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Biomedical subjects

H Hahn

Publications and source records attributed to H Hahn.

At least 109 records · Page 6Linked to original sources

Reactivity of primate sera to foamy virus Gag and Bet proteins.

In order to establish criteria for the serodiagnosis of foamy virus infections we investigated the extent to which sera from infected individuals of human and primate origin react with structural and non-structural virus proteins in immunoblot assays. Using lysates from infected cells as the source of virus antigen, antibodies were preferentially detected against the Gag proteins and the non-structural Bet protein. Both the Gag precursor molecules of 70 and 74K apparent M(r) and the cytoplasmic 60K M(r) Bet protein were found to be phosphorylated, the latter being synthesized in large amounts in infected cells. Rabbit antiserum raised against recombinant human foamy virus (HFV) Gag major capsid protein cross-reacted with foamy viruses of chimpanzee, gorilla, orang-utan, rhesus monkey and African green monkey origin. This was reflected by a broad cross-reactivity of the respective monkey sera to the Gag proteins of the various foamy virus isolates. Cross-reactivity of antisera against the Bet protein was restricted to viruses from man and the great apes. Recombinant Gag and Bet proteins expressed in prokaryotes or in insect cells were readily recognized by foamy virus-positive primate sera. Screening serum samples from chimpanzees with HFV Gag and Bet proteins expressed by recombinant baculoviruses revealed that 18 out of 35 (52%) were positive for Gag antibodies. Of these, 13 (72%) showed antibodies against the Bet protein, indicating that Bet antigen is of value in serological screening for foamy virus infections.

Animals↗

The Raf-1 serine/threonine protein kinase.

Raf-1 belongs to a family of serine/threonine protein kinases which are highly conserved through evolution in multicellular organisms. Raf-1 kinase has gained much attention due to its function as a critical shuttle enzyme that connects stimulation of growth factor receptors and protein kinase C at the cell membrane to changes in the expression of genes involved in the control of cell growth, differentiation and survival. Regulation of Raf-1 activity is complex and involves Ras, as well as several serine/threonine and tyrosine kinases. Through a series of phosphorylation events, extracellular signals are connected through the Raf-1/MAP kinase pathway to activity-regulation of several oncogene-class transcription factors via phosphorylation of specific serine residues. Under ordinary circumstances, the cascade involving Raf-1 eventually leads to changes in gene expression and protein synthesis. Upon constitutive activation of Raf-1 kinase, as a result of genetic changes, a variety of cell types acquire a transformed phenotype.

Animals↗

[The effect of the pipe material of the drinking water system on the frequency of Legionella in a hospital].

In this paper the prevalence of Legionella in water samples from cold and warm water supply systems made of copper, iron and polyethylene was determined. Water supplied by copper pipes revealed to be nearly free of Legionella (only 2% of probes positive), but water from iron (90%) or polyethylene pipes (65% probes positive) proved to be heavily contaminated. The 82 isolates were identified as Legionella pneumophila, one from serogroup 1, the others from serogroup 4.

Colony Count, Microbial↗

Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species.

The proto-oncogene bcl-2 inhibits apoptotic and necrotic neural cell death. Expression of Bcl-2 in the GT1-7 neural cell line prevented death as a result of glutathione depletion. Intracellular reactive oxygen species and lipid peroxides rose rapidly in control cells depleted of glutathione, whereas cells expressing Bcl-2 displayed a blunted increase and complete survival. Modulation of the increase in reactive oxygen species influenced the degree of cell death. Yeast mutants null for superoxide dismutase were partially rescued by expression of Bcl-2. Thus, Bcl-2 prevents cell death by decreasing the net cellular generation of reactive oxygen species.

Animals↗

The role of cytokines in experimental listeriosis.

