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Biomedical subjects

H Hahn

Publications and source records attributed to H Hahn.

At least 91 records · Page 5Linked to original sources
PubMed1996

Mutational analysis of the encephalomyocarditis virus primary cleavage.

Sixteen substitution mutations of the conserved DvExNPGP sequence, implicated in cardiovirus and aphthovirus primary polyprotein cleavage, were created in encephalomyocarditis virus cDNA, expressed, and characterized for processing activity. Nearly all the mutations severely decreased the efficiency of the primary cleavage reaction during cell-free synthesis of viral precursors, indicating a stringent requirement for the natural sequence in this processing event. When representative mutations were tested in full-length genomic contexts, they were lethal and no revertants were observed. Not only were the primary cleavage reactions deficient in these polyproteins, but subsequent cleavage of P1 by endogenous or exogenous 3C pro was also impaired. This indicates that primary cleavage has a role in the proper processing of the viral capsid precursor.

Amino Acid Sequence↗
PubMed1995

Mutations associated with amyotrophic lateral sclerosis convert superoxide dismutase from an antiapoptotic gene to a proapoptotic gene: studies in yeast and neural cells.

Familial amyotrophic lateral sclerosis (FALS) is associated with mutations in SOD1, the gene encoding copper/zinc superoxide dismutase (CuZnSOD). However, the mechanism by which these mutations lead to amyotrophic lateral sclerosis is unknown. We report that FALS mutant SODs expressed in yeast lacking CuZnSOD are enzymatically active and restore the yeast to the wild-type phenotype. In mammalian neural cells, the overexpression of wild-type SOD1 inhibits apoptosis induced by serum and growth factor withdrawal or calcium ionophore. In contrast, FALS-associated SOD1 mutants promote, rather than inhibit, neural apoptosis, in a dominant fashion, despite the fact that these mutants retain enzymatic SOD activity both in yeast and in mammalian neural cells. The results dissociate the SOD activity of FALS-associated mutants from the induction of neural cell death, suggesting that FALS associated with mutations in SOD1 may not be simply the result of a decrease in the enzymatic function of CuZnSOD. Furthermore, the results provide an in vitro model that may help to define the mechanism by which FALS-associated SOD1 mutations lead to neural cell death.

Amyotrophic Lateral Sclerosis↗
PubMed1995

L3T4(CD4)-, Lyt-2(CD8)- and Mac-1(CD11b)-phenotypic leukocytes in murine cryptococcal meningoencephalitis.

An immunohistological study of L3T4(CD4)+ and LYT-2(CD8)+ lymphocytes, Mac-1(CD11b)+ monocytes and granulocytes in experimental murine cryptococcal meningoencephalitis was conducted. To assess the concomitant inflammatory reaction in an extracerebral site, livers were examined in parallel. Mice were infected i.v. with Cryptococcus neoformans, group A/D, and organs were examined immunohistologically for CD4-, CD8- and monocyte- and granulocyte-specific CD11b-phenotypic leukocytes over a period of 60 days. Intracerebrally, agglomerations of cryptococci formed pseudocysts that were surrounded by CD4+ and CD8+ lymphocytes at the end of the second week post-infection, followed by the invasion of monocytes and granulocytes into the lesions. After the fourth week post-infection, most of the invaded lesions were transformed into glious scars. Meningitis was usually marked and showed a homogenous distribution of CD4-, CD8- and CD11b-phenotypic cells, with a predominance of monocytes and CD4+ lymphocytes. Inflammatory infiltrates in the liver were found already 4 days post-infection. CD4+ lymphocytes and monocytes were distributed homogeneously in the infiltrates, with a lower number of CD8+ lymphocytes being located rather in the periphery of the infiltrates. Comparing leukocyte kinetics in brain and liver, an important observation was the delayed immigration of immune cells at the intracerebral cryptococcal lesions as compared with the liver, and the different migration patterns of T-lymphocyte subgroups and macrophages. These results suggest that there are differential leukocyte migration patterns in the liver and brain following disseminated cryptococcosis. The immunological aspects of the observed leukocyte kinetics are discussed.

Animals↗
PubMed1995

Markers of foamy virus infections in monkeys, apes, and accidentally infected humans: appropriate testing fails to confirm suspected foamy virus prevalence in humans.

