PubMed Health⌕ Search

Biomedical subjects

H Peters

Publications and source records attributed to H Peters.

At least 19 recordsLinked to original sources
PubMed1995

Differential expression of the chicken Pax-1 and Pax-9 gene: in situ hybridization and immunohistochemical analysis.

We report the cloning, partial sequence analysis, and spatiotemporal expression of the chicken Pax-1 (chPax-1) and Pax-9 (chPax-9) gene, two closely related members of the paired box-containing (PAX) gene family. The chPax-1 gene encodes RNAs of 2.0 and 4.3 kb and a 42 kD protein while the gene products of chPax-9 are represented by 1.9 and 3.1 kb transcripts and a 39 kD protein. In situ hybridization and immunohistochemical analyses reveal chPax-1 expression in the developing pectoral girdle, in cells of the ventral part of sclerotomes, in sclerotome cells of the perichordal tube, and, later in development, in sclerotome-derived cells of the intervertebral disks. Other chPax-1 expression domains detected in the mesenchyme surrounding the atlas and axis and in chondrocytes of immature vertebral bodies, so far unreported for mouse Pax-1, correlate with as yet unexplained malformations in the mouse Pax-1 mutant undulated and Undulated-short tail. Overlapping expression of chPax-1 and chPax-9 is detected in epithelial cells of the embryonic and adult thymus and in cells of the developing intervertebral disks. Unlike chPax-1, however, chPax-9 is not expressed in those perichordal sclerotome cells which are thought to give rise to vertebral bodies. Furthermore, chPax-9 gene products are detected in circumscribed areas of mesenchyme in the metatarsus and in entodermal derivatives, i.e., in the lining epithelium of the developing pharynx and of the embryonic and adult esophagus.

Amino Acid Sequence↗
PubMed1995

Two recurrent nonsense mutations and a 4 bp deletion in a quasi-symmetric element in exon 37 of the NF1 gene.

We screened a total of 92 unrelated patients with neurofibromatosis type 1 (NF1) for mutations in exon 37 of the NF1 gene, by using temperature gradient gel electrophoresis. Two novel mutations were found: a 4 bp deletion in a so-called quasi-symmetric element (6789del-TTAC) and a recurrent nonsense mutation, which was identified in two unrelated patients, at codon 2264 (C6792A). The independent origin of the latter mutation in two families was confirmed by haplotype analysis. The nonsense mutation and the 4 bp deletion are both predicted to lead to a truncated protein product lacking the C-terminal 20% (approximately) of its sequence. The occurrence of three independent mutations among 92 NF1 patients at codons 2263-2264 (exon 37) suggests that a specific search for mutations in this area should be undertaken in screening programs for NF1 mutations.

Base Sequence↗
PubMed1995

Radioiodine therapy of Graves' hyperthyroidism: standard vs. calculated 131iodine activity. Results from a prospective, randomized, multicentre study.

The present prospective, randomized, multicentre study was performed to directly compare for the first time the effectiveness of a standard activity of 555 MBq 131iodine vs. an activity calculated to deliver 100 Gy for treatment of Graves' thyrotoxicosis. Therapeutic success was defined as the elimination of hyperthyroidism 6 months after radioiodine application (range 4.5-8 months). A success rate of more than 90% in eliminating hyperthyroidism was reported for both approaches, but only in retrospective investigations. Investigated prospectively, hyperthyroidism was eliminated in only 71% of the patients receiving standard activity (70/98) and 58% of those randomized for calculated activity (62/107). In the patients with standard activity, therapeutic success was inversely related to thyroid size. The rate was 100% for thyroid volumes < or = 15 mL, 95% for 16-30 mL, 68% for 31-45 mL, 44% for 46-50 mL, 20% for 61-75 mL and 25% for > or = 75 mL. In those patients with an activity calculated to deliver 100 Gy (except in those with a volume < or = 15 mL) this size/outcome dependency was almost compensated. The rates were 86%, 65%, 45%, 61%, 41% and 45%, respectively. Furthermore, detailed statistical analysis revealed a strong correlation between the success of therapy and the radiation dose actually absorbed by the thyroid. The rate was 11% for a target dose of 50 Gy, 50% for 100 Gy, 67% for 150 Gy, 80% for 200 Gy, 84% for 250 Gy, 88% for 300 Gy, 90% for 350 Gy and 93% for 400 Gy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Lactate transport in cultured glial cells.

