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Biomedical subjects

W Gerhard

Publications and source records attributed to W Gerhard.

At least 55 records · Page 3Linked to original sources
PubMed1987

Role of receptor-binding activity of the viral hemagglutinin molecule in the presentation of influenza virus antigens to helper T cells.

The concentration of antigen required to stimulate influenza virus-specific helper T cells was observed to be dependent upon the antigenic form bearing the relevant determinant: intact, nonreplicative virus was needed only in picomolar amounts, while denatured proteins, protein fragments, or synthetic peptides were required in micromolar concentrations for a threshold level of stimulation. Antigenic efficiency of intact virus was found to result from the attachment of virus to sialic acid residues on the surface of the antigen-presenting cell since spikeless viral particles lacking the hemagglutinin molecule were much less efficient antigens for helper T cells and continuous presence of hemagglutination-inhibiting antihemagglutinin antibodies reduced efficiency of stimulation by intact virus approximately 100-fold for both hemagglutinin and internal virion proteins. Influenza virus associated rapidly with antigen-presenting cells; less than 10 min at 20 degrees C was sufficient to introduce virus for a maximal level of T-cell stimulation. This rapid attachment was blocked by antibodies to the hemagglutinin or by pretreatment of the antigen-presenting cells with neuraminidase to remove the cellular virus receptor. Following viral adsorption by antigen-presenting cells, a lag period of 30 min at 37 degrees C was required for the expression of helper T-cell determinants. One early event identified was the movement of the virus to a neuraminidase-insensitive compartment, which can occur at 10 degrees C, but which was not equivalent to expression of helper T-cell determinants. Preincubation of cells with virus at 10 degrees C for 4 h reduced the lag period of helper T-cell determinant expression to 15 min when these cells were shifted to 37 degrees C, suggesting that transition of the virus to a neuraminidase-resistant state is a required step in presentation of T-cell antigenic determinants.

Animals↗
PubMed1987

[Value and rank of diagnostic laboratory parameters in cardiovascular diseases. Results of multivariant and discriminant analyses of the Berlin EBMO-Cor population study].

Based on present clinical-chemical parameters a representative population were studied; importance and order of rank of 10 data chosen from a total data pool are determined by means of multivariant and discriminant analysis. As a result the validity of characters with and without apriori probabilities for 5 pairs of classes (persons suffering from a heart disease in comparison to healthy persons divided in sexes and overall, as well as examination of separate sexes for healthy persons and those suffering from a heart disease) are examined (alpha less than or equal to 0.05). This calculation tested the importance of the parameters hemoglobin and creatinine in being different in males and females. To diagnose persons suffering from a heart disease (X-ray-morphologically defined suspects of heart and vessel diseases) from healthy persons, the optimized number of characteristics were determined in cholesterol, erythrocyte sedimentation rate, ASAT, blood glucose (independent of sex). By means of these results it is possible to identify persons suffering from a heart disease from healthy persons and to call for illustrative laboratory examinations using already mentioned parameters and the function of discriminance W = p sigma i = 1 ai X Xi. The determination of sensitivity and specification yielded a value of up to 98 per cent resp. 94 per cent depending on whether with or without apriori probabilities. This enables use to be modified to suit different purposes.

Adolescent↗
PubMed1986

[Behavior of so-called cardiovascular risk factors in general practice cardiac therapy--results of selected biochemical parameters of probands with suspect cardiovascular findings in a follow-up program of a 5-year intervention study].

Based on a population of defined territories of 280,000 inhabitants, heart patients, morphologically defined by roentgenological findings, were detected, and a representative sample was controlled with differing intervention under conditions of practice in a follow-up-programme of five years. Out of this programme the developments of some so-called (biochemical) risk factors belonging to the metabolical syndrome were evaluated and interpreted in their relation to cardiovascular diseases. The parameters investigated such as lipoprotein flocculation reaction, serum cholesterol, blood glucose and uric acid revealed increases of mean values as well as differences between the sexes and certain age groups during the time of observation. Causal therapeutic measures are discussed as causes of these developments. Significant differences in the cross section analysis which were also established could be confirmed in a longitudinal observation, and their relevance to cardiovascular diseases could thus be verified.

