Search PubMed⌕ Search

Biomedical subjects

T Lehmann

Publications and source records attributed to T Lehmann.

At least 109 records · Page 6Linked to original sources
PubMed1996

Severe osteoporosis due to systemic mast cell disease: successful treatment with interferon alpha-2B.

We describe a 33-year old man suffering from severe vertebral osteoporosis and urticaria pigmentosa due to systemic mast cell disease (SMCD). Because i.v. clodronate therapy could not prevent further vertebral fractures, an additional treatment with interferon alpha-2b was initiated. During 24 months of treatment, our patient had no further pain episodes, no new vertebral fractures were discovered, trabecular bone mineral density (BMD) increased significantly and urticarial symptoms improved. Nevertheless, the extent of skin lesions remained unchanged. On histological examination, a remarkable decrease of mast cells was observed in the bone marrow, but not in the skin. Five months after discontinuation of interferon alpha-2b, trabecular BMD decreased and urticarial symptoms deteriorated. These findings illustrate a beneficial effect of interferon alpha-2b on SMCD-induced osteoporosis as well as urticarial symptoms, and raise the question whether this treatment may have a diverse impact on mast cell population in different tissues.

Adult↗
PubMed1996

Weight-loss with low or high carbohydrate diet?

OBJECTIVE: With obesity being recognized as an important cardiovascular risk factor, it is important to determine the optimal hypocaloric diet for decreasing that risk. The goal of this study was to compare the effects of two hypocaloric diets of similar caloric value, but differing in carbohydrate content (25% and 45%). SUBJECTS: Sixty-eight out-patients were followed for 12 w. DESIGN: The patients were assigned to one of two groups that received either a low (25% CHO, n = 31) or a high (45% CHO, n = 37) carbohydrate hypocaloric diet (5.0 MJ/d, 1200 Kcal/d). RESULTS: After 12 w, the mean weight loss was similar and did not differ significantly between the two groups: 10.2 +/- 0.7 kg (25% CHO) and 8.6 +/- 0.8 kg (45% CHO). Furthermore, loss of adipose tissue was similar, 8.1 +/- 0.5 kg (25% CHO) and 7.1 +/- 0.7 kg (45% CHO). Despite a high protein intake (1.4 g/kg/ideal body weight) there was loss of lean body mass: 2.2 +/- 0.4 kg (25% CHO) and 1.4 +/- 0.3 kg (45% CHO). The waist/hip ratio diminished significantly (P < 0.001) and identically in both groups. The fasting blood glucose (even though normal, along with cholesterol and triglyceride concentrations, were significantly decreased after weight loss. The fasting blood insulin which was mildly elevated before weight loss decreased more markedly with the 25% CHO diet compared to the 45% CHO diet (P < 0.003). The glucose/insulin ratio improved significantly (P < 0.05) after weight loss with both diets (0.17 +/- 0.04 mmol/mU (25% CHO) vs 0.10 +/- 0.03 mmol/mU (45% CHO). CONCLUSIONS: Neither diet offered a significant advantage when comparing weight loss or other, metabolic parameters over a 12 w period. However, considering the greater improvement of fasting blood insulin, the glucose/insulin ratio and blood triglyceride, the low carbohydrate diet (25%) could be more favourable in the long-term. The improvement of fasting blood insulin could be explained by the differences in monounsaturated fat composition in the low carbohydrate diet.

Adipose Tissue↗
PubMed1995

Diffuse idiopathic skeletal hyperostosis (DISH) of the shoulder. A controlled radiological study.

The prevalence of hyperostotic spurs (HS) in different areas of the shoulder was studied in 36 probands with and 58 probands without thoracospinal hyperostosis on lateral chest radiographs. Bilateral shoulder radiographs in three projections were analysed blindly, recording the presence of HS at six separate sites (glenoid, greater tuberculum, acromion, acromioclavicular joint, coracoid and humeral shaft) and applying defined grading criteria. The prevalence of HS ranged from 11.7% of the shoulders at the coracoid to 50.0% at the glenoid. The prevalence of HS was similar on both sides [right, 30.1% of the sites versus left, 27.0%, relative risk (RR) 1.12 (95% confidence interval [Cl] 0.93-1.35)] and was not related to sex and history of work. Classification for the presence of shoulder hyperostosis was identical on both sides with the exception of one individual. In probands with thoracospinal and shoulder hyperostosis all areas analysed contributed to the classification. However, this was particularly prominent at the humeral shaft [RR 5.3 (95% Cl 2.1-13.0)] and the coracoid [RR 8.4 (95% Cl 1.9-36.4)]. These results indicated that the prevalence of HS and the specificity for the presence of diffuse idiopathic skeletal hyperostosis (DISH) vary between different sites. We suggest that future grading criteria for shoulder hyperostosis take into account the localization of HS, in addition to their number and size.

Aged↗
PubMed1995

The importance of tissue fixation for light microscopic immunohistochemical localization of peroxisomal proteins: the superiority of Carnoy's fixative over Baker's formalin and Bouin's solution.

