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Biomedical subjects

B Hofmann

Publications and source records attributed to B Hofmann.

At least 91 records · Page 5Linked to original sources
PubMed1994

Detection of cytomegalovirus DNA in serum correlates with clinical cytomegalovirus retinitis in AIDS.

The high sensitivity of nested polymerase chain reaction (PCR) offers the possibility of rapid detection of cytomegalovirus (CMV) DNA in serum. Five consecutive serum samples were examined from 52 human immunodeficiency virus (HIV)-seropositive patients (19 of whom had clinically presumed diagnosis of CMV chorioretinitis). Presence of CMV DNA in serum was shown to precede development of clinical disease. Eleven patients who developed chorioretinitis were positive for CMV DNA in serum samples obtained 3 months before clinical disease, and 3 retinitis patients who initially were negative for CMV DNA became positive with the onset of clinical retinitis. In contrast, 29 of 33 HIV-seropositive subjects without clinical CMV chorioretinitis and matched with respect to age and CD4 T cell numbers were negative for CMV DNA in all 5 serum samples. Thus, the presence of CMV DNA in serum analyzed by PCR is a good predictive marker of CMV retinitis in HIV-seropositive subjects. A positive PCR results supports the clinical diagnosis and may be useful for monitoring response to antiviral treatment.

AIDS-Related Opportunistic Infections↗
PubMed1994

Antifilarial activity of macrocyclic lactones: comparative studies with ivermectin, doramectin, milbemycin A4 oxime, and moxidectin in Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi, and B. pahangi infection of Mastomys coucha.

The avermectins ivermectin and doramectin and the milbemycins milbemycin A4 oxime and moxidectin were tested for filaricidal activity in Mastomys coucha infected with Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi, and B. pahangi. Single subcutaneous doses of 0.005-5 mg/kg (L. carinii), 0.0005-0.5 mg/kg (A. viteae), 0.5 and 5 mg/kg (B. malayi), and 5 mg/kg (B. pahangi) were injected. Necropsies were performed 42 days after treatment. The avermectins caused a strong and rapid reduction of microfilaraemia in L. carinii and A. viteae infections within a few hours after treatment but showed only moderate efficacies on microfilariae of Brugia spp. The effects of the milbemycin derivatives on L. carinii and A. viteae microfilariae were generally weaker than those of the avermectins. However, moxidectin was comparatively active against microfilariae of Brugia spp. Subsequently the parasitaemia levels of L. carinii and A. viteae infected animals remained either almost completely depressed or tended to reincrease in a dose dependent manner whereas there was generally a continuous decrease of microfilaraemia levels in Brugia spp. infected animals. Adulticidal effects were limited to A. viteae although with neither dose of neither drug > 95% reductions of adult worm counts were reached. However, pathogenic influences of the drugs were observed on intrauterine embryonic stages of the parasites.

Animals↗
PubMed1993

[Birth of clinical practice--in a historical perspective].

Modern medicine is rooted in the science and the clinical practice of the 18th and 19th century. Here it finds its aims and methods, its view of life and death, and of health and disease. The french philosopher Michel Foucault has made an original contribution to the understanding of the social and cultural aspects of the development of medicine. He seeks its foundation in the classificatory medicine of the nosology of the 18th century. The diseases were then organized in a botanical model by their essence. The doctor revealed and confirmed the natural development of the diseases. He practised an art of medicine founded on local conditions. Following the social and political demands for regulation in the 18th century, the first grand hospitals were built. Here the doctors had the opportunity to study a large number of patients, and the statistical methods led to a bloom of clinical medicine. However, before medical science was able to use the microscope, before it could find the solution to life and disease in the obduced body, much had to change. Man had to alter his view of life and death, of subject and object, of doctor and patient. Only then was it possible to carry out pathological anatomy. Michel Foucault has presented a view of the history of medicine which counterbalances deterministic management of the Asclepian heritage by science.

Disease↗
PubMed1993

Human immunodeficiency virus proteins induce the inhibitory cAMP/protein kinase A pathway in normal lymphocytes.

