Search PubMed⌕ Search

Biomedical subjects

T Weber

Publications and source records attributed to T Weber.

At least 289 records · Page 16Linked to original sources

Kainate and NMDA toxicity for cultured developing and adult rat spiral ganglion neurons: further evidence for a glutamatergic excitatory neurotransmission at the inner hair cell synapse.

In the inner ear, the excitatory amino acid glutamate is a proposed neurotransmitter acting at the synapse between hair cells and afferent auditory neurons. Using cultures of 5-day-old rat auditory neurons, we show that the afferent auditory neuronal population can be divided, on the basis of its sensitivity to the neuronotoxic effect of glutamate and its analogs, in at least 3 subpopulations, one responding to N-methyl-D-aspartate (NMDA), one responding to kainate and a third minor one unresponsive to NMDA, kainic acid and glutamate. No toxic effect of quisqualate is observed. The use of specific antagonists (kynurenate and 2-amino-5-phosphonovalerate (DAP-5) demonstrates the specificity of the receptors to the excitatory amino acids on the afferent auditory neurons. Afferent auditory neurons from adult rats can also be cultured and in these preparations only the large neurons are sensitive to glutamate, kainate and NMDA while the small neurons are not responsive, suggesting that a glutamatergic neurotransmission occurs only at this synapse between the inner hair cells and the large radial afferent auditory neurons. We also show that, in vitro, the organ of Corti releases, in response to an increased potassium concentration and in the presence of calcium, a toxic activity for the afferent auditory neurons that is antagonized by kynurenate and DAP-5. Pathophysiological implications are discussed.

2-Amino-5-phosphonovalerate↗

[Analysis of fetal ECG during delivery].

In order to render monitoring of delivery optimal, several new technological methods have found favour during the years. The few randomized investigations of foetal monitoring available do not show any effect on morbidity and mortality. Changes in the foetal ECG have been the object of intense research in the hope of obtaining a better indicator of foetal asphyxia. Experimental and also clinical investigations suggest that detailed analysis of the foetal ECG supplements cardiotocography and improves its diagnostic specificity. Many investigations have demonstrated that changes in the ST-segment, particularly increase in the T-wave are related to foetal hypoxia. The ratio between the height of the T-wave and the QRS complex (T/QRS-ratio) quantities this change in the ST-segment. Registration and quantitating of this change in the ST-segment require a microprocessor monitor to automize ECG analysis. Investigations to date suggest that this monitor can diagnose foetal asphyxia but more extensive investigations are necessary in order to establish the validity of an ECG analysis of this type during delivery.

Animals↗

The use of recombinant antigens in ELISA procedures for the quantification of intrathecally produced HIV-1-specific antibodies.

An ELISA procedure is described for the quantification of intrathecally synthesized immunoglobulin G antibodies to human immunodeficiency virus (HIV) antigens. Recombinant p17, p24, endonuclease (END), reverse transcriptase (RT), a peptide from the transmembrane region of gp41 (ENV80) and a fusion protein containing HIV-1 and HIV-2 epitopes were compared with a commercially available ELISA. Using a reference serum, antibodies in serum and cerebrospinal fluid (CSF) to all of the antigens could be measured quantitatively in a reliable and reproducible fashion. Despite the fact that the titer varied up to 10(5)-fold between CSF and serum, interassay variability ranged from 3.87% for p17 to 8.41% for RT and intra-assay variability varied from 3.9% +/- 1.2% for p17 to 14.3% +/- 3.9% for the commercial ELISA. Antibody specificity indices (ASI) obtained by relating CSF/serum titers with reference to the corresponding IgG concentrations can be used to detect intrathecal synthesis of virus specific antibodies.

Enzyme-Linked Immunosorbent Assay↗

Conformation and formation tendency of the cyclotetrapeptide cyclo (D-Pro-D-Pro-L-Pro-L-Pro): experimental results and molecular modeling studies.