We have compared the effects of fixation with three commonly used fixatives upon preservation of the antigenicity of six peroxisomal proteins in rat liver using both immunohistochemical staining and Western blotting of fixed tissue extracts. The immunoreactivity of all six peroxisomal proteins was well preserved and peroxisomes were clearly identified in material fixed in Carnoy's fixative. Moreover, the corresponding proteins stained well in Western blots prepared from extracts of Carnoy-fixed material. The intensity of the immunohistochemical staining was reduced at different rates for individual peroxisomal proteins after fixation in Baker's formalin, but peroxisomes were still well visualized with antibodies to catalase and some beta-oxidation enzymes. No evidence of immunohistochemical staining for any peroxisomal antigens was obtained after fixation in Bouin's fluid. For detection of the antibody binding sites in Carnoy's fixed material, the avidin-biotin-peroxidase complex (ABC) with aminoethyl carbazole as chromogen was found to be superior to the methods of peroxidase-antiperoxidase/diaminobenzidine and protein A-gold with silver intensification. Using Carnoy-fixative and the ABC-method, we demonstrate light microscopic immunohistochemical localization of peroxisomal antigens in several rat tissues as well as in human post-mortem liver.

Acetates↗
PubMed1995

Analysis of migration success of Onchocera lienalis microfilariae in the haemocoel of Simulium vittatum.

Migration success (i.e. the proportion of worms that reach the thorax) of Onchocerca lienalis microfilariae (mf) in the haemocoel of Simulium vittatum was studied by inoculating mf into the posterior abdomen, and recording their distribution in the blackfly body at predetermined time points. Mf arrive into the thorax by active locomotion rather than by drifting in haemolymph currents. Migration into the thorax was completed by 12 h post inoculation (pi) but was not continuous throughout this period. Migration proceeded in two phases; the first occurred 0-2 h pi and the second at 6-12 h pi. Overall, migration success 12-24 h pi was only 36%, indicating that a substantial number of mf failed to reach the thorax, either because they were eliminated by the fly's defensive response or because they remained in the abdomen. Migration success was density independent. Mf that arrive into the thorax within 2 h pi did not differ in their migration potential from mf that remained in the abdomen at this time. In flies where more mf migrated successfully there was lower mf loss, indicating that migration success was linked to mf loss. Moreover, the proportion of mf in the thorax was not correlated with mf loss, suggesting that mf loss affected the number of mf that migrated successfully, rather than the reverse causal relationship.

Abdomen↗
PubMed1995

Chemical guidance of Onchocerca lienalis microfilariae to the thorax of Simulium vittatum.

The behavioural responses of Onchocerca lienalis microfilariae (mf) to tissue factors of the surrogate black fly host, Simulium vittatum, were studied using a novel in vitro bioassay. Mf accumulated towards thoracic tissues to a density 4 times higher than towards abdominal tissues, despite the larger surface area and volume of abdominal tissues. Mf migrated toward thoracic tissues regardless of whether or not contact with thoracic tissues was possible. Therefore, mf directed themselves toward the thorax rather than arresting their movement after they make contact with thoracic tissues. Chemical cue(s) provided a principal guidance for mf to locate thoracic tissues. Mf lost their ability to differentiate thoracic and abdominal tissues following addition of thoracic attractant(s) to excised abdomens and reversed their differential response when excised thoraces were depleted of chemical cue(s). Mf did not respond to salivary gland product, but to other thoracic factor(s). Intact thorax that was connected to 1-2 abdominal segments attracted considerably less mf than excised thorax. However, intact thorax attracted more mf than excised abdomen. Abdominal tissue size did not affect thorax attractiveness. Involvement of a large molecular weight protein(s) was suggested by the high attractiveness of the 100 kDa Centricon concentrator retentate and complete precipitation of attractant(s) by ethanol.

Animals↗
PubMed1995

CoMFA investigations on two series of artificial peptide inhibitors of the serine protease thermitase. Synthesis of an inhibitor of predicted greater potency.

Comparative molecular field analysis (CoMFA) is shown to be a very useful tool in treating two series of artificial substrate analogue inhibitors, peptide methyl ketones and chloromethyl ketones, of the serine protease thermitase. The backbone structure of the native polypeptide eglin c found in the X-ray structure of its complex with the enzyme served as a template for the alignment of the inhibitors, which could be shown to be the key for success. Restricted only by the relatively small number of different amino acids representing the peptide sequence we were able to determine the regions of the compounds that are important for the value of the inhibitor constant K(i). On the basis of these results we have suggested some new structures with possibly increased inhibitory activity. One such structure was synthesized and is shown to be the most active compound tested up to now, with an experimental K(i)-value in the predicted range.

Amino Acid Sequence↗
PubMed1995

A model of the active site of dipeptidyl peptidase IV predicted by comparative molecular field analysis and molecular modelling simulations.

