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Biomedical subjects

M Hermann

Publications and source records attributed to M Hermann.

At least 91 records · Page 5Linked to original sources
PubMed1998

[Traumatology and sports injuries in equestrian acrobatics in the adolescent].

The objective of this study was to compile knowledge of athletic injuries and complaint patterns related specifically to equestrian acrobatics (e.a.). A 20-page standardized questionnaire was sent to 114 e.a. participants. The mean age of the participants in e.a. groups was 15 +/- 3 years, that of independent participants 21 +/- 3 years. A total of 489 injuries was reported, mainly to muscles and tendons (35%), skin (33%) and joints and ligaments (25%). Bone injuries (6%) and head injuries (2%) were infrequent. Analysis of the localization showed that the head-face-neck region was involved in the injury in 3.9%, the torso in 5.5%, the upper extremities in 28%, pelvis and hip region in 3.9%, and the lower extremities in 52%. More than half the injuries were categorized in severity grade I (55%) (not requiring medical attention), 25% were grade II (single medical treatment), 15% grade III (several outpatient medical treatments) and 5% grade IV (requiring hospitalization). Nearly half of the injuries to the lower extremities resulted from jumping exercises, while the cause in upper-extremity injuries was mostly falling (37%). The importance of fall training and limitation of difficulty as well as the number and height of the jumps is discussed. Regular medical examination and improved education of the trainers are demanded.

Accidental Falls↗
PubMed1998

Apolipoprotein A-I production by chicken granulosa cells.

In avian species such as the chicken, development of the oocyte is associated with massive deposition of yolk in this cell. Oocytes grow within the follicle, a compartment consisting of a very specialized set of cells and acellular structures. The oocyte is surrounded by the perivitelline layer and granulosa cells, which are separated from the thecae by a pronounced basement membrane. In addition to the production of yolk precursors in the liver, we have long implied that cells within the follicle make a direct contribution to the growth of the oocyte. Here we show that chicken granulosa cells express and actively secrete apolipoprotein A-I (apoA-I) as a part of particles with very high density. The granulosa cell-derived, apoA-I-containing material is different from the small portion of yolk high density lipoprotein that arises via transfer from the peripheral circulation. We propose that the ApoA-I-containing particles secreted by granulosa cells 1) support the growth of the rapidly growing germ cell, possibly by direct lipid transfer to the plasma membrane of the oocyte, and/or 2) deliver cholesteryl esters to the steroid-producing cells of the theca layer. These findings are discussed with respect to the proposed functions of apoE (an apolipoprotein not found in chicken) within the mammalian follicle.

Animals↗
PubMed1998

Complex alternative splicing of the GH-V gene in the human testis.

The human growth hormone variant (GH-V) gene is expressed during pregnancy in the syncytiotrophoblast and, as shown recently, in the normal human testis. In addition to the classical transcript encoding for the 22 K major form, intron D-retaining processed mRNAs (GH-V2) have also been described in both tissues. In the present study we analyzed testicular GH-V RNA alternative splicing patterns, a major source of GH variability. We observed three types of GH-V-derived mRNAs by reverse transcription-polymerase chain reaction amplification of GH/placental lactogen mRNA, subsequent cloning into appropriate vectors, vector amplification, restriction-endonuclease map-analysis and double-strand sequencing of GH-V clones. Apart from the conventional splice product encoding classical hGH-V (22K, 191 amino acids (aa)) and intron D-retaining mRNA GH-V2 (230aa), we detected an additional GH-V mRNA variant, GH-Vdelta4, utilizing a competitive splice-donor site 4 bp 5'of the conventional exon 4/intron D splice-donor site, but retaining the genuine intron D/exon 5 splice-acceptor site. This mRNA encodes a putative 25 K protein of 219 amino acids in length, having the first 124 amino acids and, thus, two and a half structural alpha-helices in common with hGH-V.hGH-Vdelta4 has lost the N-glycosylation site at Asn 140 of hGH-V, but acquires a novel site at position 148 as well as a cystein-rich domain in the 65 carboxyl-terminal amino acids, potentially involved in multiple disulfide-bridge formation. Tissue specificity and possible functions for testicular physiology remain to be investigated.

