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Biomedical subjects

J Weber

Publications and source records attributed to J Weber.

At least 19 recordsLinked to original sources

Is clearance of HIV-1 viraemia at seroconversion mediated by neutralising antibodies?

The mechanism of clearance of human immunodeficiency virus-1 (HIV-1) viraemia is not fully understood. In two patients with acute HIV-1 infection, initial high titres of free infectious virus in plasma declined rapidly to undetectable levels within 4-8 weeks, an event that was coincident with seroconversion. Neutralising antibodies directed against the first autologous isolates taken during the viraemic periods could not be detected in either patient around the time of disappearance of plasma virus. In the absence of functional neutralising antibody, it is unlikely that humoral factors are responsible for the suppression of primary viraemia in early HIV infection.

Adult

Simultaneous deficiency of sphingolipid activator proteins 1 and 2 is caused by a mutation in the initiation codon of their common gene.

Sphingolipid activator proteins (SAPs) are small, nonenzymic glycoproteins that stimulate lysosomal degradation of various sphingolipids. SAP-1, SAP-2, and two additional potential activator proteins are derived from a common precursor by proteolytic processing. A severe case of sphingolipid storage disease that led to death within 16 weeks was attributed to a possible total deficiency of the SAPs generated by this gene (Harzer, K., Paton, B. C., Poulos, A., Kustermann-Kuhn, B., Roggendorf, W., Grisar, T., and Popp, M. (1989) Eur. J. Pediatr. 149, 31-39). Analysis of the SAP precursor cDNA from the patient and his fetal sibling showed an A to T transversion in the initiation codon. Allele-specific oligonucleotide hybridization revealed that both parents are heterozygous carriers for this mutation. In pulse-chase experiments using antisera raised against SAP-1 or SAP-2, no cross-reacting material could be detected in the patients' fibroblasts.

Alleles

Structure-activity relationship between the 3D distribution of the electrophilicity of sugar derivatives and their cytotoxic and antiviral properties.

The cytotoxic activities of a series of sugar derivatives bearing electrophilic groups (1-cyanovinyl, 4-cyanochromen-2-yl and 3-nitrochromen-2-yl) have been correlated with their electrophilic properties. To this end, an electrophilic index was defined as an isovalue surface where the interaction energy with an incoming model nucleophile (H-) was equal to a predefined value. This index, calculated from extended Hückel wave functions, allows one to quantify the electrophilic character of the substrates and to describe its spatial localization within the molecular volume (at Michael acceptor sites or on other parts of the molecules). Only sugars for which Michael acceptor reactivity was predicted were retained, and they were subdivided into two groups: those showing antiviral activity against a retrovirus and those devoid of such activity. Under these conditions, good correlations between cytotoxic activity and electrophilic reactivity--positive for the first group, negative for the second--were found. In addition, the ratio electrophilicity/sum of the absolute value of the dipole plus its projection along the principal axis of inertia, Z, of the molecule allows one to predict to which of these groups a sugar derivative belongs.

Antineoplastic Agents

Catalytic properties of Escherichia coli F1-ATPase depleted of endogenous nucleotides.

Nucleotide-depleted Escherichia coli F1 was prepared by the procedure of Wise et al. (1983, Biochem. J. 215, 343-350). This enzyme had high rates of steady-state ATPase and GTPase activity. When "unisite" ATP hydrolysis was measured using an F1/ATP concentration ratio of 10, all of the substoichiometric ATP became bound to the high-affinity catalytic site and none became bound to noncatalytic sites. The association rate constant for ATP binding was 7 x 10(5) M-1 s-1 and the KdATP was 7.9 x 10(-10) M, as compared to values of 3.8 x 10(5) M-1 s-1 and 1.9 x 10(-10) M, respectively, in native (i.e., nucleotide-replete) F1. Rate constants for bound ATP hydrolysis, ATP resynthesis, and P(i) release, and the reaction equilibrium constant, were similar in nucleotide-depleted and native F1. Therefore, we conclude that occupancy of the noncatalytic sites is not required for formation of the high-affinity catalytic site of F1 and has no significant effect on unisite catalysis. In further experiments we looked for the occurrence of inhibitory, catalytic-site-bound MgADP in E. coli F1. Such an entity has been reported for chloroplast and mitochondrial F1. However, our experiments gave no indication for inhibitory MgADP in E. coli F1.

Adenosine Diphosphate

Time-saving in biological dosimetry by using the automatic metaphase finder Metafer2.

The amount of time-saving by using the Metafer2 metaphase finder for routine analysis of radiation-induced chromosome aberrations (biological dosimetry) was determined. Metaphases were prepared by standard methods from cultures of human peripheral blood lymphocytes and stained either with Giemsa or with the FPG method. The metaphase finder was used for detecting metaphases on the microscope slides and for automatically processing the evaluation data. In our laboratory, standardized analysis of 1000 metaphases requires at least 3 working days for cell culturing and slide preparation and 51.5 working hours for cytogenetic analysis. When using the metaphase finder the time required for cytogenetic analysis is reduced to 17.3 working hours (time-saving factor: 51.5/17.3 h = 3.0). In our prolonged method, including more than one scoring of each slide and karyotyping of metaphases with chromosome aberrations, the analysis times for 1000 cells are 132 and 70 working hours, respectively (time saving factor: 132/70 h = 1.9).