A molecular model of the active site of the serine protease dipeptidyl peptidase IV (DPP IV or CD26) has been developed on the basis of comparative molecular field analysis (CoMFA) of competitive inhibitors and by force field calculations. By application of CoMFA experimentally obtained inhibition constants Ki have been successfully predicted. The resulting steric and electrostatic coefficients of CoMFA were used for the development of the molecular model. The main assumptions of the model are the recognition of substrates or inhibitors by the side chains of a tyrosine (S1-position) and a tryptophan residue (S2-position). The model helps us to understand a multitude of experimental data regarding the substrate specificity of this enzyme as well as results obtained by genetic engineering experiments by other authors. General conclusions concerning a new family of serine proteases are drawn and discussed.

Binding Sites↗
PubMed1995

Vector competence of Simulium exiguum for Onchocerca volvulus: implications for the epidemiology of onchocerciasis.

In the transmission of human onchocerciasis, competence of the black fly vector influences intensity of transmission by regulating how many infective-stage larvae are produced. The disease is intensifying in Ecuador where Simulium exiguum is a highly efficient limitation-type vector comparable with African forest species in terms of the percentage of flies developing infective-stage larvae and the numbers of larvae per infected fly. In contrast, the endemic foci in Guatemala and southern Mexico have remained stable and closely circumscribed around larval development sites for S. ochraceum, a vector that exhibits a facilitation type of competence and must feed on people with comparatively high microfiladeremia to develop significant numbers of infective-stage larvae. This comparison indicates that assessments of vector competence should be included when planning regional control programs for onchocerciasis.

Adult↗
PubMed1994

Onchocerca lienalis: rapid clearance of microfilariae within the black fly, Simulium vittatum.

A rapid decrease of about a third of the number of Onchocerca lienalis microfilariae (mf) parenterally inoculated into Simulium vittatum black flies occurred within 5 hr postinoculation (pi). The change of mf counts over time was modeled by a segmented linear regression. During 2 hr pi the slope was -3.5 mf/hr (P < or = 0.001) and between 2 and 24 hr pi the slope was -0.1 mf/hr. Although significantly different from the former slope (P < 0.001), the latter was not significantly different from zero (P > 0.2). The decrease could not be attributed to excretion of mf. Microfilariae (especially those heat-killed prior to inoculation) in intermediate stages of destruction were observed in flies dissected 5 hr pi but not immediately after injection. No short- or long-term (24 hr pi) effects of the injection procedure alone on mf survival were evident. A constant proportion of mf was eliminated regardless of dose within a range of 5 to 100 mf/fly during 24 hr pi. However, a second injection of 50 mf/fly 2.5 hr following an injection of the same dose resulted in a significantly lower proportion of mf eliminated. These results suggest that the availability of an active factor(s) in the fly was reduced 2.5 hr after the first inoculation. The change in the availability of this factor(s) may partly explain the change in clearance rate occurring 2 hr pi. Soluble factor(s), rather than a sequence of cellular responses, seems to be involved in the rapid clearance because it occurred in freshly killed flies at a similar rate to that observed in live flies. The hypothesis that mf differ in their innate susceptibility to rapid clearance was rejected as mf that were recovered 2 hr pi and reinoculated into other flies were eliminated faster than unexposed controls. It is concluded that the rapid clearance of mf represents an as yet undescribed immune response to macroparasites of the fly host.

Animals↗
PubMed1994

Reinfestation analysis to estimate ectoparasite population size, emergence, and mortality.

The key components of ectoparasite vectorial capacity are poorly known, and no estimates of absolute population size for nest ectoparasites nor average longevity under natural conditions are available. A simple method to estimate these and other population parameters is suggested here, using body infestation data obtained by a specific host sampling design and the reproductive status of female ectoparasites. In contrast to mark-release-recapture techniques, this method requires minimal effort. Data on fleas, Synosternus cleopatrae (Rothschild), infesting gerbils, Gerbilus anderosoni allenbyi Thomas, were used as a preliminary test of this method. Thus, the average absolute density of female S. cleopatrae per host varied from seven in June to 24 in September; average female longevity varied from 17 to 5 d in that period. The quality of the parameter estimates was assessed by computer simulations to evaluate their variance and by comparison with the data available on fleas. The simulation indicated that estimates of absolute population size and proportion of the corporeal subpopulation were robust, but estimates of emergence rate, mortality rate, and average longevity were considerably less. The method's efficiency depends on the infestation rate and was considered suitable for medium to high counts of ectoparasites infesting solitary hosts.

Animals↗
PubMed1993

[Comparison of 2 cholesterol synthesis inhibitors (simvastatin and pravastatin)].

Inhibitors of cholesterol synthesis (HMG-CoA reductase) are the most effective cholesterol-lowering drugs. Comparison of several studies in the literature suggests that simvastatin is approximately twice as effective as pravastatin on a milligram basis. These results are confirmed by the present study, which compares treatment with simvastatin (10 mg/d) with pravastatin (20 mg/d) in the same hypercholesterolemic patients (n = 17). The reduction in LDL cholesterol is the same with twice the dose of pravastatin as with simvastatin (26 +/- 3% vs 27 +/- 2% respectively). The reductions in atherogenic ratios, total cholesterol, HDL cholesterol and ApoB/ApoA1 are similar. Undesirable effects are rare and comparable. The differences between the two inhibitors appear to be on the molecular level, in tissue selectively and regarding in vivo efficacy.

Anticholesteremic Agents↗