Alternative Splicing↗
PubMed1998

Early relapse after operation for Graves' disease: postoperative hormone kinetics and outcome after subtotal, near-total, and total thyroidectomy.

BACKGROUND: The relative merit of operation in the treatment of Graves' disease has been questioned, and the extent of surgical resection is still a matter of debate. METHODS: We have analyzed retrospectively the incidence of recurrent hyperthyroidism (frequency and time point) in 215 consecutive patients subjected sequentially to subtotal thyroidectomy (n = 63; remnant mass 6 to 8 g, based on surgeons' estimates and dimensions measured during operation), extensive subtotal thyroidectomy (n = 106; remnant mass approximately 4 g), and near-total (n = 27; unilateral capsular remnant of < 2 g) or total thyroidectomy (n = 19). In addition, we have evaluated the postoperative kinetics of thyroid hormone elimination (free triiodothyronine and free thyroxine) in 14 selected patients with hyperthyroidism who underwent operation under beta-adrenergic blockade but without any thyrostatic pretreatment. RESULTS: The size of the remnant significantly (P < .05) affected the relapse rate (23.8%, 9.4%, and 0% in subtotal, extensive subtotal, and near-total/total thyroidectomy, respectively). However, the time point at which the relapse occurred did not differ in subtotal and extensive subtotal thyroidectomy. All relapses occurred within the first 70 weeks. The incidence of complications (permanent recurrent nerve paresis and persistent hypocalcemia) was comparable in all groups. The elimination of fT3 was biphasic and rapid such that the levels were within the normal range on the second day. In contrast, 15 days were required until the fT4 level had declined below the upper limit in all patients. CONCLUSIONS: We propose that the therapeutic goal in thyroid operations is to avoid recurrent hyperthyroidism. This is not reliably achieved by subtotal thyroidectomy; in contrast, near-total and total thyroidectomy are effective and safe. On the basis of the postoperative elimination kinetics, hormone replacement is to be instituted within 2 weeks after operation.

Adolescent↗
PubMed1997

Receptor-associated protein in an oviparous species is correlated with the expression of a receptor variant.

The biosynthesis of proteins containing cysteine-rich domains requires chaperones for their correct folding. For instance, the 39-kDa receptor-associated protein (RAP) aides in the cell-surface targeting of newly synthesized members of the mammalian low density lipoprotein receptor (LDLR) gene family, which contains tandemly arranged clusters of hexacysteine repeats. In the chicken, an LDLR relative with eight such repeats is expressed as two different splice variant forms in cell type-specific fashion (Bujo, H., Lindstedt, K. A., Hermann, M., Mola Dalmau, L., Nimpf, J., and Schneider, W. J. (1995) J. Biol. Chem. 270, 23546-23551). To learn more about evolutionary aspects of RAP, its role in escorting of these different receptor splice variants, and other potential functions, we have extended our studies on the avian LDLR family to RAP. cDNA cloning, determination of tissue expression at both the transcript and the protein level, stable expression in COS cells, and binding studies with chicken RAP revealed that mammalian RAPs have retained many features of the non-amniotic proteins. However, structural details, e.g. the well defined internal triplicate repeats in the chicken protein, have been somewhat diluted during evolution. Interestingly, chicken RAP was found to correlate positively with the expression levels in somatic cells of the larger splice variant of the eight-cysteine repeat receptor, but not with those of the smaller variant, expressed only in germ cells. This is compatible with the possibility that RAP may play a role in receptor biology that could be complementing its function in assisting folding. Chicken RAP in crude extracts of the stable expressor COS cells is able to bind to LDLR relatives in ligand blots without requirement for prior purification of the ligand. Thus, in conjunction with the avian model of massive lipid transport to germ cells, these cells provide a novel comparative system amenable to investigation of the biological functions of RAP.

Amino Acid Sequence↗
PubMed1997

Tyrosine: an inhibitor of LDL oxidation and endothelial cell cytotoxicity initiated by superoxide/nitric oxide radicals.

