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Biomedical subjects

A Reuter

Publications and source records attributed to A Reuter.

At least 37 records · Page 2Linked to original sources

Age dependent different influence of carbon tetrachloride on biotransformation of xenobiotics, glutathione content, lipid peroxidation and histopathology of rat liver.

15- and 60-day-old male rats were treated with different doses of CCl4 orally. 24 h later cytochrome P-450 (P450) concentration, 7-ethoxyresorufin O-deethylation (EROD) and 7-pentoxy-resorufin O-deethylation (PEROD) activities were determined. Whereas P450 and EROD are lowered to the same extent in both ages, PEROD shows a more pronounced inhibition in the livers of younger rats. The formation of endogenous lipid peroxides (measured as thiobarbituric acid reactive substances) is drastically increased only in the livers of young rats. The hepatic glutathione (GSH) content was unaffected by CCl4 treatment whereas oxidized glutathione is more increased in the livers of adult rats. This can be caused by a higher activity of GSH-peroxidase in the livers of adult rats. The changes in NADPH-induced lipid peroxidation and chemiluminescence correlate partially with the changes in P450 and biotransformation reactions. Histopathologically the liver damage is more extensive in suckling rats. The necrosis is localized predominantly in the perivenous tissue, which has normally the highest activities of toxification and detoxification enzymes.

Age Factors↗

The human homolog of the glomerulosclerosis gene Mpv17: structure and genomic organization.

Mice carrying a retroviral insert in both alleles of the Mpv17 gene develop glomerulosclerosis and nephrotic syndrome at young age. Thus, the Mpv17 gene is a recessive disease gene in mice and this mouse strain is a potential animal model for glomerular diseases in man. We here describe the isolation and analysis of a human homolog of this gene. By interspecies hybridisation cDNA clones representing a single RNA species were isolated from human liver. Sequence analysis revealed over 90% identify in a region coding for a protein of 176 amino acids and unknown function in both species. Cloning of the genomic locus revealed a single copy gene which we mapped to the short arm of chromosome 2 at band 2p23-p21. Determination of the intron-exon structure and the junction sequences enabled us to establish a PCR based procedure to isolate the coding region from human genomic DNA. Thus, it is now possible to analyse patients suffering from candidate diseases on the basis of a blood sample if biopsy material is not available.

Animals↗

The influence of systemic hypoxia and reoxygenation on the glutathione redox system of brain, liver, lung and plasma in newborn rats.

The concentrations of reduced (GSH) and oxidized glutathione (glutathione disulfide, GSSG) in lung, liver, brain and plasma of newborn rats were investigated under the condition of reversible hypoxia. Brain and lung of newborn rats seem to be susceptible to reversible hypoxia. We found an increase in GSSG concentration after hypoxia in these organs. This alteration of the GSH-GSSG redox system was reversible within 2 hours of reoxygenation. A second increase in cerebral GSSG concentration after 4 hours of reoxygenation was connected with fasting during the experiment. In the liver we found a hypoxia dependent decrease in the GSH level, followed by a decrease in GSSG concentration. The increased GSSG concentrations in lung and brain are accompanied by an enhancement of plasma GSSG concentration.

Animals↗

[Hutchinson-Gilford syndrome].

A case report on a 6-year-old boy suffering from the extremely rare Hutchinson-Gilford syndrome (progeria) is presented. The results of histopathological and immunohistological examination of the scar-like skin lesions are reported. Subcutaneous amorphous nodules were eosinophilic, PAS- und elastica-negative und remained unstained with antibodies against collagen type IV, vimentin, and collagenase. The dense perivascular infiltration consisted of CD4+, CD8-, alpha-1-antichymotrypsin-, MAC 387-, and some vimentin-positive cells. Perinodular blood vessels were more abundant and had a thickened wall. Collagen bundles were swollen. The epidermis appeared atrophic with focal basal cell degeneration.

Adipose Tissue↗

In vivo cell activation following OKT3 administration. Systemic cytokine release and modulation by corticosteroids.

A massive and self-limited release of tumor necrosis factor and interferon gamma was detected in the systemic circulation in 35 consecutive renal allograft recipients by specific radioimmunoassays very soon following the first injection of the monoclonal antibody OKT3 (anti-CD3). Peak serum TNF and IFN gamma levels were reached, respectively, at 1 and 4 hr following the first OKT3 injection. Abnormally high serum interleukin 2 levels were also observed 4 hr following the first OKT3 injection in a minority of patients (5 cases). OKT3 had no effect on interleukin 1 beta, interferon alpha, and granulocyte/macrophage colony stimulating factor serum levels, which in all patients remained within the normal range throughout the study. This selective OKT3-induced cytokine release, which only followed the first injection, was transient (i.e., lasting a few hours). It tightly paralleled the spontaneously reversible clinical syndrome characterized by high fever, headaches, and gastrointestinal symptoms that is invariably associated with the first OKT3 administration. Importantly, when administered in adequate dosages and with adequate timing, corticosteroids influenced both the cytokine release and the systemic reaction. Thus, the highest TNF, IFN gamma, and IL-2 serum levels were detected in patients who did not receive corticosteroids. Patients who received high-dose corticosteroids (1 g solumedrol bolus) concomitantly with the first OKT3 injection still had high TNF and IFN gamma levels. Conversely, when the same corticosteroid dose was injected 15-60 min prior to the first OKT3 injection, in all cases the increase of serum TNF and IFN gamma was significantly lower as compared with the above-described groups; IL-2 levels did not rise. These data offer a direct explanation for one major side effect of OKT3 and thus provide the basis for devising means to prevent its occurrence.