Uptake of L-lactate was investigated with a radioactive tracer method in cultured rat glioma cells and in astroglia-rich primary cultures derived from rat brain. In the glioma cells, a saturable component of uptake was identified with half-maximal uptake occurring at 1.0 +/- 0.4 mM lactate. In addition, a non-saturable component dominated the uptake at high concentrations of lactate. In astroglia-rich primary cultures, no saturable component of uptake could be detected in the concentration range studied (0.1-15 mM). In conclusion, lactate uptake at physiological concentrations is predominantly mediated in the glioma cells by a carrier-dependent process, whereas in astroglial cells, simple diffusion appears to be the dominant way of lactate transport.

Animals↗
PubMed1994

On-line monitoring of monoclonal antibody production with regenerable flow-injection immuno systems.

In this paper two systems for the observation of the production of mouse-IgG during the cultivation of hybridoma cells in a perfusion reactor are presented. The direct immunosystem is based on the detection of changes in capacitance of a dielectric layer (tantalum oxide) on a metal surface (tantalum) when antibodies bind to immobilized anti-antibodies. The sensor consisted of a 25 nm tantalum oxide layer, electrochemically grown onto a laser patternized 1 micron thick tantalum layer. The indirect system is based on an automated fluorimetric sandwich ELISA system with beta-galactosidase conjugated secondary antibodies. Two cultivations of mouse hybridoma cells in a 2-1 perfusion reactor were performed. The first cultivation was monitored with the capacitance system, the second cultivation was monitored with the fluorimetric system.

Animals↗
PubMed1993

Increased expression of cytokeratins 8, 18 and vimentin in the invasion front of mucosal squamous cell carcinoma.

The immunohistochemical expression patterns of cytokeratins 8 and 18 and vimentin were examined in frozen sections of 120 human mucosal squamous cell carcinomas with special emphasis on the topological distribution in the tumour. This was done in order to evaluate in squamous cell carcinoma a particular expression pattern observed recently by us in transitional cell carcinoma of the urinary tract and designated as an 'interface phenomenon'. This phenomenon implying maximum expression of cytokeratins 8 and 18 at the tumour front, and to a lesser extent also in areas of intratumorous stroma contact, was also found in about 50 per cent of the squamous cell carcinomas examined. It was even found for vimentin, which contrasted with transitional cell carcinoma. The percentages of occurrence of the phenomenon varied for the different sites of origin of the tumour. Tumour grade did not influence the results. These findings further support the idea that invasive carcinoma cells interacting with the stromal micro-environment display a characteristic intermediate filament phenotype that deviates from the pattern expected on the basis of their direction of differentiation. These changes might reflect phenotype involved in invasive, migrating, and proliferating activities.

Carcinoma, Squamous Cell↗
PubMed1992

Expression of genes related to the human erbB, erbA, pdgf and pdgf-r in tumors of different etiology in Xiphophorus.

The melanoma determining Tu locus of the teleost Xiphophorus contains an accessory gene, x-erbB*a, which is closely related to the EGF receptor gene family, and is probably oncogenic. x-erbB*a exists in allelic forms that are specific for distinct Tu-loci, and shows high homology to a non-allelic non-oncogenic counterpart x-erbB*i which is transcribed into mRNA of 4.6 kb in non-tumorous and tumorous tissues of fish harboring and lacking Tu. Expression of a 4.0-kb mRNA in tumors (melanoma and fibrosarcoma) of different etiology is strictly correlated with the inheritance of X. maculatus x-erbB*a alleles; transcripts of 8.0 kb were detected in melanoma and carcinoma of fish harboring a certain x-erbB*a of X. variatus. The expression of the putative x-erbB*a transcripts parallels the stage of malignancy of the tumor. The expression of the xiphophorine EGF receptor gene (x-erbB) was detected in almost all tumors, is strongly enhanced in carcinoma, and is positively correlated with the degree of malignancy of melanoma and fibrosarcoma. Some tumors show expression of erbA-related genes. The PDGF receptor mRNA is expressed in all tumors analyzed and shows enhanced expression in malignant tumors of neurogenic, epithelial and mesenchymal origin. Expression of x-pdgf was observed in several cases of melanoma, but more frequently in carcinoma and fibrosarcoma. We conclude that x-erbB*a might be involved in initiation of tumors of different cellular origin and etiology in fish harboring Tu, as well as in the determination of the malignancy of the tumor. Furthermore, we assume that x-erbB*i, x-erbB, x-pdgf and x-pdgf-r play a role in secondary events in tumorigenesis by, e.g., conferring a selective growth advantage to the tumor cells.