Tyrosyl radicals can catalyze LDL oxidation. In addition to their LDL oxidizing ability, superoxide (O2.-)/nitric oxide (NO.) generate phenoxyl radicals when reacting with tyrosine. Therefore we tested if tyrosine can act as a pro-oxidant in O2.-/NO.-initiated LDL oxidation. When LDL was exposed to O2.-/NO., tyrosine exerted a strong inhibitory effect on O2.-/ NO.-initiated LDL oxidation as measured by TBARS formation and alteration in electrophoretic mobility of LDL. Tyrosine was also able to protect human endothelial cells from the cytotoxic effect of O2.-/NO.. Because O2.-/NO. can occur in vivo, the results may indicate that serum-free tyrosine could act as an efficacious physiological antioxidant in case of O2.-/NO.-initiated LDL oxidation and endothelial cell cytotoxicity.

Endothelium, Vascular↗
PubMed1997

3-Morpholinosydnonimine as instigator of a glibenclamide-sensitive reduction in the insulin secretory rate.

The nitric oxide (NO) donor SIN-1 (3-morpholinosydnonimine) induced a concentration-dependent inhibition of the secretory response to glucose. The negative insulinotropic action of SIN-1 was attenuated by the hypoglycemic sulfonylurea glibenclamide. Moreover, the NO donor enhanced 86Rb outflow from perfused islets and reduced the glucose-induced increase in 45Ca outflow. The present data provide further evidence that NO donors impair the secretory response to glucose, at least in part, by activating the ATP-sensitive K+ channels.

Animals↗
PubMed1997

Prolactin gene expression and prolactin protein in premenopausal and postmenopausal human ovaries.

OBJECTIVE: To investigate intraovarian prolactin and prolactin-receptor gene expression and to assess local prolactin synthesis with emphasis on possible differences between premenopausal and postmenopausal status. DESIGN: The RNA extracted from human premenopausal and postmenopausal tissues was subjected to reverse transcription and polymerase chain reaction by using prolactin-specific intron- and exon-spanning primers. Prolactin-receptor expression was investigated accordingly. The amplified complementary DNA fragments were analyzed by gel electrophoresis and restriction enzyme mapping. Local prolactin hormone synthesis was verified by a time-resolved immunofluorometric assay based on our monoclonal antibodies. RESULT(S): Prolactin and prolactin-receptor gene expression was observed in all analyzed human ovaries (n = 18). Several other human tissue specimens, such as lung and kidney, served as negative control tissues. Significantly elevated concentrations of prolactin were detected in cytosolic extracts of premenopausal (n = 6; mean +/- SD; 20.6 +/- 3.3 ng/g tissue wet weight) versus postmenopausal (n = 6; 3.6 +/- 3.0 ng/g tissue wet weight) ovaries. CONCLUSION(S): The human ovary not only serves as a target for endocrine prolactin action but also as a site of local prolactin hormone production. In agreement with previous reports on extrapituitary sources of prolactin, we consider prolactin as a hormone as well as an autocrine or paracrine growth or regulatory factor. Significantly increased concentrations of prolactin in premenopausal ovarian tissue verifies its role in human reproduction.

Adult↗
PubMed1997

Low density lipoprotein receptor gene family members mediate yolk deposition.

Yolk represents the last growth stage of a single cell, the oocyte, which contains, besides bona fide cytoplasm, endocytosed serum-derived lipoproteins and minor components essential for normal embryo development. Transport of bulk lipoproteins, micronutrients, and morphogens to oocytes in parallel with maintenance of somatic homeostasis is achieved by ligand targeting via cell-specific expression of receptors and subtle differences in ligand structure. Lipoprotein metabolism is the prime example of these regulatory principles, in which receptors belonging to the low density lipoprotein receptor gene family play key roles. Here, we present the laying hen's features that make it an attractive model system to dissect macromolecular transport processes at the molecular level. In addition to the characterization of a family of yolk precursor receptors, studies on systemic vs. oocyte-directed transport have uncovered new aspects of the biological rationale for simultaneous expression of closely related genes in a single organism.

Animals↗
PubMed1997

Differential expression of apoptosis, Bcl-x and c-Myc in normal and malignant lymphoid tissues.