Proliferation of normal T lymphocytes is impaired by human immunodeficiency virus (HIV) proteins. In this paper, we demonstrate important parts of this mechanism. Initially, HIV-induced impairment of proliferation was shown to be an active process involving induction of protein tyrosine kinases in both CD4 and CD8 T cells. Furthermore, the impairment of cell proliferation was demonstrated to be linked to induction of the inhibitory protein kinase A (PKA) pathway by HIV proteins. This induction of PKA was accompanied by an increase in intracellular cAMP, which is necessary for the activation of PKA. Finally, increases in cAMP/PKA activity were shown to induce biochemical changes that impaired proliferation when cells were stimulated with phytohemagglutinin. This was demonstrated by showing that (i) agents, other than HIV proteins, that increase cAMP/PKA activity (cholera toxoid and 8-bromo-cAMP) also decreased T-lymphocyte proliferation; (ii) exposure of lymphocytes to HIV or cholera toxoid led to decreased membrane activity of the proliferation promoter protein kinase C upon stimulation; and (iii) agents that reduced cAMP generation neutralized the effect of HIV proteins and restored lymphocyte proliferation. These studies show that the HIV-induced augmentation of cAMP/PKA activity may be a key part of the mechanism responsible for all or part of the HIV-induced anergy of T lymphocytes.

Amino Acid Sequence↗
PubMed1993

Purification and crystallization of 2,3-dihydroxybiphenyl 1,2-dioxygenase.

2,3-Dihydroxybiphenyl 1,2-dioxygenase, an enzyme of the biphenyl biodegradation pathway that cleaves the first of the aromatic rings, was purified to apparent homogeneity from Pseudomonas sp. strain LB400 that had been engineered to hyperexpress the bphC gene. The enzyme had a subunit molecular mass of 33.2 kDa as determined by SDS-polyacrylamide electrophoresis. Kinetic studies indicate a KM of 7 +/- 1 microM for 2,3-dihydroxybiphenyl. The enzyme is strongly inhibited by substrate (Kss = 300 +/- 10 microM). Catechol, 3-methylcatechol, and 4-methylcatechol were cleaved less efficiently and showed weaker substrate inhibition. 3,4-Dihydroxybiphenyl was not a substrate for the enzyme. Ammonium sulfate and polyethylene glycol 6000 were used as precipitants to obtain two different crystal forms. Crystals grown from ammonium sulfate and polyethylene glycol 6000 had space groups of P4(2)2(1)2 and I222, respectively. Electron microscopy indicates that the enzyme is an octamer (265 kDa) consisting of subunits arranged in two planar tetramers in a staggered conformation.

Amino Acid Sequence↗
PubMed1993

Ablation of the cornea by using a low-energy excimer laser.

We describe a new multipurpose method for corneal refractive surgery by using a focused excimer laser beam, which allows the application of a small, compact low-energy excimer laser. It is possible to ablate any area desired in the cornea without masking by scanning the focused beam. The ablation depths in freshly enucleated swine eyes were measured in relation to the number of laser pulses (at fixed fluence) and the pulse fluence at wavelengths lambda = 248 nm and lambda = 193 nm. The irradiation conditions were investigated to obtain smooth ablation of the corneal material over an area of about 1 cm2. The experiments show that smooth ablation is obtained when the ratio of the excimer laser beam spot diameter on the corneal surface and the displacement for one scanning step is given by a whole number. A simple model based on rectangular beam profiles is presented to exemplify this.

Animals↗
PubMed1993

Restoration of T-cell function in HIV infection by reduction of intracellular cAMP levels with adenosine analogues.

OBJECTIVE AND DESIGN: The impaired function of T cells is characteristic of HIV infection. It contributes to disease pathogenesis and is associated with disease prognosis. Our aim was to describe a biochemical basis for this impairment and a pharmacological way of restoring function. METHODS: Measurement of intracellular cAMP, protein kinase A (PKA) activity and proliferative capacity of T cells to recall antigens. RESULTS: HIV-seropositive individuals without AIDS showed significant increases in intracellular cAMP levels and PKA activity (inhibitors of lymphocyte function). The proliferative capacity of T cells to recall antigens correlated inversely with initial cAMP levels: poor proliferation was associated with high cAMP level in HIV infection. Moreover, drugs that reduced intracellular cAMP levels led to significant restoration of specific T-cell proliferation and cytotoxicity. CONCLUSIONS: Our findings indicate that high intracellular cAMP concentrations contribute to pathogenesis of T-cell anergy in HIV infection and that drugs that decrease intracellular cAMP levels may be beneficial in the treatment of AIDS.

Adenosine↗
PubMed1993

Defective T-cell stimulatory pathways in patients after allogeneic bone marrow transplantation (BMT) in man.

