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Biomedical subjects

A S Weiss

Publications and source records attributed to A S Weiss.

At least 55 records · Page 3Linked to original sources
PubMed1993

Elevated levels of glycoprotein gp200 in progeria fibroblasts.

The glycosylation of proteins in fibroblasts from people with the premature ageing disease Hutchinson-Gilford Progeria Syndrome (progeria) was investigated. Protein was prepared from fibroblast cell lines established from skin biopsy taken from progeria patients and control donors. Glycoproteins were labelled by the covalent attachment of the steroid hapten digoxygenin to the sugar group. After separation of total protein by SDS-PAGE and electroblotting onto Immobilon-PTM, glycoproteins were detected by enzyme immunoassay. We have observed a glycoprotein of M(r) 200 kDa which is consistently present in protein preparations from progeria fibroblasts and which is absent, or markedly reduced, in preparations from control fibroblasts. This suggests that it may be useful as a marker for progeria. Similar analysis of progeria lymphoblast and control lymphoblast cultures did not show this altered pattern of glycosylated proteins, indicating that it may be cell-type specific. Glycoproteins were also detected by labelling fibroblasts in vitro with D-[6-3H]glucosamine hydrochloride followed by SDS-PAGE of isolated protein and subsequent fluorography. Profiles of glycoproteins from progeria and control fibroblasts were consistent with those obtained from labelling of carbohydrate groups with digoxygenin. Protease digestion of cell protein verified that the band at M(r) 200 kDa contains a protein core. Characteristic features of progeria primarily involve the connective tissue and include wrinkled and loose skin, loss of soft tissue, thin limbs and stiff joints. Death of progeria patients is usually a result of cardiovascular abnormalities. The most consistent manifestations thus involve the connective tissue. The glycoprotein of M(r) 200 kDa which we have observed in progeria fibroblasts in vitro could reflect a perturbation in glycosylation which may underly the connective tissue defects seen in progeria.

Adult↗
PubMed1992

Hyaluronic acid in progeria and the aged phenotype?

Hyaluronic acid (HA) is implicated in functions such as vascularity, morphogenesis, repair, and the general integrity of the extracellular matrix. Hence, it is considered possible that HA is involved in the most conspicuous features of the progeroid phenotype. However, it is not known whether the increase in HA excretion seen in progeria patients is due to a primary genetic defect or is a secondary effect due to some deeper problem. The phenomenon of 'normal' aging is suggested to have a more complex etiology and phenotype than progeria and the role of HA levels is less well-defined.

Aging↗
PubMed1990

Does progeria provide the best model of accelerated ageing in humans?

Studies of the causes of ageing are often obscured by the complexity of this phenomenon, hindering investigations in this area. In particular, the variable characteristics of ageing complicate analysis at a molecular level. It is proposed that to gain insight into ageing, the problem must first be simplified by restricting studies to an aspect of the ageing processes. It is suggested that progeria, which presents a less complicated etiology and phenotype than other accelerated ageing diseases, allows research to focus on a regulation site involved in development and ageing.

Aging↗
PubMed1989

Transposon-mediated restriction mapping of the Bacillus subtilis chromosome.

Analysis of chromosomal DNA depends upon a knowledge of the locations of restriction sites over several thousand kilobases (kb). However determination of even a subset of these sites can be time-consuming, and it can be difficult to link genetic and physical maps. We describe here a significant improvement which can be used in concert with genetically mapped chromosomal insertions. The circular chromosome of Bacillus subtilis 168 was physically examined on contour-clamped homogeneous electric field (CHEF) gels using the restriction enzyme NotI. Restriction mapping of the 4.7-megabase (Mb) DNA was accomplished using a novel technique involving the transposon Tn917, which linked the genetic and physical maps and also significantly increased the rate at which this was performed. The DNA of 54 strains which contained Tn917 at genetically determined locations was cleaved with NotI and used to determine the approximate positions of 31 restriction fragments with sizes between 45 kb and 290 kb, totalling 3589 kb. This information should greatly assist in the construction of a more detailed map using standard methodology.

Bacillus subtilis↗
PubMed1987

Personality characteristics of Hare Krishnas.

Personality characteristics of 132 males and 94 females of the Hare Krishna movement were assessed using the Comrey Personality Scales (CPS). Subjects were sampled from eight U.S. sites. Their age averaged about 30 years, and their time in the movement averaged 8.6 years. The most prominent and surprising finding is the hallmark characteristic of the Hare Krishna personality, a strong compulsivity trait common to both genders, which is slightly stronger in males. Reduced trust in society was exhibited by both gender averages, with slightly less trust among females. Both these averages, however, were within the normal range for individuals. With the exception of compulsivity, average male CPS scores were within the normal psychological range but differed significantly from the normative male group indicating idiosyncratic traits. Average female CPS scores did not differ significantly from the normative female group except for compulsivity and trust. Study of CPS score distributions about group means supported these findings.