Antibodies, Monoclonal↗

Tumor necrosis factor and interleukin-1 serum levels during severe sepsis in humans.

In a study of serum levels of tumor necrosis factor (TNF alpha) and interleukin-1 beta (IL-1 beta) in patients developing sepsis in the ICU, high TNF alpha levels were found in patients with septic shock. Normal values are 75 +/- 15 pg/ml; in these patients, TNF alpha serum level ranged from 100 to 5000 pg/ml with a mean of 701 +/- 339 pg/ml and a median of 250 pg/ml. There was a correlation between TNF alpha level and sepsis severity score as well as with mortality. In contrast, IL-1 beta serum levels were only slightly increased and were not correlated with severity or mortality.

Adolescent↗

Production of tumour necrosis factor-alpha, interferon-gamma and interleukin-2 by peripheral blood mononuclear cells of subjects suffering from rheumatoid arthritis.

Using radio-immunoassay methods, the production of tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), and interferon-gamma (IFN-gamma) released by peripheral blood mononuclear cells (PBMC), maintained in culture and stimulated by phytohemagglutinin (PHA), was measured in normal subjects and patients with active or inactive rheumatoid arthritis (RA). Results indicated a dissociation between mitogenic response and secretion of mediators by PBMC under the influence of PHA in both normal controls and in patients with rheumatoid arthritis (RA). While [3H]thymidine incorporation was characterized by a rather bell-shaped curve with increasing concentrations of PHA, IL-2 and TNF-alpha displayed a linear dose-dependent increase. [3H]thymidine uptake by PBMC was in the same range in normal subjects as in patients with active and inactive RA, although cytokine secretion differed. The PBMC of patients with active RA produced less TNF-alpha, IL-2, and IFN-gamma than did those of the controls. In cases of inactive RA, the secretory response varied from subject to subject; mean values did not differ from those of normal subjects, except for those of IL-2 (p less than 0.01). The significance and the clinical relevance of these findings are discussed.

Adult↗

[T lymphocyte activation induced in vivo by the first injection of OKT3 monoclonal antibodies].

One of the major side effects induced by the in vivo administration of the murine monoclonal antibody OKT3 is a spontaneously reversible clinical syndrome associating in variable proportions depending on the patient: fever, chills, headaches, diarrhea and seldomly meningismus. Sera from 3 renal allograft recipients treated with OKT3 were studied and showed that a massive although transient release of some cytokines namely, Tumor Necrosis Factor alpha, Interleukin 2 and Interferon gamma is observed following the first OKT3 injection.

Antibodies, Monoclonal↗

Changes in fetal and maternal blood levels of prolactin, cortisol, and cortisone during eutocic and dystocic childbirth.

The changes in blood levels of prolactin, total and free cortisol, and cortisone were studied and compared in 51 mother-infant pairs, 30 with eutocic delivery and 21 with dystocic delivery. Regardless of the type of delivery, the newborn at term showed significantly higher prolactin and cortisone serum levels than their mothers, and significantly lower levels of free and total cortisol. In fetal distress of short duration, free cortisol levels were significantly raised in both the mother and the child, while prolactin and cortisone levels were significantly higher only in the child. In contrast to these observations, serum prolactin and cortisone levels in the mother were not altered by the occurrence of fetal distress. In the newborn at delivery there was a negative correlation between serum prolactin and the Apgar score at 1 min applied to the part of the graph between 8 and 2 Apgar scores. This study illustrates the utility of fetal prolactin measurements in evaluating the stress to which the fetus is subjected.

Adult↗

Variations in dried blood spot immunoreactive trypsin in relation to gestational age and during the first week of life.

Dry blood spot immunoreactive trypsin was measured by radioimmunoassay in 84 preterm babies and in 65 full-term newborns studied daily from the first to the fifth day of life. In a control group of 3858 full-term newborns, trypsin concentrations at days 4-6 of life exhibited a log-normal pattern distribution, the geometric mean being 18 ng/ml serum. Immunoreactive trypsin concentrations did not change significantly between days 1, 2, 3, 4 and 5 after birth. Immunoreactive trypsin was found to be significantly lower (geometric mean 9 ng/ml, P less than 0.01) in preterm newborns before 32 weeks of gestation. In hypotrophic newborns of 34 weeks gestational age, immunoreactive trypsin values were higher than those observed at 31 weeks of gestation in eutrophic newborns, the mean birth weight not being different between both groups. These data suggest that trypsin production by the pancreas is dependent on maturity but does not seem related to intrauterine nutritional status. Immunoreactive trypsin concentrations do not change after 32 weeks gestational age and during the first postnatal week.

