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Biomedical subjects

J S Anderson

Publications and source records attributed to J S Anderson.

At least 37 records · Page 2Linked to original sources
PubMed1997

Protein-tyrosine phosphatase SHP-1 is dispensable for FcgammaRIIB-mediated inhibition of B cell antigen receptor activation.

The inhibitory Fc receptor, FcgammaRIIB, provides a signal that aborts B cell antigen receptor activation, blocking extracellular calcium influx. Because the protein-tyrosine phosphatase SHP-1 binds tyrosyl phosphorylated FcgammaRIIB and FcgammaRIIB-mediated inhibition is defective in motheaten (me/me) mice, which do not express SHP-1, it was proposed that SHP-1 mediates FcgammaRIIB signaling in B cells (D'Ambrosio, D., Hippen, K. L., Minskoff, S. A., Mellman, I., Pani, G., Siminovitch, K. A., and Cambier, J. C. (1995) Science 268, 293-297). However, SHP-1 is dispensable for FcgammaRIIB-mediated inhibition of FcepsilonRI signaling in mast cells (Ono, M., Bolland, S., Tempst, P., and Ravetch, J. V. (1996) Nature 383, 263-266), prompting us to re-examine the role of SHP-1 in FcgammaRIIB signaling in B cells. We generated immortalized sIgM+, FcgammaRIIB+ cell lines from me/me mice and normal littermates. Co-ligation of FcgammaRIIB and the sIgM antigen receptor inhibits calcium influx in both cell lines. Inhibition is reversed by preincubation with anti-FcgammaRIIB antibodies, indicating that it is mediated by FcgammaRIIB. The inositol 5' phosphatase SHIP is recruited to tyrosyl-phosphorylated FcgammaRIIB in both cell lines. FcgammaRIIB-mediated CD19 dephosphorylation also occurs in the presence or the absence of SHP-1. Our results establish that SHP-1 is dispensable for FcgammaRIIB-mediated inhibition of sIgM antigen receptor signaling.

Animals↗
PubMed1997

Biosynthesis of teichuronic acid in the bacterial cell wall. Purification and characterization of the glucosyltransferase of Micrococcus luteus.

This report describes what is, to our knowledge, the first purification to near homogeneity of an enzyme involved in the biosynthesis of the teichuronic acid of Micrococcus luteus cell walls. The glucosyltransferase of M. luteus, which participates in the biosynthesis of teichuronic acid, was solubilized from cytoplasmic membrane fragments by extraction with buffer solutions containing the detergents Thesit (dodecyl alcohol polyoxyethylene ether; 1 mg/ml) and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (0.5 mg/ml). The detergent-solubilized enzyme was purified 150-fold, with a recovery of 13% by adsorbent column chromatography, ion-exchange chromatography, gel filtration, and preparative nondenaturing gradient polyacrylamide gel electrophoresis. On the basis of its mobility on native gradient gel, the glucosyltransferase was estimated to have a molecular mass of 440 kDa. The purified native enzyme was a multisubunit protein consisting of subunits of two sizes; their molecular masses were determined to be 52.5 and 54 kDa, respectively, by observation of the mobility of the protein bands in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The isoelectric point of the enzyme was approximately 5.

Anti-Bacterial Agents↗
PubMed1997

The quality of life of persons with chronic fatigue syndrome.

This descriptive study used a between-methods triangulation design to analyze the multiple dimensions of quality of life in persons with chronic fatigue syndrome (CFS). This method, which refers to the combination of both quantitative and qualitative methods in the same study, allowed the authors to obtain more comprehensive and robust data than could be obtained by either method alone. A convenience sample of 110 persons with CFS completed the quality of life index and CFS questionnaire, and a subset of 22 persons were interviewed regarding their lived experience with CFS. Overall scores on the quality of life index were significantly lower in CFS than for other chronic illness groups. Subjects reported the lowest quality of life scores in health and functioning domain. Indepth interviews provided a more complete understanding of the quality of life in CFS and further explained the low ratings that were found on the quality of life index. The findings suggest that quality of life is particularly and uniquely disrupted in CFS.