Immunological reconstitution after allogeneic bone marrow transplantation in man is characterized by a decreased lymphocyte transformation response to various mitogens and antigens during a period of from months to years. One reason for the decreased proliferative capability could be an inverted CD4/CD8 ratio; however, the present investigation demonstrates that this is not the only explanation for the immunodeficiency, since the CD4 as well as the CD8 subset, when studied in isolation, have qualitative defects, as evidenced by a reduced response of both subsets to stimulation with PHA, anti-CD2 and anti-CD3 MABs. The reason for the qualitative defect is unknown but a distorted composition of the CD4+ as well as the CD8+ T-cell subsets is suggested by the present investigations. We also observed that the PHA response was almost completely reconstituted one year after BMT, while the PWM response was still severely affected. The present study suggests that T-cell subsets which differ in their capacity to respond to PHA and PWM have different kinetics of reconstitution after BMT.

Adolescent↗
PubMed1993

Neopterin and human immunodeficiency virus infection.

Neopterin concentrations increase in serum and urine within the first week of infection with HIV and remain increased throughout the infection. In particular, changes in neopterin concentration precede decreases in CD4 T cell numbers and the development of clinical disease, and they can be used to predict the later development of AIDS. The increased neopterin concentrations show that the immune system is activated in HIV infection and demonstrate the presence of an interaction between the virus and the immune system. The most important future use of neopterin measurements may be in fast evaluation of new drugs in HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Different lymphoid cell populations produce varied levels of neopterin, beta 2-microglobulin and soluble IL-2 receptor when stimulated with IL-2, interferon-gamma or tumour necrosis factor-alpha.

Immune activation is central to many immune disorders. Clinical investigations have shown that immune activation can be quantified by measurements of soluble immune activation products in serum. Most in vitro studies of these immune activation products have focused on single products. In this study the specific cell sources and the major lymphokines inducing multiple activation products were investigated. In vitro addition of interferon-gamma (IFN-gamma) or IL-2 stimulated peripheral blood mononuclear cells to produce neopterin, beta 2-microglobulin (beta 2-M) and soluble IL-2 receptor (sIL-2R). These two lymphokines can act independently, because neutralizing antibodies to one of the lymphokines did not block the inducing activity of the other. Tumour necrosis factor-alpha (TNF-alpha) was also investigated and shown to be a less powerful inducer than IL-2 or INF-gamma. Separated lymphoid subpopulations responded differently to specific lymphokines. Monocytes produced only neopterin and only in response to INF-gamma. T cells released beta 2-M and sIL-2R in response to IL-2. B cells, however, were capable of producing all three immune activation products. Neopterin production in B cells was induced by either INF-gamma of IL-2, indicating that B cells have additional mechanisms for responding to lymphokines. To investigate whether these in vitro findings also occur in vivo, sera from patients who had received either rIL-2 or INF-gamma treatment were tested. INF-gamma administration led to substantial increases in serum neopterin but only a moderate beta 2-M increase and no increase in the serum sIL-2R levels. rIL-2 administration caused a substantial increase of all three serum immune activation products, consistent with our in vitro findings. The results confirm that increased serum levels of soluble immune activation products are indicators of increased cytokine production by lymphocytes and monocytes and also that B cells can be a prominent source of immune activation products.

B-Lymphocytes↗
PubMed1992

Phylogenetic analysis of 48 papillomavirus types and 28 subtypes and variants: a showcase for the molecular evolution of DNA viruses.

Papillomaviruses are attractive models for studying the molecular evolution of DNA viruses because of the large number of isolates that exhibit genomic diversity and host species and tissue specificity. To examine their relationship, we selected two amino acid sequences, one of 52 residues within the early gene E1 and the other of 44 residues within the late gene L1, which allowed insertion- and deletion-free alignment of all accessible papillomavirus sequences. We constructed phylogenetic trees from the amino acid and corresponding nucleotide sequences from 28 published and 20 newly determined animal and human papillomavirus (HPV) genomic sequences by using distance matrix, maximum-likelihood, and parsimony methods. The trees agreed in all important topological aspects. One major branch with two clearly separated clusters contained 11 HPV types associated with epidermodysplasia verruciformis. A second major branch had all the papillomaviruses involved in genital neoplasia and, in distant relationship, the cutaneous papillomaviruses HPV type 2a (HPV-2a), HPV-3, and HPV-10 as well as the "butcher's" papillomavirus HPV-7 and two simian papillomaviruses. Four artiodactyl (even-toed hoofed mammal) papillomaviruses, the cottontail rabbit papillomavirus, and avian (chaffinch) papillomavirus type 1 formed a third major branch. Last, four papillomaviruses exhibited little affinity to any of these three branches; these were the cutaneous types HPV-1a, HPV-4, and HPV-41 and B-group bovine papillomavirus type 4. The phylogeny suggests that some branches of papillomavirus evolution are restricted to particular target tissues and that a general process of long-term papillomavirus-host coevolution has occurred. This latter hypothesis is still conjectural because of bias in the current data base for human types and the paucity of animal papillomavirus sequences. The comparison of evolutionary distances for the most closely related types with those of 28 subtypes and variants of HPV-2, HPV-5, HPV-6, HPV-16, and HPV-18 supports the type as a natural taxonomic unit, with subtypes and variants being expressions of minor intratype genomic diversity similar to that found in the natural populations of all biological species. An exception to this seems to be HPV-2c, which has an evolutionary distance from HPV-2a of the intertype magnitude and may eventually have to be regarded as a distinct type. We describe an experimental approach that estimates the taxonomic and phylogenetic positions of newly identified papillomaviruses without viral isolation and complete genomic sequencing.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1992

Acute lymphoid changes and ongoing immune activation in SIV infection.

Two features of simian immunodeficiency virus (SIV) infection are emphasized: a transitory decrease in CD4 T cells in the first 2 weeks of infection followed by CD8 T-cell rise, and immune cell activation occurring by 4 weeks and persisting throughout the illness. The short-term changes included a fall in CD4 T cells by 2 weeks with partial recovery by 4 weeks and a CD8 rise that starts at 2 weeks. Subsequent characterization of CD4 T cells showed reduced expression of HLA-DR and CD25 (IL-2 receptor alpha chain) antigens later in SIV infection. Immune cell activation is evident in increased serum levels of neopterin and soluble CD8 antigen. Serum beta 2-microglobulin changes are less marked. Activation of CD8 T cells is reflected by increased percentages of cells expressing HLA-DR antigen. The B-cell numbers increased late in the course of SIV infection. Increased expression of the CD78 (Leu 21) activation phenotype was also seen in some monkeys. The immune activation changes (serum neopterin levels) induced by SIV infection in rhesus macaques appear to be associated with duration of illness, although the number of monkeys observed until death were too few for conclusive data. Thus, immune activation as well as T-cell deficiency may reflect significant immunopathogenic processes in SIV-induced disease.

Animals↗
PubMed1992

Purification and primary structure of pyruvate decarboxylase from Zymomonas mobilis.

Pyruvate decarboxylase (E.C. 4.1.1.1), the key enzyme in the glycolytic pathway to ethanol, was isolated in gram amounts from Zymomonas mobilis for structural studies. The primary structure was determined by automated Edman degradation and compared with that deduced from the DNA sequence of the structural gene, previously published by two groups (A. D. Neale, R. K. Scopes, R. E. H. Wettenhall, and N. J. Hoogenraad, 1987, Nucleic Acids Res. 15, 1753-1761; M. Reynen, and H. Sahm, 1988, J. Bacteriol. 170, 3310-3313). The peptide data differ from the published DNA sequences, which also deviate from each other. Crystals diffracting to about 0.3 nm resolution have been obtained by the hanging drop vapor diffusion method. The space group was identified as P4(1)22 or its enantiomorphs containing presumably one tetramer per asymmetric unit.

Amino Acid Sequence↗
PubMed1991

Inhibition of PAF-induced human platelet responses by newly synthesized ether phospholipids.

A series of 10 analogues of platelet-activating factor (PAF) was evaluated for proaggregatory and inhibitory behaviour on human blood platelets in vitro. Most of the compounds did not activate platelets but inhibited the PAF-induced aggregation. The inhibition was concentration-dependent and selective for PAF. Platelet responses to ADP and collagen were not suppressed. Schild analysis of the aggregation data was consistent with a simple competitive antagonism. The pA2 of the most effective antagonist (1-O-hexadecyl-2-O-ethylglycero-3-phosphoric acid-6'-(1-chinuclidinium)-hexylester) was 5.96. There is also evidence for its ability to inhibit the high affinity binding of [3H]PAF to the platelet receptors.

Adenosine Diphosphate↗
PubMed1991

Serum increases and lymphoid cell surface losses of IL-2 receptor CD25 in HIV infection: distinctive parameters of HIV-induced change.

