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Biomedical subjects

G Hess

Publications and source records attributed to G Hess.

At least 19 recordsLinked to original sources

Immunogenicity and safety of an inactivated hepatitis A vaccine in anti-HIV positive and negative homosexual men.

The immunogenicity, reactogenicity, and safety of an inactivated hepatitis A vaccine were assessed in anti-HIV positive homosexual men. Fourteen anti-HIV positive (group 1) and 20 anti-HIV negative (group 2) men received vaccine (containing 720 ELISA units of hepatitis A antigen per dose) intramuscularly at 0, 1, and 6 months. Twelve unvaccinated anti-HIV positive men (group 3) were included as controls to evaluate disease progression. Seroconversion (anti-hepatitis V virus (HAV) > or = 20 mlU/ml) was higher in group 2 than group 1 at months 2 (100% vs. 73%) and 7 (100% vs. 77%). Group 2 had higher antibody titres than group 1 at months 1 (201 vs. 92 mlU/ml) and 7 (1,687 vs. 636 mlU/ml). The decline in CD4+ cells between months 0 and 7 was similar in groups 1 and 3 (6.4% vs. 16.2%), showing no evidence for harmful effect of the vaccine on the course of HIV infection. This hepatitis A vaccine appears safe, well tolerated, but less immunogenic in HIV positive homosexual men.

Acquired Immunodeficiency Syndrome

Analysis of immunoassays to detect antibodies to hepatitis A virus (anti-HAV) and anti-HAV immunoglobulin M.

Two newly developed anti-HAV tests were assessed, using a total of 1835 sera. These two tests are being distributed under the trademarks Enzymun-Test anti-HAV and Enzymun-Test IgM anti-HAV. The anti-HAV test was compared to anti-HAV tests from other manufacturers and featured a high sensitivity combined with a high level of reproducibility and specificity. In terms of sensitivity, reproducibility and specificity, the IgM test proved to be comparable to other IgM anti-HAV tests used for the diagnosis of acute type A hepatitis. Combining both tests was shown to be useful to recognize an acute or past hepatitis A virus infection. In addition, the high sensitivity of the anti-HAV test makes this test extremely useful to assess the immunoresponse to the hepatitis A vaccine.

Female

N-methyl-D-aspartate receptor mediated component of field potentials evoked in horizontal pathways of rat motor cortex.

To identify potential sites of synaptic modification of intrinsic cortical circuits, the contribution of the N-methyl-D-aspartate type of glutamate receptors to field potentials evoked in horizontal and oblique intracortical pathways was examined in rat motor cortex slice preparations. Presumably monosynaptic, short latency responses with a prominent negativity (-0.4 to -2.0 mV) were recorded in both superficial (across layer III) and deep (across layer V) horizontal pathways at a distance of approximately equal to 500 microns lateral to electrical stimulation sites and in oblique V-III pathway (-0.3 to -1.6 mV). Bath application of the N-methyl-D-aspartate receptor antagonist D,L-2-amino-5-phosphonovaleric acid (100 microM) reversibly decreased field potentials. Although decreases were observed in all components of the waveform, the most pronounced effect was on the late phase of the response. D,L-2-Amino-5-phosphonovaleric acid produced on average a 22% decrease in area, 12% in initial slope and 11% in peak amplitude of responses. Combined application of 100 microM D,L-2-amino-5-phosphonovaleric acid and a non-N-methyl-D-aspartate glutamate receptor antagonist, 6-cyano-7-nitro- or 6,7-dinitro-quinoxaline-2,3- dione (10-20 microM), eliminated all but a small, early and presumably non-synaptic response. In 18 of 23 cases, the relative contribution of the D,L-2-amino-5-phosphonovaleric acid-sensitive component was unrelated to field potential magnitude, suggesting that this component is present in all fiber classes. It is concluded that glutamate is the major transmitter of horizontal connections of layers II/III and layer V, as well as in the oblique V-III pathway. While most glutamatergic transmission is relayed by other glutamate receptor subtypes, N-methyl-D-aspartate receptor activation contributes a small but consistent part of ordinary transmission in each of these pathways in vitro. The results further suggest that a potential for N-methyl-D-aspartate receptor-mediated synaptic modification exists in intrinsic horizontal pathways of both superficial and deep layers of rat motor cortex.