Blood Stains↗

Excretion of metabolites of hexachlorobenzene in the rat and in man.

From the urine of rats treated with hexachlorobenzene (HCB), 21 metabolites were separated by capillary gas chromatography. Sulfur-containing metabolites were present in larger numbers and greater amounts than phenolic compounds. In studies on the origin of pentachlorophenol in man, HCB was determined in adipose tissue and pentachlorophenol in urine, and in 48 out of 60 females, 80-90% of the daily urinary pentachlorophenol appeared to be formed from HCB.

Adult↗

Immunoreactive prolactin like material in the urine of women.

Immunoreactive prolactin-like material (Ir Prl) was detected in urines of eugonadal women during the luteal phase and in urines of pregnant and lactating women. The levels of Ir Prl urinary excretion per 24 h and of elimination per 100 ml of glomerular filtrate were highest in lactating women as compared to pregnant women; levels in pregnant women were elevated as compared to eugonadal subjects. Iv injection of thyrotropin releasing hormone (TRH, 200 micrograms) caused increased levels of urinary Ir Prl. The physiochemical characteristics of urinary Ir Prl of lactating women were investigated by filtrating urine samples on Ultragel Aca 54 in presence or absence of Trasylol. Urines, supplemented with Trasylol and analyzed either immediately or after storage at room temperature for 24 h, contained in addition to the 23,000 Mr monomeric form (25.2 +/- 7.4%), two fractions of high (greater than or equal to 70,000) or low (less than 23,000) molecular weight, respectively. The latter material largely predominated (73.5 +/- 7.3%). Urines kept at room temperature for 24 h without Trasylol showed variable but significant decreases in the monomer form with a parallel increase in high MW and fragmented forms. The extent of degradation of the monomer was directly proportional to the proteolytic activity of the urines as estimated by the Azocoll breakdown test. Contrary to what was observed with the urinary endogenous monomeric Prl, human pituitary Prl remained unaltered upon incubation in Trasylol-free urines up to 45 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, Gel↗

[Value of the measurement of SP1 protein in the early diagnosis of pregnancy induced with Pregnyl].

Successive dilutions of Pregnyl have been submitted to a radioimmunoassay of SP1. We have observed that Pregnyl cross-reacts with SP1. Chromatography of Pregnyl demonstrates that the contaminating substance is different from native SP1. As its concentration is low, it is however not detected in the serum of patients after the administration of exogenous Pregnyl. SP1 measurement can be helpful in detecting early pregnancies after hCG induction of ovulation.

Adult↗

[Are chorionic gonadotropin (HCG) and its alpha and beta subunits useful markers in non-trophoblastic tumors?].

HCG and its subunits alpha and beta are produced by trophoblastic cancers constituting an index of early detection and monitoring for these tumors. Unlike HCG-alpha, we can obtain specific HCG and HCG-beta assays with LH-neutralized antiserum. Many normal non-trophoblastic tissues exhibit a HCG-like immunoreactivity. All choriocarcinomatous testicular tumors produce HCG and HCG-beta. Half of all testicular teratomas produce HCG and its subunits while a third of all seminomas exhibit an HCG-like immunoreactivity, whether choriocarcinomatous component is present or not. Serum HCG levels are elevated in seminomas (5 to 22%) as well as teratomas '55 to 89%). Less than 15% of breast, digestive and lung cancers have increased serum levels of HCG and/or its 2 subunits. HCG is most often produced by undifferentiated lung cancers, hepatoblastomas and adrenal carcinomas. There is usually a parallel relation between these serum levels and the clinical evolution of the disease under chemotherapy. In breast cancer, these levels do not constitue a "prognosis index". HCG production by non-trophoblastic tumors can induce clinical symptoms such as precocious puberty and gynecomastia.

Breast Neoplasms↗

The value of a radioimmunological monitoring in cancer patients treated with interferon alpha.

Using a radioimmunoassay for human leukocyte interferon (IFN alpha), pharmacokinetic studies were carried out in twelve cancer patients given sequential intramuscular injections of Hu IFN alpha 2. Even though individual monitoring of serum IFN titers emphasized, for a given dose, marked quantitative variations of the observed maximum concentrations, their mean values were found to be dose-dependent (358 +/- 167 U/ml at 30.10(6) U and 1044 +/- 599 U/ml at 100.10(6) U doses). Comparison with bioassay results showed that IFN activities measured in sera were of the same order of magnitude as those calculated from radioimmunoassay standard curves. Data obtained from this series on observed peak time, half-life value and serum concentrations were consistent with those reported by the other groups using recombinant leukocyte interferon in clinical trial. Therefore, radioimmunoassay is an useful method for routinely assaying IFN alpha used either as antitumour or antivirus agent because of its high sensitivity (4 U/ml) and its simplicity.

Adult↗