Listeria monocytogenes is a Gram-positive, intracytoplasmatically replicating pathogen that elicits host reactions which are very similar in man and rodents. Using murine listeriosis as a highly reproducible and convenient experimental model for studying the immune response to infections with facultative intracellular bacteria, Mackaness developed the concept of T cell-mediated macrophage activation as the pivotal mechanism in host defense against this type of infectious agents. Continued research in listeriosis itself, however, provided paradoxical findings that challenged the original dogma. In particular, the finding that T cell-mediated inflammatory events, like DTH and granuloma formation, can be dissociated from protective effector mechanisms has provided a new impetus and experimental access to characterizing the molecular mediators responsible for these diverging phenomena. This review first summarizes the cellular basis for the dichotomy of immunological phenomena outlined above and will then relate recent findings on cytokine expression in infected tissues to these dual categories of the host response to infection. The authors will focus on data obtained from in vivo experiments and draw on evidence from in vitro systems only when appropriate in vivo verification is still lacking. The data presented will cover the developments made in the field of cytokine research since our previous review in 1981 (Rev. Infect. Dis. 3: 1221-1250). Detectable numbers of listeria-specific T cells become apparent on day 4 to 5 of a primary infection. Whereas the localized and sustained release of TNF and IFN-gamma mediated by CD4+ cells seems to be the focusing event triggering mononuclear cell accumulation, the coincidental eradication of bacteria critically depends on CD8+ and/or CD4-CD8-Thy1+ cells. Their effector functions, however, remain obscure, since cytokines cannot be identified that will substitute for their presence. None of the cytokines studied thus far has been demonstrated to effectively cure an established infection. In addition, the increased production of cytokines characteristic of an anamnestic response (IL-2, IL-3, IL-4, IFN-gamma and TNF) can be dramatically reduced by depleting CD4+ T cells without any effect on the animal's ability to eradicate high lethal doses of bacteria and Listeria-specific CD8+ T cells can mediate protection even in the presence of neutralizing antibodies to IFN-gamma. In conclusion, the murine model of Listeria infection provides an interesting experimental approach for the development of immunotherapeutic strategies aimed at reducing T cell-mediated immunopathology without interfering with innate resistance and T cell-mediated cure and prevention of disease.

Animals↗

The use of external, noninvasive pacing for the termination of supraventricular tachycardia in the emergency department setting.

STUDY OBJECTIVE: To determine the potential feasibility of external cardiac pacing for the termination of sustained supraventricular tachycardia in the emergency department setting. TYPE OF PARTICIPANTS: Three men and two women (mean age, 34 years) who presented to the ED with a narrow-complex, hemodynamically stable tachycardia that was later proven to be supraventricular in origin. INTERVENTION: Each patient underwent external overdrive pacing using a modified external pacemaker at a pulse amplitude of 120 mA and a rate between 240 and 280 pulses per minute. RESULTS: In four patients, external cardiac pacing was able to successfully terminate the tachycardia without complication. In one patient, the pacemaker was not able to terminate the tachycardia. CONCLUSION: We conclude that external, noninvasive pacing is a feasible means of terminating supraventricular tachycardia in the ED setting.

Adult↗

Role of the systemic cellular immune response in the pathogenesis of Helicobacter pylori-associated duodenal ulcer.

20 patients colonized by H. pylori (9 with duodenal ulcer, 11 with antral gastritis) were examined for the presence of a systemic cellular immune response to H. pylori using an in vitro lymphocyte transformation assay. Infiltration of the antral mucosa by myelomonocytic cells was assessed by immunohistology as a parameter of local cellular immune response. A systemic H. pylori-induced cellular reaction could be demonstrated in 11 patients all of whom showed an intense myelomonocytic infiltration of the antral mucosa. In this group 7 of 9 duodenal ulcers occurred. The findings support the hypothesis, that a specific cellular immune response might be involved in the pathogenesis of H. pylori-associated gastritis and duodenal ulcer. A protective role of systemic cellular immunity to H. pylori seems rather unlikely.

Adult↗

Influence of omeprazole on urease activity of Helicobacter pylori in vitro.

The influence of omeprazole on urease activity of 13 Helicobacter pylori strains was assessed in vitro employing different inocula of the bacteria and various concentrations of omeprazole. Bacteria were grown in liquid culture supplemented with omeprazole for 48 h. Afterwards, bacterial numbers were assessed and urease activity was measured in a spectrophotometric assay. In 10 strains, omeprazole had no influence on urease activity at concentrations up to 8 mg/l; higher concentrations had a bacteriostatic effect. Three strains were more resistant to omeprazole: These showed a marked diminution of urease activity although bacterial numbers were only slightly reduced. Thus a possible inhibitory effect of omeprazole should be taken into account when urease of Helicobacter pylori is measured for diagnostic purposes.

Helicobacter pylori↗

Usefulness of fluoxetine hydrochloride for prevention of resistant upright tilt induced syncope.

