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Biomedical subjects

E Weber

Publications and source records attributed to E Weber.

At least 325 records · Page 18Linked to original sources

Distribution of immunoreactive metorphamide (adrenorphin) in discrete regions of the rat brain: comparison with Met-enkephalin-Arg6-Gly7-Leu8.

The distribution of immunoreactive (ir)-metorphamide (adrenorphin) in 101 microdissected rat brain and spinal cord regions was determined using a highly specific radioimmunoassay. The highest concentration of metorphamide in brain was found in globus pallidus (280.1 fmol/mg protein). High concentrations of ir-metorphamide (greater than 120 fmol/mg protein) were found in 9 nuclei, including central amygdaloid nucleus, lateral preoptic area, anterior hypothalamic nucleus, hypothalamic paraventricular nucleus, interpeduncular nucleus, periaqueductal grey matter and nucleus of the solitary tract. Moderate concentrations of the peptide (between 60 and 120 fmol/mg protein) were found in 47 brain nuclei such as nucleus accumbens, bed nucleus of stria terminalis, several septal and amygdaloid nuclei, most of the hypothalamic nuclei, ventral tegmental area, red nucleus, raphe nuclei, lateral reticular nucleus, area postrema and others. Low concentrations or ir-metorphamide (less than 60 fmol/mg protein) were measured in 41 nuclei, e.g., cortical structures, hippocampus, caudate nucleus, thalamic nuclei, supraoptic nucleus, substantia nigra, vestibular nuclei, cerebellum (nuclei and cortex). The olfactory bulb has the lowest metorphamide concentration (5.8 fmol/mg protein). Spinal cord segments exhibit very low peptide concentrations.

Animals↗

Prodynorphin opioid peptides in small somatosensory primary afferents of guinea pig.

By the use of light microscopic immunohistochemistry it was shown that a significant population of small primary sensory afferents of guinea pig contains immunoreactivities to antisera directed against prodynorphin-opioid peptides, whereas immunoreactivities to antisera directed against opioid peptides exclusively contained in proenkephalin were absent. Immunoreactivities to antisera against different prodynorphin-opioid peptides were seen in small ganglionic cells and in small diameter fibers of spinal and trigeminal ganglia, of dorsal roots, of somatic peripheral nerve trunks and in cutaneous sensory nerves. There was evidence for colocalization of different prodynorphin-opioid peptides. High-performance liquid chromatography and the mouse vas deferens assay revealed opioid-active material (22.7 pmol Met-enkephalin equivalents per gram wet weight) in extracts of somatic peripheral nerves. The results indicate for the first time that opioid peptides derived from prodynorphin are peripheral and central neurotransmitter candidates of small primary somatosensory afferents.

Animals↗

Methionine and leucine enkephalin in rat neurohypophysis: different responses to osmotic stimuli and T2 toxin.

Specific radioimmunoassays were used to measure the effects of hypertonic saline (salt loading), water deprivation, and trichothecene mycotoxin (T2 toxin) on the content of methionine enkephalin (ME), leucine enkephalin (LE), alpha-neoendorphin, dynorphin A, dynorphin B, vasopressin, and oxytocin in the rat posterior pituitary. Concentrations of vasopressin and oxytocin decreased in response to both osmotic stimuli and treatment with T2 toxin, but the decrease was greater with osmotic stimulations. Similarly, concentrations of LE and dynorphin-related peptides declined after salt loading and water deprivation; LE concentrations also decreased after treatment with T2 toxin. The concentration of ME decreased after water deprivation, did not change after salt loading, and increased after T2 toxin treatment. The differentiating effects of these stimuli on the content of immunoreactive LE and ME are consistent with the hypothesis that LE and ME may be localized in separate populations of nerve endings with different roles in the posterior pituitary.

Animals↗

The effects of a combination of cigarette smoking and oral contraception on coagulation and fibrinolysis in human females.

Oral contraception as well as cigarette smoking influence haemostasis. The simultaneous effect of both on blood coagulation and fibrinolysis was studied in nine female smokers. While continuing oral contraception after a 4-week abstinence from smoking the concentration of fibrinogen, antithrombin III and alpha 1-Antitrypsin decreased (P less than 0.01 or P less than 0.04) and of plasminogen increased (P less than 0.03). The other coagulation parameters remained unchanged. Although all determinations of these parameters were in the normal range, the observed trends were statistically significant. The concentrations of the fibrinopeptide A and B 15-42 did not differ. It is concluded that the observed alteration is caused by cessation from cigarette smoking.

Adult↗

Pharmacokinetics of sulphinpyrazone and its major metabolites after a single dose and during chronic treatment.

