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Biomedical subjects

A Sing

Publications and source records attributed to A Sing.

33 records · Page 2Linked to original sources

Pneumocystis carinii carriage in immunocompetent patients with primary pulmonary disorders as detected by single or nested PCR.

Ninety-five bronchoalveolar lavage specimens from 63 immunocompetent adult patients with primary pulmonary disease were analyzed for Pneumocystis carinii colonization by primary and nested PCR. Twelve of 63 patients (19%) were PCR positive. None of them developed P. carinii pneumonia. These results suggest that P. carinii carriage may exist in immunocompetent patients with underlying pulmonary disease.

Adult↗

First-glance diagnosis of Strongyloides stercoralis autoinfection by stool microscopy.

We report a case of autoinfection due to Strongyloides stercoralis in a 27-year-old Ethiopian AIDS patient living in Germany for nearly 3 years. This case was diagnosed on the basis of a single-view field in microscopy of a freshly obtained formalin-fixed stool specimen showing both rhabditiform and filariform larvae. The diagnosis of autoinfection by microscopy is discussed in detail.

Adult↗

IL-18 (IFN-gamma-inducing factor) regulates early cytokine production in, and promotes resolution of, bacterial infection in mice.

IL-12-induced IFN-gamma production is essential for clearance of Yersinia enterocolitica infection. Similar to IL-12, the recently described cytokine IL-18 (IFN-gamma-inducing factor) is produced by macrophages and induces IFN-gamma production in spleen cells. Therefore, we have investigated the role of IL-18 in Yersinia infection of mice. Heat-killed yersinia-triggered IL-18-promoted IFN-gamma production of splenocytes was predominantly dependent on endogenous IL-12 production, whereas IL-12-promoted IFN-gamma production was not IL-18 dependent. IL-18-induced IFN-gamma production was to a higher degree dependent on IFN-gammaR-mediated mechanisms and in synergism with IL-2 resulted in at least fivefold higher IFN-gamma levels as compared with the combination of IL-12 plus IL-2. Analysis of the effect of IL-18 on IL-12 production of LPS-stimulated peritoneal macrophages revealed that IL-18 decreased LPS-induced IL-12 production, indicating that IL-18 might be involved in negative regulation of IL-12 production. In vivo studies revealed that Yersinia-resistant C57BL/6 mice expressed fourfold higher IL-18 mRNA levels than did susceptible BALB/c mice. Administration of anti-IL-18 Abs caused a 100- to 1000-fold increase in bacterial counts in the spleen of infected mice but did not change IFN-gamma production levels. Taken together, our data demonstrate that IL-18 is involved in regulation of cytokine production during the early phase of bacterial infections as well as in clearance of Yersinia infection.

Animals↗

Chronic prosthetic hip infection caused by a small-colony variant of Escherichia coli.

From two different specimens of a chronic prosthetic hip infection taken at an interval of 2 months a slow-growing gram-negative bacterium was isolated in pure culture. The strain grew with the typical features of a small-colony variant (SCV). 16S rRNA sequencing identified the bacterium as Escherichia coli. Biochemical characterization demonstrated multiple phenotypic alterations of a mutant carrying a defect in the heme biosynthetic pathway (Hem-): (i) catalase and nitrate reductase reactions were both negative, (ii) a negative benzidine reaction demonstrated the lack of heme-containing cytochromes, and (iii) growth stimulation under anaerobic conditions as well as gentamicin resistance indicated defective aerobic respiration. PCR and Southern hybridization demonstrated that the mutation of the SCV of E. coli was localized in the hemB gene and was most likely due to a deletion of the hemB gene. On blood agar plates revertants were recognized growing as normal-sized colonies between the dominant small colonies of the strain. Feeding experiments indicated that the revertants but not the small colonies were permeable for hemin. A strong antibody response against the infecting SCV of E. coli was found. To our knowledge, this is the first report of a Hem- E. coli strain as the etiological agent of a chronic bacterial infection.

Escherichia coli↗

Aquarium dermatitis: cercarial dermatitis in an aquarist.

A 33-year-old man presented with very itchy red papules on the back of his hands and forearms. These papules appeared about 90 min after he had cleaned his aquarium in which he kept native fish and watersnails. He had obtained the watersnails some weeks before from a nearby pond. Examination of water from the aquarium revealed cercariae. The clinical diagnosis of cercarial dermatitis was corroborated. Cercarial dermatitis has repeatedly been seen in swimmers but not in aquarists keeping fish in a home aquarium.

Adult↗

Contribution of the Mn-cofactored superoxide dismutase (SodA) to the virulence of Yersinia enterocolitica serotype O8.