Automation

Nocardia infection in AIDS: a clinical and microbiological challenge.

A case of Nocardia asteroides pneumonia was diagnosed after death in a patient with AIDS. Six sputum cultures and one bronchoalveolar lavage fluid contained no pathogens, and no growth was obtained from one pleural fluid aspirate. None of these specimens was incubated for more than two days. Extended incubation for mycobacteria also failed to help in the diagnosis. N asteroides was isolated from pus taken from the lung cavity during the post mortem examination. It is suggested that if nocardiosis enters the differential diagnosis all specimens should be cultured for at least two weeks and the use of selective media be considered. This case highlights the need for clinicians to maintain a high index of suspicion for this pathogen.

Acquired Immunodeficiency Syndrome

[Perimetry equivalents of glaucoma progression].

Loss of sensitivity in chronic open-angle glaucoma is generalized, but heterogeneous. Particular parts of the visual field deteriorate proportionally, which also applies to the spatial behaviour. The proportionality factor and the slope of decay are most pronounced at the nasal and superior border of the field. In single cases, the topography of the field is variable, but it follows the retinal nerve fiber lines. For follow-up, topography seems to be unimportant. A number of standard threshold programs are adequate for this task. For follow-up the same type of instrument and the same program should always be used. The optimal value for analysis in perimetric follow-up is so far unknown. Although progression is often not linear, linear regression seems to be the most suitable statistical procedure. Some new methods of visualization help to process the information like the double representation, GATT, time diagram or the gray-scale bar.

Glaucoma, Open-Angle

[Prevalence of anal incontinence in adults].

Inquiries were conducted to determine the prevalence of anal incontinence in a) the general population over 45 by a gallup poll studying 1,100 persons (A); b) 3,914 patients seen by their general practitioner or their gastroenterologist during the same week (B); c) 500 patients consulting for urinary stress incontinence (C1); d) 1,136 neurological patients suffering from micturation disorders (C2); and e) 10,157 elderly persons living in retirement homes or in hospital (D). In the general community (A), the prevalence of anal incontinence, including gas and stool incontinence, was 11 percent, the prevalence of fecal incontinence, 6 percent, the prevalence of daily or weekly fecal incontinence, 2 percent; prevalences were respectively 15.5 percent, 7.9 percent, and 3.2 percent in group B, and 27 percent, 9 percent and 3.8 percent in group C1. The prevalence of fecal incontinence was 18 percent in group C2 and 33 percent in group D. Prevalence did not depend on age in group A and C1, but was twofold higher in group C1 than in group A. The prevalence increased with age in groups B and D.

Adult

Protease of adenovirus type 2. Subcellular localization.

The subcellular localization of the adenovirus type 2 core polypeptide specific protease activity was investigated using an in vitro assay system. The protease activity was recovered exclusively from infected cell nuclei and was insoluble, sedimenting with the membrane fraction. Endogenous activity could be demonstrated in young virions which contain precursor PVII molecules. This protease activity only became sensitive to L-1-tosylamide-2-phenylethylchloromethyl ketone- or phenylmethylsulfonyl fluoride-mediated inhibition after disruption of the virus particles by sonication, suggesting that the enzyme was internally located. The putative precursors to virus particles, referred to as top components, which do not contain a full complement of viral DNA, did not contain protease activity. The protease released from sonicated virions converted exogenous PVII substrate molecules to polypeptide VII. The noninfectious H2ts1 virus particles synthesized at the nonpermissive temperature phenotypically resemble young virions, but unlike their wild type counterparts, were devoid of protease activity. The results show that the protease enters the precursor particles concurrently with the viral chromosome and that its presence is a prerequisite for the processing and subsequent maturation of infectious adenovirions.

Adenoviridae

[Determination of the quality of injuries of potato tubers due to damage and rot].

A new method is presented for determining damage to potato tuber tissue. It is based on the fact that starch can be leached with water from the damaged tissue. The starch content of the washing water informs about the extent of tissue damage. Damage assessments of the same samples yielded correlation coefficients ranging from r = 0.8 to r = 0.9 between the determinations and the assessments. The method considers both the mechanical tissue damage and the rot.

Food Handling

On the mechanism of arginine requirement for adenovirus synthesis.

The effects of arginine deprivation on the synthesis and processing of viral proteins and the assembly of incomplete and complete virions were studied during infection with human adenovirus type 2. Arginine deprivation greatly reduced the synthesis of all viral proteins, particularly the precursor to core protein VII. The inhibition was completely reversible by the addition of arginine to the medium. Arginine deprivation between 7 and 20 hours post-infection inhibited the processing of PVII to VII, suggesting that PVII is not cleaved autocatalytically. The assembly of incomplete virions was sensitive to arginine deprivation only prior to 20 hours, while the assembly of complete virions was dependent on the continuous presence of arginine. This observation supports the hypothesis that incomplete virions are precursors of complete virions. The experiments on the PVII-specific endoprotease activity showed that arginine deprivation caused only slight reduction in the in vitro activity, although no activity was observed in vivo. The present results lead to the hypothesis that arginine deficiency inhibits the synthesis of a functional protein essential for virion maturation, other than the synthesis or processing of PVII.

Adenoviruses, Human