The pharmacokinetics of sulphinpyrazone and its major metabolites (sulfide, sulfone, p-hydroxysulfone and p-hydroxy-sulphinpyrazone) were investigated in 9 volunteers after a single oral dose as well as after chronic treatment for 23 days. Chronic administration of sulphinpyrazone, in comparison with a single oral dose, led to significant changes in plasma AUC (115.86 to 42.90 mg/l . h), in renal clearance (1.06 to 1.80 l/h), in hepatic intrinsic clearance (319.0 to 598.0 l/h), and in the unbound fraction in plasma 1.15 to 1.69%) and in tissue (2.73 to 1.31%). The volume of distribution changed from 20.24 to 52.04 l. The steady state concentrations predicted from the single dose were significantly higher than the values found after chronic treatment. The results suggest that sulphinpyrazone induces its own metabolism. The metabolism of the sulfone, p-hydroxysulfone and the p-hydroxy-sulphinpyrazone to further degradation products was also induced. Chronic treatment with sulphinpyrazone reduced the plasma AUC of the sulfide and caused a decrease in its elimination half-life (20.9 to 14.3 h). Since considerable amounts of the sulfide are formed in the G.I. tract, it is suggested that besides the induction of metabolism, bacteria which reduce sulphinpyrazone to the sulfide may also be responsible for the observed pharmacokinetic changes.

Adult↗

The analgesic and respiratory depressant actions of metorphamide in mice and rabbits.

Metorphamide (MET) elicited a potent, dose-dependent analgesia and respiratory depression in mice and rabbits. MET induced-analgesia was naloxone reversible and potentiated by bestatin. Naloxonazine, a relatively selective mu 1 blocker, at certain dosage (50 micrograms per rabbit, icv), could abolish the analgesia but not the respiratory inhibition produced by MET. Our result indicates that mu 1 receptors mediate the MET induced-analgesia but not its respiratory effect. Since MET is a mu- and kappa-ligand with very low delta activity, the MET induced respiratory depression may be mediated by mu 2 or kappa binding sites.

Analgesics↗

[Problems and limits of mammographic cancer diagnosis. Comparison of preoperative radiologic diagnosis with histologic findings in 335 patients with subcutaneous mastectomy].

Subcutaneous mastectomy was performed in 335 patients between 1974 and 1982. In 265 of these, original mammographies were available which were analysed retrospectively and compared with the final histological finding of the subcutaneous mastectomy preparation. The rate of newly discovered non-invasive carcinomas in this was 11%, whereas the rate of invasive carcinomas was 8%. Radiological criteria: high degree of dysplasia, difficult assessment and mastopathy associated with large cysts, are associated with a significantly increased number of malignant histological findings. The radiological criteria of mastopathy, such as adenosis, fibrosis, indurating oedema of stroma, small-cyst mastopathy, as well as parenchymal patterns according to Wolfe, are not important with regard to our group of patients in respect of further selection of risk patients. Criteria of malignancy which are typical of carcinoma, are on the whole rarely recognised, because their assessment is often difficult. In patients with preceding carcinoma of the other breast, indication for subcutaneous mastectomy in case of "unclear" mammography has proved justified: In 4 out of 18 cases, a non-invasive or invasive carcinoma was found. Indication for primary subcutaneous mastectomy was too liberal in case mammography had been assessed as "benign", for the carcinoma rate was only 1/73. In radiologically "unclear" findings, the number of subsequently discovered non-invasive and invasive carcinomas was distinctly higher (in each case 6 out of 58). In such cases an attempt should be made to confirm preoperative diagnosis by means of additive measures before performing subcutaneous mastectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Duodenal gamma-glutamyltransferase activity in human biopsies: effect of chronic ethanol consumption and duodenal morphology.

Gamma-glutamyltransferase activity was determined in duodenal biopsies, and in the sera of forty-six non-alcoholic and eighteen alcoholic patients with a daily alcohol consumption of more than 80 g. Additionally, duodenal morphology was examined in biopsy material obtained at the same time. In both alcoholics (P less than 0.05) and in non-alcoholics (P less than 0.001) the duodenal gamma-glutamyltransferase activity revealed a significant positive correlation with duodenal villus length. In addition, alcoholics exhibited a significant decrease in duodenal villus length (338 +/- 13 vs. 363 +/- 13 microns, P less than 0.01), and a significant increase in duodenal gamma-glutamyltransferase activity (13.0 +/- 1.4 vs. 8.4 +/- 0.6 mU mg-1 protein, P less than 0.01) when compared to controls. No significant correlation was found between duodenal and serum gamma-glutamyltransferase activity in alcoholics and non-alcoholics. During follow up of two patients, duodenal gamma-glutamyltransferase activity decreased and duodenal villus length increased after withdrawing alcohol. These data underline the damaging effect of alcohol on the duodenal mucosa and demonstrate that chronic alcohol intake reversibly effects duodenal gamma-glutamyltransferase. In addition, the small intestine appears of minor importance as an origin for the elevated serum gamma-glutamyltransferase activities seen in the alcoholic.