Foamy viruses (FVs) persist in healthy individuals of various mammalian species, including nonhuman primates. Laboratory markers of FV infection are (1) virus in throat epithelium or peripheral blood lymphocytes (PBLs), (2) proviral DNA sequences in PBLs and various solid organs, and (3) antibodies reactive to viral antigens on Western blots, in radioimmunoprecipitation tests, and in immunofluorescence assays. Using PCR and serological tests, we readily detected FV markers in naturally infected African green monkeys, rhesus monkeys, and chimpanzees, as well as in accidentally infected humans. Transmission of simian foamy viruses to humans (by bite or inadvertent laboratory infection) leads to viral markers, without affecting the recipient. Reports on FV-associated clinical disorders (e.g., thyroid or neurological) have remained controversial. In this study we failed to detect, by PCR, viral sequences in the samples from 223 patients, including 16 HIV-infected Africans, 46 Graves' disease patients, and 28 patients with the de Quervain's thyroiditis. Evaluation of 2688 sera from suspected high-risk areas (e.g., Central and East Africa, or high-risk groups such as HIV-infected individuals and patients with AIDS, thyroid, and neurological disorders) did not reveal FV-specific antibodies in a single case. Previously reported FV seroprevalence in various populations has never been verified by appropriate confirmatory tests. The strain of "human foamy virus" has remained a unique isolate. In conclusion, FVs are unlikely--at present--to circulate in human populations.

Africa↗
PubMed1995

Encephalomyocarditis viruses with short poly(C) tracts are more virulent than their mengovirus counterparts.

We have constructed three cDNA clones of encephalomyocarditis virus strain R (EMCV-R) with poly(C) tracts of C4, C9, and C20. RNA transcribed from these cDNAs was infectious to HeLa cells, and the resultant viruses grew well in this system, albeit with plaque sizes that were proportional to the poly(C) length. When injected into mice, the progeny viruses were only slightly less pathogenic than EMCV-R, and the observed degree of attenuation was not nearly as dramatic as for equivalent mengoviruses with similar short poly(C)s. Short-tract poly(C)-mediated attenuation is therefore highly dependent on viral genomic context.

Animals↗
PubMed1995

Comparison of fosfomycin and teicoplanin in serum bactericidal activity against staphylococci.

A serum bactericidal test was established employing human sera of volunteers after intravenous administration of fosfomycin (CAS 23155-02-4) and teicoplanin (CAS 61036-62-2) against 40 staphylococcal strains (20 Staphylococcus aureus and 20 coagulase-negative staphylococci, 10 of each group being susceptible and 10 being resistant to oxacillin). Median serum inhibitory titres were highest for fosfomycin against oxacillin-susceptible Staphylococcus aureus. In the three other groups of strains, the activity of fosfomycin was comparable to that of teicoplanin. The killing curves showed over 99% killing within 24 h for both antibiotics. Here, fosfomycin exerted a rapid killing activity within 4-6 h and was more effective in bacterial growth reduction. It can be concluded that fosfomycin and teicoplanin exerted comparable serum bactericidal antibacterial activity against staphylococci.

Adult↗
PubMed1995

[Thoracic trauma in childhood. Radiologic findings].

In childhood blunt trauma to the chest wall is more frequent than penetrating injuries. Most of these are the result of traffic accidents. Solitary or serial rib fractures are seen more often than fractures of the sternum. Complications of thoracic injuries are pulmonary contusion, hemothorax and, less frequently, pneumothorax. Pulmonary contusion can result in post-traumatic pneumatocele or chronic pulmonary hematoma. Injuries of the heart, the great vessels and bronchotracheal rupture, presenting initially with pneumothorax, followed by atelectasis, rarely occur. Blunt thoracic trauma is frequently associated with further injuries (head and/or blunt abdominal trauma). The prognosis also depends on the concurrent injuries. The initial evaluation of an injured child is based on the chest X-ray and abdominal ultrasound examination. Additional information can be obtained by a CT scan in mediastinal injuries.

Child↗
PubMed1995

[Blunt abdominal trauma in childhood. Value of conventional radiologic and ultrasound diagnosis].

In blunt abdominal trauma in children, the basic diagnostic work-up should include, in addition to history, physical examination, routine laboratory and X-ray studies, ultrasound and color Doppler ultrasonography. With these methods, most lesions can be identified both in the acute phase and in follow-up. They are also helpful to decide if surgery is indicated or if conservative management is justified. The diagnostic hallmarks of the most common organ lesions are summarized. Additional imaging studies, e.g. CT, angiography, or MRI, should be reserved for specific questions.

Abdominal Injuries↗
PubMed1994

BCG-induced immunomodulation of DTH to heterologous erythrocytes leads to Mac-1-independent myelomonocytic cell recruitment.

BCG(mycobacterium bovis)-modulated delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) differs from that in nonmodulated mice with respect to kinetics of expression, cellular composition of inflammatory foci, and susceptibility to specific suppressor mechanisms. We investigated whether the differences between these two types of SRBC-specific DTH reactions are based on different T cell subpopulations involved or on differences in the mechanisms of myelomonocytic cell recruitment induced by the same T cell subset. We demonstrate that both types of DTH are exclusively mediated by CD4+ T cells, but significantly differ in the mechanisms of inflammatory cell extravasation. While the expression of nonmodulated DTH to SRBC is markedly inhibited by anti-Mac-1 mAb 24 hr after challenge, the BCG-modulated DTH is totally resistant to such treatment. Thus, BCG modulation of the DTH response to SRBC most probably results in the generation of qualitatively different, antigen-specific CD4+ T cells, which induce the activation of adhesion molecules able to circumvent the Mac-1 dependency of the nonmodulated skin response.

