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Biomedical subjects

F Weber

Publications and source records attributed to F Weber.

At least 91 records · Page 5Linked to original sources
PubMed2000

Anti-GM1 antibodies can block neuronal voltage-gated sodium channels.

Anti-GM1 antibodies, frequently found in the serum of patients with Guillain-Barré syndrome (GBS), have been suggested to interfere with axonal function. We report that IgG anti-GM1 antibodies, raised in rabbits, can reversibly block the voltage-gated Na(+) channels of nerve cells, thus causing a reduction of the excitatory Na(+) current. The block was, however, only substantial when the antibodies were applied together with rabbit complement factors. A solution containing anti-GM1 sera (dilution 1:100) and complement (1:50) reduced the Na(+) current to 0.5 +/- 0.2 times control (mean value +/- SD). Applications of the antibody by itself, complement by itself, or anti-GM2 or anti-GM4 antibodies (1:100) plus complement had little effect. The complexes of anti-GM1 antibodies and complement factors block the ion-conducting pore of the channel directly. In addition, they increase the fraction of channels that are inactivated at the resting potential and alter channel function by changing the membrane surface charge. The described effects may be responsible for conduction slowing and reversible conduction failure in some GBS patients.

Animals↗
PubMed2000

Transrectal Doppler sonography of uterine blood flow.

Transrectal Doppler ultrasound was used for the noninvasive investigation of uterine blood flow in cows. Both the left and right Aa. uterinae were scanned to obtain blood flow velocity waveforms over 2 consecutive estrous cycles. Blood flow was reflected by the resistance index (RI) and the time-averaged maximum velocity (TAMV). Intra-observer reproducibility of Doppler measurements was evaluated. The intra-class correlation coefficient (Intra-CC) was 0.97 for the RI and 0.95 for TAMV. While RI values did not differ between the left and right A. uterina (P > 0.05), differences in TAMV occurred between both vessels in 2 cows. These differences were not related to the ovary bearing the dominant follicle or to the corpus luteum (P < 0.001). As in all cows, changes of RI and TAMV values between the left and right artery during the estrous cycle were correlated (correlation coefficient r > 0.72; P < 0.0001); the mean values of both sides were used for subsequent analyses. Variance component estimates for the effect of cow on RI and TAMV were 8 and 13% and for the influence of day of estrous cycle they were 70 and 47%, respectively (P <0.0001). Between estrous cycles no significant differences could be measured within cows (P > 0.05). The highest RI and lowest TAMV values occurred on Day 0 (= day of ovulation) and Day 1, while the lowest RI and highest TAMV values were measured between Days -3 and -1 of the estrous cycle, respectively. There was a positive correlation between TAMV and estrogen concentrations and a negative correlation between RI and plasma estrogen levels. Plasma progesterone levels and TAMV were negatively correlated, but no correlation could be measured (P > 0.05) between RI values and plasma progesterone concentrations. While there were no differences in plasma concentrations of estrogens and progesterone between estrous cycles within cows, the levels of these hormones differed between cows. The results show that transrectal Doppler sonography is a useful, noninvasive method for examining uterine blood flows in cows. If there is an influence of uterine perfusion on fertility in cows its role needs further investigation.

Animals↗
PubMed2000

Permeability barrier disorder in Niemann-Pick disease: sphingomyelin-ceramide processing required for normal barrier homeostasis.

Prior studies have established the requirement for enzymatic hydrolysis of glucosylceramides to ceramide for epidermal barrier homeostasis. In this study, we asked whether sphingomyelin-derived ceramide, resulting from acid-sphingomyelinase activity, is also required for normal barrier function. We showed first, that a subset of Niemann-Pick patients with severe acid-sphingomyelinase deficiency (i.e., <2% residual activity) demonstrate abnormal permeability barrier homeostasis, i.e., delayed recovery kinetics following acute barrier disruption by cellophane tape-stripping. To obtain further mechanistic insights into the potential requirement for sphingomyelin-to-ceramide processing for the barrier, we next studied the role of acid-sphingomyelinase in hairless mouse skin. Murine epidermis contains abundant acid-sphingomyelinase activity (optimal pH 5.1-5.6). Two hours following acute barrier disruption by tape-stripping, acid-sphingomyelinase activity increases 1. 44-fold (p<0.008 versus vehicle-treated controls), an increase that is blocked by a single topical application of the acid-sphingomyelinase inhibitor, palmitoyldihydrosphingosine. Furthermore, both palmitoyldihydrosphingosine and desipramine, a chemically and mechanically unrelated acid-sphingomyelinase inhibitor, significantly delay barrier recovery both 2 and 4 h after acute barrier abrogation. Inhibitor application also causes both an increase in sphingomyelin content, and a reduction of normal extracellular lamellar membrane structures, in the stratum corneum. Both of the inhibitor-induced delays in barrier recovery can be overridden by co-applications of topical ceramide, demonstrating that an alteration of the ceramide-sphingomyelin ratio, rather than sphingomyelin accumulation, is likely responsible for the barrier abnormalities that occur with acid-sphingomyelinase deficiency. These studies demonstrate an important role for enzymatic processing of sphingomyelin-to-ceramide by acid-sphingomyelinase as a mechanism for generating a portion of the stratum corneum ceramides for permeability barrier homeostasis in mammalian skin.

