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Biomedical subjects

B Ernst

Publications and source records attributed to B Ernst.

At least 19 recordsLinked to original sources
PubMed1996

The role of somatic mutation in the generation of the protective humoral immune response against vesicular stomatitis virus.

During most clinically relevant infections with cytopathic viruses, neutralizing antibodies are generated early, i.e., within the first week of infection. As early as 4 days after immunization of mice with vesicular stomatitis virus (VSV), a cytopathic virus closely related to rabies virus, hybridomas could be isolated that secreted virus-neutralizing IgGs. Such antibodies were devoid of somatic mutations, showed high binding avidities (approximately 10(9) M-1), and used V gene fragments predominantly belonging to the VHQ52 and VK19-28 families. In contrast, most secondary and hyperimmune response IgGs isolated 12 and 150 days after infection used several additional V gene combinations. These, which used the VHQ52/VK19-28 combination of early IgGs, were point mutated but showed only marginally enhanced binding avidities. Since all VHQ52/ VK19-28-positive IgGs bound to one subsite within the major antigenic site of VSV-G irrespective of the presence or absence of somatic point mutations, fine specificity diversification of secondary and hyperimmune responses was achieved by newly appearing V gene combinations.

Amino Acid Sequence↗
PubMed1996

Uric acid lowering effect of oxipurinol sodium in hyperuricemic patients - therapeutic equivalence to allopurinol.

OBJECTIVE: Oxipurinol has been shown to be sufficiently absorbed after oral administration as a rapid release preparation of oxipurinol sodium. We compared the uric acid lowering affect of allopurinol and oxipurinol. METHODS: In a multicenter, randomized, double blind crossover trial in 99 hyperuricemic patients with normal renal function we investigated the uric acid lowering effect of oxipurinol sodium (O) in daily amounts equimolar to 300 mg allopurinol (A). Mean pretreatment plasma uric acid concentrations in groups A/O and O/A were 8.3 +/- 1.4 and 8.7 + /- 1.4 mg/dl, respectively. RESULTS: In group A/O the mean plasma uric acid decreased to 5.4 +/- 1.2 mg/dl with allopurinol treatment, and increased slightly to 5.7 + /- 1.3 mg/dl during the consecutive oxipurinol period. In group O/A plasma uric acid declined to 6.0 +/- 1.4 mg/dl with oxipurinol and was 5.6 + /- 1.3 mg/dl at the end of the allopurinol period. The overall average reduction compared to baseline was 3.0 mg/dl with allopurinol and 2.6 mg/dl with oxipurinol. The difference between the 2 treatments was small but significant (multiple p=0.027,2 tailed). The corresponding mean plasma oxipurinol concentrations were 9.24 mu g/dl at the end of the allopurinol period and 9.9 mu g/dl after treatment with oxipurinol (NS). CONCLUSION: Oxipurinol is well absorbed and sufficiently effective in hyperuricemic patients when administered as a rapid release preparation of oxipurinol sodium. Oxipurinol sodium could be a substitute for allopurinol in hyperuricemic patients and possibly also with new uses for allopurinol.

Adult↗
PubMed1995

Thymic selection and cell division.

Cell division during thymic selection was studied with a system in which purified populations of T cell antigen receptor (TCR)- CD4+8+ (double-positive [DP]) cells and fetal thymic epithelial cells (TEC) were reaggregated in tissue culture. In this system, immature DP cells differentiate into mature single-positive (SP) CD4+8- and CD4-8+ TCRhi cells within 3-4 d, indicative of positive selection. By adding the DNA precursor, bromodeoxyuridine, to the cultures and staining cells for bromodeoxyuridine incorporation, T cell division in reaggregation cultures was found to be high on day 1, low on day 2, and high on days 4-5. Cell separation studies established that cell division on day 1 was restricted to DP blast cells. In the absence of blast cells, small DP cells failed to proliferate and differentiated into SP cells without cell division, thus indicating that proliferation is not an essential component of positive selection. This applied to SP cells generated within the first 2-3 d. Surprisingly, the SP cells generated later in culture showed a high rate of cell division; the proliferating SP cells were TCRhi and included both CD4+8- and CD4-8+ cells. Turnover of TCRhi SP cells was also prominent in the normal neonatal thymus and in TEC reaggregation cultures prepared with adult lymph node T cells. We speculate that division of mature SP cells in the perinatal thymic microenvironment is driven by stimulatory cytokines released from TEC. Such proliferation could be a device to expand the mature T cell repertoire before export to the periphery.