The title compound represents the smallest member of cyclic proline peptides corresponding to the general formula c(DDLL-Pro4)n with a strictly D,D,L,L double-alternating sequence of the chiral amino acid residues. The cyclopeptides with n greater than or equal to 2 could be synthesized from both DDLL-Pro4 (1) and DLLD-Pro4 (2). The cyclic monomer (n = 1) resulted only from 2, whereas not even a trace could be found by cyclization of 1. The peptide exists in a strongly strained Ci symmetrical conformation (x-ray analysis) with alternating cis and trans peptide bonds (ctct form I). The cis peptide bonds deviate from planarity (omega = 22 degrees); two of the pyrrolidine rings show a "South" conformation (phi = -94 degrees), whereas the other residues exhibit C alpha-endo puckering (phi = -124 degrees). Two of the psi angles surprisingly occur at +41 degrees (anti-cis'), the others are located in the trans' region. A quantitative ring opening occurs with trifluoroacetic acid at room temperature. In solution the existence of an isomeric ctcc sequence (form Ia) is indicated. Dreiding model studies also suggested a favorable conformation with a tctc sequence (form II). Consequently, we performed molecular mechanics calculations, based on the CHARMM force field and semiempirical quantum mechanical AM1 calculations (MOPAC program). Pronounced differences in the backbone parameters were found using these two methods. However, the theoretical studies evidenced the experimentally obtained differences in the cyclization tendencies of the linear precursors.

Amino Acid Sequence↗

Aspects related to mevalonate biosynthesis in plants.

We purified and characterized a membrane-associated enzyme system from radish (Raphanus sativus L.) that is capable of converting acetyl-CoA into 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA). The enzyme system apparently comprises acetoacetyl-CoA thiolase (EC 2.3.1.9) and HMG-CoA synthase (EC 4.1.3.5). Its activity in vitro can be strongly stimulated by FeII. When ferrous ions are applied chelated with ethylenediaminetetraacetate, citrate or adenosine 5-triphosphate (ATP), the stimulation is further increased. Stimulation is due to a higher catalytic efficiency as indicated by an increase in Vmax, whereas the affinity of the enzyme towards acetyl-CoA remains constant (Km = 6 micro M). A considerable portion of HMG-CoA lyase activity is associated with the same membranes. HMG-CoA lyase (EC 4.1.3.4) is also solubilized and partially co-purified. Its activity requires comparatively high concentrations of Mg2+. The conversion of HMG-CoA to mevalonic acid is catalyzed by HMG-CoA reductase (EC 1.1.1.34) that is associated with the same membranes. By cDNA encoding the Arabidopsis HMG-CoA reductase, we isolated a corresponding gene from a cDNA library newly established from etiolated radish seedlings. This full-length cDNA, referred to as lambda cRS3, encodes a polypeptide 583 amino acids with a molecular mass of about 63 kDa. The hydropathy profile suggests the presence of two hydrophobic membrane-spanning domains within the N-terminal 165 amino acids. The carboxy-terminal part, where the catalytic site resides, is highly conserved in all eukaryotic HMG-CoA reductase genes sequenced so far.

Acetyl Coenzyme A↗

3-p-hydroxyphenylpropionic acid--a sensitive fluorogenic substrate for automated fluorometric enzyme immunoassays.

The application of 3-p-hydroxyphenylpropionic acid (HPPA), a fluorogenic substrate of horseradish peroxidase (HRP) to an automated microplate fluorometric enzyme immunoassay is described. Fluorescence intensity of the end product was highly dependent on the pH of the buffer and on the concentrations of the substrate mixture ingredients. The determination of human thyrotropin (TSH) and recombinant hepatitis B surface antigen (rHBsAg) were performed using a fluorometric enzyme immunoassay (FEIA) with HPPA as the substrate, and a colorimetric one with tetramethylbenzidine (TMB) as the chromogenic substrate. The sensitivity of both types of assays proved comparable. The distinct advantage of a fluorometric assay is the possibility to perform a quantitative detection of analyte over a very wide dynamic range. Clinical evaluation of both assays showed good correlation between the FEIA and conventional methods.

Evaluation Studies as Topic↗

TGFSS1 modulates bFGF receptor message expression in cultured adult auditory neurons.

Basic fibroblast growth factor (bFGF) has been shown to have neuronotrophic effects on cultured neurons. Transforming growth factor beta (TGFss1) has been implicated in the modulation of cellular receptors for bFGF in several cell types. In this study, we show that TGFss1 is expressed in cultured adult mouse auditory neurons in response to explanation injury and acts in an autocrine fashion to increase the level of expression of bFGF receptors message in these same neurons. Based on these in-vitro results, we propose that these trophic factors (i.e. TGFss1 and bFGF) play a significant role in the response to injury by the mature auditory system.

Animals↗

The current status of intrapartum continuous fetal tissue pH measurements.

Continuous tissue pH monitoring during labor has now been possible for 15 years. Tissue pH is measured in the intercellular fluid, and the value differs in some cases from the blood pH value because of local capillary flow and local metabolism. The fetal scalp seems to be an area where tissue pH and capillary blood pH values are very close, but in acute acidosis there may be a time lag of 10-15 min before tissue pH is equilibrated. Normal values of scalp tissue pH are 7.38 in early labor declining by 0.016 per hour during the first stage of labor and by 0.12 per hour during the second stage of labor. Tissue pH values below 7.15 are defined as pathological. The correlation coefficient to umbilical artery blood pH (0.71), success rate (67%) and electrode drift (below 0.04) from the largest study of tissue pH monitoring using glass pH electrodes (n = 337) are described.

Acid-Base Equilibrium↗

[Incidence of tricuspid valve prolapse].

The incidence of tricuspid valve prolapse and its association with mitral valve prolapse was studied in 100 patients with right- and left-ventricular angiography. Coronary artery disease was present in 81 patients (pts), a dilative cardiomyopathy in 6 pts, and a hypertrophic cardiomyopathy in 2 pts. 11 pts were angiographically normal. A total of 27 pts had a tricuspid valve prolapse, and 15 pts had a mitral valve prolapse. In 19 pts prolapse of the tricuspid valve was isolated, and in 8 pts it was associated with a mitral valve prolapse. The associated finding of a prolapse of the tricuspid and mitral valve was statistically significant (p less than 0.02). Patients with a tricuspid valve prolapse experienced a higher right-ventricular ejection fraction (58 + 10 vs 53 +/- 10%; p less than 0.05) and smaller end-systolic right ventricular volume indices (39 +/- 16 vs 47 +/- 17 ml/m2; p less than 0.05) compared to those without tricuspid valve prolapse. There was no further difference in clinical and hemodynamic parameters between those with and those without tricuspid valve prolapse. The clinical significance of a tricuspid valve prolapse is still undefined.

Adolescent↗

[Technology use in connection with delivery in Danish maternity departments].

With the object of obtaining information about the technology use employed in Danish maternity departments, a questionnaire was sent to the 58 maternity departments which existed in Denmark in May 1989. These maternity departments covered 99% of the 55,660 births in Denmark (in 1987). Deliveries at home (a total of 511) and delivers in departments with less than four deliveries annually (a total nine) were responsible for the remaining 1%. 100% of the departments returned a completed questionnaire. The following percentages are based on the deliveries included in this investigation. The review revealed that 93.5% of Danish women are delivered in departments with access to carditocographic equipment (CTG), 34% in departments where this is offered routinely to all parturient women. Sixteen departments which did not possess CTG equipment all had fewer than 400 deliveries per annum and 12 of these stated that they wished they had had CTG. Only four of the 58 maternity departments (managing 3.4% of the deliveries in 1987) never employ human placental lactogen (HPL) or oestriol (O3) analyses. The most commonly employed hormone parameter is HPL which is undertaken on appropriate indications in 51 of 54 departments and routinely in the remaining three. Scalp-pH is carried out in 13 of the Danish maternity departments. Thus 41.7% of all the parturient women have access to this analysis. However, only 20% are delivered in maternity departments where this test is employed frequently. Cord-blood-pH is employed routinely in 31.7% of the neonates. Measurement of intrauterine pressure is employed in six out of the 58 maternity departments which are responsible for 25% of Danish deliveries. It is concluded that the slightly increased employment of technology use during delivery in 1989 as compared with practice in 1984 may primarily be due to the closing of several small maternity units during the past five years. In general, the use of technologies are less intensive than in England, Germany, France and the USA.

Cardiotocography↗

[Observation and follow-up of premature rupture of the membranes. A pilot study of women at term with immature cervix and premature rupture of the membranes, without contractions].

In a material of 88 patients with premature rupture of the membranes and unripe cervix, a comparative investigation was undertaken to compare the effects of prostaglandin E2 (PGE2) vaginal tablets and intravenous oxytocin on induction of labour. The patients were subdivided at random into two groups: 42 patients treatment with PGE2 and 46 treatment with intravenous oxytocin. The results did not reveal any significant differences in the numbers of successful inductions regardless of the Bishop score at the commencement of stimulation but the duration of induction was found to be briefer in the oxytocin group. No significant differences were observed in the numbers of instrumental interventions in the two groups nor in the frequencies of side effects and in the employment of analgesics. Treatment with PGE2 vaginal tablets is considered to be more acceptable by the patients and easier for the staff to use. The tablets were just as safe and reliable in use as intravenous oxytocin for induction of labour in cases of premature rupture of the membranes and Bishop scores less than 6, but the duration of induction was significantly longer.

Adult↗

The influence of penbutolol and placebo on blood sugar levels and insulin consumption in the glucose-controlled insulin infusion system ("artificial endocrine pancreas").