Adolescent↗
PubMed1996

An essential role for Bruton's [corrected] tyrosine kinase in the regulation of B-cell apoptosis.

Mutations of the Bruton's tyrosine kinase (btk) gene cause X-linked agammaglobulinemia (XLA) in humans and X-linked immune deficiency (Xid) in mice. To establish the BTK role in B-cell activation we examined the responses of wild-type and Xid B cells to stimulation through surface IgM and CD40, the transducers of thymus independent-type 2 and thymus-dependent activation, respectively. Wild-type BTK was necessary for proliferation induced by soluble anti-IgM (a prototype for thymus independent-type 2 antigen), but not for responses to soluble CD40 ligand (CD40L, the B-cell activating ligand expressed on T-helper cells). In the absence of wild-type BTK, B cells underwent apoptotic death after stimulation with anti-IgM. In the presence of wild-type but not mutated BTK, anti-IgM stimulation reduced apoptotic cell death. In contrast, CD40L increased viability of both wild-type and Xid B cells. Importantly, viability after stimulation correlated with the induced expression of bcl-XL. In fresh ex vivo small resting B cells from wild-type mice there was only barely detectable bcl-XL protein, but there was more in the larger, low-density ("activated") splenic B cells and peritoneal B cells. In vitro Bcl-XL induction following ligation of sIgM-required BTK, was cyclosporin A (CsA)-sensitive and dependent on extracellular Ca2+. CD40-mediated induction of bcl-x required neither wild-type BTK nor extracellular Ca2+ and was insensitive to CsA. These results indicate that BTK lies upstream of bcl-XL in the sIgM but not the CD40 activation pathway. bcl-XL is the first induced protein to be placed downstream of BTK.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1994

Regional differences in bone density of young men involved in different exercises.

In this cross-sectional, retrospective study, the bone mineral content (BMC) and density (BMD) of the whole skeleton, upper limbs, lower limbs, femoral neck, and lumbar vertebrae were measured using dual photon absorptiometry and the results compared in healthy young males involved in: weight-lifting, running, cross-training, or recreational exercises. When adjusted for body weight, the upper limb BMD was highest in those engaged solely in weight-lifting (mean 1.021, SE 0.019, and 95% CI 0.981-1.061) and lowest in runners (mean 0.908, SE 0.019 and 95% CI 0.869-0.946). These differences were significant (P = 0.0004). There were no significant differences in upper limb BMD between weight-lifters and cross-trained athletes and between runners and those engaged in recreational exercises. Significant differences in BMD were observed between weight-lifters and recreational athletes (P = 0.001) and between cross-trained athletes and runners (P = 0.03). No other significant differences were observed. These data suggest that healthy, young, adult males reporting a history of intensive weight-lifting had significantly greater bone mass of the upper limb bones than those reporting a history of non-weight-lifting exercises. These results imply a specific versus generalized effect of mechanical load on bones of the skeleton.

Adult↗
PubMed1993

Structural requirements for the interaction between tissue factor and factor VII: characterization of chymotrypsin-derived tissue factor polypeptides.