Adolescent↗
PubMed2000

MxA GTPase blocks reporter gene expression of reconstituted Thogoto virus ribonucleoprotein complexes.

Human MxA protein accumulates in the cytoplasm of interferon-treated cells and inhibits the multiplication of several RNA viruses, including Thogoto virus (THOV), a tick-borne orthomyxovirus that transcribes and replicates its genome in the cell nucleus. The antiviral mechanism of MxA was investigated by using two alternative minireplicon systems in which recombinant viral ribonucleoprotein complexes (vRNPs) of THOV were reconstituted from cloned cDNAs. A chloramphenicol acetyltransferase reporter minigenome RNA was expressed either by T7 RNA polymerase in the cytoplasm of transfected cells or, alternatively, by RNA polymerase I in the nucleus. The inhibitory effect of MxA was studied in both cellular compartments by coexpressing wild-type MxA or TMxA, an artificial nuclear form of MxA. Our results indicate that both MxA proteins recognize the assembled vRNP rather than the newly synthesized unassembled components. The present findings are consistent with previous data which indicated that cytoplasmic MxA prevents transport of vRNPs into the nucleus, whereas nuclear MxA directly inhibits the viral polymerase activity in the nucleus.

Animals↗
PubMed2000

Thogoto virus matrix protein is encoded by a spliced mRNA.

Thogoto virus (THOV) is a tick-transmitted orthomyxovirus with a segmented, negative-stranded RNA genome. In this study, we investigated the coding strategy of RNA segment 6 and found that it contains 956 nucleotides and codes for the matrix (M) protein. The full-length cDNA contains a single, long reading frame that lacks a stop codon but has coding capacity for a putative 35-kDa protein. In contrast, the M protein of THOV has an apparent molecular mass of 29 kDa as assessed by polyacrylamide gel electrophoresis. Therefore, we investigated the possibility of posttranscriptional processing of segment 6 transcripts by reverse transcription-PCR and identified a spliced mRNA that contains a stop codon and is translated into the 29-kDa M protein. Interestingly, the nontemplated UGA stop codon is generated by the splicing event itself. Thus, the unusual M coding strategy of THOV resembles that of Influenza C virus.

Amino Acid Sequence↗
PubMed2000

Electrodiagnostic examination of lumbosacral radiculopathies.

To determine the diagnostic efficacy of late responses and of magnetic stimulation in the electrodiagnostic evaluation of lumbosacral radiculopathies, 42 patients with acute monoradiculopathies of L5 or S1 were examined. We performed conventional nerve conduction studies, F-wave studies, needle electrode examination (NEE) and magnetic stimulation. The results were compared with a control group of 36 persons. In the patients with weakness, we found a diagnostic sensitivity for NEE of 90% in L5 and of 80% in S1. F-waves had the same sensitivity as NEE in the patients with weakness and were more sensitive in the group of patients without weakness (L5 80%, S1 67%). Magnetic stimulation had a sensitivity of 40% in all groups. There were also abnormalities of NEE and of F-wave studies in the patients with abnormal magnetic stimulation. It is concluded that NEE is the single most effective method in acute LSR and that F-wave studies are able to provide complementary information. Magnetically evoked motor nerve root stimulation was not found of clinically relevant diagnostic value.

Action Potentials↗
PubMed2000

[Abdominopelvic ultrasonography in suspected acute appendicitis: prospective study in adults].

STUDY AIM: The aim of this prospective descriptive study was to evaluate the accuracy of abdomino-pelvic ultrasonography in suspected acute appendicitis in adults. PATIENTS AND METHODS: From March to July 1998, 100 consecutive patients, 63 women, 37 men (mean age: 25 years), after examination by a visceral surgeon for suspected acute appendicitis, had an abdominal ultrasonography (US) examination with high frequency transducer (7.5 to 9 MHz). The US examination concerned appendice, periappendicular tissues and neighbouring organs. The US data were correlated with the histopathologic findings in operated on patients, and with the clinical and biological follow up in non operated patients. RESULTS: Fourty-seven patients had acute appendicitis; 53 were operated on and 47 non operated. Analysis of US data revealed sensitivity 91.5%, specificity 94.3%, positive predictive value 93.5%, negative predictive value 94.3%, accuracy 93%; 75% of the other diagnosis were found by US. CONCLUSION: Systematic abdominal ultrasonography in suspected acute appendicitis is recommended in adults.

