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Biomedical subjects

M Hermann

Publications and source records attributed to M Hermann.

At least 73 records · Page 4Linked to original sources
PubMed1998

Expression and conservation of apolipoprotein AIV in an avian species.

In birds, intestinally derived lipoproteins are thought to be secreted directly into the portal vein rather than to enter the circulation via the lymphatic system as in mammals. Hepatic clearance of these so-called portomicrons must be rapid, but the protein(s) mediating their catabolism, presumably analogues of the 36-kDa mammalian apolipoprotein E, have not been identified. In searching for such a mediator(s), we have isolated a hitherto unknown 38-kDa protein from chicken serum, which we identified by microsequencing and molecular cloning as a counterpart to mammalian apolipoprotein AIV (apoAIV). Mature chicken apoAIV consists of 347 amino acids, lacks cysteine residues, and displays 57% sequence identity with human apoAIV and, to a significantly lesser extent, with apoAIVs of rodents. This first nonmammalian apoAIV characterized is the smallest homologue reported so far, because of the lack of repeated motifs at the carboxyl terminus with the consensus sequence Glu-Gln-Glu/Ala-Gln, a hallmark of mammalian apoAIVs. Chicken apoAIV (isoelectric point, 4.65) is also considerably more acidic than its human counterpart. Agarose gel electrophoresis revealed that unlike human apoAIV, which migrates to a pre-alpha-position, chicken apoAIV shows fast alpha migration. Functional characterization demonstrated that the avian protein is able to activate the enzyme lecithin:cholesterol acyltransferase. Roosters and hens express apoAIV predominantly in the gut, one-fifth as much in the liver, and no other sites of expression are identifiable by Northern blot analysis. Although pronounced intestinal synthesis is common to apoAIVs, the features of the avian protein support the notion that it represents a prototype of an apoprotein that evolved to acquire possibly distinct functions in mammals and birds.

Amino Acid Sequence↗
PubMed1998

Reduced phagocytosis of apoptotic cells in malignant lymphoma.

Efficient removal of lymphocytes undergoing programmed cell death (apoptosis) by macrophages plays an important role for the proper function of normal immune system. Furthermore, in malignant lymphoma, elimination of apoptotic tumor cells by phagocytes contributes to the anti-tumor immune response. It is unknown, however, whether macrophages in normal and malignant lymphoid tissues differ in their ability to recognize and remove apoptotic cells. Our present results demonstrate that normal and malignant lymphoid tissues differ according to the extent of the infiltration by macrophages. The highest densities of macrophages (p < 0.0001) were detected in diffuse large B-cell lymphoma, centroblastic (DLBCL-CB) and immunoblastic variants and Burkitt's lymphoma. The grade of the macrophage infiltration correlated with the proliferation rates of the tumors (p < 0.0001). Compared with normal lymphoid organs, malignant lymphoma contained lower percentages of apoptotic cells phagocytosed by tissue macrophages (p < 0.001). Of all lymphomas tested, mantle cell lymphoma and DLBCL-CB expressed the lowest percentages of phagocytosed apoptotic cells (p < 0.0001).

Apoptosis↗
PubMed1998

Equinins in equine neutrophils: quantification in tracheobronchial secretions as an aid in the diagnosis of chronic pulmonary disease.

Equinins are a closely related group of proteins found in equine neutrophil granules. They demonstrate proteinase inhibiting activity restricted to microbial proteinase K and subtilisin, and they also possess antibacterial and antiviral properties. Antiproteinase K activity was measured in tracheobronchial secretions (TBS) of horses with mild (n = 15), moderate (n = 30) and severe (n = 16) chronic pulmonary disease, to determine its usefulness as an indicator of severity of disease and to measure neutrophil content. Determination of proteinase K inhibiting activity was based on a colorimetric assay measuring the suppression of 4-nitroaniline liberation from the synthetic substrate succinyl-L-alanyl-alanyl-alanin-4-nitroanilid, a process mediated by proteinase K. Proteinase K inhibiting activity proved to be a valid and simple indicator for assessing neutrophil content in TBS and a useful parameter to determine the severity of chronic pulmonary disease in the horse.

Animals↗
PubMed1998

Preventive strategies in endothelin-induced renal failure.

The endothelial vasoconstrictor endothelin (ET) can induce acute renal failure when fibrinolysis and vasodilatory prostanoids (PGs) are inhibited. This study compares therapeutic agents preventing ET-induced acute renal failure in anesthetized female pigs. We investigated the effect of four ET boli (1.5 microg/kg, i.v.) after pretreatment with indomethacin (2 mg/kg) and epsilon-aminocaproicacid (100 + 50 mg/kg) alone (controls, group 1) or during additional nifedipine (10 microg/kg/h; group 2), hirudin (0.5 mg/kg; group 3), or enalapril (2 x 0.15 mg; group 4) on coagulation, PGs, and renal function. The ET-induced blood pressure increase was lower in groups 2 to 4 (lowest in group 3, P < 0.05). PG synthesis was blocked in all groups. The initial hypercoagulability (controls) resulted in disseminated intravascular coagulation that was prevented by hirudin and was attenuated in groups 2 and 4. At the end of the experiment, creatinine clearance was significantly (P < 0.05) decreased. The recovery of renal function two hours after the last ET bolus was most pronounced in the hirudin group. All therapeutic drugs attenuated ET-induced impairment of renal function. Hirudin seems to be the most potent protective drug. Prevention of further ET release evoked by ET-mediated secretion of thrombin might explain this. These results suggest three important pathways for ET's hemodynamic and renal effects.

Acute Kidney Injury↗
PubMed1998

Reassessment of the role of human placental lactogen in physiological non-pregnant and pathological conditions.

The recent demonstration of ectopic production of human placental lactogen (PL) in the human testis and ovary prompted us to reassess its role under non-pregnant physiological and pathological conditions. Possible physiological hPL concentrations and potential age-related changes in the sera of healthy young and elderly individuals (n = 75) selected according to the SENIEUR-protocol were investigated by a highly sensitive (detection limit: 2 pg/ml) and specific (cross-reactivity with prolactin and human growth hormone (hGH) of less than 0.001% and 0.0001%, respectively) monoclonal antibody-based time-resolved fluoroimmunoassay (IFMA) established in our laboratory. All individuals, even the aged probands (mean age: 72 +/- 3a), had hPL-levels below 20 pg/ml, in contrast to glycoprotein hormones, such as luteinizing hormone or human chorionic gonadotropin (hCG). To determine the significance of hPL as a tumour marker, serum samples of 12 testicular cancer patients with highly elevated levels of holo-hCG (mean: 42.490 ng/ml) at diagnosis were followed over 6-12 months and analysed with the hPL-IFMA. Elevation of hPL was seen in 10 patients, but the respective levels were 2-3 orders of magnitude smaller than those of holo-hCG and returned earlier to undetectable values. These in vivo data were compared to the hPL secretion pattern of the choriocarcinoma cell lines JAR and BeWo in vitro. In tissue culture supernatants of the two cell lines hPL was detected only in JAR cells, whereas both cell lines secreted holo-hCG. In conclusion, the fact that hPL is not physiologically present in peripheral blood but is produced ectopically in the human testis and ovary suggest auto/paracrine functions of this molecule. The significance of hPL as a tumour marker for patients with testicular cancer is limited as it provides no additional information to holo-hCG.

Adult↗
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↗