Adolescent↗
PubMed1986

Functional analysis of influenza-specific helper T cell clones in vivo. T cells specific for internal viral proteins provide cognate help for B cell responses to hemagglutinin.

We compared the effects of adoptively transferred Th cell clones specific for the influenza hemagglutinin (HA), matrix (M), or nucleoprotein (NP) on the antibody response of nude mice infected with A/PR/8/34 influenza virus. We show that the production of antibodies to the HA absolutely requires the presence of virus-specific Th cells. Further, transfer of a Th clone specific for the internal proteins, M or NP, was as effective as was transfer of an HA-specific clone in supporting an antibody response to the HA. With each of the clones, the kinetics of the response were accelerated by approximately 3 d compared with the antibody response of normal BALB/c mice. The HA- and M-specific clones supported an isotype switch from IgM to IgG and IgA similar to that which occurs during a normal antibody response. Finally, as shown by coinfection experiments, the response required a cognate T-B interaction whether the determinants recognized by the Th and B cell are located on the same viral protein or on different viral proteins within the same virus particle. The implications of these findings for understanding the T-B interactions that occur during an effective antiviral antibody response are discussed.

Animals↗
PubMed1986

[Significance of laboratory diagnostic study parameters of the hepatobiliary system in the evaluation of cardiovascular diseases--results of cross sectional and longitudinal studies in patients with suspicious cardiovascular findings in an epidemiologic follow-up study].

With the help of an approx. 280 000 inhabitants check of x-ray-morphological suspects of a heart disease the laboratory parameters thymol turbidity test, zinc-sulphate turbidity test, total protein, serum protein electrophoresis and the enzymes "ASAT" and "ALAT" in longitudinal section and cross-section were examined in an intervention study during 5 years. All these parameters show standard values on the average, but compared to a healthy reference they showed significant differences, which relations to heart and vessel diseases could be deduced from. This referred especially to age-inverse behaviour of the transaminases only concerning male test persons. The examination of the longitudinal section confirmed exactly the results of the cross-section analysis. On the one hand it underlines the results got from the cross-section and in the second place it contributes to the efficient diagnostics by learning undone a repetition of these laboratory examinations during the period of 5 years with such a defined population. The relations of the particularities mentioned obviously refer to subclinical fields. Effects of therapy do not reflect in the laboratory findings.

Adolescent↗
PubMed1986

[Redundancy reduction in laboratory studies--evaluated by the laboratory diagnostic follow-up program of an epidemiologic cardiovascular study].

In addition to our information about significant relations of certain laboratory parameters concerning probationers suspected of heart and vessel diseases, who were identified by means of x-ray screening (EBMO-Cor Berlin) is reported on laboratory parameters applied to follow-up examinations, which proved to be redundant for what was expected (referring the heart and vessel diseases). It refers to the parameters of total protein in the serum, serum electrophoresis, zinc-sulphate test, hematocrit and hemoglobin. The results are supported by mathematic--statistical returns. With regard to the exponential laboratory load in the result of screening and follow-up examination under suspicion of heart and vessel disease the necessity of such considerations is underlined. The statement gains in its significance by the original material concerning the population.

Blood Chemical Analysis↗
PubMed1986

Structural and functional implications of a restricted antibody response to a defined antigenic region on the influenza virus hemagglutinin.

A group of hybridoma antibodies that recognize structurally overlapping epitopes on the influenza virus hemagglutinin have been analyzed for the sequence of their immunoglobulin heavy and light chain variable regions. All VH regions derive from the same gene family, and only two Vk genes, from different families, are involved. The repetitive and restricted use of these variable region genes indicates that considerable structural requirements influence the generation of antibodies specific for this region of the hemagglutinin. The degree of amino acid variability which is permissive for interaction with this region suggests that two thirds of the possible replacement mutations may abolish either antibody function or specificity. Analysis of the somatic mutation which occurred in the individual antibodies indicates that the light chains acquired replacement mutations at the rate predicted for random mutation. The heavy chains, however, accumulated a 3-fold excess of replacement mutations over that predicted for random accumulation, correlating with the dominant role they apparently play in determining fine differences in the specificity of these antibodies. The effect of somatic mutation on the clonal amplification and diversification of these B cell lineages is discussed.

Animals↗
PubMed1986

Selection of influenza A virus adsorptive mutants by growth in the presence of a mixture of monoclonal antihemagglutinin antibodies.

The influenza virus hemagglutinin contains four major regions that are recognized by antibodies able to neutralize viral infectivity. To investigate the effect of an antibody response directed against each of these sites on viral evolution, influenza virus A/PR/8/34 (H1N1) was grown in allantois-on-shell cultures in the presence of a mixture of monoclonal antihemagglutinin antibodies. This selection mixture contained antibodies (two or three antibodies per antigenic site) whose concentrations were adjusted to achieve equal neutralization titers against each of the four antigenic sites. By varying the ratio of input virus to selection mixture concentration, we observed that variant viruses emerged under conditions of partial neutralization. Each of the four variants characterized in detail differed from the parental virus in its interaction with cellular receptors and exhibited minimal changes in antigenicity. Thus, these variants were virtually indistinguishable from wild-type viruses, as assessed by the binding of 103 monoclonal antihemagglutinin antibodies in an indirect radioimmunoassay. Despite this, many of the same antibodies demonstrated decreased titers to the variants in hemagglutination inhibition tests. The magnitude of the differences depended on the indicator erythrocytes used (much greater differences were detected with chicken erythrocytes than with human erythrocytes). Hemagglutination mediated by the variants was more resistant to neuraminidase treatment of erythrocytes than hemagglutination mediated by the parental virus. These findings are consistent with the idea that the variants were initially selected by virtue of their increased avidity for host cell receptors. Sequencing of viral RNA revealed that each of the variants differed from the parental virus by a single amino acid alteration in its HA1 subunit. Two of the changes were close to the proposed receptor binding site on hemagglutinin and could directly alter receptor binding, while a third was located near the trimer interface and may have increased receptor binding by altering monomer-monomer interactions.

Adhesiveness↗
PubMed1985

[Behavior of biochemical parameters in probands with suspect cardiovascular findings in relation to age and sex. Studies of a representative sample following roentgen image screening (the Berlin cardiac detection and monitoring model)].

Based on the high prevalence of cardiovascular diseases and the necessity of improved treatment, selected biochemical results from a complex follow-up examination after x-ray screening are presented. Significant differences (alpha less than or equal to 0.05) were found for LTT, cholesterol, glucose, uric acid and erythrocyte-sedimentation rate compared to a healthy control group. Furthermore, a significant age-dependent increase of creatinine as well as an age-dependent decrease of transaminases only in men were found. The results show the value of the x-ray screening method in persons with risk of cardiovascular disease characterized by morphologic x-ray findings, and can be referred to population.

Adolescent↗
PubMed1985

Inter- and intraclonal diversity in the antibody response to influenza hemagglutinin.

This study focuses on 10 BALB/c anti-influenza virus (A/PR/8/34) hemagglutinin antibodies that have light chains encoded by the same variable region kappa chain (V kappa) gene, V kappa 21C. A comparison of antibodies from lymphocytes of independent origin reveals the contribution of germline diversity (combinatorial joining and association) to this response. Although combinatorial joining and association contribute to sequence diversity, they appear to have little effect on the fine specificity of these antibodies. Somatic mutation, in addition to contributing to the sequence diversity of these antibodies, creates differences in their fine specificity. The extent of mutation and its effect on fine specificity can be seen by comparing antibodies of lymphocytes from the same clone. These intraclonal comparisons also indicate that somatic mutation is an ongoing process occurring at a high rate (estimated to be at least 10(-3) mutations per base pair per division) in the expressed V region heavy chain (VH) and V kappa genes. Furthermore, both the nature and distribution of these mutations suggest that amino acid replacement mutations in the light but not the heavy chain are selected for by antigen.

Animals↗
PubMed1985

Characterization of host cell binding variants of influenza virus by monoclonal antibodies.

