PubMed Health⌕ Search

Biomedical subjects

B Hofmann

Publications and source records attributed to B Hofmann.

At least 73 records · Page 4Linked to original sources
PubMed1997

Heterozygosity for a deletion in the CKR-5 gene leads to prolonged AIDS-free survival and slower CD4 T-cell decline in a cohort of HIV-seropositive individuals.

OBJECTIVE: Recently, it has been shown that a homozygous 32 base-pair deletion in the gene encoding CKR-5, a major coreceptor for HIV-1, leads to resistance to infection with HIV-1. We have investigated whether HIV-seropositive individuals who were heterozygous for the CKR-5 deletion had a different course of the disease. DESIGN: Thirty-five high-risk HIV-seronegative and 99 HIV-seropositive Danish homosexual men followed form 1985 to 1996 and 37 blood donors were analysed for their CKR-5 genotype by polymerase chain reaction. RESULTS: Two (6%) of the 35 HIV-seropositive subjects at high-risk of infection were homozygous and seven (20%) were heterozygous for the CKR-5 deletion. This was not significantly different from the distribution in normal donors. Twenty-two (22%) of the 99 HIV-seropositive subjects were heterozygous and none was homozygous. Two subgroups of patients who had an opposite course of the HIV disease were identified. Of nine long-term non-progressors, six (66%) were heterozygous for the deletion. This frequency is significantly higher than in nine rapid progressors of whom non was heterozygous. The frequency of heterozygotes in long-term non-progressors was also significantly higher than in the cohort as a whole. A Kaplan-Meier plot of the HIV-seropositive subjects, of whom 57 developed AIDS, showed a significantly better prognosis within the first 7 years of follow-up for those who were heterozygous for the deletion. Heterozygous individuals also had a significantly slower decrease in CD4 T-cell count per year. CONCLUSION: Individuals who are heterozygous for the 32-base-pair deletion in the CKR-5 gene have a slower decrease in their CD4 T-cell count and a longer AIDS-free survival than individuals with the wild-type gene for up to 11 years of follow-up.

CD4 Lymphocyte Count↗
PubMed1997

Specificity of human cytotoxic T lymphocytes induced by a human papillomavirus type 16 E7-derived peptide.

In order to establish tumour-specific cytotoxic T lymphocyte (CTL) cell lines, T cells from a human papillomavirus (HPV) type 16-positive patient with a cervical carcinoma in situ and from a healthy volunteer were stimulated in vitro with autologous dendritic cells loaded with peptides derived from the viral transforming proteins E6 and E7 and corresponding to potential HLA-A*0201-restricted T cell epitopes. From each donor a small number of low-affinity CTL lines against the peptide E7/86-93 was obtained, which specifically lysed HLA-A*0201-expressing B-lymphocytes (cell line 721) loaded with this peptide. Cytotoxicity was also observed against two HLA-A*0201-E7-positive epithelial cell lines, the cervical carcinoma cell line CaSki and the HPV-16-immortalized foreskin-keratinocyte cell line HPK IA. However, since none of the CTL recognized both cell lines, and E7-expressing 721 transfectants were never lysed, it was concluded that the reactivity against CaSki and HPK IA cells was due to cross-reactivity on allogeneic HLA molecules rather than to E7 recognition, which emphasizes that the specificity of tumour cell lysis by peptide-induced CTL has to be interpreted with caution.

Carcinoma in Situ↗
PubMed1997

Specific information concerning taxonomy, pathogenicity and methicillin resistance of staphylococci obtained by a multiplex PCR.

