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Biomedical subjects

W Vogel

Publications and source records attributed to W Vogel.

At least 271 records · Page 15Linked to original sources
PubMed1993

Assessment of diabetic neuropathy: definition of norm and discrimination of abnormal nerve function.

One hundred one normal subjects and 46 patients were investigated. Various objective and subjective tests for polyneuropathies were compared. Motor and sensory nerve conduction velocities are the most sensitive tests. In normals, age hardly influenced nerve conduction velocities. This is believed to be a result of the strict exclusion criteria. Diagnostic sensitivity is also high with the vibration fork test and with vibratometry at the big toe. Results with the method of limits are as reliable and sensitive as more cumbersome techniques, such as the titration method and the forced choice method. Thermal thresholds and cardiovascular tests are less sensitive. The most correct overall classification is attained with a combination of tests reflecting the function of different nerve fiber classes in the peripheral and autonomic nervous systems.

Adolescent↗
PubMed1993

A prospective cytogenetic study of third-trimester placentae in small-for-date but otherwise normal newborns.

Data in the literature suggest that confined placental mosaicism might be associated with intrauterine growth retardation. However, this association may be coincidental and due to bias of ascertainment. We therefore started a prospective study based on the cytogenetic evaluation of placentae derived from growth-retarded newborns. We further minimized possible bias by excluding those small-for-date infants displaying findings which already could explain intrauterine growth retardation (mothers who are smokers, multiple pregnancies, gestosis, dysmorphic infants). In a collection of 71 small-for-gestational age newborns, we did not see a single case of true confined placental mosaicism.

Cells, Cultured↗
PubMed1993

Cytogenetic diagnoses after chorionic villus sampling are less reliable in very-high-or very-low-risk pregnancies.

An increasing number of cytogenetic prenatal diagnoses are performed on chorionic villus samplings. The accuracy of this method is influenced by chromosomal mosaicism, mostly confined to direct preparation methods. Especially those investigators who have experienced false-negative and false-positive findings propagate the combined use of direct and culture methods. Yet large collaborative studies have shown that in approximately two-thirds of diagnostic cases only one procedure is applied. Moreover, the accuracy of a cytogenetic investigation depends not only on the ontogenetic origin of the tissues investigated, but also on interacting factors such as the 'a priori risk' and the 'predictive value of a cytogenetic finding'. On this basis a differentiated prenatal diagnostic procedure is discussed, including either sole short-term culture (STC), combined STC and long-term culture (LTC), primary amniocentesis (AC), or primary percutaneous umbilical blood sampling (PUBS). The predictive value of the cytogenetic diagnosis from CVS varies significantly dependent on the a priori risk of a chromosome aberration and, in the case of an abnormal karyotype, on the specific chromosome involved. A non-mosaic and 'non-lethal' trisomy detected in STC is highly representative of the embryo/fetus, but there are exceptions of limited predictive value, e.g., trisomy 18. Guided by the strategy of an optional follow-up by LTC, AC, or PUBS in 1317 successive CV samplings, we are not aware of a false-negative diagnosis, but probably had one false-positive diagnosis: 47,XXY after STC; 46,XY after LTC. When referring to the rate of fetuses with an unbalanced karyotype expected in the different indication groups, a relative increase of false-positive findings in the very-low-risk group (maternal age < or = 35 years of age) and of false-negative findings in the very-high-risk group (abnormal ultrasonographic findings) of pregnant women when only performing CVS becomes obvious. Because of this dilemma, AC or--especially in the latter group--PUBS might be primarily offered to these indication groups instead of CVS.

Adult↗
PubMed1993

Human decorin gene: intron-exon junctions and chromosomal localization.

All of the protein-encoding exons and the 3' flanking region of the human decorin gene have been cloned and partially sequenced. The locations of the intron-exon junctions within the coding portion of the gene were identical to those found for the homologous human gene, biglycan. The sizes of the introns in the decorin gene, however, were substantially larger than those of the same introns of the biglycan gene. Portions of introns 1, 2, and 3 as well as exon 1 were not found during our extensive screening process. The 5' end of intron 2 was found to have an AG-rich region followed immediately by a CT-rich region. Furthermore, the 5' end of intron 3 was very rich in thymidine, whereas the 3' end of intron 7 was rich in adenosine. Several cDNA clones constructed from cultured human bone cell mRNA were found to contain a different sequence at the 5' end compared to that previously published for mRNA from a human embryonic fibroblast cell line. We were also unable to find the alternate 3' flanking region of the previously published cDNA sequence. We have mapped the human decorin gene by in situ methods to chromosome 12q21.3.