2-Amino-5-phosphonovalerate

Molecular analysis of the erythropoietin receptor system in patients with polycythaemia vera.

Erythropoietin (EPO) is a potent regulator of the viability, proliferation and differentiation of erythroid progenitor cells. Its effect is mediated by binding to the erythropoietin receptor (EPO-R), a member of a new cytokine receptor family. Alterations of the EPO/EPO-R system have recently been shown to be involved in the pathogenesis of familial erythrocytosis and polycythaemia vera (PV). In order to define whether genetic changes in the EPO-R gene and its ligand play a role in the development of PV, the structure and expression levels of the EPO-R and EPO genes were examined in samples from bone marrow and/or peripheral blood mononuclear cells of 24 patients with PV. As expected, EPO serum levels were low and no detectable level of EPO mRNA was found by reverse polymerase chain reaction (RT-PCR) in the peripheral blood mononuclear cells of our PV patients. To search for structural alterations of the EPO-R, cDNA samples were subjected to PCR and SSCP analysis as well as sequencing. Heterogenous expression of EPO-R mRNA was observed without any structural changes, as revealed by RT-SSCP analysis using overlapping primers spanning the whole coding region of the EPO-R gene. Structural integrity of the EPO-R was further confirmed by sequencing of cloned PCR products. These data suggest that the mechanisms for the development of PV do not involve structural changes of the EPO-R gene.

Adult

Diagnosis of human immunodeficiency virus (HIV) infection: multicenter evaluation of a newly developed anti-HIV 1 and 2 enzyme immunoassay.

A new anti-human immunodeficiency virus type 1 and 2 (anti-HIV 1 and 2) test is described. It uses recombinant p24 and peptides covering gp32, gp41, and gp120 to identify HIV-1 and HIV-2 infections. This test has been shown to be specific (99.5%) and sensitive (99.8%). In this respect, the assay was equal or superior to anti-HIV 1 and 2 tests run as references. The test was able to discriminate sera from patients with HIV infections from those from uninfected individuals with excellence; it also exerted high intra- and interassay precisions. The "modular" concept of the test allows the use of single components (gp32 or gp41) to separate between HIV-2 and HIV-1 infections, respectively.

Diagnosis, Differential

Long-term potentiation of horizontal connections provides a mechanism to reorganize cortical motor maps.

1. Field potential recordings were used in rat motor cortex (MI) slice preparations to investigate the potential for activity-dependent modifications in the effectiveness of synaptic connections formed by layer II/III horizontal projections. 2. Long-term potentiation (LTP) of synaptic efficacy in MI horizontal pathways could be produced at short (0.5 mm) and long (1.0 mm) distances by theta burst stimulation (TBS), but only during local, transient application of the gamma-aminobutyric acid-A (GABAA) receptor antagonist, bicuculline methiodide (bic) immediately before TBS. Mean increase of the field potential amplitude measured 25-35 min after LTP induction ranged between 24 and 34%. Cooperative effects of conjoint TBS of two horizontal pathways on LTP induction were observed. 3. These results demonstrate that persistent changes in the functional interactions of cortical neurons can arise by activity-dependent mechanisms within the local horizontal connections and suggest a likely mechanism to recognize cortical representation patterns.

Animals

Toward routine diagnosis of hepatitis B virus desoxyribonucleic acid.

Although a multitude of hepatitis B markers are available to discriminate different states of hepatitis B virus (HBV) infection, there remains a need to detect the HBV DNA itself. The HBV DNA test is the only test that can quantify the number of complete virions. As shown in this review, the diagnostic value of testing for HBV DNA depends on quantification, and there are situations in which in vitro amplification is necessary and others in which testing for HBV DNA without preamplification is best. Indications for analysis of HBV DNA include the early recognition of chronic hepatitis B, discrimination of different HBsAg carrier states, recognition of the evolution of variants, indication and follow-up of anti-viral therapy with interferon, and assessment of blood products for infectivity. In each of these cases quantification of HBV DNA improves the diagnosis of HBV infection and will become an important tool in the routine diagnosis of hepatitis B virus infection in the future.