Tissue Factor (TF) is the cellular receptor for coagulation Factor VII/VIIa (FVII/VIIa). TF binds to FVIIa and promotes the rapid activation of the zymogen substrates Factors IX and X (FIX and FX) to the respective serine proteinases. In order to probe structure-function relationships in TF, we have subjected the truncated membrane-bound variant, TF 1-243, to proteolytic digestion in SDS-containing gels. Three major polypeptide fragments were generated by proteolysis of TF 1-243 with chymotrypsin, producing cleavages C-terminal to residues 34, 76 and 103. All three polypeptides, TF 35-243, 77-243 and 104-243, bound biotinylated human FVII in a highly specific ligand blot assay. High-performance electrophoretic chromatography was used to isolated chymotrypsin-derived fragments of TF. These purified fragments bound FVII in ligand blots, and two of the three polypeptides exhibited much reduced, but significant, procoagulant activity in a chromogenic assay for the generation of Factor Xa in the presence of FVIIa and Ca2+. The smallest chymotrypsin-derived TF polypeptide, TF 104-243, showed reduced binding of FVII in ligand blot analyses, inhibited the activity of the full-length molecule, but had no procoagulant activity. These data suggest that a part of the binding site for FVII is contained within the TF sequence 104-243. The sequence TF 1-34 either contains a part of the FVII-binding domain or its removal leads to dysfunctional folding, disrupting binding sites elsewhere in the molecule.

Amino Acid Sequence↗
PubMed1991

Purification and characterization of factor VII 304-Gln: a variant molecule with reduced activity isolated from a clinically unaffected male.

Factor VII (FVII) is the plasma serine protease zymogen which, on binding to its cellular receptor tissue factor (TF), initiates blood coagulation. A 47-year-old man with no clinical bleeding tendency was found to have undetectable plasma FVII activity when tested in a one-stage assay using rabbit brain TF, but 0.3 U/mL using recombinant human TF and 1.04 U/mL FVII antigen. Variant FVII purified from his plasma showed an identical migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis to wild-type zymogen. By enzyme kinetic analysis the Km of the variant using FX as a substrate was 12-fold higher than that of normal FVII. Also, the variant FVII was unable to compete with wild-type FVII for limited rabbit TF binding sites. A ligand blot procedure was used to directly demonstrate reduced binding of recombinant human TF to the variant FVII compared with normal FVII. Genetic analysis of leukocyte DNA showed a G to A mutation in the propositus' gene at codon 304 that results in the substitution of a glutamine for an arginine residue in the catalytic domain of the protease. We conclude that this region of the FVII molecule is important for its function.

Amino Acid Sequence↗
PubMed1991

Brain tumor resection aided with markers placed using stereotaxis guided by magnetic resonance imaging and computed tomography.

In the operative resection of brain tumors, defining and locating edges of deep-seated tumors or those with indistinct color and consistency can be difficult. This report presents a simple yet precise, alternative method, using the basic Brown-Roberts-Wells or Cosman-Roberts-Wells stereotactic frame, for placement of visual markers to aid in tumor resections. The method can also be extended to the Leksell system. Using routine computed tomographic scanning or magnetic resonance imaging after stereotactic frame application, multiple points along tumor edges were used as target points. In the operating room, standard techniques were used for the skin incision, removal of the bone flap, and opening the dura. At each target point, after opening the dura and using stereotactic coordinates and equipment, a microbiopsy forceps was used to place "micropatties" (each with a string tail) or small catheters with pledgets or catheter tips located at tumor edges. After removing the arc, the tumor resection was accomplished in a conventional nonstereotactic manner by simply following string tails or catheters to the tumor. Gross tumor edges were determined from positions of actual patties or catheter tips. These simple but accurate techniques offer the possibility of tumor resections under stereotactic guidance with equipment readily available to most neurosurgeons. The fidelity of marker placement is also maintained in relation to tumor edges despite shifts in the tumor and/or brain as cystic areas are drained or large amounts of the tumor are resected.

Adult↗
PubMed1991

Effects of angiotensin converting enzyme inhibition with cilazapril on intimal hyperplasia in injured arteries and vascular grafts in the baboon.