Animals↗
PubMed1995

Synthesis and biological activity of oligosaccharide libraries.

Random glycosylation has proven remarkably effective for the generation of mixtures of oligosaccharides. Clearly, not all of the possible glycosidically-linked isomers are formed in equal quantity in these reactions. In the instances where product structures have been thoroughly investigated, however, all have been shown to be present. So far, only one random glycosylation step has been performed and the challenge will be to see if two tandem steps can generate a useful oligosaccharide library. Whether or not the present formulation of random glycosylation succeeds as a dominant strategy for the synthesis of oligosaccharide libraries, this important challenge is open to many approaches where creativity in both formulating the problem, as well as experimentally addressing it, warrants a major international effort.

Carbohydrate Sequence↗
PubMed1995

Genotoxicity of sediment extracts obtained in the vicinity of a creosote-treated wharf to rainbow trout hepatocytes.

Genotoxicity and cytotoxicity were evaluated in rainbow trout hepatocytes exposed to sediment extracts obtained in the vicinity of a creosote-treated wharf. Sediment cores were collected at the intertidal and subtidal sections of the wharf at distances of 1, 5, 40 and 50 m. Moreover, subsamples were also taken at different depths of the cores ranging from 2 to 10 cm below the sediment/water interface. Sediment samples were air-dried and extracted in dichloromethane followed with an exchange into dimethylsulfoxide (DMSO). Rainbow trout hepatocytes were exposed for 24 h at 15 degrees C to several concentrations of the sediment extract. Afterwards, the cells were collected, and cell viability was assayed along with genotoxicity using the nick translation and the alkaline precipitation assays. Results showed that the wharf contained high concentration of polycyclic aromatic hydrocarbons (PAHs), displayed genotoxicity and cytotoxicity to hepatocytes. In addition, PAHs, cytotoxicity and sometimes genotoxicity were detected in all sediment samples and tended to decrease with distance. Chemical contamination and (geno)toxic effects were greater in sediment extracts from the intertidal section than from the subtidal section. However, no evident change in chemical or toxicological characteristics was noted between samples obtained at different depths. Spearman rank-correlation analysis revealed some trends between levels of some PAHs and (geno)toxicity in hepatocytes exposed to sediment extracts.

Analysis of Variance↗
PubMed1995

Enhanced virus resistance of transgenic mice expressing the human MxA protein.

MxA is a GTPase that accumulates to high levels in the cytoplasm of interferon-treated human cells. Expression of MxA cDNA confers to transfected cell lines a high degree of resistance against several RNA viruses, including influenza, measles, vesicular stomatitis, and Thogoto viruses. We have now generated transgenic mice that express MxA cDNA in the brain and other organs under the control of a constitutive promoter. Embryonic fibroblasts derived from the transgenic mice were nonpermissive for Thogoto virus and showed reduced susceptibility for influenza A and vesicular stomatitis viruses. The transgenic animals survived challenges with high doses of Thogoto virus by the intracerebral or intraperitoneal route. Furthermore, the transgenic mice were more resistant than their nontransgenic littermates to intracerebral infections with influenza A and vesicular stomatitis viruses. These results demonstrate that MxA is a powerful antiviral agent in vivo, indicating that it may protect humans from the deleterious effects of infections with certain viral pathogens.

Animals↗
PubMed1994

Increased glycosylation of human lens epithelial basement membrane in diabetes mellitus.

We studied the nonenzymatic glycosylation of lens epithelial basement membranes (LEBM) of senile cataractous lenses of both diabetic and nondiabetic patients. The human LEBMs were isolated from surgically removed senile cataracts and purified by osmotic lysis and detergent treatments. Glycosylation assay of LEBMs was done using the colorimetric method of Flückiger and Winterhalter. The glycosylation value ranged from 16.39 to 92.56 n mol/mg protein overall, with a mean of 63.54 +/- 24.56 n mol/mg protein for the diabetic specimens and a mean of 29.97 +/- 14.48 n mol/mg protein for the nondiabetic controls (P = 0.009). The study confirms our previous observation of in vivo glycosylation of the LEBM and further establishes that diabetic patients have a twofold increase in the amount of LEBM glycosylation when compared to their nondiabetic counterparts.

Aged↗
PubMed1994

Facile preparation of 1,6-anhydrohexoses using solvent effects and a catalytic amount of a Lewis acid.