Acute Disease

Evaluation of the automated 'Enzymen-Test Anti HIV-1 + 2' and 'Enzymen-Test Anti HIV-1/2 selective' for the combined detection and differentiation of anti-HIV-1 and anti-HIV-2 antibodies.

A new, modular automated ELISA (test 1) for HIV-1 and HIV-2 antibody detection and differentiation (Enzymun-Test Anti HIV-1 + 2; anti HIV 1/2 selective, Boehringer Mannheim) was compared with 3 alternative enzyme immunoassays (Abbott recombinant HIV-1/HIV-2 3rd generation EIA, Abbott (test 2); Enzygnost HIV 1 + 2, Behringwerke (test 3); and Wellcozyme HIV recombinant, Murex (test 4)) and Western blot (New LAV I Blot and New LAV II Blot; Diagnostics Pasteur). 380 serum samples from HIV-1 and HIV-2 seropositive patients at different stages of disease, high risk individuals, patients with conditions unrelated to AIDS and from healthy blood donors were used in this evaluation along with 6 seroconversion panels, 6 serum dilution series and 'tricky' sera (repeatedly positive results in ELISA, but negative or undeterminate in Western blot; n = 67). Using the Western blot as reference assay, the overall sensitivity of the four ELISAs was 100%. Test 4 showed the highest sensitivity for antibody detection in seroconversion and dilution series. A high specificity was achieved with test 1 (100%) and test 2 (99.4%). A relatively high rate of false positive results were obtained with test 2 (n = 12) and test 3 (n = 10) by testing 'tricky' sera or samples obtained from healthy blood donors. In comparison to Western blot, a clear differentiation between HIV-1 and HIV-2 antibody serum samples was achieved with the Enzymun-Test. The results of the present study show that the Enzymun-Test provides reliable selective HIV-1 and HIV-2 antibody detection at a cost which is significantly lower than the costs of Western blot tests. Furthermore, the evaluation of test 1 suggests, that it is a highly specific assay for HIV antibody detection.

AIDS Serodiagnosis

Rotational and translational water diffusion in the hemoglobin hydration shell: dielectric and proton nuclear relaxation measurements.

The dynamic properties of water in the hydration shell of hemoglobin have been studied by means of dielectric permittivity measurements and nuclear magnetic resonance spectroscopy. The temperature behavior of the complex permittivity of hemoglobin solutions has been measured at 3.02, 3.98, 8.59, and 10.80 GHz. At a temperature of 298 K the average rotational correlation time tau of water within a hydration shell of 0.5-nm thickness is determined from the activation parameters to be 68 +/- 10 ps, which is 8-fold the corresponding value of bulk water. Solvent proton magnetic relaxation induced by electron-nuclear dipole interaction between hemoglobin bound nitroxide spin labels and water protons is used to determine the translational diffusion coefficient D(T) of the hydration water. The temperature dependent relaxation behavior for Lamor frequencies between 3 and 90 MHz yields an average value D(298K) = (5 +/- 2) x 10(-10)m2 s-1, which is about one-fifth of the corresponding value of bulk water. The decrease of the water mobility in the hydration shell compared to the bulk is mainly due to an enhanced activation enthalpy.

Animals

Clinical significance of quantitative anti-HBc IgM assay in acute and chronic HBV infection.

