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Biomedical subjects

J Weber

Publications and source records attributed to J Weber.

At least 631 records · Page 35Linked to original sources
PubMed1983

Chemical modification of the small intestinal Na+/D-glucose cotransporter by amino group reagents. Evidence for a role of amino group(s) in the binding of the sugar.

Some amino group reagents inactivate the small-intestinal Na+/D-glucose cotransporter, as measured either as a catalyst of Na+-dependent D-glucose transport or as a Na+-dependent phlorizin ligand. The amino group(s) studied in this paper are not identical with those investigated previously (Biber, J., Weber, J. and Semenza, G. (1983) Biochim. Biochim. Acta 728, 429-437): these are protected from inactivation by the simultaneous presence of Na+ plus sugar substrates. They are thus likely to be located within the substrate-binding site.

Animals↗
PubMed1983

Genetic identification of an endoproteinase encoded by the adenovirus genome.

The temperature-sensitive adenovirus type 2 mutant H2ts1 is defective for polypeptide processing at the non-permissive temperature. We have in the present study mapped the mutation by marker rescue and DNA sequencing techniques: the mutation is a C/T transition located at map co-ordinate 61.1. Previous sequencing studies have identified an uninterrupted translational reading frame in this part of the adenovirus genome, encoding a hypothetical 23 X 10(3) Mr polypeptide. The mutation leads to a proline/leucine substitution in the 23 X 10(3) Mr polypeptide.

Adenoviruses, Human↗
PubMed1983

In vitro cleavage specificity of the adenovirus type 2 proteinase.

Two in vitro proteinase assay systems were developed and used to study the peptide bond specificity and substrate specificity of the adenovirus endoproteinase. Five adenovirus precursor proteins (PVI, PVII, PVIII, 87K, 11K), all found in the virion of the ts1 mutant grown at the nonpermissive temperature, were digested by the proteinase. All, except 11K, were cleaved to their mature counterparts. Some of the proteins, particularly the 87K terminal protein, were processed via cleavage intermediates similar to those found in vivo. The data suggest that the proteinase specifically hydrolyses Gly-Ala bonds. The high specificity for the natural substrates and the failure to cleave foreign proteins suggest that cleavage activity is determined not only by primary sequence but also by other physical features of the substrate. Enzyme activity was inhibited by diisopropylfluorophosphate, showing that it is a serine proteinase.

Adenoviruses, Human↗
PubMed1983

Small-intestinal Na+/D-glucose cotransport. Inactivation of sugar transport and phlorizin binding by thiol-group and amino-group reagents.

It has previously been shown that mercurials acting from the cytoplasmic side or from within the hydrophobic part of the membrane inactivate the small intestinal Na+/D-glucose cotransporter by blocking essential SH-groups (Klip, A., Grinstein, S. and Semenza, G. (1979) Biochim. Biophys. Acta 558, 233-245). Another (set of) sulfhydryl(s) which are critical for phlorizin binding and sugar transport function and which may lie on the luminal side of the brush border membrane, can be blocked by DTNB and 4,4'-dithiopyridine but not by N-ethylmaleimide. In addition, modification of amino groups by fluorescamine, reductive methylation and (under certain conditions) DIDS also lead to inactivation of the carrier's binding and transport functions. No evidence was obtained that any of the above groups is directly involved in the binding of either Na+/D-glucose or phlorizin, since none of these compounds prevented inactivation of the cotransporter.

Animals↗
PubMed1983

Quantitative measurement of retinal blood flow in human beings by application of digital image-processing methods to television fluorescein angiograms.

A method is presented that allows the quantitative determination of the blood flow in retinal arteries in human beings. Television fluorescein angiograms are used as input. This method does not need any gauge procedures since all the necessary information is taken from the image itself. Also, the patients' eye movements do not introduce errors because their influence is removed by the computer program.

Fluorescein Angiography↗
PubMed1983

Morphometric estimates of diffusing capacity in lungs fixed under zone II and zone III conditions.