Alleles↗
PubMed1992

Rat hepatocytes in primary culture synthesize and secrete cellular fibronectin.

Fibronectins, involved in cell-matrix interactions and cell attachment, are glycoproteins which show a remarkable heterogeneity, due to alternative splicing. The type III-related domains, ED-A and ED-B, are present in cellular fibronectin in a variety of ratios whereas they are absent in circulating plasma fibronectin. Fibronectin synthesis by hepatocytes which are accepted as suppliers of plasma fibronectin was studied in primary cultures during a 6-day culture period. Using site-specific antibodies we demonstrate that rat hepatocytes are also able to synthesize and secrete fibronectin bearing the ED-A domain from Day 3 on after inoculation. By immunocytological characterization of the hepatocyte monolayer with antibodies directed against desmin, laminin, collagen IV, alpha-SM-actin, or ED-1 or factor VIII-related antigen, contaminating mesenchymal hepatic cell-types as a source for cellular fibronectin production could be ruled out. Dexamethasone treatment caused enhanced fibronectin synthesis and cellular fibronectin was already detectable at Day 1 after plating. Elevation of cellular fibronectin synthesis after prolonged culture-terms and by dexamethasone could also be demonstrated on mRNA steady-state level, using ED-A cDNA as a probe in hybridization analysis. Dot blot hybridisation proved a prominent response of cellular fibronectin mRNA level to dexamethasone at Day 1 when dexamethasone treatment resulted in an increased contribution of ED-A-positive fibronectin transcripts to total fibronectin mRNA level.

Animals↗
PubMed1992

Determination of bone mineral density by quantitative computed tomography and single photon absorptiometry in subclinical hyperthyroidism: a risk of early osteopaenia in post-menopausal women.

OBJECTIVE: There is evidence that treatment with L-thyroxine increases the risk of early osteopaenia. The aim of our study was to investigate the effect of subclinical hyperthyroidism in patients on TSH-suppressive L-thyroxine in view of the increased risk of decalcification. DESIGN: Measurements of bone mineral density were performed in patients with subclinical hyperthyroidism at different scanning sites of varying trabecular portion. Bone mineral values as well as biochemical data were compared to those of normal controls. PATIENTS: Fifty patients (nine men, 25 premenopausal and 16 post-menopausal women) on TSH-suppressive doses of L-thyroxine were investigated after removal of thyroid cancer. MEASUREMENTS: Dual energy quantitative computed tomography was used for osteodensitometry in the lumbar spine. Single photon absorptiometry from a 125I source was applied to the calcaneus, midshaft radius and distal as well as proximal scanning sites of the distal radius. Normal bone mineral values for each measurement site were taken from healthy reference populations. RESULTS: A significant decrease of bone mineral density in the calcaneus was found in 26 of 50 patients. Bone mass assessment yielded a 9.1% decrease of mean bone mineral content in all patients compared to controls (P less than 0.01). The decrease in post-menopausal women was 22% (P less than 0.001). In premenopausal women bone mineral density changes in the calcaneus were not statistically significant. Cortical measurement sites like the midshaft radius and the proximal scanning site of the distal forearm showed a 14.8% (P less than 0.05) and 10.8% (P = NS) decalcification in post-menopausal women but normal values at the distal scanning site. The lumbar spine was not affected by subclinical hyperthyroidism in either pre or post-menopausal women. In hypoparathyroid patients, bone density did not essentially differ from normals. There was no significant correlation between bone mineral values and duration of treatment or osteocalcin values. CONCLUSIONS: Our data suggest that TSH suppressive L-thyroxine treatment has a detrimental effect on the appendicular skeleton in post-menopausal women. Additional effects of oestrogen deficiency and subclinical hyperthyroidism might lead to accelerated bone loss requiring close supervision to determine the smallest dose needed for suppression of the pituitary-thyroid axis.