Enteric pathogens harbor a set of enzymes (e.g., superoxide dismutases [SOD]) for detoxification of endogenous and exogenous reactive oxygen species which are encountered during infection. To analyze the role of the Mn-cofactored SOD (SodA) in the pathogenicity of yersiniae, we cloned the sodA gene of Yersinia enterocolitica serotype O8 by complementation of an Escherichia coli sodA sodB mutant and subsequently constructed an isogenic mutant by allelic exchange. Sequence analysis revealed an open reading frame that enabled the deduction of a sequence of 207 amino acids with 85% identity to SodA of E. coli. In a mouse infection model, the sodA null mutant was strongly attenuated in comparison to its parental strain. After intravenous infection, the survival and multiplication of the mutant in the spleen and liver were markedly reduced. In contrast, inactivation of sodA had only minor effects on survival and multiplication in the gut and Peyer's patches, as could be demonstrated in the orogastric infection model. The reduction in virulence was accompanied by a low but significant increase of susceptibility of the soda mutant to bacterial killing by polymorphonuclear leukocytes (PMN) and an alteration of the intracellular chemiluminescence response of PMN. These results suggest that the resistance of Y. enterocolitica to exogenous oxygen radicals produced by phagocytes involves the Mn-cofactored SOD. The important role of sodA for the pathogenicity of Y. enterocolitica could also be due to detoxification of endogenous, metabolically produced oxygen radicals which are encountered by extracellular enteric pathogens during the invasion of the host.

Animals↗

Induction of CD14 expression in Lpsn, Lpsd and tumor necrosis factor receptor-deficient mice.

The involvement of CD14 in lipopolysaccharide (LPS) recognition and signaling has been demonstrated in several studies. For this reason, we investigated whether the resistance of Lpsd mice to LPS might be related to an impaired CD14 expression. We compared the in vivo and in vitro expression of CD14 in Lpsn (LPS sensitive) and Lpsd mice, and its modulation by LPS, killed gram-negative and gram-positive bacteria and double-stranded (ds)RNA. Untreated Lpsn and Lpsd cultured macrophages (M phi), expressed similar amounts of CD14 mRNA and membrane-bound (m)CD14. LPS enhanced CD14 expression only in Lpsn M phi, while all bacteria, or dsRNA, enhanced CD14 in Lpsn and Lpsd M phi. Similarly, in vivo administration of LPS induced or enhanced CD14 mRNA in different organs of Lpsn mice only, while bacteria or dsRNA in both types of mouse. Furthermore, exogenous recombinant tumor necrosis factor (TNF) induced in vivo and in vitro enhanced CD14 expression in Lpsn, Lpsd and also in TNF receptor 2-deficient (TNFR2-/-) mice, but failed to do so in TNFR1-/- mice, showing that TNFR1 mediates the effect of TNF on CD14. However, LPS, bacteria and dsRNA induced CD14 in both TNFR2-/- and TNFR1-/- mice to a similar extent, revealing that this induction does not require TNF signaling.

Animals↗

Interferon beta, a cofactor in the interferon gamma production induced by gram-negative bacteria in mice.

The interferon (IFN) gamma production of splenocytes from closely related C57BL/10ScSn (Sn) and C57BL/10ScCr (Cr) mice was compared. Concanavalin A and CD3 monoclonal antibodies induced high levels of IFN-gamma in both Sn and Cr splenocytes. By contrast, treatment with gram-negative bacteria induced IFN-gamma only in Sn splenocytes; in Cr splenocytes, the IFN-gamma response was heavily impaired. The IFN-gamma induction by bacteria requires the cooperation of IFN-gamma-producing cells with macrophages. Depletion of macrophages from Sn splenocytes resulted in the loss of ability to produce IFN-gamma after bacterial stimulation. Reconstitution with new Sn macrophages restored the IFN-gamma responsiveness, whereas reconstitution with Cr macrophages failed to do so. Normal function of IFN-gamma-producing cells and a defective function of macrophages of Cr mice was demonstrated by evidence showing that whole or macrophage-depleted Cr splenocytes, when supplemented with Sn macrophages, acquire the ability to produce IFN-gamma in response to bacteria. A similar effect was achieved by supplementing Cr splenocytes with supernatants of bacteria-stimulated Sn macrophages or with recombinant murine IFN-beta or IFN-alpha. Preincubation of active macrophage supernatants with antibodies to IFN-beta suppressed the helper activity for Cr splenocytes. Moreover, the bacteria-induced production of IFN-gamma by Sn splenocytes could be inhibited by antibodies to murine IFN-beta. The results provide evidence that IFN-beta is an important cofactor of IFN-gamma induction, which is not induced in Cr mice by gram-negative bacteria.