The use of DNA amplification techniques such as the polymerase chain reaction (PCR) in modern diagnostic microbiology not only allows the sensitive and specific identification of micro-organisms but also the detection of specific antibiotic resistance genes. This study describes a multiplex PCR on bacterial colonies picked directly from agar plates without preceding DNA preparation. Eubacteria and staphylococci were identified by, 16S rRNA specific PCR products. In parallel, specific primers were used for the detection of staphylococcal coa and mecA genes. This 4-h multiplex PCR, consisting of four sets of primers, was evaluated for rapid and specific differential diagnosis of methicillin-resistant and methicillin-susceptible strains of Staphylococcus aureus and coagulase-negative staphylococci. To analyse specificity of the amplification products, 100 non-staphylococcal, eubacterial isolates and 20 Candida albicans strains were tested. In a first step, specificity of all four single sets of primers was evaluated before the co-amplification within the multiplex PCR procedure was performed. The results were compared with those of conventional susceptibility and typing methods. The specific 16S rRNA PCR product for eubacterial isolates (n = 786) and staphylococci (686) was found in all strains tested. The coa gene was detected only in S. aureus (488) strains with a specificity of 100%, and was not detected in any of the coagulase-negative staphylococci (198). The mecA gene was detected in 98% of methicillin-resistant staphylococci (393) and in 2% of all methicillin-susceptible staphylococci (293). The multiplex PCR with co-amplification of different determinants provides rapid reliable information on staphylococcal identification and methicillin susceptibility supporting the diagnosis, treatment and control of staphylococcal infections.

Bacterial Proteins↗
PubMed1997

The serotonin analogue buspirone increases the function of PBMC from HIV-infected individuals in vitro.

HIV infection is characterized by the loss of CD4+ T cell numbers as well as loss of T cell function leading to severe immunodeficiency. The proliferative capacity of T cells, measured in vitro as response to antigens and mitogens, is severely reduced during HIV infection. An increased level of the intracellular second messenger cAMP has been demonstrated to cause impaired proliferative capacity of PBMC from HIV-infected individuals in vitro. We have identified a serotonin analogue, buspirone, that inhibits the activity of adenylyl cyclase, the enzyme responsible for regulation of intracellular levels of cAMP. Using this inhibitor the proliferative responses of PBMC to a polyclone activator in vitro were increased in 28/30 HIV-seropositive individuals (p < 0.00001). Further, we demonstrated that this was due to proliferation of CD4+ T cells and that buspirone induced expression of IL-2 mRNA.

Adult↗
PubMed1996

Crystal structure of a bacterial lipase from Chromobacterium viscosum ATCC 6918 refined at 1.6 angstroms resolution.

The crystal structure of a lipase from the bacterium Chromobacterium viscosum ATCC 6918 (CVL) has been determined by isomorphous replacement and refined at 1.6 angstroms resolution to an R-factor of 17.8%. The lipase has the overall topology of an alpha/beta type protein, which was also found for previously determined lipase structures. The catalytic triad of the active center consists of the residues Ser87, Asp263 and His285. These residues are not exposed to the solvent, but a narrow channel connects them with the molecular surface. This conformation is very similar to the previously reported closed conformation of Pseudomonas glumae lipase (PGL), but superposition of the two lipase structures reveals several conformational differences. r.m.s. deviations greater than 2 angstroms are found for the C alpha-atoms of the polypeptide chains from His15 to Asp28, from Leu49 to Ser54 and from Lys128 to Gln158. Compared to the PGL structure in the CVL structure, three alpha-helical fragments are shorter, one beta-strand is longer and an additional antiparallel beta-sheet is found. In contrast to PGL, CVL displays an oxyanion hole, which is stabilized by the amide nitrogen atoms of Leu17 and Gln88, and a cis-peptide bond between Gln291 and Leu292. CVL contains a Ca2+, like the PGL, which is coordinated by four oxygen atoms from the protein and two water molecules.

Amino Acid Sequence↗
PubMed1996

[ADP-based records in primary health care. Rationalization or reorganization?].

Computer-based patient record systems have become very common in the primary health service, but their effects have seldom been documented. Three surveys were carried out in the municipality of Sør-Varanger, in 1993, 1994 and 1995, to discover how such a system has affected the running of the municipal medical centres. The most significant changes were organisational. Certain tasks changed hands, others were dispensed with, and new ones were added. Information on patients became more readily available, and services to the public were improved. Many more patients received an answer to questions concerning information in the case record, and far fewer forms had to be filled in manually. Despite this, computerisation had seemingly led to little change in effectiveness, and the total load of work remained the same. The survey also showed that simple extensions to the system could produce marked improvements.

Efficiency, Organizational↗
PubMed1996

Penalty methods for the inverse problem in EIT.

The conductivity profiles arising in medical applications of electrical impedance tomography (EIT) are often of 'blocky' structure, i.e. they are relatively constant inside an organ and are rapidly varying at its boundary. Standard regularization methods for the inverse problem tend to blur these sharply defined edges. A penalty method is proposed which is especially designed for a better reconstruction of discontinuous conductivity profiles.

Electric Impedance↗
PubMed1996

Buspirone, a serotonin receptor agonist, increases CD4 T-cell counts and modulates the immune system in HIV-seropositive subjects.

OBJECTIVE: We have previously shown that drugs that decrease intracellular cAMP levels increase/restore the proliferative and cytotoxic capacity of T cells from HIV-seropositive subjects in vitro. Buspirone, a serotonin receptor agonist, indirectly decreases intracellular cAMP levels in T cells and has the same increasing/restoring effect on T-cell proliferation in lymphocytes from HIV-seropositive subjects in vitro. DESIGN: Buspirone was given as a single high dose to six HIV-seropositive subjects, or as continuous medication with increasing dosage over 6 weeks to nine HIV-seropositive subjects, with CD4 T-cell counts of 150-300 x 10(6)/l. RESULTS: Significant increases in CD4 T cells, CD4 percentage and CD4/CD8 ratio were found 1 week after a single high dose of buspirone was administered. With continuous administration, a significant increase in CD4 T cells was observed after 1 and 4 weeks. Serum HIV RNA showed a significant decrease 1 h after a single dose of buspirone was administered. With continuous administration of buspirone, plasma HIV RNA first increased within the first 2 weeks of treatment and then decreased towards and below baseline concurrently with a significant decrease in CD8T cells. The proliferative T-cell response to poke weed mitogen and membrane expression of IL-2R increased significantly during continuous treatment with a significant decrease in expression of HLA-DR on CD8+ T cells. Development of "flu-like' symptoms, so severe that two patients withdrew from the study and two patients ceased medication before time, was a clinical indication of modulation of the immune system by buspirone. CONCLUSION: The study shows that buspirone modulates the immune system and leads to changes in the CD4 and CD8 T-cell numbers, functional capacity, cell maturation and viral load.

Adult↗
PubMed1996

A multiparameter, PC-based telemetry unit for biomedical signals.

A low-cost, general-purpose telemetry system was developed for use in rural health centres, hospitals, ambulances and clinics. It was designed to transmit a range of analogue biomedical signals using various communications media. The system was tested using different telephone systems, including mobile telephony. The results showed a maximum sample rate of 1.6 kHz using the public telephone network. With three data channels the system produced sample rates of 500 Hz at 8 bit/sample. Typical overall delay times were below 100 ms. Mobile tests showed that the GSM telephone was superior to the Nordic mobile telephone (NMT 900). In field tests, sample rates of 990 Hz were obtained using GSM telephony. Bit error rates were less than 10(-7) for all applications and high-fidelity regeneration was obtained at the receiver. The tests showed that the system was well suited for telemetry of analogue biomedical signals in a broad range of telemedicine applications.

Ambulances↗
PubMed1995

[The normal and the pathological].

The main problem of modern health care is to express its goals and its limits. To do this it is necessary to answer the fundamental question: what is normal and what is pathological? The French physician and philosopher Georges Canguilhem has tried to answer this question. He claims that for medicine, the difference between these fundamentals is determined by normativity and not by science. In doing this he wishes to save the autonomy of the individual patient and to delimit medicine from science.

Disease↗
PubMed1995

Increased frequency of homozygosity of abnormal mannan-binding-protein alleles in patients with suspected immunodeficiency.