Absorptiometry, Photon↗
PubMed1992

Tumor necrosis factor beta gene polymorphisms in Graves' disease.

The physical mapping of tumor necrosis factor alpha (TNF alpha) and lymphotoxin (TNF beta) genes to the short arm of chromosome 6 in man between the loci for histocompatibility leucocyte antigens (HLA)-B and the complement system focused attention to this genetic region that controls immune responses in many ways. It also holds susceptibility genes for a variety of autoimmune disorders that are linked to specific alleles of loci in the HLA D subregion. We have recently identified a TNF restriction fragment length polymorphism with the enzyme NcoI (K. Badenhoop, G. Schwarz, J. Trowsdale, et al. Diabetologia. 1989;32:445-8). The less frequent fragment of 5.5 kilobase (kb) is in strong linkage disequilibrium with the HLA haplotype A1B8DR3. Since Graves' disease is linked to A1B8DR3, we analyzed TNF gene polymorphisms in a large group of Graves' disease patients and normal controls derived from four Centers. We show here a significant association of TNF beta polymorphisms with Graves' disease. The patients have less homozygotes for the 10.5 kb band (60 of 174, 34%) and more heterozygotes 10.5/5.5 kb (96 of 174, 55%), than 173 controls (49% homozygotes 10.5 kb and 42% heterozygotes; chi 2 = 7.45, P less than 0.03). When DR3+ patients and controls were analyzed separately, heterozygotes were still significantly increased in DR3+ Graves' disease patients (54 of 77, 70%) compared to DR3+ controls (21 of 45, 47%; chi 2 = 6.6, P less than 0.04). Furthermore, TNF fragment heterozygotes were found predominantly in patients, who had TSH-receptor antibodies (29/45, 64%, P less than 0.007), implying that these patients might represent an immunogenetic subset of the disease. Although TNF beta polymorphisms are linked to A1B8DR3, these results suggest that they represent an additional susceptibility marker in Graves' disease.

Autoantibodies↗
PubMed1992

HLA-DR/DQ gene variation in nongoitrous autoimmune thyroiditis at the serological and molecular level.

The etiology of autoimmune diseases is multifactorial with genetic factors being an important prerequisite. There are two clinical manifestations of autoimmune thyroiditis: the goitrous form (Hashimoto's thyroiditis) and the atrophic variant, which is characterized by hypothyroidism (primary myxoedema). Different genetic markers were assumed to be predisposing factors for the distinct clinical presentation. In the present study, we determined HLA A,B,C,DR,DQ alloantigens serologically and HLA-DQ by gene analysis in patients with nongoitrous autoimmune thyroiditis and randomly chosen controls. To verify the exact classifications, thyroid volume (median 5.85 ml) was measured by ultrasonography. HLA-DR5 was found in 16 of 36 (44%) patients with nongoitrous autoimmune thyroiditis and in only 26 of 175 controls (15%) (Pc = 0.0018). There was a tendency towards a lower frequency of HLA-DR7 with 6% positivity in patients vs. 29% in controls (Pc = 0.052). Regarding HLA-DQ, DQ7 was found in 17 of 35 patients (48%) vs. 21 of 98 controls (21%) (Pc = 0.028) (relative risk 3.5). No other association was found with HLA-A,B,C and HLA-DR and -DQ. Our data indicate that the genetic susceptibility to autoimmune nongoitrous thyroiditis is closely associated to HLA-DR5 and DQ7 and not distinct from goitrous disease. We conclude that factors other than genetic ones explain the different immunological and clinical manifestation of chronic lymphocytic thyroiditis.

