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Biomedical subjects

M Grossmann

Publications and source records attributed to M Grossmann.

89 records · Page 5Linked to original sources
PubMed1993

Regulation of the 5'-flanking region of the mouse androgen receptor gene by cAMP and androgen.

Both androgens and cAMP-mediated hormones are known to regulate expression of the androgen receptor (AR) gene. In order to determine whether these effects occur at the transcriptional level, transfection studies were conducted with a 1.5-kilobase fragment of the 5'-flanking region of the mouse AR gene coupled to a chloramphenicol acetyltransferase (CAT) reporter gene. We demonstrated that the cAMP pathway regulates expression of the mouse AR (mAR) 5'-CAT construct in mouse pituitary (alpha T3-1), rat pituitary (GC), and quail fibroblast (QT6) cell lines. Deletional analysis indicated that several areas of this clone, including a region containing a putative cAMP response element (CRE), are involved in mediating cAMP regulation of the AR gene. Oligonucleotides containing a putative CRE, linked to the thymidine kinase promoter of pBLCAT2, conferred increased forskolin induction of CAT activity. Furthermore, overexpression of a CRE binding protein up-regulated expression of the mAR 5'-CAT constructs. Bandshift data demonstrated that the putative CRE forms specific, competable complexes with nuclear proteins from alpha T3-1 and QT6 cells. Additional experiments indicated that AR can modulate both basal and forskolin-induced CAT activity in an androgen-dependent fashion. These data provide evidence that the 5'-flanking region of the mAR gene contains sequences which mediate the effects of both cAMP and androgens.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Chronic multifocal osteomyelitis, a new recessive mutation on chromosome 18 of the mouse.

Mice with tail kinks and deformities in their lower extremities were observed in a litter of C.D2-Qa-2+N6F15 mice. A mutant line that exhibits this phenotype in 100% of its offspring was established by subsequent breeding. The abnormalities resembled to some degree those found in a human syndrome termed chronic recurrent multifocal osteomyelitis (CRMO). Accordingly, we name the new mutation chronic multifocal osteomyelitis (cmo). Breeding analysis showed that the defect was determined by a single autosomal recessive gene. Restriction fragment length polymorphism (RFLP) analysis of progeny from a backcross between Mus musculus domesticus (CLA) and C.D2-Qa-(2+)-cmo/cmo indicated that the cmo gene resides on mouse Chromosome 18.

Animals↗
PubMed1991

Double-blind, randomized study of the anti-anginal and anti-ischaemic efficacy of fendiline and diltiazem in patients with coronary heart disease.

In a 6-week, randomized, double-blind trial, the drug effects of the calcium antagonists, fendiline (75 mg twice daily) and diltiazem (90 mg twice daily), as measured by subjective and objective parameters of coronary heart disease, were studied in 79 patients with stable angina pectoris. The statistical analysis included the data of 71 patients. The results of exercise-ECG tests showed that both medications were effective anti-ischaemic agents. Fendiline was found to be effective in reducing ST-segment depression at maximum comparable load (71 watts) as well as at the time of reaching the individual maximum tolerated load (discontinuation of exertion). Diltiazem, on the other hand, proved effective only at maximum comparable load (72 watts). There was no significant difference between the groups with regard to the reduction after 6 weeks. As regards work tolerance, the duration of exercise and time until appearance of a ST-segment depression of 0.1 mV, before and after treatment comparisons revealed significant changes only in the group receiving diltiazem and the differences between fendiline and diltiazem were statistically significant with regard to these three parameters. Reduction in the frequency of anginal attacks and the diminution of nitroglycerin consumption were comparable in both medication groups, and the changes from baseline were statistically significant. Assessment of the efficacy and tolerability of the medications by patients as well as by investigators revealed no statistically significant differences between the two groups. Blood pressure and heart rate were clearly lowered by diltiazem, whereas fendiline induced only a slight decrease in blood pressure. The results indicate that both medications are equally suited for the treatment of stable angina pectoris.