The applicability and clinical usefulness of anti-HBc IgM quantification in acute and chronic hepatitis type B by a single run of undiluted sera is largely unknown. Serum anti-HBc IgM concentrations were measured in 153 patients with various forms of acute and chronic HBV infection by a new commercially available qualitative ELISA/2-step capture assay applying streptavidin technology. The absorbance values were expressed in anti-HBc IgM U/ml using a calibration curve produced by a series of anti-HBc IgM standards. The results were compared with those obtained with another second generation qualitative anti-HBc IgM method also in undiluted sera applying the Microparticle Enzyme Immune Assay (MEIA). In acute hepatitis B, anti-HBc IgM was always > 600 U/ml (median: > 800 U/ml) declining to median values of 135 and 85 U/ml at months 3 and 6, respectively. Values above 600 U/ml were seen in 4 out of 20 (20%) HBsAg carriers with episodes of severe HBV-induced liver damage resembling acute hepatitis B (group 2) and in 2 out of 35 (5.6%) patients with HBV induced chronic active hepatitis (group 3). Values above 100 U/ml, representing the cutoff levels for the diagnosis of acute hepatitis B in the qualitative assays, were detected in 55% (11/20) and 45.7% (16/35) of the above patients of groups 2 and 3, respectively. Anti-HBc IgM was negative or under 20 U/ml in 96.7% (29/30) of HBsAg carriers with acute or chronic liver damage unrelated to HBV (HDV, HCV or drug-induced) and in 91% (41/45) of HBsAg carriers with persistently normal ALT levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

[Viral hepatitis as a traveler's disease].

At the present time, at least five different forms of viral hepatitis can be distinguished. The hepatitis A and E viruses are transmitted via a fecal-oral route, and are associated with poor hygiene. Hepatitis E is restricted to Central Africa, parts of Asia, and Central America. Hepatitis B, C and D are transmitted not via the fecal-oral route but, in the case of B and D mainly by sexual intercourse, and in the case of hepatitis C by infected blood products. Even after the introduction of interferon alpha, treatment possibilities are limited. Immune prophylaxis (hepatitis A and B) and general preventive measures are of considerable importance, not merely with respect to travelling.

Hepatitis, Viral, Human

Quantal parameters of "minimal" excitatory postsynaptic potentials in guinea pig hippocampal slices: binomial approach.

Binomial distributions of amplitudes of excitatory postsynaptic potentials (EPSPs) mixed with Gaussian noise were simulated. The objective of Monte Carlo simulations was, firstly, to study influences of sampling size (N) and noise standard deviation (Sn) on estimates of mean quantal content (m), quantal size (v) and binomial parameters (n and p) by four methods of quantal analysis (histogram, variance, failures and combined method) based on the binomial model and, secondly, to modify these methods on the basis of comparison of estimated with simulated parameters. Reliable estimates (within +/- 10% of the simulated values) were obtained for large sample sizes (N = 500-1000) with Sn less than or equal to v by the histogram (deconvolution) method and with Sn less than or equal to 2v by the other three methods. Similar results were obtained by averages from about 10 simulations if smaller samples were used (N = 50-200). In electrophysiological experiments on slices, "minimal" EPSPs were recorded from CA1 pyramidal cells after low-intensity stimuli to stratum radiatum or stratum oriens. Amplitudes of minimal EPSPs fluctuated in a manner predicted by the quantum hypothesis. Amplitude distributions of EPSPs in the non-facilitated state were adequately described either by binomial statistics with an average p equal to about 0.4 (a range of 0.3-0.7) and an average n of about 3 (range 2-6) or by Poisson statistics with m of about 1. The quantal analysis suggests that typical values of m and v for a single activated fibre in stratum radiatum might be about 0.5-1 and 300-400 microV, respectively, with low p (0.1-0.3) and n (2-4). However, the estimates of binomial parameters should be considered as coarse approximations in view of the simulation results and a possible nonuniformity of parameter p. The comparison of results of various methods based on the binomial model, in both simulation and physiological experiments, indicates the reliability of estimates of basic quantal parameters (m and v) under realistic conditions of physiological experiments. The methods are considered to be sufficiently sensitive to make use of them for studies on mechanisms of long-term synaptic plasticity.

Animals

Statistical analysis of long-term potentiation of large excitatory postsynaptic potentials recorded in guinea pig hippocampal slices: binomial model.