We have previously shown that a plaque-type mutant of influenza virus A/WSN has a growth advantage in MDBK cells because its hemagglutinin (HA) has a greater affinity for host cell receptors than does the HA of the parent virus. We show here that the mutant is also less sensitive than the parent to neutralization by antibodies to epitopes in at least two regions on the HA. WSN-specific monoclonal antibodies which had higher radioimmunoassay (RIA) titers against the parent than the mutant virus also had higher plaque inhibition (PI) and hemagglutination inhibition (HI) titers. In contrast, cross-reacting antibodies bound equally well to the parent and mutant viruses as judged by RIA but those which bound to the Cb region of the HA exhibited higher PI and HI titers against the parent virus. The results suggest that preferential neutralization of the parental virus by antibodies can contribute to the selective advantage of mutants which have increased affinity for cellular receptors.

Animals↗
PubMed1985

Possible relationship between antigenic properties and isolation history of HSV-1 strains.

29 monoclonal anti-herpes simplex virus (HSV)-1 antibodies were produced and characterized with regard to virus neutralizing activity, intracellular or cell-surface location of viral antigens and, where possible, molecular weight of the viral protein recognized. 13 antibodies recognized viral antigens expressed on the surface of infected cells and 16 were directed to intracellular viral components. Only two antibodies exhibited virus neutralizing activity. Application of these antibodies to an antigenic comparison of standard laboratory HSV-1 strains F, HFEM, mP, Glasgow-17 and MAC revealed unique antigenic differences among these strains. The antibodies were further used in an antigenic comparison of 45 human HSV-1 isolates with defined isolation history. Except for two paired isolates from left and right trigeminal ganglia of two human cadavers, the antibody panel revealed antigenic differences among all isolates, including paired isolates from three additional cadavers. Overall, isolates from different human donors showed greater antigenic dissimilarity from each other in cell-surface associated than in intracellular antigens. The data suggest the possibility of a correlation between antigenic and biologic properties of HSV-1.

Animals↗
PubMed1985

Monoclonal antibodies detect different forms of influenza virus hemagglutinin during viral penetration and biosynthesis.

Monoclonal antibodies specific for the influenza virus A/PR/8/34 hemagglutinin (HA) were used to examine the structure of the HA glycoprotein by immunofluorescence techniques during infection of MDCK cells. One antibody (Y8-10C2), shown previously to detect conformational alterations in the HA coinciding with the acid induction of viral fusion activity, bound to internalized virus but not to virus adsorbed to the cell surface. The binding of Y8-10C2 was completely inhibited by ammonium chloride treatment of the cells. These findings are consistent with the idea that Y8-10C2 detects conformational changes in the HA which accompany the acid-induced fusion of viral and endosomal membranes. The same antibody also bound to newly synthesized HA but not to later forms of cytoplasmic HA or to HA incorporated into the cell membrane during virus maturation. A possible common denominator of the antigenic changes detected by antibody Y8-10C2 during virus entry and replication may be alterations in the structural relationship among the three HA monomers which form the mature HA molecule.

Adsorption↗
PubMed1985

A synthetic decapeptide of influenza virus hemagglutinin elicits helper T cells with the same fine recognition specificities as occur in response to whole virus.

The immunogenicity of an isolated murine helper T cell determinant was studied. Mice were immunized with a synthetic peptide corresponding to amino acid residues 111-120 of the influenza PR8 hemagglutinin (HA) heavy chain, a region previously identified as a major target of the helper T cell response to the HA molecule in virus-primed BALB/c mice. Lymph node T cells from these mice were fused with BW 5147 cells to produce T hybrids for clonal analysis of their recognition specificities. Three T cell hybridoma clones, obtained from two different mice, responded to the immunizing peptide when presented by syngeneic antigen-presenting cells. All of these clones responded also to antigen provided as intact wild-type PR8 virus. The fine specificity of the peptide-induced T cell hybridomas, in response to a panel of mutant and variant influenza viruses, was indistinguishable from the fine specificities of T cells to the corresponding region of the HA1 chain of the HA molecule which had been generated by priming of mice with intact wild-type virus. These results suggest that an immunogenic determinant is contained within the 111-120 sequence that is able to elicit anti-influenza virus T cells with a similar repertoire to those elicited by immunization with whole virus.

Amino Acid Sequence↗