Refluxing solutions of monosaccharides, unprotected at the 6-position and carrying O-methyl, S-ethyl, O-acetyl and OH-groups at the anomeric center, in acetonitrile containing a catalytic amount of a Lewis acid (O.1-0.4 equiv.) yielded 1,6-anhydrohexopyranoses in good to high yields. Best results were obtained with methyl 2,3,4-tri-O-dideuteriobenzyl-alpha-D-glycosides (87-91%). Dideuteriobenzyl protective groups were used to facilitate NMR spectral interpretations.

Acids↗
PubMed1994

Increased levels of soluble adhesion molecules in type 2 (non-insulin dependent) diabetes mellitus are independent of glycaemic control.

Patients with Type 2 (non-insulin dependent) diabetes mellitus are at increased risk of thrombosis and the premature development of atherosclerosis. This may be related to damage to the endothelium (which may be the primary target tissue for the disease process) resulting from a loss of normal glycaemic metabolic control. Thus changes in endothelial cell function, such as modified release of soluble leukocyte and platelet adhesion molecules, may be important. Accordingly, E-selectin, von Willebrand factor (vWf), vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM) were measured in serum from 60 patients and 76 controls. Raised levels of vWf (p = 0.0002), E-selectin (p < 0.0001) and VCAM (p = 0.003) in patient's samples failed to correlate with glycaemic control as assessed by levels of fructosamine and glycated haemoglobin, or with 24 h urine albumin. Levels of ICAM were not increased in our patients. Levels of the two endothelial cell products, vWf and E-selectin, failed to correlate although E-selectin correlated with low density lipoprotein cholesterol (p = 0.016). vWf correlated with VCAM (p < 0.001) and hypertension (p = 0.032). We conclude that levels of soluble adhesion molecules vWf, E-selectin and VCAM are raised in Type 2 diabetes mellitus. The mechanisms for these changes appear to be independent of glycaemic control but may relate to concurrent hypertension and/or hypercholesterolaemia.

Aged↗
PubMed1993

Power spectral analysis of temporomandibular joint sounds in asymptomatic subjects.

Very little has been done to quantify temporomandibular joint (TMJ) sound amplitudes and background noise and to determine the spectrum from healthy TMJs. Thus, the aim of this study was to record acoustically the sounds emitted by healthy TMJs with and without mandibular movements, for determination of baseline spectra. TMJ sounds were recorded bilaterally from 40 subjects with healthy joints by means of a self-developed recording system using miniature capacitor microphones inserted into the earpieces of a medical stethoscope placed in the meatus of the auditory canal. The recordings were performed without mandibular movements and during three consecutive opening and closing movements. The signals were high-pass-filtered at 50 Hz, low-pass-filtered at 2 kHz, and analyzed by fast Fourier transform computation on a 1024-point window (fs = 5 kHz). The linearly weighted average baseline spectrum recorded without motion showed maximum values of 31 dBSPL (sound pressure level) with a standard error of +2 to -3 dB. The linearly weighted average movement spectrum had a peak of 66 dBSPL at 156 Hz and decreased almost linearly by about 40 dB/decade to 25 dBSPL at 2000 Hz with a standard error of +/- 2 dB. Thus, the TMJ sound spectrum of mandibular movements in asymptomatic subjects differed at low frequencies by up to 35 dB from the baseline spectrum in absence of motion.

Adolescent↗
PubMed1993

Prolonged biochemical and morphological stability of encapsulated liver cells--a new method.

In this work a new type of polyelectrolyte complex capsules is introduced as an artificial housing for liver cells. Male Wistar rat hepatocytes were encapsulated using cellulose sulphate and polydimethyldialyllammonium chloride as polyelectrolytes. Amino acid metabolism rate and urea synthesis of the cells increased over the investigation period in contrast to the decrease observed in control monolayer cultures. The encapsulated cells were morphologically characterized. The described procedure represents a sufficient method for the cultivation of living cells in mechanically stable semipermeable microcapsules.

Amino Acids↗
PubMed1992

Growth of epithelial cells in the thymic medulla is under the control of mature T cells.