Recurrent vasovagally mediated episodes of hypotension and bradycardia are a common cause of recurrent syncope that can be identified by head-upright tilt table testing. Although the use of beta blockers, transdermal scopolamine, disopyramide, and fludrocortisone may be helpful in preventing further episodes, some patients are intolerant of or respond poorly to each of these agents. Following anecdotal observations, we investigated the utility of fluoxetine (a serotonin re-uptake antagonist) in preventing head-upright tilt induced hypotension/bradycardia in patients unresponsive to or intolerant of standard therapy. Sixteen patients (7 men and 9 women, mean age 42 +/- 21 years) with recurrent syncope and positive head-upright tilt studies (refractory to normal therapy) were placed on fluoxetine and restudied 5-6 weeks afterward. Three patients were intolerant of the medication. Of the 13 patients who underwent repeat tilt studies, seven patients (53% of the patients retested or 44% of the total group) were rendered tilt table negative, and, over a mean follow-up period of 19 +/- 9 months, have remained asymptomatic. We conclude that fluoxetine may be an effective therapy in patients with recurrent vasovagally mediated syncope refractory to other forms of therapy.

Adult↗

Adaptive rate pacing controlled by right ventricular preejection interval for severe refractory orthostatic hypotension.

A 72-year-old African-American man with frequent recurrent syncope was found to have severe refractory orthostatic hypotension with concomitant supine hypertension. Pharmacotherapy was successful in controlling his supine hypertension but was unable to resolve his severe orthostatic hypotension. Temporary fixed rate tachypacing was only minimally effective in preventing syncope during upright tilt, while variable rate pacing based on degree of blood pressure fall was far superior. Following these observations, an adaptive rate pacing system controlled by right ventricular preejection interval was implanted (Precept DR Model 1200). The system adequately sensed the patient's fall in blood pressure when sitting or standing and augmented its rate accordingly, thus preventing syncope. While supine, the pacing rate fell to 60 ppm, thereby, avoiding an exacerbation of his concomitant supine hypertension. Over a 3-month follow-up period, he has had no further orthostatic or syncopal episodes. We conclude that adaptive rate pacing using right ventricular preejection interval may be an effective treatment for severe refractory orthostatic hypotension.

Aged↗

Functional analysis of human foamy virus accessory reading frames.

Foamy viruses belong to the retroviruses which possess a complex genome structure. The human foamy virus (HFV) isolate bears three open reading frames (the so-called bel genes) in the 3' region of the genome which have been reported to give rise to possibly six different proteins via alternative splicing (W. Muranyi and R. M. Flügel, J. Virol. 65:727-735, 1991). In order to analyze the requirements of these proteins for HFV replication in vitro, we constructed a set of single and combinatory bel gene mutants of an infectious molecular clone of HFV. The mutant which lacked the transacting activator, bel-1, was found to be replication incompetent. All other mutants replicated equally well and gave rise to comparable titers of infectious cell-free virus. When HFV proviruses were put under the control of a heterologous promoter (simian virus 40), none of the accessory gene products was found to be required for expression of structural (gag) proteins. There was no evidence for a posttranscriptional regulatory protein that is present in other complex retroviruses.

Base Sequence↗

Tilt table testing in the evaluation and management of athletes with recurrent exercise-induced syncope.

Recurrent idiopathic exercise-related syncope in the young athlete is often a challenging and frustrating condition. Vasovagally mediated hypotension and bradycardia is believed to be a common, but difficult to prove, cause of this form of syncope. This study evaluated the usefulness of head-upright tilt table testing in the evaluation and management of young athletes with recurrent idiopathic exercise-related syncope. Twenty-four trained young athletes (12 male, 12 female mean age 18 +/- 3.4 yr) with recurrent unexplained exercise-related syncope were evaluated by use of an upright tilt table test for 30 min, with or without an infusion of isoproterenol (1-3 micrograms.min-1 given intravenously) in an effort to provoke bradycardia, hypotension, or both. Ten control patients with no history of syncope were also studied. Syncope occurred in 10 patients (41%) during the baseline tilt and in nine patients (37%) during the isoproterenol infusion (total positives 79%). Seventeen patients who had positive test results eventually became tilt table negative with pharmacotherapy, and over a mean follow-up period of 23 +/- 7 months, no further syncopal episodes have occurred. Two patients refused pharmacotherapy and have continued to experience syncope. We conclude that head-upright tilt table testing combined with isoproterenol infusion is useful in the diagnosis of vasovagal syncope in young athletes with recurrent exercise related syncope, and in the evaluation of prophylactic pharmacotherapy.

Adolescent↗

Kinetic analysis of cytokine gene expression in the livers of naive and immune mice infected with Listeria monocytogenes. The immediate early phase in innate resistance and acquired immunity.