Lymphocyte activation induces production of soluble IL-2 receptor (sIL-2R) which is a large portion of the CD25 membrane molecule and which is detectable in serum. Serum sIL-2R is reported here to increase as a direct effect of the HIV infection and not to be due to secondary opportunistic infections. sIL-2R increased promptly after HIV seroconversion in 83% of 50 initially seronegative homosexual men. The sIL-2R serum levels stabilized in the third year after seroconversion and were then predictive of later CD4 T cell levels and development of AIDS. In two studies of 59 and 395 seropositive men, beta-2 microglobulin (B2M) and neopterin levels in serum correlated closely with each other but not with sIL-2R levels. Thus, increased production of sIL-2R may reflect pathological processes distinct from those determining B2M and neopterin increases. Membrane CD25 expression on peripheral blood lymphocytes, unexpectedly, was found to be decreased in HIV infection. This contrasted with the increased sIL-2R in serum. Investigations with sensitive flow cytometry technics showed that CD25 was expressed at reduced levels and averaged only 12% of lymphocytes from HIV-infected individuals in contrast to 25% in noninfected individuals. All major lymphoid populations showed reductions in CD25 positive cells. This reduction in lymphoid membrane CD25, however, was not inversely correlated with the increased serum levels of sIL-2R or with other parameters of immune deficiency or activation. Thus, surface CD25 loss and serum sIL-2R increase are separate and independent consequences of HIV infection.

CD4-Positive T-Lymphocytes↗
PubMed1991

Serum soluble CD8 molecule is a marker of CD8 T-cell activation in HIV-1 disease.

To characterize CD8 T-cell activation during HIV-1 infection we measured serum soluble CD8 (sCD8) levels longitudinally in seroconverters and in individuals with established HIV infection who were in different stages of illness. CD8 T-cell activation occurs very early in HIV infection. Serum sCD8 levels were elevated in 91.5% of the first seropositive samples in seroconverters. Furthermore, CD8 T-cell activation persists throughout HIV infection. sCD8 predicted the occurrence of AIDS in HIV-seropositive individuals and so the addition of serum sCD8 levels to CD4 T-cell measurements increased the power in predicting the onset of AIDS. The serum level of sCD8 was particularly relevant to the prediction of subsequent CD4 T-cell fall relatively early in infection, for example, in the 3 years after seroconversion. However, later in HIV infection, for example within 2 years prior to development of AIDS, sCD8 levels were less predictive. sCD8 correlated with levels of beta 2-microglobulin and neopterin, which reflect activation of cell types other than CD8. Thus, serum sCD8 level can be a useful marker of specific CD8 T-cell activation, and is an independent predictor of prognosis in HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Extracellular lipase of Pseudomonas sp. strain ATCC 21808: purification, characterization, crystallization, and preliminary X-ray diffraction data.

A procedure for the purification of a very hydrophobic lipase from Pseudomonas sp. strain ATCC 21808 was elaborated by avoiding the use of long-chain detergents in view of subsequent crystallization of the enzyme. The purification procedure included chromatography on Q-Sepharose in the presence of n-octyl-beta-D-glucopyranoside, Ca2+ precipitation of fatty acids, and Octyl-Sepharose chromatography. The enzyme was purified 260-fold to a yield of 35% and a specific activity of 3,300 U/mg. The molecular weight was determined as 35,000; a polyacrylamide gel under nondenaturing conditions revealed a band at 110,000, and the isoelectric point proved to be at 4.5 to 4.6. The lipase crystallized with different salts and ethylene glycol polymers in the presence of n-octyl-beta-D-glucopyranoside and one alkyloligooxyethylene compound (CxEy) in the range from C5E2 to C8E4. The crystals diffract to a resolution of about 0.25 nm. Precession photographs revealed that they belong to space group C2 with lattice constants of a = 9.27 nm, b = 4.74 nm, c = 8.65 nm, and beta = 122.3 degrees, indicating a cell content of one molecule per asymmetric unit of the crystal. In hydrolysis of triglycerides, the lipase showed substrate specificity for saturated fatty acids from C6 to C12 and unsaturated long-chain fatty acids. Monoglycerides were hydrolyzed very slowly. The N-terminal sequence is identical to that of the lipase from Pseudomonas cepacia. Treatment with diethyl-p-nitrophenylphosphate affected the activities toward triolein and p-nitrophenylacetate to the same extent and with the same velocity.

Amino Acid Sequence↗