Excitatory postsynaptic potentials (EPSPs) were recorded in guinea pig hippocampal slices (area CA1) from 15 neurons after stimulation of stratum radiatum (str. rad.) and stratum oriens. EPSP amplitudes increased in 8 neurones (10 post-tetanic regions) recorded 15 to 45 min after tetanic stimulation of str. rad. The increase was considered to represent long-term potentiation (LTP). Quantal analysis was performed by two methods assuming binomial statistics: the histogram method using deconvolution of noise and the variance method. According to both methods, LTP was associated with an increase in mean quantal content (m) which correlated with LTP magnitude. A statistically significant increase in quantal size (v) was found only by the histogram method and the increase was not correlated with LTP magnitude. A separate analysis of EPSPs with small LTP magnitude demonstrated that with the histogram method only v was increased but not m. A smaller increase in m for the pooled data of both methods did not correlate with LTP magnitude for this EPSP subset. The increase in m for the whole EPSP set corresponds to previous results on the quantal analysis of LTP in in vivo preparations and favours a presynaptic location of major mechanisms underlying LTP maintenance. The increase in v indicates the existence of another mechanism responsible for the maintenance of a small part of LTP. This mechanism might involve either pre- or postsynaptic changes or both.

Algorithms

Quantal analysis of long-term potentiation of "minimal" excitatory postsynaptic potentials in guinea pig hippocampal slices: binomial approach.

"Minimal" excitatory postsynaptic potentials (EPSPs) were recorded from 13 neurones in area CA1 of guinea pig hippocampal slices after double-pulse stimulation of stratum radiatum (str. rad.) and stratum oriens (str. or.). Amplitudes of EPSPs significantly increased in 8 neurones 5 to 55 min after 9 tetanizations in str. rad.. The increase was considered to represent long-term potentiation (LTP). Altogether 26 EPSPs (42 post-tetanic regions) were statistically analysed by four methods of the quantum hypothesis assuming the binomial model of transmitter release: the deconvolution (histogram), the variance, the failures, and the combined (variance-failures) methods. The mean quantal content (m) significantly increased after LTP induction according to all methods used. Quantal size (v) also tended to increase but according to some methods, the increase was not statistically significant and it did not correlate with LTP magnitude. However, for an EPSP subset with a LTP magnitude of less than 1.55, the increase in v correlated with LTP magnitude, whereas the increase in m did not. The relative contribution of the increase in v to LTP magnitude was larger for cases with small LTP than for the whole EPSP set. In general, the increase in m corresponds to previous studies and favours the presynaptic location of major mechanisms of LTP maintenance, i.e. an increase in the average number of transmitter quanta released by each presynaptic volley. The post-tetanic increase in v might reflect some additional mechanisms which presumably include an increase in the amount of transmitter in one quantum.

Animals

Influence of vaccination schedules and host factors on antibody response following hepatitis B vaccination.

In a prospective multicentre trial, the influence of schedule, compliance, age, sex and weight on the antibody response to hepatitis B vaccination was investigated. Comparison of the vaccination schedules 0, 1, 6 months (group 1; n = 143) and 0, 1, 2, 12 months (group 2; n = 141) was performed in months 3, 7 and 12. In addition, the antibody response was compared one month after the third and one and six months after the last vaccination. Seroprotection rates (anti-HBs greater than 10 IU/l) and antibody titres, given as geometric means (GMTs), were higher in group 1 at month 12 as well as one month after completion of three immunizations. More vaccinees of group 2, however, showed seroprotection at month 3 with higher GMTs. In addition, GMTs in group 2 were higher both one month and six months after the last vaccine dose. Determination of parallel corrected correlation factors demonstrated that age was the most important single factor, followed by body weight and sex. However, no more than 3% of the variation in the GMT can be explained by the influence of age. Due to decreased compliance with the four-dose schedule with a drop-out rate of approximately 10% of the vaccinees, the total percentage of initial vaccinees who in the end developed protective antibody levels was higher in the 0, 1, 6 months schedule. Thus, it can be concluded that subjects likely to comply will benefit from the 0, 1, 2, 12 months schedule as more rapid protection is obtained and the higher antibody levels after the booster vaccination at month 12 provide longer protection. However, vaccinees whose compliance might be questionable over a period of 12 months, should be selected for the vaccination 0, 1, 6 months schedule as compliance is at a higher level over this period and advantage can be taken of the booster effect of the third dose given in month 6.