The anamnestic response to infection with Listeria monocytogenes is characterized by the rapid elimination of normally lethal doses of bacteria and accelerated granuloma formation. These phenomena are mediated by listeria-specific memory T cells within the first 24 h after reinfection. In order to elucidate the mechanisms operative during this decisive phase of infection, we conducted a comprehensive kinetic and quantitative analysis of cytokine gene expression in the livers of naive and immune mice. Organs were removed at 30 min, and 1, 2, 6, and 24 h after primary and secondary infections, and PCR3-assisted messenger RNA (mRNA) amplification was performed on matched samples using primers specific for IL-1 beta, IL-6, M-CSF, GM-CSF, TNF-alpha, IFN-gamma, IL-10, IL-4, IL-2, IL-3 and I1-2Rp55. The cytokine pattern characteristic of secondarily infected animals differed qualitatively by the expression of mRNA for IL-2, IL-2Rp55, IL-3, and IL-4, demonstrating the accumulation and activation of specific T cells in the livers as early as 1 to 2 h after reinfection. Combined in vivo depletion of both CD4+ and CD8+ T cells before reinfection almost completely abrogated the differentiated cytokine profile typical of the anamnestic response. Using competitive PCR for semiquantitative determination of mRNA levels, the amount of IL-1 beta and IL-6 mRNA was found to be very similar during primary and secondary infection, whereas TNF-alpha mRNA was found to be increased by approximately 10-fold 2 h and IFN-gamma mRNA by approximately 50 to 100-fold 6 h after reinfection when compared with a primary challenge. Combined in vivo depletion of both CD4+ and CD8+ T cells before reinfection resulted in a substantial (approximately 10-fold) decrease in IFN-gamma mRNA expression. To correlate these findings with cytokine secretion, spleen cells from naive and immune as well as normal and CD4+ and CD8+ cell depleted mice infected 6 h previously were cultured for 48 h, and supernatants were analyzed for the amount of the above mentioned cytokines. Semiquantitative PCR-assisted mRNA amplification is demonstrated to be a superior tool in dissociating the mediators of innate resistance from those operative in protective immunity and granuloma formation.

Animals↗

Head-upright tilt-table testing in evaluation and management of the malignant vasovagal syndrome.

Vasovagally mediated cardiac asystole has been proposed as a potential cause of sudden cardiac death. To assess this possibility and identify characteristics that define patients with vasovagally mediated asystole, head-upright tilt-table testing was performed in 50 consecutive patients (26 women and 24 men, mean age 42 +/- 10 years) with recurrent unexplained syncope. The upright tilt-table test was performed in the fasting state for 30 minutes, with or without the use of intravenous isoproterenol (1 to 3 micrograms/min). The production of ventricular asystole lasting greater than 4 seconds was considered a positive result. All patients with tilt-induced asystole received therapy with either beta blockers, disopyramide, transdermal scopolamine or atrioventricular permanent pacing, the efficacy of which was evaluated with serial tilt-table tests. Reproducible tilt-induced asystole occurred in 10 patients (7 men and 3 women, mean age 23 +/- 12 years) (7 patients during baseline tilt, and 3 during isoproterenol infusion). Analysis of this group revealed that they had significantly more frequent and severe syncopal episodes (3 patients had episodes needing bystander cardiopulmonary resuscitation) than did those patients with tilt-induced syncope without asystole. All patients who had tilt-induced asystole eventually became tilt-table negative with therapy (4 with beta blockers, 2 with disopyramide, and 4 with atrioventricular permanent pacing), and over a mean follow-up of 21 +/- 6 months no further syncopal episodes occurred. It is concluded that patients with recurrent tilt-induced asystole represent a distinct subgroup that has recurrent severe syncope that may mimic or result in sudden cardiac death. Thus, the predischarge electrophysiologic study could predict late outcome with recurrence of preexicitation or supraventricular tachycardia in patients who had undergone surgical ablation of the accessory pathway with an overall predictive accuracy of 95% (107 of 113 patients), negative predictive value of 96% (103 of 107), and positive predictive value of 67% (4 of 6).

Adolescent↗

Comparative activity of the topical quinolone OPC-7251 against bacteria associated with acne vulgaris.

The antibacterial activity of the topical quinolone OPC-7251 against bacteria commonly found in acne vulgaris was tested in vitro by an agar dilution method. The MIC50 was 0.25 mg/l for Propionibacterium acnes, 0.125 mg/l for Propionibacterium granulosum, 0.03 mg/l for Staphylococcus aureus and 0.06 mg/l for coagulase-negative staphylococci. Compared with seven other antibiotics tested (ciprofloxacin, penicillin, erythromycin, tetracycline, clindamycin, fusidic acid and gentamicin), OPC-7251 had potent activity against both propionibacteria and staphylococci and the lowest incidence of resistant strains.

Acne Vulgaris↗