A low plasma concentration of mannan-binding protein (MBP) impairs opsonisation and phagocytosis. Three different mutations in the MBP gene have a dominant effect on MBP concentration. We investigated the frequency of the abnormal MBP alleles in 228 unrelated patients suspected of various non-HIV-related immunodeficiencies. The frequency of heterozygotes for the abnormal alleles was not different from that in the background population (36.0% and 37.4%, respectively). By contrast, the frequency of homozygotes for the abnormal alleles was significantly increased (8.3% and 0.8%, respectively; p = 0.0017). This finding implies that homozygotes for abnormal MBP alleles are predisposed to recurrent infections.

Alleles↗
PubMed1995

Rapid identification of elaiophylin and geldanamycin in Streptomyces fermentation broths using CPC coupled with a photodiode array detector and LC-MS methodologies.

During the course of screening microbial broth extracts in various high through-put bioassays (eg receptor binding or enzyme inhibition), several actinomycete cultures were discovered to produce active metabolites. The natural products elaiophylin and/or geldanamycin are produced by several Streptomyces violaceusniger strains, and the bioactivity of the extracts from these cultures was frequently associated with the fractions containing these metabolites. CPC coupled to a photodiode array detector and LC-MS techniques were applied to these broth extracts to ascertain rapidly when these natural products were present. These methodologies allowed us to identify the metabolites quickly in the crude extract, and the application demonstrated further the utility of CPC-photodiode array detection and LC-MS as powerful, initial analytical tools in analyses of the complex metabolite profiles produced by microorganisms.

Anti-Bacterial Agents↗
PubMed1994

Isolation and characterization of a Bacillus subtilis secA mutant allele conferring resistance to sodium azide.

A mutation has been isolated in the Bacillus subtilis secA gene (secA10) which allows cell growth and residual protein translocation in the presence of 1.5 mM sodium azide. Besides conferring resistance to sodium azide, the corresponding SecA10 mutant protein, in which glutamic acid at position 338 has been changed to glycine, seems to possess a secretion defect even in the absence of azide. In addition, the secA10 mutant protein was found to be recessive to wild-type secA with regard to azide resistance. Our results strongly suggest that, like the situation in Escherichia coli, the B. subtilis SecA protein is a main target for the lethal action of sodium azide.

Azides↗
PubMed1994

Crystallization and preliminary X-ray analysis of a lipase from Chromobacterium viscosum.

Lipase from Chromobacterium viscosum has been purified to homogeneity and crystallized in a form suitable for X-ray diffraction analysis from 10-14% polyethylene glycol 4000 and 10-14% 2-methyl-2,4-pentane diol at pH 6.4 in the presence of 0.25%(w/v) n-octyl-beta-D-glucopyranoside. These crystals belong to space group P2(1)2(1)2 with refined lattice constants a = 41.1 A, b= 156.8, c = 43.6 A, indicating a cell content of one monomer per asymmetric unit of the crystal. The crystals diffract to a resolution of 2.2 A.

Journal Article↗
PubMed1994

Differential effect on serum neopterin and serum beta 2-microglobulin is induced by treatment in Pneumocystis carinii pneumonia.

Forty-three human immunodeficiency virus-infected patients with Pneumocystis carinii pneumonia (PCP) were enrolled in a study of adjunctive corticosteroid treatment for 10 days versus placebo, in addition to antimicrobial treatment. Levels of neopterin and beta 2-microglobulin (beta 2M) were determined in consecutive serum samples. Initiation of antimicrobial treatment resulted in significantly increased neopterin levels, whereas beta 2M levels slightly decreased from pretreatment levels. In patients treated with corticosteroid, both neopterin and beta 2M decreased, by approximately 50% and approximately 30%, respectively, and returned to baseline after discontinuation of corticosteroid treatment. Antimicrobial treatment alone did not affect either neopterin or beta 2M in healthy controls. Results indicate that treatment has a differential effect on the immune response: increased macrophage activation leading to neopterin production and decreased production of beta 2M by lymphocytes. Further, addition of corticosteroids modified and decreased this immune activation and may explain the earlier demonstrated beneficial effect of corticosteroids in PCP treatment.

AIDS-Related Opportunistic Infections↗