To determine the importance of angiotensin converting enzyme (ACE) activity in the development of arterial proliferative lesions in a primate model, the response to vascular injury was studied in five baboons treated with oral cilazapril (20 mg/kg/day) and in five untreated control animals. Each animal underwent three procedures: 1) carotid artery endarterectomy, 2) balloon catheter deendothelialization of the superficial femoral artery, and 3) surgical placement of bilateral aorto-iliac expanded polytetrafluoroethylene (Gore-Tex) vascular grafts. Cilazapril therapy was initiated 1 week preoperatively and continued throughout the study interval. At 1 and 3 weeks postoperatively, plasma ACE activity was inhibited by more than 96% versus control values. After animals were killed at 3 months, injured vessel and graft segments were evaluated morphometrically. Although the response between animals was variable, average cross-sectional areas of neointima did not differ between the cilazapril-treated and control groups at sites of carotid endarterectomy (0.26 +/- 0.12 versus 0.34 +/- 0.17 mm2, respectively; p greater than 0.5), femoral artery ballooning (0.15 +/- 0.08 versus 0.11 +/- 0.01 mm2; p greater than 0.5), or at graft anastomoses (1.86 +/- 0.50 versus 1.72 +/- 0.50 mm2; p greater than 0.5). Thus, cilazapril did not reduce intimal thickening over 3 months in these primate arterial injury models. However, a possible beneficial effect of cilazapril, which might be apparent at earlier time points or with larger animal groups, cannot be excluded.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

The Medical Outcomes Study Instrument (MOSI)--use of a new health status measure in Britain.

The Medical Outcomes Study Instrument (MOSI), a 20 item functional health status measure was sent to all women aged 30-40 years (n = 486) in a General Practice (list size 6447). There was a 73% response rate to two mailings. Lower scores on all six dimensions of the MOSI were associated with the number of diagnoses and identified mental illness on the patient summaries, unemployment and with positive scores on the Nottingham Health Profile. In two categories, General Health Perceptions and Mental Health, the scores were lower for those on long-term medication. The paper suggests that the MOSI may be a candidate for Health Status measurement in research and audit in primary care, but further research is required.

Adult↗
PubMed1990

Teichuronic acid reducing terminal N-acetylglucosamine residue linked by phosphodiester to peptidoglycan of Micrococcus luteus.

Teichuronic acid-peptidoglycan complex isolated from Micrococcus luteus cells by lysozyme digestion in osmotically stabilized medium was treated with mild acid to cleave the linkage joining teichuronic acid to peptidoglycan. This labile linkage was shown to be the phosphodiester which joins N-acetylglucosamine, the residue located at the reducing end of the teichuronic acid, through its anomeric hydroxyl group to a 6-phosphomuramic acid, a residue of the glycan strand of peptidoglycan. 31P nuclear magnetic resonance spectroscopy of the lysozyme digest of cell walls demonstrated the presence of a phosphodiester which was converted to a phosphomonoester by the conditions which released teichuronic acid from cell walls. Reduction of acid-liberated reducing end groups by NaB3H4 followed by complete acid hydrolysis yielded [3H] glucosaminitol from the true reducing end residue of teichuronic acid and [3H]glucitol from the sites of fragmentation of teichuronic acid. The amount of N-acetylglucosamine detected was approximately stoichiometric with the amount of phosphate in the complex. Partial fragmentation of teichuronic acid provides an explanation of the previous erroneous identification of the reducing end residue.

Acetylglucosamine↗
PubMed1990

Polymer length of teichuronic acid released from cell walls of Micrococcus luteus.

Teichuronic acid released from its phosphodiester linkage to peptidoglycan in the cell walls of Micrococcus luteus by mild acid treatment is resolved into a ladderlike series of bands by electrophoresis on polyacrylamide gels in the presence of borate. Each band of the ladder differs from its nearest neighbor by one disaccharide repeat unit, ----4)-2-acetamido-2-deoxy-beta-D-mannopyranuronosyl-(1----6)- alpha-D-glucopyranosyl-(1-. Acid-fragmented teichuronic acid, after conversion to the phenylamine derivative, was fractionated by preparative-scale molecular sieve column chromatography, which produced a series of elution peaks. Fast-atom-bombardment mass spectrometry of the smallest member of the series determined its molecular weight and established its identity as the phenylamine derivative of one disaccharide repeat unit of teichuronic acid. Homologous fractions of the same series were used to index the ladder of bands obtained by polyacrylamide gel electrophoresis from samples containing a more extensive distribution of polymer lengths. Nearly native teichuronic acid consists of polymers with a broad range of molecular sizes ranging from 20 to 55 disaccharide units. The most abundant species are those which have 25 to 40 repeat units. Prolonged treatment of teichuronic acid with the acid conditions used to release it from peptidoglycan causes gradual fragmentation of the teichuronic acid.