Abdominal Pain↗
PubMed2000

CDI Blood Parameter Monitoring System 500--a new tool for the clinical perfusionist.

Sarns/3M Health Care has recently introduced the CDI 500 Blood Parameter Monitoring System. In addition to parameters previously available, this system now offers continuous monitoring of the patient's oxygen consumption (VO2/min) and potassium concentration ([K+]). The purpose of this study was: (1) to compare the [K+] from the CDI 500 with the [K+] derived from our hospital's laboratory; and (2) to compare the VO2/min from the CDI 500 with the results obtained utilizing the "gold-standard" Fick equation. The mean absolute difference in [K+] was 0.10 mEq/L with a mean percentage error of only 3.93%. The mean absolute difference in VO2/min was 18.78 ml O2/min, with a mean percentage error of 11.63%. We concluded that the [K+] correlated well and that 9.13% of the oxygen consumption percentage error was attributable to the exclusion of dissolved oxygen in the calculation used by the CDI 500, with the remaining 2.5% attributable to differences in technology. We recommended that future upgrades to the CDI 500 should include dissolved O2 when measuring oxygen consumption and consideration should be given to increasing the operating range for [K+].

Blood Gas Analysis↗
PubMed1999

A phase 1-2 clinical trial of gene therapy for recurrent glioblastoma multiforme by tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir. GLI328 European-Canadian Study Group.

This study has investigated the effects of herpes simplex thymidine kinase gene (HSV-tk) transfer followed by ganciclovir treatment as adjuvant gene therapy to surgical resection in patients with recurrent glioblastoma multiforme (GBM). The study was open and single-arm, and aimed at assessing the feasibility and safety of the technique and indications of antitumor activity. In 48 patients a suspension of retroviral vector-producing cells (VPCs) was administered by intracerebral injection immediately after tumor resection. Intravenous ganciclovir was infused daily 14 to 27 days after surgery. Patients were monitored for adverse events and for life by regular biosafety assaying. Tumor changes were monitored by magnetic resonance imaging (MRI). Reflux during injection was a frequent occurrence but serious adverse events during the treatment period (days 1-27) were few and of a nature not unexpected in this population. One patient experienced transient neurological disorders associated with postganciclovir MRI enhancement. There was no evidence of replication-competent retrovirus in peripheral blood leukocytes or in tissue samples of reresection or autopsy. Vector DNA was shown in the leukocytes of some patients but not in autopsy gonadal samples. The median survival time was 8.6 months, and the 12-month survival rate was 13 of 48 (27%). On MRI studies, tumor recurrence was absent in seven patients for at least 6 months and for at least 12 months in two patients, one of whom remains recurrence free at more than 24 months. Treatment-characteristic images of injection tracks and intracavity hemoglobin were apparent. In conclusion, the gene therapy is feasible and appears to be satisfactorily safe as an adjuvant to the surgical resection of recurrent GBM, but any benefit appears to be marginal. Investigation of the precise effectiveness of this gene therapy requires prospective, controlled studies.

Adult↗
PubMed1999

Cyclosporin A induces prepro endothelin-1 gene transcription in human endothelial cells.

Cyclosporin A employed in treatment of organ allograft rejection, is associated with hypertension possibly due to endothelin-1. We studied transcriptional regulation of endothelin-1 by cyclosporin A in human endothelial cells using cell transfection experiments and reporter gene assays. Human umbilical vein endothelial cells were established expressing a fusion gene of the coding sequence of the firefly luciferase gene, placed under the control of the rat endothelin-1 promoter. Luciferase assays demonstrate 2.8-fold stimulation of the reporter gene by cyclosporin A (P < 0.01), and Northern blot analysis shows induction of prepro endothelin-1 mRNA. Transcription is tightly repressed in the absence of the immunosuppressant, its regulation occurs Ca(2+)-dependent. Lack of extra- or intracellular Ca2+ prevents cyclosporin A-dependent endothelin-1 gene transcription and mRNA induction. These data demonstrate transcriptional regulation of endothelin-1 over a range of several orders of magnitude in human umbilical vein endothelial cells by cyclosporin A via Ca(2+)-dependent mechanisms. They support the critical role of endothelin- in cyclosporin A-associated hypertension.