Bcl-x and c-Myc have an important role for the immune response by regulating the programmed cell death (apoptosis) of lymphocytes. Dysfunction of these selection processes can lead to the development of malignant lymphoma. The present study aimed at defining the differential expression of apoptosis, Bcl-x and c-Myc in normal and in malignant lymphoid tissues. Follicular centre lymphoma (FCL-F) and mantle cell lymphoma (MCL) contained the lowest apoptotic indices (AIs), whereas Burkitt's lymphoma (BL) had the highest AIs. The AIs correlated significantly with the growth rates of the tumours and with the extent of Bcl-x expression. Bcl-x was expressed in almost all BL cells, but in few tumour cells in FCL-F and in MCL. c-Myc, in contrast, was found in the majority of the tumour cells in FCL-F and in MCL, but not in BL. Whereas the extent of Bcl-x expression correlated positively with the growth rates, an inverse correlation was observed between the percentages of c-Myc-positive tumour cells and the growth rates of the tumours. We conclude that normal and malignant lymphoid tissues have a distinct pattern of apoptosis and that expression of Bcl-x and c-Myc in B cell lymphoma is differentially regulated.

Apoptosis↗
PubMed1997

Paracetamol catalyzes myeloperoxidase-initiated lipid oxidation in LDL.

The oxidative modification of LDL may play a significant role in atherogenesis. Myeloperoxidase (MPO) expressed in human atherosclerotic plaques has been suggested to be operative in vivo, making LDL atherogenic. Tyrosyl radicals generated by MPO have been shown to act as physiological pro-oxidants of lipid peroxidation in LDL. Assuming that a variety of phenolic compounds are able to form phenoxyl radicals when exposed to peroxidases, we tested the ability of paracetamol, a known analgesic drug with a tyrosine-like monophenolic structure, to act as a pro-oxidant of lipid peroxidation in LDL. Spectroscopic analyses indicated that paracetamol, similar to tyrosine, could undergo peroxidase-induced phenoxyl radical formation, which was inhibited by the radical scavenger ascorbic acid as well as by heme poisons and catalase. Measurement of conjugated dienes and lipid hydroperoxides in LDL preparations exposed to MPO/H2O2 in the absence or presence of paracetamol revealed that the drug could act as a catalyst of lipid oxidation in LDL. Similar results were found when LDL oxidation was performed with activated human neutrophils, which use MPO to promote lipid peroxidation. In conclusion, the results suggest that paracetamol could act, via a phenoxyl radical, as a catalyst of LDL oxidative modification by MPO.

Acetaminophen↗
PubMed1997

Genistein, the dietary-derived angiogenesis inhibitor, prevents LDL oxidation and protects endothelial cells from damage by atherogenic LDL.

There is now growing evidence that the oxidative modification of LDL plays a potential role in atherosclerosis. In this study, genistein, a compound derived from a soy diet with a flavonoid chemical structure (4',5,7-trihydroxyisoflavone), which was found to inhibit angiogenesis, has been evaluated for its ability to act as an LDL antioxidant and a vascular cell protective agent against oxidized LDL. The results showed that genistein was able to inhibit the oxidation of LDL in the presence of copper ions or superoxide/nitric oxide radicals as measured by thiobarbituric acid-reactive substance formation, alteration in electrophoretic mobility, and lipid hydroperoxides. Bovine aortic endothelial cell- and human endothelial cell-mediated LDL oxidation was also inhibited in the presence of genistein. The 7-O-glucoside of genistein, genistin, was much less effective in inhibiting LDL oxidation in the cell-free and cell-mediated lipoprotein-oxidating systems. Incubating human endothelial cells in the absence or presence of genistein and challenging the cells with already oxidized lipoprotein revealed that in addition to its antioxidative potential during LDL oxidating processes, genistein effectively protected the vascular cells from damage by oxidized lipoproteins. The tyrosine kinase inhibitor genistein was found to block upregulation of two tyrosine-phosphorylated proteins of 132 and 69 kDa in endothelial cells induced by oxidized LDL. Parallel experiments with the inactive analogue daidzein, however, showed that the cytoprotective effect of the isoflavones seems not to be dependent on tyrosine phosphorylation. Our findings will support the suggested and documented beneficial action of a soy diet in preventing chronic vascular diseases and early atherogenic events.

Animals↗
PubMed1997

Selective growth hormone/placental lactogen gene transcription and hormone production in pre- and postmenopausal human ovaries.