Amino Acid Sequence↗
PubMed1993

Assignment of the human aggrecan gene AGC1 to 15q25-->q26.2 by in situ hybridization.

The human aggrecan gene (AGC1) has been localized to 15q25-->q26.2 by in situ hybridization. Although no genetic diseases of connective tissue map to this location, the malignant melanoma-associated surface antigen mel-CSPG is located here; mel-CSPG is a chondroitin sulfate proteoglycan. This raises the possibility that AGC1 and mel-CSPG may be the same gene.

Aggrecans↗
PubMed1993

A method for rapid exchange of solutions at membrane patches using a 10-microliters microcapsule.

A rapid exchange (less than 2 ms) of the bath solution facing a membrane patch is accomplished by driving the tip of a pipette from the bath through a 100-microns oil layer into a small capsule filled with 10 microliters test solution. The microcapsule method can be applied to both excised patch configurations, inside-out and outside-out patches. On and off reactions of Ca(2+)-activated K+ channel activity have been recorded after changing the intracellular Ca2+ concentration using an inside-out patch. A blockade of these K+ channels by external tetraethylammonium ions is demonstrated with an outside-out patch. The blocking kinetics of delayed-rectifier K+ channels by a purified peptide toxin from snake venom, dendrotoxin, could be measured with our microcapsule method. Using tiny volumes of test solutions this method can be helpful in experiments involving scarce or expensive solutions.

Animals↗
PubMed1993

Pilot study of natural human interleukin-2 in patients with chronic hepatitis B. Immunomodulatory and antiviral effects.

Ten patients with chronic hepatitis B received increasing doses of nIL-2 (30,000 U, 100,000 U, 300,000 U, 1.0 million U) subcutaneously in a phase I trial. Each dose was applied once per week over 3 weeks. Serum samples were taken before and 2, 12, 24, 48 and 72 h after the first application of each dose level. Serum concentrations of interleukin-1 (IL-1), IL-2, IL-6, interferon-alfa (IFN-alpha), IFN-gamma, tumor necrosis factor-alpha (TNF-alpha) and GM-CSF as well as the cytokine-dependent serum components neopterin, beta-2-microglobulin (B2M), C-reactive protein (CPR), soluble IL-2-receptor (sIL-2R) and 2'-5'-oligoadenylate synthetase (2-5 OA) were assayed using ELISAs and RIAs. None of the samples tested contained measurable cytokine levels other than IL-2. A low and non-toxic dose of 300,000 U nIL-2 was already biologically active with induction of neopterin, B2M and sIL-2R. Dose-dependent changes peaked 24-48 h after application. The same patients were then enrolled in a phase II trial. Treatment in five of the patients was continued twice per week for 3 months with a biologically active dose of 300,000 U nIL-2 subcutaneously. Two of these patients as well as another five patients from the original group were treated with 1.0 million U nIL-2 subcutaneously, twice weekly for 3 months. Neither a biologically active but non-toxic dose of 300,000 U nIL-2, nor a toxic dose of 1.0 million U resulted in permanent clearance of hepatitis B early antigen (HBeAg).(ABSTRACT TRUNCATED AT 250 WORDS)

2',5'-Oligoadenylate Synthetase↗
PubMed1993

Mitotic stability of fragile X mutations in differentiated cells indicates early post-conceptional trinucleotide repeat expansion.

We demonstrate here that somatic variation of CGG repeat length is based on a mosaic of cells with different but stable FMR-1 alleles and does not reflect permanent mitotic instability. The length of a particular allele in an individual cell was maintained in progeny cells establishing a clone. The mutation patterns of multiple repeats in the DNA of fetal tissues were identical and did not significantly change during proliferation in vitro. It is proposed that genotype mosaicism and expansion to full mutation are generated post-conceptionally by the same molecular mechanism in a particular window of early development.

Alleles↗
PubMed1993

Enhanced expression of the murine FMR1 gene during germ cell proliferation suggests a special function in both the male and the female gonad.