Epithelial cells in the thymic medulla are conspicuous in normal adult mice, but sparse in the early fetal thymus and the thymus of adult T cell-deficient SCID mice. To examine whether growth of medullary epithelial cells (MEC) depends upon local contact with mature T cells, we used the finding that the SCID thymus is unusually permeable to mature T cells entering from the bloodstream. When SCID mice received multiple injections of mature lymph node T cells from birth, the thymus accumulated large numbers of mature TCR+ T cells of resting phenotype, but contained virtually no immature (CD4+8+) cells. The injected T cells localized in the medullary region of the thymus and led to marked regeneration of MEC. These and other data suggest that the growth of MEC is under the control of mature T cells. Placing MEC under T cell control might be a device for regulating the size and integrity of the medulla, especially during the phase of rapid thymic growth. Maintaining the cellular components of the medulla in proper balance could be critical for ensuring efficient self tolerance induction.

Animals↗
PubMed1992

Biosynthesis and chemical synthesis of carboxyl-linked glucuronide of lithocholic acid.

The glucuronidation of lithocholic acid (LA) by phenobarbital-induced male Fischer 344 rat liver microsomes supplemented with UDP-glucuronic acid was studied. A single radioactive metabolite was formed and its structure was determined by high pressure liquid chromatography/particle beam/mass spectrometry (HPLC/PB/MS), both with and without prior methylation and acetylation of the sample. The reaction product was rigorously identified as the 1-O-acyl-beta-D-glucuronide of LA by comparison with a chemically synthesized standard. The chemical synthesis of the acyl glucuronide of LA was accomplished via a condensation reaction using benzyl 2,3,4-tri-O-benzyl-D-glucopyranuronate. The latter compound was prepared in two steps from benzyl 2,3,4-tri-O-benzyl-1-O-methyl-alpha-D-glucopyranuronate via the 1-O-acetyl derivative. The stereoselective beta coupling of LA with 2,3,4-tri-O-benzyl-D-glucopyranuronate was achieved by the Mitsunobu reaction, in the presence of the free hydroxyl function of LA, using triphenylphosphine and diisopropyl azodicarboxylate in THF followed by preparative TLC. The benzylic ester and ether groups were cleaved by hydrogenation with Pd on charcoal as the catalyst. Positive identification of the glucuronide was established by HPLC/PB/MS and 1H-NMR spectra. No side products formed by acyl migration were detected, but the free acyl glucuronide underwent rapid transesterification in methanol.

Acetylation↗
PubMed1992

Thymus-grafted SCID mice show transient thymopoiesis and limited depletion of V beta 11+ T cells.

To seek direct evidence for the notion that stem cells in the thymus need to be constantly replenished from the bone marrow (BM), fetal (day 15) thymuses from normal BALB/c mice were grafted into T and B cell-deficient C.B-17 SCID mice (both H-2d, I-E+). The thymus grafts in these mice showed normal thymopoiesis for the first 3 wk postgrafting but then developed sudden atrophy with near complete loss of CD4+8+ cells by 4-5 wk. Such atrophy was not seen when the thymus-grafted mice were cotransplanted with normal BM cells. The lymph nodes of SCID mice receiving thymus grafts alone contained mature T cells but virtually no B cells. This lack of B cells was associated with aberrant I-E-restricted V beta deletion: the depletion of V beta 3+ and V beta 5+ T cells was near complete, whereas V beta 11+ cells showed only marginal depletion.

Animals↗
PubMed1992

[Superoxide dismutase activity of Ginkgo biloba extract].

The Ginkgo biloba extract is obtained from green leaves of the Ginkgo biloba tree. Preparations with this active substance are among others used for the treatment of disturbances of the cerebral function and arteriosclerotic diseases. In in-vitro and in-vivo studies antagonistic effects of radical scavenger and PAF (platelet activating factor) were described. In this study a concentration-depending superoxide dismutase activity of the Ginkgo biloba extract rökan liquid could be made evident.

Diterpenes↗
PubMed1990

Measurements of plasma colloid osmotic pressure, total protein and sodium concentration during haemodialysis: can single-pool sodium modelling explain the results?

Considering the plasma colloid osmotic pressure (COP) as a possible parameter for the monitoring of dialysis treatment compatibility, a characteristic time course was found. The COP and the total protein concentration very often do not increase significantly during the first treatment hour in spite of ultrafiltration. An increase in the plasma sodium concentration, which was higher than expected, was found to be the reason for a plasma dilution effect. This can be explained by a transcapillary sodium transfer coefficient which is not infinitely high as assumed in single-pool sodium modelling. From a 2-pool model considering the plasma volume as a separate pool and including capillary filtration time courses for plasma sodium, total protein concentration and COP could be calculated, which was very similar to the measured curves.

Blood Proteins↗