Adult↗

Isolation and characterization of an endogenous C-terminal fragment of the alpha-neo-endorphin/dynorphin precursor from bovine caudate nucleus.

Antibodies have been raised to a synthetic peptide corresponding to the C-terminal 15-amino acid residues of prodynorphin, the common precursor to the neo-endorphins and dynorphins. The amino acid sequence of the antigen was based on the sequence deduced from mRNA isolated and cloned from porcine hypothalamus (Kakidani, H., Y. Furutani, H. Takahashi, M. Noda, Y. Morimoto, T. Hirose, M. Asai, S. Inayama, S. Nakanishi, and S. Numa (1982) Nature 298: 245-248). Using a radioimmunoassay developed from these antibodies we have isolated an endogenous prodynorphin C-fragment from bovine caudate nucleus. The isolated peptide displayed characteristics on gel filtration similar to those of synthetic prodynorphin C-fragment predicted from the porcine mRNA sequence but had low cross-reactivity in the radioimmunoassay. Sequencing and amino acid analysis showed a substitution of serine for asparagine at position 6 in the porcine sequence. Dynorphin B (rimorphin), which is adjacent to prodynorphin C-fragment in the precursor, was isolated from the same extract. Amino acid analysis and elution position on a gel filtration column confirmed its structure as that previously characterized from bovine pituitary extracts. The release of prodynorphin C-fragment and the C-terminus of dynorphin B from the porcine precursor would require cleavage at a single arginine residue. However, a terminal arginine was not present on either of these prodynorphin peptides isolated from bovine caudate. The data would suggest that processing at a single arginine residue results in elimination of the arginine, a feature in common with processing at paired basic residues.

Animals↗

[Local recurrence following anterior rectum resection--manual versus stapler suture].

A retrospective study was carried out on 88 hand sewn and 34 stapled anastomoses following anterior resection to evaluate the impact of suture technique on local recurrence rate. The patient groups were comparable with one exception: there were significantly more Dukes C lesions resected and sutured using the stapling gun (35% versus 15%, X2 = 6.33, p less than 0.05). Stage-corrected recurrence rate was similar in both groups, Dukes A: 8%, Dukes B 21%, Dukes C 52%, all recurrences being detected within 24 months following operation. Significantly fewer protective colostomies were needed using the staple gun (15% versus 34%, X2 = 4.50, p less than 0.05). Otherwise, no significant difference or benefit was observed comparing the two suture techniques.

Colonic Neoplasms↗

Morphological aspects in phase-contrast and transmission electron microscopy of senescent cultures of bovine aortic endothelial cells.

Some cultures of bovine aortic endothelial cells underwent an early senescence process, which may have been favoured by a special differential attachment trypsinization procedure. In order to better characterize this phenomenon, the cultures were observed at phase-contrast and electron microscopy at various passages. In phase-contrast microscopy, senescent cells were always larger than "younger" cells, and giant cells were very frequent. A great heterogeneity both of shape and size was present and the cells appeared shrunken, rigid and unable to cover the whole surface of the flask. In many senescent cells long fibres, running from one to the other side of the cytoplasm and often bridging over the nucleus were found. At transmission electron microscopy, together with a great abundance of rough endoplasmic reticulum, mitochondria and lysosomes, and the occasional presence of Weibel-Palade bodies, peripheric bundles of filaments, probably referable to actin or acto-myosin were found. These fibres may be interpreted as "stress fibres" and, as they are expression of a tension not accompanied by an effective cell motility, it seems of interest that they appear in senescent cells, which are often unable to cover the whole surface of flasks by migrating and subsequently proliferating in empty areas.

Animals↗

[Treatment in a heparin-induced skin reaction with a low-molecular heparin analog].

Deep vein thrombosis in the leg and pelvis was seen in a 26-year old woman during the seventh month of pregnancy. 20 days after initial administration of heparin sodium, a local, markedly progressing erythema and induration was observed at the subcutaneous injection sites. The same cutaneous reactions occurred after application of heparin calcium. Following oral anticoagulation treatment with phenprocoumon, the patient was treated towards the end of pregnancy and directly post partum with a low-molecular semisynthetic heparin analogue without any side effects. The skin test again showed good tolerance of another heparin analogue and a low-molecular heparin.

Adult↗

Regional distribution of metorphamide in rat and guinea pig brain.