Comparative morphometric estimates of the diffusing capacity (DL) were made in rabbit lungs fixed by vascular perfusion under lower zone II and zone III conditions and in lungs fixed by instillation of fixatives into the airways. Owing to a reduction of both capillary volume and membrane diffusing capacity DL of zone II lungs (0.074 +/- 0.007 (SD) ml . sec-1 . mbar-1). was found to be lower by some 25% than DL of instillation-fixed lungs (0.102 +/- 0.012 (SD) ml . sec-1 . mbar-1). The average value of DL of air-filled zone III lungs, on the other hand, almost matched the DL of instillation-fixed lungs. However, DL is not equal in all regions but increases along the vertical axis of zone III lungs. Hence, the previous conclusion that morphometric estimates of DL in instillation-fixed lungs reflects a structural limit for O2 diffusion, which cannot be reached under physiologic conditions, must be revised.

Animals↗
PubMed1983

Biological and structural studies with an adenovirus type 2 temperature-sensitive mutant defective for uncoating.

We compared some of the biological and structural features of an adenovirus type 2 temperature-sensitive mutant (ts1) defective for maturation cleavages and uncoating with wild-type (WT) virus. The cleavage defect caused ts1 to produce virions at 39 degrees that contained five precursor proteins (pTP, 11K, PVI, PVII, PVIII). Coinfection of cells with such ts1 virions and a variety of mutants or WT virus not only failed to complement ts1 but actually depressed the infection by the second virus. The uncoating defect could only be overcome by multiplicity-dependent leakiness. The structure of the ts1 virion was compared with that of WT virus by iodination with chloramine-T, chloroglycoluril and lactoperoxidase, by cross-linking, and by digestion with proteases. Aside from the presence of precursor proteins and the greater stability of ts1 virions, no other differences were found that could account for the uncoating defect. Therefore, we postulate that this defect was caused by the greater stability imparted to the virion by precursor proteins PVI, PVII and PVIII.

Adenoviruses, Human↗
PubMed1983

Influence of adjuvant irradiation on shoulder joint function after mastectomy for breast carcinoma.

The influence of postoperative radiation therapy on ipsilateral shoulder function following mastectomy was evaluated from a series of 52 women with primarily operable carcinoma of the breast. Mastectomy and partial axillary dissection were carried out in all patients. In addition, 29 of the patients received postoperative irradiation with 36.6 Gy applied mid-axillarily in 12 fractions with irradiation twice a week. A significant impairment of the active shoulder mobility was found in the irradiated group (p less than 0.01). The passive mobility did not differ significantly between the two groups. The impairment of active shoulder mobility is suggested to be caused by radiation induced subcutaneous fibrosis.

Adult↗
PubMed1983

Multistage tumor development in the human esophagus - the first identification of cocarcinogens of the tumor promoter type as principal carcinogenic risk factors in a local life style cancer.

An experimental analysis is described which demonstrates that the epidemiologically established high rate of esophageal cancer among blacks and creoles in Curacao most likely is the result of a multistage process involving initiators and promoters. As part of local lifestyle, the group at risk utilizes for various purposes plant parts of an indigenous bush Croton flavens L. ("Welensali"). Moreover they consume, as an everyday beverage, a "bush tea" made from the leaves of the bush. The roots, leaves and tea are shown to contain a multitude of irritant croton factors which are characterized as diterpene esters of the tigliane type. In mouse skin these exhibit strong promoting activity comparable to that of TPA. As the latter, also the croton factors isolated, show no solitary carcinogenic activity. One cup of Welensali tea contains the equivalent of about 12-times the irritant dose of croton factor F1; in addition, the equivalent of about 1.4-times the irritant dose 50 of the corresponding "cryptic" promoter F1-20-decanoate is present. These amounts are considered sufficient to maintain chronic irritation of the esophagus as an important element of co-carcinogenesis, especially of tumor promotion. Also, persons at risk in Curacao have been exposed at times previously to certain initiators. Mice treated by an initiation/promotion protocol with DMBA (or other initiators) and TPA develop tumors of the forestomach. Therefore, esophageal cancer on Curacao may be considered the first case for cocarcinogens of the tumor promoter type being principal risk factors in a life style cancer.

Animals↗
PubMed1983

[Late reoperations in cancer surgery of the lung].

In early reoperations following surgery of the lung haemorrhage comes first. In the late phase of reoperations, i.e. more than 3 months till 6.5 years after surgery, 12 secondary operations were performed for metachronic carcinomatous tumours and due to insufficient "radical" surgery. The postoperative mortality rate was 0. The results obtained are in favour of secondary operations because they are able to prolong the life expectancy of those patients.

Adult↗
PubMed1982

Structure of adenovirus chromatin.

The structure of adenovirus type 2 chromatin isolated from wild-type and ts1 virions was investigated by micrococcal nuclease digestion and electron microscopy. Partial digestion of wild-type and ts1 chromatin with micrococcal nuclease generated a multimeric DNA smear devoid of the 200 basepair nucleosome repeating pattern characteristic of cellular chromatin. However, 11 S monomer cores of 150 basepairs were detectable. The chromatin of ts1 (39 degrees C) was more resistant to digestion by micrococcal nuclease. Two-dimensional electrophoresis of the monomer core showed that wild-type core contained protein VII while ts1 (39 degrees C) core contained PVI and PVII. Protein V appears to be located on the variable-length intermonomer region. Crosslinking studies suggest that proteins PVII and VII exist in dimeric form within the monomer core. Electron microscopy revealed a 5.5-fold-condensed two-micron-long beaded structure with about 200 monomer particles spaced irregularly. Based on these observations, a model for adenovirus prochromatin and chromatin is proposed that differs in important aspects from the model proposed previously (Corden, J., Engelking, H.M. and Pearson, G.D. (1976) Proc. Natl. Acad. Sci. USA 73, 401-404).

Adenoviruses, Human↗
PubMed1982

Interaction of high-affinity nucleotide binding sites in mitochondrial ATP synthesis and hydrolysis.

The present study contributes to the problem of the dynamic structure of mitochondrial F1-ATPase and the functional interrelation of so-called tight nucleotide binding sites. Nucleotide analogs are used as a tool to differentiate two distinct functional states of the membrane-bound enzyme, proposed to reflect corresponding conformational states; they reveal F1-ATPase as a "dual-state" enzyme: ATP-synthetase, and ATP-hydrolase. The analogs used are 3'-naphthoyl esters of AD(T)P, and 2'(3')-O-trinitrophenyl ethers of AD(T)P. Both types of analogs act inversely to each other with respect to their relative effects on oxidative phosphorylation and on ATPase in submitochondrial vesicles. The respective ratios of Ki versus both processes are 250/1 compared to 1/170. It is also shown that in the presence of the inhibitory 3'-esters oxidative phosphorylation deviates from linear kinetics and that these inhibitors induce a lag time of oxidative phosphorylation depending on the initial pattern of nucleotides available to energized submitochondrial vesicles. The duration of the lag time coincides with the time course of displacement of the analog from a tight binding site. The conclusions of the study are: (a) the catalytic sites of F1-ATP-synthetase are not operating independently from each other; they rather interact in a cooperative manner; (b) F1-ATPase as a "dual-state" enzyme exhibits highly selective responses to tight binding of nucleotides or analogs in its "energized" (membrane-bound) state versus its "nonenergized" state, respectively.

Adenosine Triphosphate↗
PubMed1982

Stable integration of adenovirus DNA is not required for the induction of mutations in the hypoxanthine phosphoribosyltransferase gene in Chinese hamster cells.

Adenovirus type 2 induces EMS-like mutations at the hpt13 locus coding for hypoxanthine phosphoribosyl transferase (HPRT) in Chinese hamster cells (J. Virol., 38, 184--190, 1981). In this report we show that: (a) the hpt- 13 mutation is in the structural gene of HPRT, (b) adenovirus induces intracistronic reversion mutations which suppress the hpt- 13 phenotype, and (c) the stable integration of adenovirus DNA is not required for the induction of these mutations.

Adenoviruses, Human↗
PubMed1982

Discrete subgenomic DNA fragments in incomplete particles of adenovirus type 2.

Discrete subgenomic DNA fragments were found in three out of thirty-two preparations of adenovirus type 2 incomplete particles grown in human Hep-2 cells and examined over the course of 1 year. One preparation contained three fragments corresponding to 5, 14 and 19% of the genome, another contained a 37% fragment and the third a 40% fragment. Each fragment hybridized exclusively to the left end of the genome. Digestion of the nick-translated 37% fragment with HindIII confirmed that it contained the left 37.3% of the genome. Synthesis of these fragments was not dependent on high input multiplicity of infection. Comparable fragments were not found in unpackaged DNA from the corresponding infected cells. This is consistent with the hypothesis that such fragments are generated during virus assembly or, alternatively, may reflect the very small proportion of these fragments relative to the pool of unpackaged DNA within the cells. The possibility that they are generated by errors in DNA replication is discussed.

Adenoviruses, Human↗