Carbohydrate Sequence↗
PubMed1990

Biosynthetic elongation of isolated teichuronic acid polymers via glucosyl- and N-acetylmannosaminuronosyltransferases from solubilized cytoplasmic membrane fragments of Micrococcus luteus.

Cytoplasmic membrane fragments of Micrococcus luteus catalyze in vitro biosynthesis of teichuronic acid from uridine diphosphate D-glucose (UDP-glucose), uridine diphosphate N-acetyl-D-mannosaminuronic acid (UDP-ManNAcA), and uridine diphosphate N-acetyl-D-glucosamine. Membrane fragments solubilized with Thesit (dodecyl alcohol polyoxyethylene ether) can utilize UDP-glucose and UDP-ManNAcA to effect elongation of teichuronic acid isolated from native cell walls. When UDP-glucose is the only substrate supplied, the detergent-solubilized glucosyltransferase incorporates a single glucosyl residue onto each teichuronic acid acceptor. When both UDP-glucose and UDP-ManNAcA are supplied, the glucosyltransferase and the N-acetylmannosaminuronosyltransferase act cooperatively to elongate the teichuronic acid acceptor by multiple additions of the disaccharide repeat unit. As shown by polyacrylamide gel electrophoresis, low-molecular-weight fractions of teichuronic acid are converted to higher-molecular-weight polymers by the addition of as many as 17 disaccharide repeat units.

Cell Fractionation↗
PubMed1990

Aspirin-independent antithrombotic effects of acutely attached cultured endothelial cells on endarterectomized arteries.

We have compared the acute antithrombotic effects of aspirin-treated versus normal endothelial cell (EC) coverage of endarterectomized baboon aortic segments (EAS) incorporated into chronic exteriorized arteriovenous shunts in baboons. Human ECs grown in culture were incubated in control medium or medium containing aspirin (100 mumols/ml) and then attached at saturation density by incubating EC suspensions (6 x 10(5) cells/100 microliters) within EAS for 20 minutes. Nonendarterectomized aortic segments and untreated EAS served as negative and positive controls, respectively. The inhibitory effect of aspirin treatment on EC production of prostacyclin was confirmed by radioimmunoassay of its stable metabolic breakdown product, 6-keto-prostaglandin F1 alpha in supernatant medium. Thrombus formation in vivo was measured as the accumulation of indium 111-labeled platelets on endarterectomy sites in real time by scintillation camera imaging. 111In-labeled platelets were deposited rapidly, reaching a plateau by 60 minutes of 4.40 +/- 0.89 x 10(9) platelets/cm, compared with 111In-labled platelet deposition on nonendarterectomized segments of 0.89 +/- 0.26 x 10(9) platelets/cm (p = 0.008). Coverage of EAS with normal cultured ECs significantly reduced platelet deposition on EAS (1.05 +/- 0.45 x 10(9) platelets/cm; p = 0.009 at 1 hour compared with EAS not incubated with ECs). Aspirin-treated ECs also produced a marked reduction in platelet disposition (0.71 +/- 0.24 x 10 platelets/cm; p = 0.007 compared with EAS without ECs) that was equivalent to the effect of non-aspirin-treated ECs (p greater than 0.5). Scanning and transmission electron microscopy confirmed the antithrombotic effects of attached ECs. We conclude that endarterectomy of normal arteries produces a highly thrombogenic surface and the thrombogenicity is abolished by acutely attaching cultured human ECs.

Animals↗