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Biomedical subjects

C Herzog

Publications and source records attributed to C Herzog.

At least 19 recordsLinked to original sources

Site-directed mutagenesis of the lower parts of the major substrate channel of yeast catalase A leads to highly increased peroxidatic activity.

Five single replacement mutants of catalase A from Saccharomyces cerevisiae were prepared (F148V, F149V, F156V, F159V, and V111A). The exchanges were expected to relieve steric constraints in the lowest part of the major substrate channel. The overall stability of the isolated enzymes is unaffected by the respective amino acid exchanges, but some modifications lead to decreased protohaem binding. All isolated mutants (most pronounced the V111A-species) show decreased catalatic and markedly increased peroxidatic activity, both with aliphatic and aromatic substrates. These effects can in part be explained by steric effects, but also reveal destabilisation of compound I.

Amino Acid Sequence

Purification of the sequence-specific transcription factor CTCBF, involved in the control of human collagen IV genes: subunits with homology to Ku antigen.

The common promoter region of the human collagen type IV genes COL4A1 and COL4A2 comprises a C5TC7 sequence ('CTC box') which is specifically recognized by the recently identified transcription factor CTC box binding factor (CTCBF) involved in the control of divergent transcription of the two genes. This factor has now been purified by affinity chromatography on heparin-agarose and CTC-Sepharose. The CTCBF contains two subunits, CTC75 and CTC85, with molecular weights of 75 and 85 kDa, respectively. Sequence analysis of LysC-derived peptides of the two subunits revealed identity or close homology to p70 and p80 subunits of the human autoantigen Ku. The sequence-specific binding CTCBF represents a presumably tetrameric complex composed of two CTC75/85 heterodimers with an apparent molecular weight of 360-400 kDa. UV crosslinking experiments, the use of Ku-specific antibodies in gel retardation assays and immunoblotting proved that both subunits are involved in sequence-specific interaction with the CTC box motif. The tetrameric complex dissociates in a concentration-dependent manner to CTC75/85 heterodimers which now bind sequence independently to DNA. Three lines of evidence indicate that TATA binding protein (TBP) is additionally involved in the formation of CTCBF: (i) TBP can be detected in purified CTCBF; (ii) the addition of recombinant TBP stimulates formation of the CTCBF-DNA complex; and (iii) antibodies directed against TBP interfere strongly with the formation of the specific protein-DNA complex. The results presented support the idea that the subunits CTC75 and CTC85 (identical or homologous to p70 and p80 of the Ku antigen) are integral parts of CTCBF, and give a first indication of the importance of TBP in the formation of CTCBF.

Amino Acid Sequence

[Mumps epidemiology--worldwide].

Mumps is an acute viral infection that is endemic worldwide and that occurs primarily in school-age children and adolescents. The most prominent manifestation is tender swelling of the parotid gland. The course of the disease is usually mild and selflimited. Meningitis and orchitis, the latter more common in postpubertal persons, are less frequent manifestations of this disease. As characteristic of many viral infections the severity of the illness increases with age. In the present review first the most important epidemiologic parameters of mumps are presented, as well as the various clinical manifestations and complications. Further the epidemiology of mumps in developing and in industrialized countries is discussed. Breakthrough infections with mumps occurring with either low or high vaccination coverage are described.

Adolescent

[Hepatitis A outbreak in a kindergarten].

In November/December 1990 eight out of 38 children of a kindergarten in Basle were involved in an outbreak of hepatitis A, and further cases occurred among family members and friends of the children. A questionnaire survey and a serologic analysis including all families associated with the kindergarten was undertaken to investigate the source, extent and spread of the hepatitis A. Among 147 persons examined, 20 clinical cases of hepatitis A were diagnosed (9 adults, 11 children), 5 more children were unapparently infected. The hepatitis A virus was imported by an adult who contracted the disease during a journey to Mexico. The virus spread from person to person, the third case being the kindergarten child, who was responsible for the actual outbreak. In a first phase, 11 persons were affected, 6 of them children from the kindergarten. The second phase involved 5 adults and another child from the kindergarten. The hygienic measures undertaken in the kindergarten proved to be efficacious; only one further child was infected thereafter. Immunoglobulin was protective if administered in time. Only 2 out of 21 passively immunized persons who had had contact with hepatitis A patients contracted an unapparent infection, but without further transmission. Among 82 persons who were passively immunized too late or not at all, 20 fell clinically ill with hepatitis A and 3 were unapparently infected. Use of the newly available hepatitis A vaccine is discussed.

Child Day Care Centers

[Quantification of mRNA using the polymerase chain reaction--cytokines in rheumatoid arthritis].

A method for quantitation of specific mRNA species by the polymerase chain reaction (PCR) has been developed by using a synthetic RNA as an internal standard. The specific target mRNA and the internal standard are co-amplified in one reaction in which the same primers are used. The amount of mRNA is then quantitated by extrapolating against the standard curve generated with the internal standard. The synthetic internal standard RNA consists of a linear array of the sequence of upstream primers of multiple target genes followed by the complementary sequences to their downstream primers in the same order. This quantitative PCR method provides a rapid method of quantifying the amount of a specific mRNA in a sample of less than 0.1 ng of total RNA. In addition, the same internal standard RNA is used, with appropriate primer pairs, to quantitate multiple different mRNA species in parallel. This technique affords a very sensitive means of measuring important regulatory cytokines in the local inflammatory tissue of rheumatoid arthritis (RA).

Arthritis, Rheumatoid

Partial trisomy 8q. Two case reports with maternal translocation and inverted insertion: phenotype analyses and reflections on the risk.

Partial trisomy 8qter-->q23 or q24.1 has been reported in 15 literature cases. We add two further case reports here. Patient 1 inherited the derivative (2) of a balanced maternal reciprocal translocation t(2;8)(qter;q2300) after 2:2 disjunction and adjacent-1 segregation, and is trisomic for the segment 8qter-->q2300. Patient 2 inherited a recombinant (8) of a balanced maternal inverted insertion inv ins(8)(q1300;q2300q24.2) and is trisomic for the segment 8q24.2-->q2300. The phenotype of both patients is described and compared to the spectrum of symptoms established from the 15 literature cases. This spectrum contains all features observed with a frequency of > = 50%. Patient 1 had 35% of the features of this spectrum; Patient 2 had 47%. The intrauterine survival probability of unbalanced offspring is assumed to be the same in both cases, as nearly the same segments are trisomic. The pedigrees indicate that the inversion carrier may have a reduced production probability of unbalanced gametes and therefore a reduced risk compared to the translocation carrier.

Abnormalities, Multiple

Effect of fleroxacin and ciprofloxacin on the formation of human mature colonies of healthy donor versus transplanted hemopoietic progenitor cells.

The effect of fleroxacin and ciprofloxacin on hemopoietic progenitor cells was tested in vitro. Cryopreserved bone marrow samples from 5 patients with acute myeloid leukemia who underwent bone marrow transplantation as well as samples from the respective donors were investigated in parallel. Regarding burst and/or colony formation by erythroid, neutrophil and macrophage precursors, no significant differences were detected with donor and transplanted bone marrows between control cultures and cultures containing 100 mg/l fleroxacin, while 100 mg/l ciprofloxacin inhibited cell proliferation completely. At 50 and 10 mg/l ciprofloxacin had a 50% and no inhibitory effect, respectively.

Bone Marrow Cells

[Active and passive immunization: 1991 status].

Contrary to the regular immunization schedule for children, the majority of immunization are done in adulthood in case of special risks only, such as old age, chronic illness or exposure. The protection against a variety of communicable diseases has to be monitored and if necessary to be boosted regularly. Based on the routine vaccination scheme 1991 of the Federal Department of Public Health, the following vaccinations which are commercially available in Switzerland are discussed in this review: diphtheria, Haemophilus influenzae, hepatitis B, influenza, measles + mumps + rubella, meningococci, pertussis, pneumococci, poliomyelitis, tetanus, rabies, tuberculosis, varicella and tick encephalitis. Furthermore, the current recommendations are given for the prophylactic and therapeutic use of immunoglobuline preparations.

Adolescent

Anti-CD4 antibody treatment of patients with rheumatoid arthritis: I. Effect on clinical course and circulating T cells.

Eight patients with arthritis (seven with rheumatoid, one with psoriatic arthritis) were treated for 7 d with a daily injection of 10 mg of mouse monoclonal anti-CD4 antibodies (three with VIT4, five with MT151). With the exception of a short-lasting low-grade fever in one patient, no side effects were observed. Clinical symptoms (morning stiffness, number of swollen joints, pain assessment and Ritchie articular index) improved in all patients within 7 d of treatment. Improvement lasted from 3 weeks to greater than or equal to 5 months (mean approximately 11 weeks). Rheumatoid factors, immune complexes and other laboratory parameters did not change during or after treatment. Skin reactivity to recall antigens was suppressed in four out of six patients during treatment but returned to pretreatment levels within 6 weeks. Immunofluorescent analysis revealed a short-lasting drop of T cells, mainly of the CD4+ CDw29+ subset, but monocytes were also affected. The injected antibody was detectable on circulating cells for about 10 h. Within 20-24 h, the cell distribution returned to pretreatment levels. In six out of eight patients an anti-mouse-Ig response was seen. We conclude that mouse anti-CD4 monoclonal antibody (MoAb) treatment is well tolerated and that the cellular immunological changes observed are short-lasting. The low incidence of side effects may justify further clinical studies to evaluate the clinical efficacy of such treatment.

Antibodies, Anti-Idiotypic

Anti-CD4 antibody treatment of patients with rheumatoid arthritis: II. Effect of in vivo treatment on in vitro proliferative response of CD4 cells.

In treating rheumatoid arthritis (RA) patients with anti-CD4 antibodies (MT151 10 mg/day, 7 d) we observed diminished skin-test response to recall antigens and reduced proliferative response to antigens and mitogens (in vitro) 2-4 h following the injection. To investigate whether this diminished response is due to functional impairment of CD4+ cells, we analyzed the proliferative response of CD4+ cells to various stimuli, in conditions where the CD4 structure was either cross-linked or not. We found that in vivo anti-CD4-antibody-coated cells could be induced to proliferate if the anti-CD4 antibody was cross-linked with an anti-CD3 antibody [BMA030-F(ab')2] added in vitro and per se non-mitogenic. Also, without cross-linking the cell-bound anti-CD4 antibodies, no impairment of the proliferative capacity of CD4-antibody-coated cells could be detected; double fluorescence analyses of phytohaemagglutinin (PHA)- or CD3-stimulated cells showed that a similar proportion of CD4+ cells proliferated before and after anti-CD4-antibody treatment. The diminished proliferation observed following anti-CD4 treatment correlated to the reduced number of CD3+ and CD4+ cells in culture, which suggests that altered cell distribution might be one factor contributing to the impaired immune response.

Antibodies, Monoclonal

[10 years' experience of cryosurgery in the maxillofacial area].

The author informs through statistical statements about the ten years use of cryosurgery in the maxillofacial region and discusses and analyses the cryotherapy of selected groups of affection. Affections of any superficial, but of minor depth-effect--for instance leukoplakias--may generally be treated cryosurgical with much success. Good results are obtainable also with soft neoplasms, as hemangiomas, where distinct functional and aesthetic advantages are emphasized.

Cryosurgery

Fleroxacin: in-vitro activity worldwide against 20,807 clinical isolates and comparison to ciprofloxacin and norfloxacin.

By June 1987 worldwide investigators from 37 centres in 12 countries had completed epidemiological susceptibility testing studies comparing the in-vitro activity of fleroxacin with that of ciprofloxacin, norfloxacin and other antibacterials. In this paper the results of these studies, expressed primarily as MIC90S, are reviewed and analysed for centre to centre variability. Twenty thousand eight hundred and seven strains were evaluable for comparative analysis. All three quinolones exhibited high in-vitro activity against Enterobacteriaceae (MIC90 less than or equal to 0.125-2 mg/l), other common aerobic Gram-negative bacilli or coccobacilli (MIC90 less than or equal to 0.125-1 mg/l) and staphylococci, including selected resistant isolates (MIC90 less than or equal to 0.5-4 mg/l), and moderate to weak activity against streptococci and anaerobes (MIC90 = 1- greater than or equal to 8 mg/l). The activity of fleroxacin and norfloxacin was quite similar, but was usually inferior to that of ciprofloxacin. Comparison of data from the various investigating centres showed divergent results for many bacterial species, the MIC90S for the same quinolone varying by two to four dilution steps or more from centre to centre.

Anti-Infective Agents

Influence of cardiac function on the diuretic and hemodynamic effects of the loop diuretic piretanide.

The influence of cardiac function on the diuretic and hemodynamic effects of the loop diuretic piretanide was investigated in nine patients with congestive heart failure. The diuretic response to piretanide correlated significantly with the pretreatment cardiac index (r = 0.90). Furthermore, a significant correlation was found between the pretreatment fractional sodium excretion and the cardiac index (r = 0.85). The fractional sodium excretion is reciprocal to the renal sodium and water reabsorption. No change in the hemodynamics was observed prior to the onset of diuresis. At 120 minutes after administration of piretanide, the reduction of mean pulmonary capillary wedge pressure (r = 0.88) and mean right atrial pressure (r = 0.80) was significantly related to the diuretic response. We conclude that the reduced diuretic response to piretanide in patients with low cardiac index is due to increased renal sodium and water reabsorption. The hemodynamic changes following the administration of piretanide are dependent on the diuresis.

Adult