The aim of the study was to investigate the influence of 40 mg of the beta-blocker penbutolol (Betapressin TM; Hoechst Ltd., Frankfurt/Main) in comparison to placebo on the insulin consumption on the blood sugar profile in twelve insulin-dependent diabetes (IDDM) patients. The patients were treated with penbutolol and placebo for a period of three days, and then were examined with the help of the glucose-controlled insulin infusion system. The blood sugar profile and insulin consumption over a 24 hour period was not affected by either penbutolol or placebo, nor could any changes be measured in these parameters when measured after food intake. After a submaximal exercise load on the bicycle ergometer (1 watt per kg body weight) following an evening meal, no difference could be observed between penbutolol and placebo in the above-mentioned parameters. The same was also true for hormonal parameters as STH, ACTH, cortisol, and catecholamines. These findings demonstrated that medication of penbutolol over a three-day period has no influence on the baseline blood sugar profile and insulin consumption or on insulin consumption after food intake during rest and physical exercise.

Adolescent↗

Potassium-induced release of an endogenous toxic activity for outer hair cells and auditory neurons in the cochlea: a new pathophysiological mechanism in Menière's disease?

In Menière's disease, the increase of extracellular potassium concentration in the perilymph is thought to play a key role in determining the progressive loss of cochlear hair cells. In this paper, we describe a serum-free culture preparation of hair cells from 5 day-old rat and report the release by the cochlea, in response to an increase of extracellular potassium concentration, of a cytotoxic activity active on hair cells and auditory neurons. The toxic activity is associated with low molecular weight (less than 10,000 Dalton) molecule(s) as revealed by ultrafiltration. Morphological studies performed on the organ of Corti incubated during 24 h in the presence of the cochlea-derived toxic activity (CTA), show that this factor is toxic for hair cells and not for supporting or surrounding cells. The release of CTA occurs both in the spiral ganglion and in the organ of Corti. We suggest that this cochlea-derived toxic activity may play an important role in the pathophysiology of the hearing loss that occurs during the progression of Menière's disease.

Animals↗

[Induction of early first trimester abortion with a prostaglandin E1 analogue. A pilot study].

A pilot investigation employing prostaglandin (PG) induced early abortion (maximal 56 days of menostasia) was planned with the object of investigation whether this non-surgical method was as effective, safe and acceptable as vacuum aspiration. The investigation was planned to include 20 women to be treated with 1 mg PGE1-vagitories at intervals of three hours up to five times in 24 hours. If abortion did not occur after 24 hours as assessed by gynaecological examination and sonography, the uterus was evacuated. After seven women had participated, the investigation was abandoned because of complications and violent pain in several women and because very few of the woman ashed to participate desired to do so, i.e. they preferred vacuum aspiration under general anaesthesia. It is concluded that the method employed here did not prove acceptable for Danish women on account of the severe pain involved and the protracted course of the procedure.

Abortifacient Agents↗

Neuronotrophic effect of developing otic vesicle on cochleo-vestibular neurons: evidence for nerve growth factor involvement.

In the developing inner ear, the existence of a neuronal death and of a peripheral target-derived trophic effect on cochleovestibular neurons has been documented. Using cultures of rat cochleovestibular neurons, we show that the E12 otic vesicle releases a factor promoting the survival and the neuritogenesis of these neurons, and that this effect is mimicked by NGF. The effect of the optic vesicle conditioned medium (OVCM) on cochleovestibular neurons is suppressed by anti-NGF antibodies. OVCM is neuronotrophic for NGF-sensitive sympathetic neurons, an effect that is also suppressed by anti-NGF antibodies, further demonstrating the presence of biologically active nerve growth factor.

Adrenergic Fibers↗

Class differentiation of immunoglobulin-containing cerebrospinal fluid cells in inflammatory diseases of the central nervous system.

An immunocytochemical technique allowing repeated use of antisera is applied to identify immunoglobulin-containing cells (ICC) of the IgG, IgA, and IgM class in the cerebrospinal fluid (CSF) of 298 patients with various neurological disorders. The demonstration of ICC in the CSF is highly indicative of an inflammatory disease (p less than 0.0001; Chi-square test). In the group of noninflammatory disorders ICC are only found in three cases of lymphomas, two dysgerminomas, and one glioblastoma. ICC of all classes are seen in acute viral and bacterial infections of the CNS including tick-borne meningopolyneuritis Bannwarth. IgG-positive ICC predominate in chronic inflammatory disorders like multiple sclerosis and HIV encephalitis. In HIV-positive patients IgA- or IgM-positive cells are strongly indicative of an opportunistic infection of the brain. Persistent high levels of ICC in three patients with bacterial meningitis are associated with a fatal outcome.

AIDS Dementia Complex↗