Autoimmune Diseases↗
PubMed1991

The relevance of genetic susceptibility in Graves' disease and immune thyroiditis.

It has been known for a long time that there is an increased incidence of Graves' disease and immune thyroiditis in certain families. Genetic research of this disease has shown that it is most probably transmitted in a multifactorial way, i.e. that environmental as well as genetic factors play a role in the genesis of the diseases. This hypothesis is supported by the fact that the rate of concordance is maximally 50% in identical twins. The following model of threshold values is conceivable for the formal genetics of Graves' disease and immune thyroiditis: the diseases break out whenever the sum of environmental (viruses, bacteria, iodine excess, hormones, stress) and genetic (MHC and non MHC-restricted) factors is higher than a given threshold. One of the major genes influencing the genesis of the diseases seems to be HLA-DR3 (or a closely linked gene in strong linkage disequilibrium). If this gene is present, fewer environmental factors are possibly needed.

Disease Susceptibility↗
PubMed1991

Phenotypic features of smooth muscle cells during the evolution of experimental carotid artery intimal thickening. Biochemical and morphologic studies.

Balloon catheter denudation of rat carotid artery that results in significant medial damage is followed by marked intimal smooth muscle cell (SMC) proliferation associated with limited endothelial regrowth. In this report we demonstrate that: (a) SMC of the carotid media, preceding their intimal proliferation, develop a cytoskeletal profile and morphology consistent with a de-differentiated SMC phenotype; and (b) both medial and intimal SMC subsequently revert to a cytoskeletal profile and morphology reflecting incomplete but significant re-differentiation toward normal SMC phenotype. Specifically, early after balloon injury, SMC of the media and those that have migrated into the intima contain decreased amounts of actin, desmin, and tropomyosin and increased amounts of vimentin; moreover, beta-actin becomes the dominant actin isoform, whereas alpha-actin decreases as compared with that found in normal medial SMC. Late after balloon injury, actin is still less abundant, however, desmin, tropomyosin, and vimentin return toward normal values and both medial and intimal SMC again show a predominance of alpha-actin, although the endothelium does not regenerate over the central surface of intimal thickening in this model. The SMC surface to volume ratio significantly decreases early after balloon injury, whereas it is not significantly different late after balloon injury as compared with that of SMC of the normal carotid media. We demonstrate, furthermore that: (c) adjacent luminal SMC are interconnected by gap junctions and develop focal tight junctions, a feature not reported previously to occur in smooth muscle; these cells however do not form any well defined membrane specialization with the leading edge of endothelium, supporting the view that presence of modified SMC on the luminal surface of chronically denuded vessels is not responsible for the cessation of endothelial regrowth.

Actins↗
PubMed1990

[What is the recurrence rate for Basedow's disease treated with thyrostatic agents. Answers from a prospective study].

Graves' disease is an autoimmune disease whose development involves immunogenetic and exogenous factors such as viruses, bacteria and iodine excess. In a number of patients the disease follows a chronic recurrent course. A recurrence rate of 50% can be expected one year after the end of therapy. Based on the preliminary results of the prospective study presented here, this recurrence rate does not differ in groups where patients underwent long-term treatment with 10 or 40 mg thiamazole. Retrospectively obtained data suggest that the time at which euthyroidism occurs under low-dose treatment is dependent on the alimentary iodine supply. A number of groups have attempted to develop clinically applicable methods to identify patients at risk for recurrence at the end of treatment. All the studies yielded controversial results. A prospective multicenter study was undertaken to reinvestigate the importance of measuring TSH receptor antibodies and performing the TRH test and the suppression test at the end of therapy in connection with this problem. In 451 patients the recurrence rate was 50.3% one year after the end of treatment. The patients in the recurrence group had a significantly higher rate of persistent antibody activity, no increase in TSH after TRH (negative TRH test), no normal suppressibility of thyroid 123 iodine uptake (negative suppression test) and larger goiter. The calculation of sensitivities and specificities shows, however, that these differences are not large enough to be of clinical importance for the individual patient.

Autoantibodies↗