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Biomedical subjects

M Moser

Publications and source records attributed to M Moser.

At least 145 records · Page 8Linked to original sources
PubMed1997

Comparative analysis of AP-2 alpha and AP-2 beta gene expression during murine embryogenesis.

Transcription factor AP-2 has been identified as playing important roles during embryonic development of the neural tube, neural crest derivatives, skin, and urogenital tissues. Recently, we isolated a second AP-2 transcription factor, AP-2 beta, which is 76% homologous to the previously known AP-2 alpha gene, and showed that both genes are coexpressed in murine embryos at day 13.5 and 15.5 post coitum (pc). In the current study, we used specific cRNA probes to study comparatively AP-2 alpha and AP-2 beta expression by in situ hybridization of murine embryonic tissue sections. Our results reveal that expression of both genes starts at day 8 pc in the lateral head mesenchyme and extraembryonic trophoblast. The expression pattern was identical until day 10 pc but diverged significantly during later stages of development. From day 11 forward, specific expression patterns of AP-2 alpha and AP-2 beta mRNA were observed. Specific AP-2 beta signals were detected in the midbrain, sympathetic ganglia, adrenal medulla, and cornea. Specific AP-2 alpha signals were present in the limb buds, dorsal root ganglia, tooth germs, and Moll's and Meibom's glands. In contrast, expression of both genes occurred in skin, facial mesenchyme, spinal cord, cerebellum, and renal tubular epithelia. Our results indicate that both genes are expressed with different temporal and spatial patterns during embryonic development.

Animals↗
PubMed1997

Mouse CD-RAP/MIA gene: structure, chromosomal localization, and expression in cartilage and chondrosarcoma.

A cDNA encoding a novel protein has been previously isolated from two independent sources: melanoma cell cultures and chondrocytes. The protein from human melanoma cell lines and tumors is called melanoma inhibitory activity (MIA) (Blesch et al. [1994] Cancer Res. 54:5695-5701) and the protein from primary bovine chondrocytes and cartilaginous tissues is called cartilage-derived retinoic acid-sensitive protein (CD-RAP) (Dietz and Sandell [1996] J. Biol. Chem. 271:3311-3316). In order to investigate the gene regulation and function of CD-RAP/MIA, the mouse gene locus was isolated and analyzed. Developmental expression was determined by in situ hybridization to mouse embryos. Expression was limited to cartilaginous tissues and was initiated with the advent of chondrogenesis, remaining abundant throughout development. The mouse gene was isolated and sequenced from a 129Sv library and sequenced directly from an additional strain, B6C3Fe. The mouse CD-RAP/MIA gene is 1.5 kbp and consists of four exons. The promoter sequence of the gene contains many potential regulatory domains including 8 basic helix-loop-helix protein-binding domains and an AT-rich domain, both motifs shown to be present in the cartilage-specific enhancer of the type II procollagen gene. Other potential cis-acting motifs include binding sites for GATA-1, NF-IL6, PEA3, w-elements, NF kappa B, Zeste and Sp1. The gene, called cdrap, was localized to the end of an arm of chromosome 7 at the same site as the transforming growth factor beta 1 (Tgf-beta 1) and the glucose phosphate isomerase 1 (Gpi 1) genes. Potential mouse mutants that mapped to the same region of chromosome 7 were identified. Two of the potential mutants with skeletal phenotypes were sequenced, pudgy (pu) and extra toes with spotting (XsJ); however, no mutations were found in the coding sequence. To determine whether CD-RAP/MIA is associated with tumors of cartilage, mRNAs from a variety of rodent tissues and cell lines were screened. Expression was detected in a rodent tumor, the Swarm rat chondrosarcoma and a chondrosarcoma cell line derived from it, but not in other tissues or tumors of non-cartilage origin. Immunolocalization revealed CD-RAP/MIA protein localized in cartilage only. These results show that the normal expression of CD-RAP/MIA is limited to cartilage; however, pathologically, it is expressed both in melanoma and chondrosarcoma. The restricted expression of CD-RAP/MIA may provide an opportunity to monitor cartilage metabolic activity as well as the tumor activity of melanoma and chondrosarcoma.

Amino Acid Sequence↗
PubMed1997

Effect of interleukin-10 on dendritic cell maturation and function.

The main function of dendritic cells (DC) is to induce the differentiation of naive T lymphocytes into helper cells producing a large array of lymphokines, including interleukin (IL)-2; interferon-gamma (IFN-gamma), IL-4, IL-5 and IL-10. The potent immunostimulatory properties of DC develop during a process of maturation that occurs spontaneously in vitro. Since IL-10 has been shown to inhibit Th1 responses, we determined its effect on DC maturation and accessory function. Our data show that DC that have undergone maturation in vitro in the presence of IL-10, have an impaired capacity to induce a Th1-type response in vivo, leading to the development of Th2 lymphocytes. Their inability to promote the synthesis of IFN-gamma seems to correlate with a decreased production of IL-12, an heterodimeric cytokine necessary for optimal generation of Th1-type cells. These results suggest that IL-10 skews the Th1/Th2 balance to Th2 in vivo by selectively blocking IL-12 synthesis by the antigen-presenting cells that play a role of adjuvant of the primary immune response. The cytokines present in the environment at the presentation step may, therefore, determine the class of the immune response induced by DC in vivo, i.e. Th0, Th1 and/or Th2.

Animals↗
PubMed1997

Angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists and calcium channel blocking agents: a review of potential benefits and possible adverse reactions.