Animals↗
PubMed1999

Effect of interferon beta on human myelin basic protein-specific T-cell lines: comparison of IFNbeta-1a and IFNbeta-1b.

The effect of interferon (IFN)beta-1a and IFNbeta-1b on human myelin basic protein-reactive T-cell lines was investigated. Both drugs inhibited proliferation and production of lymphotoxin (LT), whereas the production of interleukin-4 was not altered and interleukin-10 was induced. Comparing equal numbers of units IFNbeta-1a and -1b showed almost identical results. These in vitro data indicate that the immunomodulatory capacity of both interferons with respect to T cells paralleled their antiviral effect.

Analysis of Variance↗
PubMed1999

[Shy-Drager syndrome: a rare cause of orthostatic hypotension].

HISTORY AND ADMISSION FINDINGS: A 71-year-old man was admitted because of treatment-resistant orthostatic hypotension of unknown aetiology. When aged 64 years he developed some impotence and later urinary incontinence and urinary frequency. At 68 years he noted vertigo on physical activity, and a year later he had signs of reversible cerebral ischaemia. At this point the Schellong test demonstrated vasovagal circulatory dysfunction. After his 70th birthday the unsteadiness on walking and standing got worse and he had recurrent syncopes. He was in a wheel-chair when hospitalized and even the unsteady walk he could maintain for only a few seconds. INVESTIGATIONS: Plasma and urinary concentrations of catecholamines were at the lower limit of normal but failed to increase during orthostasis. Hormonal, cardiological and infectious causes of the orthostatic hypotension were excluded. Orthostatic tests after Schellong and with the tilting table showed orthostatic hypotension without increased sympathetic activity but hypertensive blood pressure levels during the recumbent period. Intravenous infusion of norepinephrine produced an excess rise in blood pressure (raised norepinephrine sensitivity). The recurrent urinary infection was shown to be due to a hypotonic bladder detrusor muscle. Neurological examination revealed cerebellar dysfunction, signs of pyramidal tract abnormality and sensory polyneuropathy. A Shy-Drager syndrome was diagnosed on the basis of the history, absent blood pressure rise and lack of catecholamine release during orthostasis with increased epinephrine sensitivity and characteristic neurological signs. TREATMENT AND COURSE: Physiotherapy and elastic stockings with administration of mineralocorticoids as well as of one direct (norfenefrine) and one indirect (amezinium) sympathomimetic drug failed to improve adequately the abnormal orthostatic response. But on additional administration of an alpha 2-receptor antagonist (yohimbine) the patient was able to stand and walk for a few minutes, but the urinary incontinence and the other neurological signs remained treatment-resistant. CONCLUSION: If orthostatic hypotension occurs together with neurological symptoms, a Shy-Drager syndrome should be taken into account.

Adrenergic alpha-Antagonists↗
PubMed1999

A small sodium channel blocking factor in the cerebrospinal fluid is preferentially found in Guillain-Barré syndrome: a combined cell physiological and HPLC study.

The cerebrospinal fluid (CSF) of patients with Guillain-Barré syndrome (GBS) contains a low molecular weight factor with sodium channel blocking activity. This study investigated whether such activity also exists in the CSF of patients with other neurological diseases. Further, using high-performance liquid chromatography (HPLC) we tested whether the electrophysiological effect of the CSF is correlated with the size of the corresponding peak in the chromatograms. The existence of sodium channel blocking activity was tested in 27 native CSF samples of three groups of patients (group 1: GBS, n = 13; group 2: other inflammatory diseases, n = 8; group 3: controls, n = 6). NH15-CA2 neuroblastoma x glioma cells in the whole-cell recording configuration was used as a system for assaying the sodium channel blocking activity of CSF specimens. CSF shifted the steady-state inactivation curve of the sodium channels reversibly by -10.2 +/- 4.4 mV in group 1, -6.7 +/- 3.9 mV in group 2, and - 3.5 +/- 2.8 mV in group 3 (P < 0.01). The shift was greater in demyelinating (9.3 +/- 4.7 mV) than in nondemyelinating (5.6 +/- 3.9 mV) diseases (P < 0.04). HPLC analysis of CSFs showed a well separated peak containing the substance responsible for the electrophysiological effect at about 41 min elution time. The peak covered the molecular weight range of 600-800 Da. Sodium channel blocking activity of CSFs and areas of the corresponding peak in the chromatograms were well correlated. We conclude that sodium current inhibition by a low molecular weight factor is generally present but increased in GBS.

Cerebrospinal Fluid↗