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Biomedical subjects

H Peters

Publications and source records attributed to H Peters.

At least 109 records · Page 6Linked to original sources
PubMed1995

Pharmacodynamics of a liposomal preparation for local anaesthesia.

A phospholipid containing formulation with tetracaine (CAS 94-24-6) for topical anaesthesia was developed. In vitro drug liberation as well as in vivo efficacy and duration of the anaesthetic effect were investigated. The in vitro liberation constant was 0-.626 +/- 0.005 mg/(cm2.square root of h for a liposomal gel formulation containing 2% (m/l) tetracaine. The gel showed high efficacy in anaesthetizing the skin after topical application. After 60 min of application complete anaesthesia of the skin was observed with all volunteers. The duration of anaesthesia after removing the application system was 150 min on average. The determination of the in vivo penetration rate resulted in values between 0.010 and 0.015 mumol/min.cm2 tetracaine.

Administration, Topical↗
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↗
PubMed1994

Bereavement care: relationships between the intensive care unit and the general practitioner.

This study examines relationships between an intensive care unit and the general practitioners within a local health authority in respect of bereavement care. A questionnaire to all 113 local general practitioners generated a response from 67 (59.3%). While about two-fifths of respondents reported at least one of their patients dying on the intensive care unit, half said that they were often first informed by relatives. Although four-fifths of inner city general practitioners offered some form of bereavement service, it ranked lowest in terms of priority on time, and a further one-seventh provided no service at all. Half the respondents thought that hospital staff could do more to help. The implications for practice are discussed.

Bereavement↗
PubMed1994

Engineering surface charges in a subtilisin: the effects on electrophoretic and ion-exchange behaviour.

The introduction or removal of multiple charged amino acid residues in the subtilisin Savinase by genetic engineering allowed us to modify the electrostatic properties of this enzyme in a systematic way. The effects of these charge changes were investigated experimentally using ion-exchange chromatography and electrophoretic mobility in native gels all under identical conditions. The experiments clearly demonstrated that the overall charge of a given protein is not the only factor determining electrophoretic mobility at low or moderate ionic strengths. For a series of variants having identical overall positive charge a linear relation was observed between mobility towards the cathode and the total number of charged residues present. This effect was found to depend on the type of (chloride) salt used: calcium ions give rise to complete screening of all negative charges, whereas only partial screening is found for magnesium and sodium ions. In contrast, in the presence of sodium phosphate the overall charge of the enzyme becomes slightly negative. These data indicate that cations as well as anions may strongly perturb the overall charge of proteins depending on the type of salt and on the number of charged amino acid residues present. The ion-exchange behaviour demonstrated similar results, i.e. showing stronger enzyme adsorption with increasing numbers of surface charges on a cation-exchange column run below the isoelectric point of the proteins. However, the apparent sign reversal noted above for electrophoresis with sodium phosphate did not appear in the ion-exchange experiments. This work provides further insight into the adsorption of proteins to surface and the role played by small ions, particularly when electrostatic forces dominate the adsorption process.

Amino Acid Sequence↗
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↗
PubMed1993

Recombinant immunoblot in the serodiagnosis of Lyme borreliosis. Comparison with indirect immunofluorescence and enzyme-linked immunosorbent assay.

A recombinant immunoblot was developed for detection of IgM and IgG antibodies in patients with Lyme borreliosis. The recombinant antigens were the chromosomal-encoded Borrelia burgdorferi proteins p100, the flagellin and an internal flagellin fragment thereof as well as the plasmid-encoded outer surface proteins A (OspA) and C (OspC). A panel of 144 sera from patients with Lyme borreliosis (erythema migrans, n = 31; neuroborreliosis state II, n = 60; Lyme arthritis, n = 24 and acrodermatitis chronica atrophicans, n = 19) have been investigated and the results have been compared to the immunofluorescence absorption test (IFA-ABS) and to two different enzyme-linked immunosorbent assays [the flagellin ELISA and a newly developed ELISA (OGP-ELISA)]. The two ELISAs were comparable in sensitivity, whereas the IFA-ABS was less sensitive for IgM antibody but equally sensitive for IgG antibody detection. Immunoblot analysis revealed that IgG antibodies are mainly reactive with p100 and the internal flagellin fragment (sensitivity 51% and 32%, respectively) and rarely with OspC (14%). All patients with late Lyme borreliosis had IgG antibodies against the p100. IgM antibodies were predominantly directed against OspC (43%) and in a lower extent against the internal flagellin fragment and p100 (15% and 13%, respectively). The complete flagellin was not useful due to a high number of unspecific reactions with control sera and the OspA was only exceptionally reactive in Lyme borreliosis patients. The sensitivity of IgM antibody detection could be increased in cases with early Lyme borreliosis from 46% to 65% when the OspC blot was performed in addition to the flagellin ELISA, or from 56% to 65% when performed in addition to the OGP-ELISA. The recombinant blot is, therefore, a valuable diagnostic test to increase sensitivity of early antibody detection and is regarded as a valuable confirmatory test also in late disease.

Antibodies, Bacterial↗
PubMed1993

Subclinical hypothyroidism and hyperlipoproteinaemia: indiscriminate L-thyroxine treatment not justified.

It is still under discussion whether subclinical hypothyroidism is a biochemical syndrome or a disease associated with an increased risk for development of vascular diseases due to lipid elevation. Therefore, we investigated lipid values in 40 patients with subclinical hypothyroidism, which is defined in terms of normal (N = 26) or slightly increased (N = 14) basal TSH values and/or an exaggerated TSH response (N = 34) to TRH (> 25 mU/l). Patients with increased lipid values were treated with L-thyroxine and reanalysed three months later. Mean levels of total cholesterol. LDL- and HDL-cholesterol and triglycerides in patients with subclinical hypothyroidism were comparable with those in normal subjects. Individual analysis, however, revealed hyperlipoproteinaemia (HL) in 22.5% of the patients investigated (HL type IIa in seven, type IV in two patients). Thyroid function was the same in affected patients as in those with normal lipid values, whereas higher age was significantly more often associated with this syndrome (p < 0.01). Treatment with L-thyroxine resulted in a significant decrease in total and LDL-cholesterol (p < 0.05), although a normalization of their lipid values could be obtained only in half of the patients. None of the subjects with hyperlipoproteinaemia had a history or clinical signs of actual vascular disease. Although the incidence of hyperlipoproteinaemia in our study group of patients with mild subclinical hypothyroidism (22.5%) is comparable to that of the normal population (21.5%), it is more severe in the former group (LDL-cholesterol in patients 5.26 +/- 0.58 vs 4.8 +/- 0.56 mmol/l in controls; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
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↗