A review of recent studies suggests that the use of angiotensin-converting enzyme (ACE) inhibitors may be preferred (usually along with a diuretic drug) as initial therapy in several subsets of hypertensive patients (i.e., those with diabetes and nephropathy or with diminished left ventricular function with or without symptoms of heart failure). Limited long-term data are available for the angiotensin II receptor antagonists. The use of nondihydropyridine calcium channel blocking agents (CCBs) appears to reduce reinfarction in patients with ischemic heart disease (however, mortality is not reduced). Long-acting formulas of CCBs appear to decrease congestive heart failure in patients with dilated, but not ischemic, cardiomyopathy and to decrease strokes and arrhythmias in hypertensive subjects. Short-acting agents (primarily those that increase heart rate) may increase coronary heart disease events in hypertensive patients. There is little evidence at present that CCBs offer a major advantage over other antihypertensive agents or that they should be recommended as initial therapy, except in special situations.

Angiotensin Receptor Antagonists↗
PubMed1997

Diuretics in the prevention and treatment of congestive heart failure.

Diuretics, either as monotherapy or in combination with other drugs in the management of hypertension, have retarded the development of left ventricular hypertrophy and congestive heart failure in many patients. Diuretics also remain one of the most effective therapies in the treatment of congestive heart failure, when given with an ACE inhibitor and digoxin.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Clinical trial results with a new plasminogen activator.

Thrombolysis has become an accepted form of therapy for acute myocardial infarction. As demonstrated in the Global Utilization of Streptokinase and t-PA for Occluded Arteries trial, early, complete and sustained patency of the infarct-related coronary artery is correlated with reduced mortality. However, current thrombolytic regimens are able to achieve such patency within 90 min in only 81% of cases. To improve the risk/benefit ratio of thrombolytic therapy, newer agents such as reteplase have been developed to establish more rapid, more complete and more stable coronary artery patency, thus reducing mortality. This report summarizes the pharmacological properties of reteplase. It also summarizes the findings from various animal and clinical studies in which reteplase was compared with alteplase and streptokinase and the findings from animal and clinical studies evaluating infusion, single-bolus, double-bolus, doses of reteplase.

Amino Acid Sequence↗
PubMed1997

Effects of an eight-day space flight on microvibration and physiological tremor.

Microgravity was used to study accelerometrically recorded microvibration (MV) and postural tremor (PT) at reduced muscle tone on one cosmonaut before, during, and after an 8-day space flight on the Russian Mir station. MV of the relaxed forearm in the 1 g environment showed the typical 7- to 13-Hz resonance oscillations triggered by the heart beat. In 0 g, these pulsations shifted to below 5 Hz and the waveform became similar to an ultralow frequency acceleration ballistocardiogram. PT of the arm stretched forward showed an irregular waveform in 1 g. In 0 g, the higher-frequency components were reduced and again an ultralow frequency ballistocardiogram emerged. As a control, hand force tremor was recorded as well; it was not affected by the gravity condition. A second-order analog with muscle stiffness (C) as parameter was used to evaluate the measurements. For MV it could be shown that cardiac impacts produce damped resonance oscillations when C is high enough (1 g). At low C (0 g), this resonance phenomenon is essentially filtered out. For PT both neuromuscular and cardiovascular forces produce an irregular output; when C is lowered (0 g) the higher-frequency content is strongly reduced. It is concluded that both MV and PT waveforms are sensitive to musculoskeletal stiffness, such that at the lowest stiffness achieved the cardiac impact dominates. In 1 g, the cosmonaut's data were not significantly different from the results in a control group (n = 6).

Adult↗
PubMed1997

Reteplase (r-PA): a new plasminogen activator.

Reteplase (r-PA) is a genetically engineered deletion mutant of wild-type tissue-type plasminogen activator. The structural differences lead to different functional properties, such as a prolonged half-life. The compound demonstrated good thrombolytic efficacy in in vitro as well as in animal studies. In angiographically controlled patency studies (GRECO, GRECO-2 RAPID-1, RAPID-2), the double-bolus application scheme was established, and a superior patency profile for reteplase in comparison to alteplase was demonstrated. Mortality studies established reteplase as a safe drug with a 30-day mortality at least equivalent to streptokinase (INJECT) and very similar to alteplase (GUSTO-3). A possible advantage may be the double-bolus application without a need for weight adjustment, especially in a prehospital setting. Thus, reteplase can be regarded as an excellent alternative to streptokinase or alteplase for thrombolytic therapy in acute myocardial infarction.

Journal Article↗
PubMed1997

Decreased nociceptive sensitivity: a biological risk marker for opiate dependence?

In recent studies using a cold pressor test we could show that former opiate addicts are persistently less pain-sensitive than healthy controls, indicating a neurophysiologic dysfunction in these patients. In the present study we addressed the issue of whether this dysfunction was caused by the drug abuse or already existed prior to the heroin addiction, and whether it is restricted to pain sensitivity or affects somatosensory or nociceptive sensitivity in general. After validating the method we obtained retrospective ratings for the pain, cold and warmth sensitivity for the time before addiction, during addiction and during detoxification. Ex-addicts perceive themselves less pain- and cold-sensitive than healthy controls, and no difference was detectable between the pre-addiction and the rehabilitation ratings, although nociceptive sensitivity is highly increased during detoxification. Warmth sensitivity was not different to healthy controls and was not affected by drug withdrawal. Our findings suggest that a decreased nociceptive sensitivity may already precede opiate addiction pointing to physiological dysfunctions in heroin pre-addicts.

Adult↗