order. Mg2+ functions in steps i and ii. The extracellular protein C. equi was purified to homogeneity and found to be a phospholipase C capable of hydrolyzing ceramide phosphate, phosphatidic acid, and all of the isolated major phospholipids of mammalian erythrocyte membranes. The principal features of the synergistic hemolytic system could be reproduced in experiments involving liposomes containing either sphingomyelin or ceramide phosphate and trapped [14C]glucose. We inferred that sphingomyelin of sheep erythrocytes is first converted to ceramide phosphate by C. ovis phospholipase D. On the basis of results with liposomes, we propose that the ceramide phosphate is then converted to ceramide by C. equi phospholipase C. We believe that the resulting in situ ceramide then undergoes dislocation by chilling and perhaps also by virtue of an affinity between ceramide and C. equi phospholipase C. The dislocation of ceramide presumably disorganizes the lipid bilayer sufficiently to result in cell lysis.

Animals↗

Acute and subchronic toxicity of pentachlorobenzene.

Oral LD50 values for pentachlorobenzene (QCB) in rats were 1125, 1080, and 940 mg/kg for adult males, adult females, and weanling females, respectively. The oral LD50 values in mice were 1175 mg/kg for males and 1370 mg/kg for females. Clinical signs of toxicity included tremors and narcosis. Dermal application of 2500 mg/kg did not produce clinical signs in rats. In subchronic studies weanling male rats were fed 0, 125, or 1000 ppm QCB for 100 days and weanling females fed 0, 125, 250, 500, or 1000 ppm for 180 days. No clinical signs of toxicity or effects on growth were observed in these rats throughout the exposures. QCB accumulated in adipose tissues at approximately 1.5-2.2 times the dietary concentrations. Porphyrin measurements were made only in females. Terminal values for urinary uro-and coproporphyrin and accumulation of liver porphyrins were not remarkably different in control and QCB-treated groups. In groups fed 1000 ppm, the WBC was increased and red blood cell indices were generally decreased compared to controls. The rats were pair-bred with untreated partners after 67 days of treatment. Fertility and fecundity were unaffected in either sex; however, suckling pups of QCB-treated mothers fed 250 ppm or more developed tremors and at 1000 ppm most died before weaning. Adrenal weights in males and kidney weights in both sexes were increased in adults fed 1000 ppm. In groups fed 250 ppm or more liver/body weight ratios were increased in both adults and in weanling offspring of QCB-treated dams. Hepatocellular enlargement was particularly evident in the 500 and 1000 ppm groups. In the kidneys of adult males, more numerous and larger foci of tubular atrophy and lymphocytic infiltration were seen at 1000 ppm than were seen in controls and dose-related increases in hyaline droplet formation occurred at 125 and 1000 ppm.

Adipose Tissue↗

Nature and mechanism of action of the CAMP protein of group B streptococci.

The extracellular product of group B streptococci responsible for the CAMP reaction was purified to near homogeneity. It is a relatively thermostable protein having a molecular weight of 23,500 and an isoelectric pH of 8.3. It was found that the CAMP reaction could be simulated by substituting [14C]glucose-containing liposomes prepared from sphingomyelin, cholesterol, and dicetyl phosphate for sheep erythrocytes. In the belief that the liposome system is a valid model, the mechanism of the CAMP reaction was further investigated by using liposomes in which N-acylsphingosine (ceramide) was substituted for sphingomyelin. In this system disruption of liposomes, as measured by release of trapped [14C]glucose, was effected by CAMP protein alone. As judged from thin-layer chromatography, CAMP protein caused no reduction in the amount of ceramide present in ceramide-containing liposomes, nor were split products demonstrable. However, binding of CAMP protein to ceramide-containing liposomes could be shown. It is inferred that in sheep erythrocytes CAMP protein reacts nonenzymatically with membrane ceramide formed by the prior action of staphylococcal sphingomyelinase and that binding of CAMP protein to ceramide disorganizes the lipid bilayer to an extent that results in cell lysis.

Amino Acids↗

Effect on sphingomyelin-containing liposomes of phospholipase D from Corynebacterium ovis and the cytolysin from Stoichactis helianthus.

The toxic, sphingomyelin-specific phospholipase D (phosphatidylcholine phosphatidohydrolase EC 3.1.4.4) from Corynebacterium ovis was purified to near homogeneity. It has a molecular weight of 31 000 and a pI of approx. 9.8. Although not cytolytic itself, it protected red cells from hemolysis by staphylococcal sphingomyelinase (beta-hemolysin) and helianthus toxin. The apparently non-enzymatic cytolysin (helianthus toxin) from the sea anemone Stoichactis helianthus also interacts with membrane sphingomyelin. C. ovis and helianthus toxins were compared with regard to their effects on liposome model membranes, and they were found both to produce changes analogous to those in erythrocytes. Only helianthus toxin caused release of trapped glucose marker, but liposomes could be protected from release by pretreatment with C. ovis toxin. Both toxins demonstrated binding to sphingomyelin-containing liposomes, but only the bacterial sphingomyelinase catalyzed the release of choline from these vesicles.

Corynebacterium↗

Solubilization and characterization of the partially purified penicillin sensitive D-alanine carboxypeptidase of Neisseria gonorrhoeae.

Treatment of crude gonococcal cell envelopes with a solution of 2 M KCl + 1% Brij 36T resulted in the solubilization of a portion of the D-alanine carboxypeptidase activity of Neisseria gonorrhoeae envelopes. This soluble enzyme preparation was partially resolved by chromatography on a column of DEAE-cellulose. The partially purified enzyme eluted from the column with a gradient of NaCl (0-1 M), catalysed the release of D-alanine from a radioactively labelled UDP-N-acetylmuramyl-pentapeptide with a pH optimum of 8.6. The Km for the soluble enzyme acting on this substrate was 0.18 mM. The enzyme activity was sensitive to inhibition by low concentrations of the beta-lactam antibiotics, penicillin G, ampicillin, oxacillin and mecillinam.

Carboxypeptidases↗

Interaction between sphingomyelin and a cytolysin from the sea anemone Stoichactis helianthus.

The cytolytic toxin from the sea anemone Stoichactis helianthus was inhibited up to 90--95% by suspensions of sphingomyelin but not by phosphatidylcholine or other membrane lipids. When the toxin was incubated with sphingomyelin and the mixture fractionated either by isoelectric focusing or Sephadex gel filtration, the residual hemolytic units migrated together with the lipid and not as free toxin. Incubation with phosphatidylcholine, however, did not shift the toxin peak in either type of column. A toxin-ferritin conjugate retaining hemolytic activity was observed by negative staining to bind to liposomes prepared with sphingomyelin but not with liposomes containing phosphatidylcholine. The results provide evidence that the membrane binding site of the toxin is sphingomyelin.

Animals↗