Animals↗
PubMed1994

Evaluation of a commercial rRNA target amplification assay for detection of Mycobacterium tuberculosis complex in respiratory specimens.

Seventy-one respiratory samples were analyzed in a new commercially available target rRNA amplification assay aimed at detecting Mycobacterium tuberculosis complex directly in patient specimens. The assay (Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test) correctly identified 26 of 27 samples positive for Mycobacterium tuberculosis and 43 of 44 samples negative for Mycobacterium tuberculosis in culture. When appropriate controls are performed, the assay also performs well with other specimens, such as tissue biopsies, lymph node or bone marrow aspirates and pleural and ascitic exudates.

Humans↗
PubMed1994

A case of disseminated toxoplasmosis-value of PCR for the diagnosis.

Extracerebral toxoplasmosis has recently gained greater attention as a consequence of the AIDS epidemic. Serological techniques are unreliable, while isolation of the parasite is either time-consuming or insensitive. We here report a case of disseminated toxoplasmosis in a patient with AIDS. Diagnosis was suggested by serological tests and confirmed by PCR and Southern blot hybridisation or nested PCR. Detection of specific DNA was feasible in bronchoalveolar fluid, blood, serum and tissue samples. Direct detection of parasite-specific DNA by PCR and by nested PCR proved to be a promising, sensitive and rapid method for the diagnosis of disseminated toxoplasmosis, enabling us to promptly initiate specific treatment.

AIDS-Related Opportunistic Infections↗
PubMed1994

The mRNA-phenotype of granuloma formation: CD4+ T cell-associated cytokine gene expression during primary murine listeriosis.

In murine listeriosis, elimination of bacteria and immunity to reinfection critically depend on Thy1+ CD4- cells, while cell-mediated inflammatory phenomena such as DTH and granuloma formation are mostly mediated by CD4+ T cells. In an attempt to correlate T cell phenotype and function with a particular set of cytokines produced, we examined the cytokine gene expression profile associated with the presence or absence of Thy1+, CD4+ and/or CD8+ cells in the livers of mice during a primary infection with L. monocytogenes. The presence of CD4+ cells was found to be closely associated with mRNA expression for IL-2, IL-3 and IL-4, a 5-fold increase in expression of TNF-alpha and GM-CSF and a 25-fold increase in expression of IFN-gamma and TNF-beta mRNAs, and temporally coincided with the development of granulomatous lesions. In vivo neutralization of TNF-alpha and, to a lesser extent, IFN-gamma resulted in abrogation of granuloma formation. A similar correlation between the presence of CD8+ cells and mRNA expression for any one of the cytokines studied did not exist, pointing to a qualitatively different mechanism of CD8+ T cell mediated cure of listeriosis.

Animals↗
PubMed1994

Antibacterial efficacy of ciprofloxacin in a case of endocarditis due to Cardiobacterium hominis.

Endocarditis due to Cardiobacterium hominis is rare and may be treated with a variety of antibiotics. We isolated the bacteria from blood cultures of a patient with Cardiobacterium hominis endocarditis who could be successfully treated with ciprofloxacin. The bacterial features of Cardiobacterium hominis are presented, and susceptibility to ciprofloxacin is documented with bacterial killing curves employing peak and trough specimens of patient's serum.

Adult↗
PubMed1994

CD4+ T cell associated cytokine gene expression during experimental infection with Listeria monocytogenes: the mRNA phenotype of granuloma formation.

In murine listeriosis, elimination of bacteria and immunity to re-infection critically depend on Thy-1+CD4- cells, while cell-mediated inflammatory phenomena like delayed-type hypersensitivity and granuloma formation are mediated by CD4+ T cells. In an attempt to correlate T cell phenotype and function with a particular set of cytokines produced in vivo, we examined the cytokine gene expression profile associated with the presence or absence of CD4+ and/or CD8+ cells in the livers of mice during experimental infection with Listeria monocytogenes. T cell subset depletion was achieved by i.p. administration of saturating amounts of the appropriate mAbs, and mRNA detection was carried out using a qualitative and semi-quantitative polymerase chain reaction-based mRNA amplification protocol. In both primary and secondary infection, the presence of CD4+ cells was a prerequisite for granuloma formation, and was found to be closely associated with mRNA expression for IL-2, IL-3 and IL-4, a 5-fold increase in expression of tumor necrosis factor (TNF)-alpha and granulocyte macrophage colony stimulating factor, and a 25-fold increase in expression of IFN-gamma and TNF-beta mRNAs, suggesting a role for these cytokines in granuloma formation. In striking contrast, depletion of CD8+ cells did not result in reduced mRNA expression for any one of the cytokines studied, implying that CD8+ T cell mediated cure and prevention of listeriosis may operate via qualitatively distinct mechanisms.

Animals↗