Journal Article↗
PubMed1986

An immobilized fork as a termination of replication intermediate in Bacillus subtilis.

The structure of a DNA intermediate associated with termination of chromosome replication in Bacillus subtilis and derived from a unique BamHI 24.8 X 10(3) base-pair (bp) region of the chromosome has been investigated. The intermediate has properties expected for a forked structure. Gel electrophoresis followed by Southern transfer and hybridization to cloned DNA has shown it to comprise single strands of 15.4 X 10(3) bp and 24.8 X 10(3) bp, in approximately equimolar amounts. After purification away from the bulk of chromosomal DNA, electron microscopy of the intermediate established that 15% of the DNA was present as branched molecules and a significant proportion (11 of 31) of these contained two arms of matching length. The average dimensions (best estimates) of this unique class of Y-shaped molecule were 9.5(+/- 0.3) X 10(3), 15.1(+/- 0.4) X 10(3) and 24.6 24.6(+/- 0.6) X 10(3) bp for the stem, arms and end-to-end length, respectively. These values are consistent with the single strand composition of the intermediate as found. Furthermore, hybridization of the single strands to DNA from known locations within the BamHI 24.8 X 10(3) bp region has established the orientation of the forked intermediate relative to the genetic map. The intermediate presumably reflects the immobilization of the clockwise replication fork within the 24.8 X 10(3) bp region, at a location approximately 15.4 X 10(3) bp from the right end.

Bacillus subtilis↗
PubMed1984

Impediment to replication fork movement in the terminus region of the Bacillus subtilis chromosome.

The terminus regions of the chromosomes of three strains of Bacillus subtilis 168 were radioactively labelled by supplying [3H]thymine towards the end of a round of replication. These strains lacked or contained the prophage SP beta c2. Following restriction endonuclease digestion of the purified DNA and fluorography, an SP beta c2-related perturbation of the terminus-labelling profile was observed, which was completely consistent with the previously suggested existence of an impediment to replication fork movement (terC) within a BamHI 24.8 X 10(3) base fragment (Weiss & Wake, 1983). The present data suggest that terC is located within the 11.4 X 10(3) base BamHI + SalI double-digest portion of this BamHI fragment.

Bacillus subtilis↗
PubMed1984

A unique DNA intermediate associated with termination of chromosome replication in Bacillus subtilis.

A unique DNA structural intermediate associated with termination of replication in Bacillus subtilis has been identified. This was achieved by probing for the Bam HI DNA fragment within which the terminus of the chromosome (terC) resides. The intermediate migrates more slowly than the bulk of digested chromosomal DNA upon electrophoresis. It is more readily detected in DNA from a merodiploid strain in which the clockwise fork should be immobilized at terC for longer than usual, and it is destroyed by S1 nuclease. The intermediate may be a forked or related structure. These findings provide evidence for the existence of a specific, sequence-based termination site that blocks or severely impedes the movement of at least the clockwise fork, which is the first to encounter it.

Bacillus subtilis↗
PubMed1983

Restriction map of DNA spanning the replication terminus of the Bacillus subtilis chromosome.

The Bacillus subtilis 168 dna-1 chromosome was labelled during sporulation with [3H]thymine for five minutes immediately before termination of replication. The isolated radioactive DNA was cleaved with BamHI (or SalI) and the resulting restriction fragments separated by agarose gel electrophoresis. The individual fragments, fractionated into a series of slices cut from the gel, were then cleaved with SalI (or BamHI) and the double-digest fragments identified by electrophoresis and fluorography. All major fragments and most minor ones present in a whole double-digest were assigned to BamHI and SalI parents. Such information enabled the construction of an unambiguous restriction map of 150 X 10(3) bases of the approximately 250 X 10(3) bases of DNA labelled in the five minutes. In conjunction with published data on the order of replication of restriction fragments as termination is approached, it was clear that most (105 X 10(3) bases) of the mapped DNA was replicated by a major fork moving in one direction towards a BamHI 24.8 X 10(3) base fragment. The 45 X 10(3) bases extending to the other side of this region were labelled only slightly, and presumably was replicated by a fork that approached the other in an opposite direction until its progress was blocked or severely impeded within this region at a site, referred to as terC, sometime (less than 5 min) earlier. The regions of the map replicated in the final 2.5 and 1.0 minute by the major fork were also identified.