Adolescent

Hepatitis C virus antibody secretion in vitro by peripheral blood lymphocytes.

A recombinant polypeptide corresponding to a virus-specific cDNA clone (c100-3) serves as the antigen for a hepatitis C virus (HCV) antibody assay. Previous investigations have shown an 80% prevalence of HCV antibodies in sera of patients suffering from post-transfusional chronic hepatitis non-A, non-B, but positive results were also obtained for 30 to 70% of sera from patients with chronic hepatitis B or autoimmune hepatitis. In this study we show that HCV antibodies are secreted by peripheral blood lymphocytes (PBL) in vitro. PBL from 12/35 patients with chronic non-A, non-B hepatitis and 1/6 patients with chronic active hepatitis B spontaneously secreted HCV antibodies in cell culture supernatants. The results were confirmed by neutralisation assay and ELISAs using recombinant and synthetic polypeptides derived from the c100-3 antigen and from the HCV core antigen. Two patients suffering from non-A, non-B hepatitis were negative for HCV antibodies in serum, but their PBL produced HCV c100-3 antibodies in vitro. PBL from patients suffering from autoimmune chronic hepatitis, primary biliary cirrhosis, toxic-liver injury and healthy blood donors did not produce antibodies to HCV c100 antigen irrespective of HCV antibody test results in their sera. Polyclonal B cell activation or mitogenic stimulation of T helper cells led to increased immunoglobulin synthesis by PBL in vitro, but did not lead to enhancement of specific HCV antibody production. In addition, HCV antibody production was not induced by these stimulation procedures in control lymphocytes. This spontaneous HCV antibody production in vitro suggests persistent antigenic stimulation of the B cells in vivo.

B-Lymphocytes

Hepatitis A vaccination: schedule for accelerated immunization.

Hepatitis A vaccine, strain HM175, was investigated for immunogenicity and tolerability in a prospective multicentre trial. The following vaccination schedules and antigen contents were evaluated: days 0 and 14 with 720 ELISA units (El.U) of antigen, days 0 and 28 with 720 El.U and days 0 and 28 with 360 El.U. In all study groups, the seroconversion rates following two vaccinations were between 95 and 100%. Higher geometric mean concentrations of antibody to hepatitis A virus (anti-HAV) were reached by the vaccine containing 720 El.U of HAV antigen. The vaccine was equally well tolerated in all groups. In addition, an abbreviated schedule, in which 720 El.U of HAV antigen was given on days 0 and 14, resulted in 100% seroconversion by day 28 and a level of anti-HAV that was substantially higher than that observed after passive immunization. This implies that such a vaccine could replace immune globulin administration if time permits.

Adult

Sub-acute effects of interferon-alpha 2 on adrenocorticotrophic hormone, cortisol, growth hormone and prolactin in humans.

This study investigated the chronic effects of interferon-alpha 2 (IFN-alpha 2) on hormonal secretion in humans. Six patients suffering from chronic hepatitis B or C infection received SC doses of 3 million IU IFN-alpha 2 three times a week for 4 mo. Each patient was examined for hormone secretion four times: the day before initial IFN-alpha 2 administration (day 0), the day of the first injection (day 1), and 4 wk after start of IFN therapy on days 27 (without IFN administration) and 28 (with IFN administration). Adrenocorticotrophic hormone (ACTH), cortisol, growth hormone (hGH), and prolactin (PRL) were measured in plasma samples drawn at 30-min intervals between 1600h and 2400h. Acute administration of IFN-alpha 2 stimulated the release of ACTH to 423% (p = 0.02 vs. day 0) and cortisol to 393% (p = 0.01 vs. day 0) of control values in each patient. In five of the six patients, the plasma levels of hGH were higher on day 1 than on day 0. IFN-alpha 2 did not affect the secretion of prolactin. On day 27, the plasma levels of the four hormones were similar to the baseline levels on day 0. When IFN-alpha 2 was given on day 28, there were no significant differences in the release of ACTH (135% of control, p = 0.4) or cortisol (124% of control, p = 0.5) in comparison to day 27. These findings indicate that IFN-alpha 2 stimulation of hormone release is restricted to specific hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone