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Biomedical subjects

S Böhm

Publications and source records attributed to S Böhm.

At least 37 records · Page 2Linked to original sources
PubMed2000

High genetic variability of the group-specific a-determinant of hepatitis B virus surface antigen (HBsAg) and the corresponding fragment of the viral polymerase in chronic virus carriers lacking detectable HBsAg in serum.

Chronic carriers of hepatitis B virus (HBV) usually show hepatitis B surface antigen (HBsAg) in their sera, which is considered the best marker for acute and chronic HBV infection. In some individuals, however, this antigen cannot be detected by routine serological assays despite the presence of virus in liver and peripheral blood. One reason for this lack of HBsAg might be mutations in the part of the molecule recognized by specific antibodies. To test this hypothesis, the HBV S gene sequences were determined of isolates from 33 virus carriers who were negative for HBsAg but showed antibodies against the virus core (anti-HBc) as the only serological marker of hepatitis B. Isolates from 36 HBsAg-positive patients served as controls. In both groups, a considerable number of novel mutations were found. In isolates from individuals with anti-HBc reactivity only, the variability of the major hydrophilic loop of HBsAg, the main target for neutralizing and diagnostic antibodies, was raised significantly when compared with the residual protein (22. 6 vs 9.4 mutations per 1000 amino acids; P<0.001) and with the corresponding region in the controls (22.6 vs 7.5 exchanges per 1000 residues; P<0.001). A similar hypervariable spot was identified in the reverse transcriptase domain of the viral polymerase, encoded by the same nucleotide sequence in an overlapping reading frame. These findings suggest that at least some of the chronic low-level carriers of HBV, where surface antigen is not detected, could be infected by diagnostic escape mutants and/or by variants with impaired replication.

Amino Acid Substitution↗
PubMed1999

A novel deletion mutant of hepatitis B virus surface antigen.

HBsAg is the most important serological marker for acute or chronic hepatitis B. Nevertheless, there are reports of HBsAg-negative virus carriers, either with anti-HBc as the only marker for hepatitis B virus (HBV) infection or even positive for anti-HBs and anti-HBc. We report isolates from a patient, in which a deletion in the HBs-gene was associated with persisting viremia in the presence of anti-HBs. The 62-year-old female, infected most likely by her husband, had detectable markers of chronic active hepatitis B, such as HBsAg, HBeAg, and anti-HBc-IgM, for 2 years. The patient then seroconverted to anti-HBs, although HBeAg and anti-HBc-IgM remained detectable. At this time, semiquantitative polymerase chain reaction showed about 10(4) viral genomes per milliliter of serum. Direct sequencing of the amplified products revealed a major population of DNA molecules with a deletion of nucleotide 31 of the HBs-gene, which up to now has not been described. This deletion led to a frame-shift and introduced a stop-codon after 21 amino acids of the sHBsAg. We suspect that this deletion, and the resulting HBsAg lacking the major epitopes recognized by specific antibodies, could favor ongoing viral replication, despite the presence of anti-HBs. However, because the reading frame of the polymerase was also severely damaged by this deletion, it is assumed that a minor population of intact genomes was present to help in the formation of virus particles.

Amino Acid Sequence↗
PubMed1999

An integrated micromachined electrochemical pump and dosing system.

In this paper a micromachined electrochemically driven pump capable of dosing precise nanoliter amounts of liquid is presented. The pump consists of a micromachined channel structure realized in silicon by reactive ion etching. On top of this structure a Pyrex((R)) cover piece with noble metal electrodes was bonded. The fluid to be dispensed is stored in a meander shaped reservoir which is part of the channel structure. This meander starts in an electrolyte solution containing reservoir, on top of which two noble metal electrodes are positioned. By the electrochemical production of gas bubbles by electrolysis of water at these electrodes, liquid can be driven out of the meander. The measured volume displacements were in close agreement with theory. Pump rates as low as a few nl/s could accurately be controlled via the actuation current through the electrodes. By applying current pulses rather than a continuous current, preset amounts of fluid in the nanoliter range could be dosed successfully. Because the resulting device consists of simple channel structures and metal electrodes it can easily be integrated in miniaturized chemical analysis systems to dose reagents or calibration solutions.

Journal Article↗
PubMed1999

A case of severe chronic active infection with Epstein-Barr virus: immunologic deficiencies associated with a lytic virus strain.

Infectious mononucleosis (IM) is a self-limiting, lymphoproliferative disease induced by primary infection with the Epstein-Barr virus (EBV). Infection with EBV leads in general to lifelong asymptomatic persistence of the virus. We report the case of a woman who acquired IM at the age of 15 years and then suffered from recurrent high fever, fatigue, and signs of immunologic disorder for more than 12 years until she died of liver failure. In an attempt to describe and to define the course of chronic active infection with EBV, we performed immunologic and molecular assays that demonstrated lytic replication of EBV in the B and T cells of the peripheral blood. In addition to signs of humoral and cellular immune deficiency, we detected an EBV strain with an impaired capability to immortalize B cells and a tendency to lytic replication, thus contributing to the pathogenesis of this chronic active infection.

Adult↗
PubMed1999

Dose intensification of platinum compounds with glutathione protection as induction chemotherapy for advanced ovarian carcinoma.

Based on previous clinical experience indicating the tolerability and efficacy of high-dose cisplatin with glutathione protection in the treatment of advanced ovarian cancer, this study was undertaken to explore the efficacy and feasibility of an alternative high-dose, platinum-based approach including a combination of high-dose cisplatin plus carboplatin as induction chemotherapy of advanced ovarian carcinoma and intervention surgery. Fifty consecutive eligible patients with untreated stage III or IV epithelial ovarian cancer received 40 mg/m(2) cisplatin daily on days 1-4 and 160 mg/m(2) carboplatin on day 5. The cycle was repeated after 28 days. Patients received glutathione (2,500 mg) before each cisplatin or carboplatin administration and standard intravenous hydration. After 2 courses of induction chemotherapy, the patients underwent surgical reevaluation with debulking, when possible, followed by a further 3 cycles of 120 mg/m(2) cisplatin (i.e. 40 mg/m(2) daily for 3 consecutive days plus 600 mg/m(2) cyclophosphamide on day 3) except in instances of lack of response. All eligible patients were assessed for response and toxicity. The toxicity was moderate with lack of significant nephrotoxicity. Neurotoxicity and ototoxicity were acceptable and in no patient was treatment discontinued for those toxic effects. Myelotoxicity was somewhat more severe than that observed with our previous study with high-dose cisplatin and probably related to the addition of carboplatin. Of the 40 responsive patients, 23 (46%) had a pathological complete response and 4 (8%) had a clinical complete response (without second-look laparotomy). The efficacy of the present protocol was also documented by overall survival (median survival >48 months), which appeared to be better than expected with the current therapy in this group with advanced/bulky disease. The impressive efficacy suggests a possible contribution of reduced glutathione itself in improving the outcome, as supported by preclinical studies. The results of this study should be placed in context with current platinum-based therapy including paclitaxel.

Adult↗
PubMed1997

Variations of the C2H2 zinc finger motif in the yeast genome and classification of yeast zinc finger proteins.

The PROSITE pattern Zinc_Finger_C2H2 was extended to permit the detection of all C2H2 zinc fingers and their parent proteins in the recently completed sequence of the yeast genome. Additionally, a new computer program was written that extracts other zinc binding motifs (non C2H2 'fingers'), overlapping with the classical zinc finger pattern, from the found set of yeast C2H2 fingers. The complete and correct detection of all fingers is a prerequisite for the classification of the yeast zinc finger proteins in functional terms. The detected 53 yeast C2H2 zinc finger proteins do not contain finger clusters with 10 or more repeats, as is frequently found in higher eukaryotes. Only three proteins contain four or more fingers in a cluster. Moreover, nearly all 27 yeast proteins with tandem arrays of two or three finger domains can be classified into nine subgroups with high sequence conservation in their finger clusters, in particular of their DNA recognition helices. These results and application of the recently elaborated finger/DNA recognition rules suggest that the yeast proteins belonging to the same subgroup may recognize identical or very similar DNA sites.

Amino Acid Sequence↗
PubMed1997

[Hypoglossal paralysis after septum correction with intubation anesthesia].

BACKGROUND: We report a case of irreversible unilateral hypoglossal nerve palsy in connection with nasal septum surgery in intubation anaesthesia. On account of the spatial distance, there is no danger of injuring the hypoglossal nerve during nasal surgery. However, in the otorhinolaryngological and anaesthesiological literature, some cases of hypoglossal palsy following endotracheal intubation, use of the laryngeal mask airway, bronchoscopy and laryngoscopy are reported. CASE REPORT: One day after uneventful nasal septoplasty in intubation anaesthesia in a 45-year-old male patient, an unilateral hypoglossal nerve palsy and a hematoma in the area of the ipsilateral lingual tonsil were observed. A detailed diagnostic work-up failed to provide additional insights into the cause of the nerve injury. Despite pharmacological treatment, the palsy was irreversible and the patient sued for recovery of damages. DISCUSSION AND CONCLUSIONS: According to the available publications, it must be assumed that in the process of intubation pressure from the MacIntosh blade was the cause of the hypoglossal palsy. This complication is extremely rare, so that routine preoperative briefing of the patient does not appear necessary.

Adult↗
PubMed1997

Combining partial liquid ventilation with nitric oxide to improve gas exchange in acute lung injury.

OBJECTIVE: To assess the effects of increasing concentrations of inhaled nitric oxide (NO) during incremental dosages of partial liquid ventilation (PLV) on gas exchange, hemodynamics, and oxygen transport in pigs with induced acute lung injury (ALI). DESIGN: Prospective experimental study. SETTING: Experimental intensive care unit of a university. SUBJECTS: 6 pigs with induced ALI. INTERVENTIONS: Animals were surfactant-depleted by lung lavage to a partial pressure of oxygen in arterial blood (PaO2) < 100 mmHg. They then received four incremental doses of 5 ml/kg perflubron (Liqui-Vent). Between each dose the animals received 0, 10, 20, 30, 40, and 0 parts per million (ppm) NO. MEASUREMENTS AND MAIN RESULTS: Blood gases, hemodynamic parameters, and oxygen delivery were measured after each dose of perflubron as well as after each NO concentration. Perflubron resulted in a dose-dependent increase in PaO2. At each perflubron dose, additional NO inhalation resulted in a further significant (ANOVA, p < 0.05) increase in PaO2, with a maximum effect at 30 +/- 10 ppm NO. The 5 ml/kg perflubron dose led to a significant decrease in mean pulmonary artery pressure, which decreased further with higher NO concentrations. CONCLUSIONS: PLV can be combined with NO administration and results in a cumulative effect on arterial oxygenation and to a decrease in pulmonary artery pressure, without having any deleterious effect on measured systemic hemodynamic parameters.

Administration, Inhalation↗
PubMed1997

Mechanisms attenuating cellular responses to neuropeptides: extracellular degradation of ligands and desensitization of receptors.

Neuropeptides make up one of the largest and functionally most diverse groups of signaling molecules. They exert their effects by interacting with members of the large family of G-protein-coupled receptors, which transmit information about the extracellular environment to the interior of the cell by interacting with the heterotrimeric G-proteins. Cellular responses to neuropeptides are usually rapidly attenuated. Mechanisms of signal attenuation include removal of peptides from the extracellular fluid and receptor desensitization. Peptides are removed from the extracellular fluid principally by enzymatic degradation by cell surface enzymes, exemplified by neutral endopeptidase. Receptor desensitization is mediated by receptor phosphorylation by G-protein receptor kinases and second messenger kinases, interaction of receptors with arrestins, and consequent receptor uncoupling from G-proteins. Peptides also induce endocytosis of their receptors, which may contribute to desensitization by depleting the cell surface of high-affinity receptors. Recycling and processing of internalized receptors, which include dissociation of receptors from their ligands and receptor dephosphorylation, contribute to resensitization of cellular responses. These regulatory mechanisms are important for they determine the ability of cells to respond to agonists, and defects may result in uncontrolled stimulation of cells, which could cause disease. A greater understanding of the processes that modulate signaling by neuropeptides may lead to the development of novel receptor antagonists and agonists and help to explain the mechanism of drug tolerance.

Animals↗
PubMed1996

Characterization of antisera specific to NK1, NK2, and NK3 neurokinin receptors and their utilization to localize receptors in the rat gastrointestinal tract.

Understanding the physiological role of tachykinins requires precise cellular and subcellular localization of their receptors. We raised antisera by immunizing rabbits with peptides corresponding to portions of the intracellular tails of the rat neurokinin 1, 2, and 3 receptors (NK1-R, NK2-R, NK3-R). Receptors were localized by immunofluorescence and confocal microscopy. NK1-R, NK2-R, and NK3-R were detected at the plasma membrane of transfected cells with minimal intracellular stores. Staining was abolished by preabsorption of the antisera with the peptides used for immunization. Nontransfected cells were unstained. Each antiserum only stained cells transfected with the appropriate receptor and did not stain cells transfected with the other receptors. Therefore, the antisera are specific and do not cross-react with other neurokinin receptors. We examined the distribution of the neurokinin receptors in the gastrointestinal tract of the rat. NK1-R was detected in myenteric and submucosal neurons and in interstitial cells of Cajal. NK2-R was localized to circular and longitudinal muscle cells and to nerve endings in the plexuses. NK3-R was detected in numerous myenteric and submucosal neurons. Some neurons expressed both NK1-R and NK3-R. Receptors were detected at the plasma membrane and in endosomes. Cells expressing the receptors were closely associated with tachykinin-containing nerve fibers. Thus, NK1-R and NK3-R mediate neurotransmission by tachykinins within enteric nerve plexuses, and NK1-R and NK2-R mediate the effects of tachykinins on interstitial and smooth muscle cells, respectively.

Animals↗
PubMed1996

A comparative study of p53 gene mutations, protein accumulation, and response to cisplatin-based chemotherapy in advanced ovarian carcinoma.

The p53 protein is a multifunctional transcriptional regulator involved in cellular response to DNA damage and has been implicated as a putative determinant of sensitivity of tumor cells to cytotoxic agents. Since the p53 gene becomes inactivated in over one-half of advanced ovarian carcinoma, in this study we have examined the relationships between p53 gene alterations, p53 immunoreactivity, and response to cisplatin-based chemotherapy in ovarian cancer patients. All patients had advanced (FIGO stage III or IV) ovarian carcinoma and, with one exception, were untreated at the time of collection of tumor specimens. After initial debulking surgery, patients received high-dose cisplatin therapy. Tumor samples were analyzed for p53 gene mutations and for p53 protein accumulation, and the findings were correlated with tumor responsiveness. Of the 33 tumors examined, p53 gene mutations were found in 20 cases, including 15 missense mutations, 2 deletions, 2 nonsense mutations, and a base substitution at splice site. Twenty tumors showed positive immunostaining for p53. Only missense mutations were associated with positive immunostaining. In addition, p53 overexpression was detected in five tumors in the absence of mutations. Most (12 of 14) of the missense mutations associated with p53 protein stabilization were found refractory to therapy, as well as tumors overexpressing wild-type p53 (4 of 5). A significant correlation has been found between p53 accumulation, type of mutation (i.e., missense mutations), and pathological response to cisplatin-based therapy. In conclusion, the present results are consistent with a role of p53 as a determinant of chemosensitivity of ovarian carcinoma.

Alleles↗
PubMed1996

Proinflammatory cytokines interleukin 1 beta and tumor necrosis factor alpha inhibit growth hormone stimulation of insulin-like growth factor I synthesis and growth hormone receptor mRNA levels in cultured rat liver cells.

Low levels of insulin-like growth factor I (IGF-I) in critical illness are observed despite increased or normal levels of growth hormone (GH). The mechanisms for this apparent GH resistance have not been elucidated. As many of the acute inflammatory responses in critical illness are mediated by the proinflammatory cytokines interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha), the present studies evaluated IL-1 beta and TNF-alpha effects on steady-state and GH-stimulated IGF-I synthesis and GH receptor mRNA levels. In rat hepatocytes in primary culture, IGF-I released into culture medium was determined by radioimmunoassay, and quantitative competitive polymerase chain reaction was used to measure IGF-I mRNA and GH receptor mRNA concentrations. Growth hormone increased GH receptor mRNA, IGF-I mRNA and IGF-I protein secreted into the culture medium. In cells not stimulated with GH, modest inhibitory effects of IL-1 beta on GH receptor mRNA, IGF-I mRNA and IGF-I protein levels were seen. However, the stimulatory effects of GH were inhibited in a dose-dependent manner both by IL-1 beta and TNF-alpha, and at higher cytokine concentrations no stimulatory effects of GH were observed. Both IL-1 beta and TNF-alpha in submaximal dose had additive inhibitory effects on IGF-I protein concentrations but these effects did not result in irreversible damage to cells, as indicated by restoration of IGF-I and GH receptor mRNA levels to normal after withdrawal of cytokines. In conclusion, we demonstrated that in rat hepatocytes in primary culture IL-1 beta and TNF-alpha inhibited GH-stimulated IGF-I synthesis. Diminished GH receptor mRNA concentrations in response to IL-1 beta and TNF-alpha indicate that low IGF-I levels during severe illness, despite high circulating GH levels, may at least partially be a consequence of suppression of hepatic GH receptor synthesis by IL-1 beta and TNF-alpha.

Animals↗
PubMed1994

Control of nausea and vomiting by granisetron in ovarian cancer patients treated with different cisplatin-based regimens.

AIMS: The study evaluated the safety and efficacy of granisetron as an antiemetic drug in ovarian cancer patients treated with cisplatin-based chemotherapy. STUDY DESIGN: Two groups of consecutive patients were considered: the first (Group A) with advanced disease, receiving 4-day cisplatin therapy in a 40 mg/m2 daily dose; the second (B), with minimal disease after radical surgery at high risk of recurrence, treated by single-day chemotherapy with a 90 mg/m2 dose. In both groups, 3.0 mg of granisetron was administered as a 10 min. intravenous infusion, 30 min. before cisplatin infusion. The treatment schedule included in all patients the administration of 125 mg i.v. of methylprednisolone 2 h before chemotherapeutic infusion. No further doses of granisetron were allowed within each 24 h study period for breakthrough nausea and vomiting. Assessment for nausea and vomiting was made at 24 h intervals through the 6-day study period for both groups using a diary card. RESULTS AND CONCLUSION: In group A, 25 patients were collected and evaluated; in group B, 25 were recruited and 13 evaluated. In both groups, excellent control of nausea and vomiting was achieved, since in group A we had a global major antiemetic efficacy of granisetron in 69.2% of patients (54.4% complete control and 14.8% major control); in group B, global major efficacy was present in 83.3% of cases (31.6% complete control and 51.7% major control). The antiemetic effect in the days following antiblastic treatment lasted longer in group A.

Antineoplastic Combined Chemotherapy Protocols↗