Aged↗
PubMed1990

Erythrocyte sodium transport and renal sodium excretion after saline loading in young and adult spontaneously hypertensive (SHR) and normotensive (WKY) rats.

Adult SHR aged 19-21 weeks, subjected to osmotic diuresis, responded to an intravenous 1.8% saline loading (15 ml/kg b.w.) with greater sodium excretion than age-matched WKY. Young (6-7 weeks old) SHR and WKY also responded to saline loading with an increased sodium excretion but there were no differences in the relative changes of sodium excretion between young WKY and SHR. In adult WKY, saline loading induced a faster erythrocyte 22Na uptake as compared with adult SHR or young WKY. This suggests that volume and/or sodium loading increased sodium turnover of red cells only in adult WKY. The sodium transport differences found in erythrocytes of adult SHR and WKY could be caused by some membrane differences or could be due to different hormonal and nonhormonal response(s) to saline loading. If similar alterations would also occur in other tissues, they might be important for the sodium excretion pattern.

Animals↗
PubMed1990

[Abdominal complications following heart surgery using the heart-lung machine].

Reported in this paper are 17 abdominal complications among 2,161 patients, following cardiac surgery, using cardiopulmonary bypass. This incidence is comparatively low, accounting for only 0.78 percent, whereas figures between 0.3 and 1.6 percent have been reported in the international literature. Lethality worldwide has been quoted to be between 25 and 50 percent and amounted to 23.5 percent for the above patients. This seems to underscore the great importance of early decision-making on appropriate therapy. Haemorrhage from the upper gastro-intestinal tract due to stress-related ulcers had been the predominant finding in this study. Acute pancreatitis developed in two patient, one of them ending in death. Acute cholecystitis and ischaemic colonic gangrene were additional complications. No significant extension of perfusion periods was established, which was in deviation from findings made by other authors.

Acute Disease↗
PubMed1989

Plasma levels of soluble CD8 antigen and interleukin-2 receptor antigen in patients with hairy cell leukemia, relationship with splenectomy and with clinical response to therapy.

A soluble form of CD8 antigen (sCD8) has been shown to be released by activated CD8 + lymphocytes. Measurements of sCD8 may serve as an index of suppressor/cytotoxic cell activity. To assess the clinical significance of this observation in response to malignancy, we have investigated the sCD8 concentrations in 38 patients with hairy cell leukemia (HCL) not yet treated with any systemic therapy. The median plasma sCD8 level of the 20 nonsplenectomized patients was 1,025 U/ml and was significantly higher than that in the 18 patients who had previous splenectomy (median = 200 U/ml, p less than 0.0001), or in 14 normal controls (median = 350 U/ml, p less than 0.0001). Compared to controls, splenectomized patients had also significantly lower levels of sCD8 (p less than 0.01). The median concentration of soluble interleukin-2 receptor (sIL2R) in nonsplenectomized patients was 14,500 U/ml and was in the same range as in splenectomized patients (15,000 U/ml). There was no overlap in sIL2-R levels between controls (median = 300 U/ml) and patients. Investigation of serial plasma samples in 7 patients who received deoxycoformycin (DCF) and 11 patients treated with interferon alpha (IFN-alpha) showed a normalization of sCD8 levels and a decrease of sIL2R concentrations in those patients who showed hematological improvement. Normalization of sIL2R was, however, only observed in patients with complete remission. Our observation indicates that splenectomy might cause a reduction of the activation of suppressor/cytotoxic cells in patients with HCL. Treatment with either DCF or IFN-alpha also modulates the sCD8 levels to normal range. Measurements of sCD8 and sIL2-R might give more insight into the pathogenesis of HCL and serve as parameters for monitoring different phases of the disease and response to therapy.

Antigens↗
PubMed1987

Acute and chronic effects of xanthine oxidase on lung thorax-compliance in guinea pigs.