In addition to effects of pituitary-derived gonadotropins, human GH modulates and regulates intraovarian reproductive processes in a dose-dependent manner via the endocrine GHRH/GH/insulin-like-growth-factor I (IGF-I) axis. Based on increasing evidence that ovarian regulation involves a complex system of putative para/autocrine factors, we investigated the possibility of gene-selective intraovarian GH/placental lactogen (PL) hormone production, with emphasis on differences between pre- and postmenopause. Analysis of both premenopausal (n = 8) and postmenopausal (n = 10) ovarian-derived messenger ribonucleic acid by reverse transcription-PCR, which amplifies all major gene products of the five-member GH/PL gene cluster GH-N, GH-V, PL-A/B, and PL-L, revealed specific transcripts in all specimens. Their share in gene selective expression by analytical restriction enzyme digestion was determined. The expression pattern of GH/PL messenger ribonucleic acid shows PL-A/B > GH-N, which sets it apart from those of pituitary and placenta. Local production of the respective protein hormones was verified by two time-resolved immunofluorometric assays for human PL-A/B and GH-N; significant amounts of these hormones were detected in cytosolic extracts of premenopausal (n = 6; 555.5 +/- 171 ng PL-A/B and 0.8 +/- 0.6 ng GH-N/g tissue wet wt) and postmenopausal (n = 6; 5.2 +/- 2.7 ng PL-A/B and 0.9 +/- 0.6 ng GH-N/g tissue wet wt) ovaries. No difference was observed between pre- and postmenopausal ovarian GH-N contents, but PL values were 2-3 orders of magnitude lower in postmenopausal tissue (P < 0.001). Serum levels of healthy premenopausal (n = 21) and postmenopausal (n = 16) women were less than 0.02 ng PL/mL. In summary, ovarian-derived GH-N and PL-A/B synthesis correlates well with the established local cascade of GHRH, GHRH receptor, GH receptor, IGF-I, and IGF-I receptor as a putative para/autocrine regulator of ovarian reproductive function.

Adult↗
PubMed1997

Estrogen dependence of synthesis and secretion of apolipoprotein B-containing lipoproteins in the chicken hepatoma cell line, LMH-2A.

The chicken hepatoma cell line LMH-2A, which permanently overexpresses the chicken estrogen receptor, was used to study the synthesis and secretion of lipoproteins in response to treatment with estrogen. In the absence of the hormone, only small amounts of apolipoprotein B (apoB) and no apolipoprotein VLDL II (apoII) were found in cell extracts. After treatment of cells with moxestrol, a stable estrogen derivative, for 24 to 48 h, a dramatic increase in the quantities of these lipoproteins was observed both in cell extracts and in the medium. As determined by pulse-chase experiments, both proteins also showed enhanced rates of synthesis after estrogen induction, and secretion of the newly synthesized proteins was essentially complete by 6 h. The secreted apoB-containing lipoprotein particles have a density corresponding to that of very low density lipoprotein (VLDL). Furthermore, in estrogen-stimulated cells, the secreted particles also contain apoII, as shown by co-immunoprecipitation of apoII, and apoB. It appears that vitellogenin, the product of another estrogen-regulated gene in egg-laying species, is not synthesized by LMH-2A cells. Taken together, the data suggest that LMH-2A cells provide a new and promising cell system to investigate lipoprotein synthesis, assembly, and secretion in an estrogen-dependent manner.

Animals↗
PubMed1997

Identification of critical nucleotide positions for plastid RNA editing site recognition.

Transcripts in higher plant cell organelles undergo RNA editing by C-to-U conversion. Both the mechanistic steps and the factors involved in this process are largely unknown. To gain a better understanding of the molecular interactions involved in organellar RNA editing, we have begun to identify critical nucleotide positions for plastid RNA editing-site recognition. We performed a scanning point mutagenesis on a sequence motif separating editing sites IV and V in the tobacco ndhB transcript. The constructs were integrated into the chloroplast genome by the biolistic process and the effect of each point mutation on editing of both the upstream and the downstream site was measured. In addition to a previously identified sequence element located upstream of both sites, only few nucleotide positions 5' and 3' of an editing site turned out to be of critical importance. Unexpectedly, our study revealed that mutation of the upstream site leads to loss of editing at the downstream site. However, our results also indicate that, even though closely adjacent editing sites can share common recognition elements in cis, they are edited independently and not in a polar fashion.

Biolistics↗