To elucidate the function of the FMR1 gene, we applied RNA in situ hybridization to cryosections of mice from different developmental stages. The murine Fmr-1 was found transcribed in a ubiquitous manner with an expression pattern similar to glyceraldehyd phosphate dehydrogenase, Gapdh, which was used as a control gene. A significant difference in the Fmr-1 expression pattern, however, was markedly enhanced expression specifically confined to the testis and the fetal ovary. In the immature and mature testis an elevated level of Fmr-1 expression is found in type A1 spermatogonia. Expression in the testis is observed in fetal life, reaches the highest level in the immature testis, and declines early in adult life. In the mature ovary no specific Fmr-1 expression signal was found but enhanced levels were seen in the fetal ovary. At this developmental stage proliferation of oogonia takes place. It is suggested that FMR1 serves a special function during germ cell proliferation in males and females. These findings are discussed in the light of the current observation that fragile X patients produce only sperm with a premutation sized allele. Two hypotheses are put forward: (1) In males lack of FMR1 function results in a premeiotic defect preventing spermatogonia with a full mutation to reach meiosis. A fragile X mutation can be passed on to offsprings only as a premutation (selection hypothesis). (2) Transition of a premutation allele to full mutation occurs in a postzygotic stage after separation of the germ line and is restricted to soma cells (restriction hypothesis). Expression of FMR1 in proliferating germ cells is in line with both hypothesis.

Aging↗
PubMed1993

Spontaneous bacterial peritonitis is associated with high levels of interleukin-6 and its secondary mediators in ascitic fluid.

We investigated 37 patients with ascites and liver cirrhosis in order to examine whether on the basis of correlation of cytokines and acute phase proteins of the ascitic fluid, prognosis of spontaneous bacterial peritonitis can be made. Significantly enhanced levels of interleukin-6, as well as acute phase reactants alpha-1-antitrypsin and C-reactive protein were found in the ascitic fluid of patients with spontaneous bacterial peritonitis. The levels of tumour necrosis factor alpha (TNF-alpha), neopterin, interleukin 2-receptor and granulocyte-macrophage colony stimulating factor were higher in patients with spontaneous bacterial peritonitis, but without statistical significance, whereas no differences were found between the interferon gamma, interleukin-2 and interleukin-1 levels. In addition, interleukin-6, TNF-alpha and neopterin levels were found to correlate significantly with the outcome of the disease. These findings show that acute phase reaction occurs in the ascitic compartment in correlation with the development of spontaneous bacterial peritonitis.

Acute-Phase Proteins↗
PubMed1993

Single voltage-dependent potassium channels in rat peripheral nerve membrane.

1. Voltage-dependent potassium channels were investigated in rat axonal membrane by means of the patch-clamp recording technique. Three different types of channels (F, I and S) have been characterized on the basis of their single-channel conductance, activation, deactivation and inactivation properties. 2. The fast (F) channels were activated smoothly at potentials (E) between -50 and 50 mV (E50 = 4.6 mV). They had a conductance of 55 pS for inward current and 30 pS for outward current in solutions containing 155 mM K+ (high K+) on both sides of the membrane at 21-23 degrees C. The F-channels demonstrated the fastest deactivation, within 1-2 ms, and inactivated in a few hundreds of milliseconds. The time constant of inactivation was 143 ms at E = +40 mV. 3. The intermediate (I) channels activated steeply between E = -70 and -50 mV (E50 = -64.2 mv) and had a single-channel conductance of 33 pS for inward and 18 ps for outward currents. The I-channels deactivated with intermediate kinetics with the time constants of 20.4 ms and 10.1 ms at E = -80 mV and E = -100 mV, respectively. Complete inactivation of the channels developed over tens of seconds. The time constant of inactivation was 7.4 s at E = +40 mV. 4. The slow (S) channels were active at potentials positive to -90 mV. Their conductance was 10 pS for inward currents. The time constant of activation of the S-channels was strongly potential dependent. At a holding potential of -100 mV the channels deactivated during a long time interval between 30 ms and 1 s, producing long-lasting tail currents. The mean time constant of deactivation for S-channels was 129 ms. 5. The conductances of F- and I-channels measured under normal physiological conditions (Ringer solution in bath) were 17 and 10 pS, respectively. 6. Tetraethylammonium (TEA), the classic blocker of potassium channels, suppressed F-, I- and S-channels. It gradually reduced the apparent amplitude of unitary currents in a dose-dependent manner with IC50 equal to 1.2 mM for F-channels, 0.6 mM for I-channels and 1.4 mM for S-channels. Dendrotoxin (DTX), a toxin from the green mamba snake, considerably inhibited the I tail currents at nanomolar concentrations (IC50 = 2.8 nM) while the amplitudes of single I-channel currents were not affected. 7. The K+ channels of F, I and S types form the basis of the potassium conductivity in mammalian peripheral myelinated axon.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