Xanthine oxidase was given intratracheally in a single dose to guinea pigs. Lung compliance was measured after 4 h and 14 days respectively. Lung-thorax compliance was significantly lower compared with saline-treated controls both 4 h and 14 days after application of fluid. At 14 days there was a dose-related response between lung-thorax compliance and xanthine oxidase administered in the range 0-1.0 U. Superoxide dismutase (SOD) had a protective effect on xanthine oxidase action at 4 h, but not after 14 days. We suggest that the decreased lung-thorax compliance was caused by superoxide radicals, produced by the hypoxanthine-xanthine oxidase system, damaging lung tissue. We speculate that free oxygen radicals produced by the hypoxanthine-xanthine oxidase system could be an important contributory pathogenetic factor in producing both acute and chronic lung damage in, for instance, premature babies or adults, with respiratory distress syndrome.

Animals↗
PubMed1977

Evidence that proteins bound to the polysomal messenger RNA exist also free in the cytoplasm of HeLa cells.

The cytoplasm of HeLa cells contains a series of proteins with affinity for RNA. These proteins were detected by affinity chromatography on RNA-Sepharose. Several proteins are tightly bound to RNA; there is no preference for mRNA as the same proteins bind to any free RNA, even poly(A). At least two of these proteins coincide with proteins of genuine ps-mRNP-proteins (Mr. 50 000 and 75 000). The column yields a protein (Mr. 37 000) which has an affinity for the matrix rather than for the coupled RNA. Complexes formed from mRNA and cytosol proteins do not bind to ribosomes, whereas ps-mRNPs does. We suggest that some of the polysomal mRNP proteins pre-exist unbound in the cytosol.

Chromatography, Affinity↗
PubMedDate not supplied

Does Ca2+/Mg(2+)-free medium have an effect on the survival of the preimplantation mouse embryo after biopsy?

The way in which the different technical aspects of clinical preimplantation genetic diagnosis affect the survival of the biopsied embryo is not well understood. One of these aspects is the influence of Ca2+/Mg(2+)-free medium on the developmental capacity of the biopsied embryo and the biopsied cell itself. Therefore, we used an experimental design involving 4-cell mouse embryos to evaluate the effect of performing the biopsy procedure under such conditions. Our results indicate that the use of Ca2+/Mg(2+)-free medium has no detrimental effect (at least in mouse embryos) on the viability of the biopsied embryos and their biopsied cells when used during relatively short times of exposure.

Animals↗
PubMedDate not supplied

[Circadian blood pressure variations in young and in older patients].

Elevated blood pressure in the elderly is common despite they are normotensive. This "pseudo-hypertension" is probably a white-coat effect or depends on the increased arterial stiffness. Ambulant blood-pressure monitoring (by portable automated oscillometry) provides a reasonable accurate estimate of the blood pressure level throughout the day and better predicts cardiac end-organ damage. In normotensive elderly volunteers the systolic arterial pressure and the blood pressure amplitude was higher than in young normotensive subjects. The circadian profile of the two groups was comparable. Specific habits like an afternoon nap significantly influenced the blood pressure of the elderly. The blood pressure variability in geriatric hypertensives with antihypertensive therapy was smaller than in normotensive elderly controls. Any severe blood-pressure nadir at night was not registered in both groups. 24-hour ambulatory blood pressure monitoring is a careful method and should be used to determine the need and the effectiveness of antihypertensive treatment in the elderly.

Adult↗
PubMedDate not supplied

[The peculiarities of the orthostasis reaction in advanced age].

The hemodynamic response to postural stress (75 degrees foot-down tilt) was observed in 14 elderly normotensives (age range 61-92 years) and 15 younger controls (20-30 years). Both the immediate heart-rate response and the increase of the diastolic blood pressure was reduced in elderly individuals, although they didn't suffer from postural hypotension. The suppression of heart-rate oscillation after tilting could be a possible sign of aging alterations. It is concluded, that drug-dependent "normal" blood pressure levels in elderly patient decrease the orthostatic tolerance if the baroreflex is impaired.

Adult↗