Bacillus subtilis↗
PubMed1983

Comparative pharmacological properties and autoradiographic distribution of [3H]ethylketocyclazocine binding sites in rat and guinea pig brain.

[3H]Ethylketocyclazocine (EKC) binds to a single class of sites under various incubation conditions in both rat and guinea pig brain. Ligand selectivity patterns strongly suggest that [3H]EKC binds to kappa opiate receptors in both species and under both incubation conditions. Moreover, the autoradiographic distribution of [3H]EKC binding sites is very similar under both incubation conditions. In guinea pig brain, [3H]EKC binding sites are highly concentrated in deep layers of the cortex, caudate-putamen, and nucleus accumbens. In rat brain, kappa opiate receptors are mainly found in caudate-putamen, nucleus accumbens, amygdala, and thalamus. [3H]EKC binding sites are not concentrated in deep layers of the cortex in rat brain. Thus, the autoradiographic distribution of kappa opiate receptors is species-dependent.

Analgesics, Opioid↗
PubMed1983

Cloning DNA from the replication terminus region of the Bacillus subtilis chromosome.

DNA from the Bacillus subtilis 168 prototroph, SB19, was partially cleaved with MboI and cloned into the BamHI site of the Escherichia coli cosmid vector, pHC79. [3H]thymine-labelled DNA from the replication terminus region of the B. subtilis dna-1 chromosome was used to identify, by hybridization, clones harboring recombinant cosmids carrying inserts from the terminus region. Restriction maps have been constructed for two such cosmids carrying overlapping DNA inserts that cover or extend into four of the previously identified five SalI fragments which are replicated last. The composite map of the cloned region, together with the available data on the replication order of fragments within it, is consistent with its replication being achieved by the unidirectional movement of a fork through it and towards the late replicating 16.2-kb SalI fragment. Most, if not all, of the terminus sequences in at least one of the recombinant cosmids are missing from a viable strain of B. subtilis that carries a deletion in the SP beta-gltA region of the chromosome.

Bacillus subtilis↗
PubMed1978

Toxicity of D-penicillamine in rheumatoid arthritis. A report of 63 patients including two with aplastic anemia and one with the nephrotic syndrome.

To assess toxicity of D-penicillamine a retrospective chart review was performed on 63 patients with rheumatoid arthritis receiving penicillamine. These patients had a total of 83 courses of therapy. The mean age of patients was 52 years and the mean duration of disease was 10.07 years. Laboratory data showed an increase in hematocrit values from 36 per cent to 40 per cent and a decrease in the erythrocyte sedimentation rate from an average of 50 to 29 mm/hour. The platelet count also decreased with treatment from 394,000 to 267,000/mm3. The over-all complication rate was 53 per cent. Life-threatening complications occurred in two patients including one case of aplastic anemia and one case of nephrotic syndrome. One additional patient was referred with aplastic anemia. Minor complications include rash in 18 per cent, loss of taste in 6 per cent, dyspepsia in 11 per cent, oral ulceration in 7 per cent and proteinuria of less than 3 g/day in 8 per cent. In summary, 53 per cent of the courses of penicillamine were associated with toxicity including one episode of aplastic anemia and one case of nephrotic syndrome. Therapy was stopped due to complications in 39 per cent of the patients in this series.

Adult↗
PubMed1974

Fletcher factor deficiency. A diminished rate of Hageman factor activation caused by absence of prekallikrein with abnormalities of coagulation, fibrinolysis, chemotactic activity, and kinin generation.

Fletcher factor-deficient plasma is deficient in prekallikrein and therefore generates no bradykinin upon activation with kaolin. It also possesses a diminished rate of kaolin-activable coagulation and fibrinolysis and possesses a defect in kaolin-activable chemotactic activity. These abnormalities are also corrected by reconstitution with purified prekallikrein. Addition of intact activated Hageman factor corrected the coagulation, fibrinolytic, and chemotactic defects and addition of Hageman factor fragments corrected the fibrinolytic defect and partially corrected the chemotactic defect; neither of these corrected the kinin-generating defect. Although the Hageman factor-dependent pathways appear to be initiated by contact activation of Hageman factor, the kallikrein generated activates more Hageman factor; this feedback is necessary for the Hageman factor-dependent pathways to proceed at a normal rate. It is the absence of this feedback in Fletcher factor-deficient plasma that accounts for the diminished rate of activation of Hageman factor and therefore a diminished rate of activation of the coagulation and fibrinolytic pathways. The ability of prekallikrein to correct the coagulation, fibrinolytic, kinin-generating, and chemotactic defects of Fletcher factor-deficient plasma is consistent with the identity of the Fletcher factor and prekallikrein.

Blood Coagulation↗