Animals↗

Genetic modification of T cell clones to improve the safety and efficacy of adoptive T cell therapy.

Our laboratory has developed methods to isolate human antigen-specific cytolytic CD8+ T cell clones and to expand such clones in vitro to numbers sufficient for T cell therapy of human diseases. Studies in immunocompromised bone marrow transplant patients at high risk for disease associated with cytomegalovirus have demonstrated that administration of more than 10(9) CD8+ T cell clones is safe and can effectively reconstitute a deficient human immune response. Our laboratory is applying this strategy of adoptive therapy to the treatment of human cancer, starting with the subset of patients with Hodgkin's disease who show expression of proteins encoded by the Epstein-Barr virus in their malignant Reed-Sternberg cells. The development of efficient systems such as retroviral vectors for the introduction of genes into primary cells has made it possible to consider overcoming some of the limitations of the effector T cells that normally mediate response to an antigen. Our laboratory is attempting to modify T cell clones by the introduction of genes before transfer as a means to improve the safety and/or efficacy of T cell therapy.

Antigens, Viral↗

Clonotypic antibodies which stimulate T cell clone proliferation.

We have prepared a variety of antisera which recognize the T cell receptors on both alloreactive and antigen-specific functional clones. The antisera specifically stimulate the immunizing T cell clones to proliferate without cross-stimulating a variety of other clones and are thus clonotypic. The antisera specifically precipitate an 82k molecular weight complex unique to the immunizing clone and an independent common component present on all the helper T cell clones tested. The 82k molecular weight complex consists of a heterodimer, which can be resolved into an acidic (a) chain and a more basic (beta) chain. The beta subunit differs in its isoelectric focusing pattern when isolated from two A derived clones which recognize and respond to different alloantigens. Thus, the functional specificity of the antibodies is reflected in identifiable changes in molecules at the biochemical level.

Animals↗

Comparison of the sensitivity of sputum and brush cytology in the diagnosis of lung carcinomas.

OBJECTIVE: To describe the role of sputum and brush cytology in the diagnosis of lung carcinoma and to elucidate the influence of tumor location, histologic tumor type and stage on the sensitivity of both methods. STUDY DESIGN: Retrospective and performed on 415 lung cancer patients. Two hundred of them were investigated only by sputum collection, 119 only by brushing and 96 by both methods. RESULTS: The overall sensitivity of the sputum technique was 0.403 and that of the brush method 0.500, while a combination of both showed a sensitivity of 0.640. The diagnostic yield depended on tumor location, histologic tumor type and stage. Sputum specimens were most valuable in the detection of early and peripheral carcinomas, whereas brushing was superior in finding more advanced and centrally located malignancies. Regarding tumor type, squamous cell carcinomas were diagnosed to the greatest extent by both methods. CONCLUSION: A complementary role of both cytologic techniques can be postulated by our data as well as by a literature review.

Adenocarcinoma↗

Problems and risks of unsolicited e-mails in patient-physician encounters in travel medicine settings.

BACKGROUND: International travel and use of modern information technology are expressions of modern life style. Seeking on-line travel health advice via E-mail for preventive (teleprevention) or diagnostic reasons may become increasingly popular among patients with financial resources and Internet access. This study was undertaken to compare the behavior of travel clinic or tropical medicine physicians and other providers of travel-related medical information services toward unsolicited E-mails from fictitious patients in pretravel and post-travel scenarios. We also wanted to test the potential of E-mail advice for preventive medicine (teleprevention), and to find out how the "Good Samaritan Law" is observed. METHODS: Two different E-mails were posted to E-mail addresses of 171 physicians (members of travel health and/or tropical medicine societies) and services offering advice on travel health issues identified by an AltaVista search. These E-mails, from two different fictitious travelers, were asking for advice regarding malaria prophylaxis in a pretravel scenario and describing symptoms suggesting acute malaria. RESULTS: Of the contacted addresses 43.3% and 49.7% respectively, replied to the pre- and post-travel E-mail. Of those suggesting antimalarial chemoprophylaxis in the pretravel scenario, 13.2% proposed inadequate regimens, and at least 3.5% of the post-travel replies were inappropriate. The "Good Samaritan Law" was observed by a significant number of physicians. CONCLUSION: Both patients and physicians have to be aware of the limitations of E-mail communication. Guidelines protecting physicians against legal and ethical consequences of this new communication technology are urgently needed.

Computer Communication Networks↗