A specific radioimmunoassay was developed for metorphamide, an endogenous, amidated opioid octapeptide, originally isolated from bovine brain and human pheochromocytoma tissues. The radioimmunoassay was used to determine the concentration of immunoreactive metorphamide in extracts from dissected regions of rat and guinea pig brain. Radioimmunoassay interfacing with Sephadex gel filtration and reverse phase high performance liquid chromatography confirmed that the immunoreactive substance measured corresponded to authentic metorphamide. Metorphamide was found to be widely distributed in brain regions from both species. However, the concentrations of immunoreactive metorphamide in regions from guinea pig brain were up to 5 times higher than the concentrations of immunoreactive metorphamide in rat brain regions. The results suggest that metorphamide is a specific processing product from proenkephalin in rodent brain.

Animals↗

The effect of methyl-2-tetradecylglycidate (McNeil 3716) on heart mitochondrial metabolism in rats.

Methyl-2- tetradecylglycidate (MTG), one of a new class of hypoglycemic agents, given to healthy rats, prompted uncoupling of oxidative phosphorylation in heart mitochondria (measured ex vivo) without a concomitant effect on mitochondrial electron transfer reactions. At the same time heart creatinephosphate -kinase was inhibited and subsequently the semipermeability of the inner mitochondrial membrane was impaired as demonstrated by an influx of creatine. The triglyceride and total phospholipid content of heart tissue and its mitochondria showed a transient elevation. The hearts were enlarged, flabby and discoloured and had dilated ventricles. These effects could be the account of an adverse effect of MTG on the heart energy metabolism.

Animals↗

[Effect of low-molecular heparin on blood coagulation].

The coagulation-inhibiting effect of subcutaneously administered commercial and a low-molecular heparin was compared in healthy volunteers. Global clotting activity, measured as activated partial thromboplastin time as well as thrombin activity were inhibited almost equally by commercial and low-molecular heparin. Low-molecular heparin caused a ten-fold stronger inhibition of factor Xa. The effect on factor Xa increased nearly logarithmically with the injected dose. Half-life of heparin measured in terms of the inhibition of factor Xa was 5.5 hours for the low-molecular and 3.5 hours for the commercial preparation. These results indicate that low-molecular heparin has a high specificity in the inhibition of factor Xa. A lower dose of low-molecular heparin, administered once daily, may have an anti-thrombotic effect while reducing the risk of bleeding.

Adult↗

Distribution of immunoreactive dynorphin B in discrete areas of the rat brain and spinal cord.

The distribution of immunoreactive (ir)-dynorphin B in 101 microdissected rat brain and spinal cord regions was determined using a specific radioimmunoassay. The highest concentration of dynorphin B in brain was found in the substantia nigra (1106.2 fmol/mg protein). Very high concentrations of ir-dynorphin B (greater than 400 fmol/mg protein) were also found in the lateral preoptic area, parabrachial nuclei and globus pallidus. Relatively high concentrations of ir-dynorphin B (250-400 fmol/mg protein) were found in 19 nuclei, including the periaqueductal gray matter, anterior hypothalamic nucleus, median eminence, nucleus accumbens and hippocampus. Moderate levels of the peptide (between 100 and 250 fmol/mg protein) were found in 42 brain nuclei such as the perifornical nucleus, nucleus of the diagonal band, medial forebrain bundle, and dorsal premamillary nucleus. Low concentrations of ir-dynorphin B (less than 100 fmol/mg protein) were found in 28 brain areas, e.g. cerebral cortical structures (parietal, cingulate, frontal), claustrum, olfactory bulb, lateral and periventricular thalamic nuclei. The cerebellar cortex has the lowest dynorphin B concentration (53.7 fmol/mg protein). Spinal cord segments exhibit low or moderate (cervical segment) levels of the peptide. The neurointermediate lobe of the pituitary gland is extremely rich in ir-dynorphin B (11,047.1 fmol/mg protein).

Animals↗

A method for testing the specificity of influenza A virus-reactive memory cytotoxic T lymphocyte (CTL) clones in limiting dilution cultures.

This paper describes a system for determining the frequency and fine specificity of influenza A virus-immune memory cytotoxic T cell (CTL) clones from limiting dilution (LD) microcultures. We found that such experiments can only be performed (1) by analyzing the clonal response of CTL from wells of replica plates containing fractions of one original plate, (2) when it has been ascertained that splitting is possible at the clonal level, and that each fraction of a microculture well gives an identical response on target cells infected with the stimulating virus. With these requirements fulfilled we found that short term CTL clones from LD microcultures from influenza A virus (A/X-31)-immune mice (C57BL/6) occur at a frequency of f = 1:546 to f = 1:6303. The effector cells carry the Lyt-2.2 marker and are specific for target cells infected with the immunizing virus (influenza virus A/X-31). They do not lyse NDV (Newcastle disease virus) or HSV (herpes simplex virus)-infected or NK (YAC) target cells.

Animals↗