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Biomedical subjects

L Hammond

Publications and source records attributed to L Hammond.

18 recordsLinked to original sources

Negative regulation of Scl-70/topoisomerase I by zinc and an endogenous macromolecule.

Scl-70/topoisomerase I (topo I), a target of autoantibodies in the human disorder scleroderma, may be linked to collagen overproduction. We report that physiologic concentrations of zinc (greater than or equal to 80 microM) potently inactivate human and rat topo I in the presence of a 125-fold molar excess of MgCl2. We also describe a highly acidic nuclear molecule which competitively inhibits topo I. 89kD complexes of topo I and inhibitor can be separated from active 70kD monomers by glycerol density gradient centrifugation. The complexes have a 20-fold higher Km for DNA than monomers. Dissociation by dilution results in a 50-fold increase in rat liver and a 47-fold increase in human fibroblast specific activity. Zinc inhibition is non-competitive, and independent of the endogenous inhibitor. Our studies suggest that the majority of topo I is normally maintained in an inactive state by physiologic inhibitors, and loss of negative regulation may have pathogenetic consequences.

Animals

A survey of Tourette syndrome patients and their families: the 1987 Ohio Tourette Survey.

A large sample of patients (N = 763) with Tourette syndrome (TS) responded to a questionnaire dealing primarily with symptoms, treatment history, and associated disorders. The shrinking duration between symptom onset and diagnostic confirmation confirms that diagnostic awareness of TS is increasing. A significant proportion of the sample identified several common factors that occurred in the year before symptom onset. A significantly lower proportion of subjects whose initial symptoms included facial tics reported a positive response to haloperidol. Obsessive characteristics were associated with age and were more common in females. Patients with attention deficit disorder (ADD) had earlier age at onset of TS symptoms and were diagnosed earlier than patients without ADD. In general the data provide some support for a stress-diathesis model and also support previous suggestions about the genetics of Tourette syndrome and related conditions.

Adolescent

Antibiotic resistance in general practice.

With the addition of several new oral antibiotics to those already available, there is the implication that bacterial resistance has become a significant problem in general practice. To test this hypothesis it is worth examining the susceptibilities of the major bacterial pathogens isolated from community based infections.

Adolescent

AIDS and hepatitis B. Protection strategies.

Everyone must be concerned to prevent the spread of AIDS, for which there is no effective treatment and no likelihood of an early vaccine. Infection control measures that have been developed to prevent the spread of hepatitis B virus can be used to protect health care workers against the human immunodeficiency viruses that cause AIDS. The current infection control recommendations are discussed in this article.

Acquired Immunodeficiency Syndrome

Office sterilisation.

An autoclave is the most efficient method of sterilising reusable medical instruments. Even so, great care must be exercised in the cleaning of equipment prior to moist heat sterilisation and in the care of the autoclave.

Family Practice

Influence of tumor necrosis factor-alpha on the modulation by interferon-gamma of HLA class II molecules in human thyroid cells and its effect on interferon-gamma binding.

Cytokines are important modulators of immunological reactions, but it has been postulated that they might act on other unrelated epithelial cells. We studied the effects of recombinant interferon-gamma (rIFN gamma) and recombinant tumor necrosis factor-alpha (rTNF alpha) on normal human thyroid cells. We found that the combination of these two cytokines enhanced HLA class II molecule expression on these cells compared with the effect of rIFN gamma alone. This was proven by both immunofluorescence as well as a more sensitive and quantitative RIA. rTNF alpha alone had no effect on HLA class II molecule induction on the same thyrocytes, suggesting a synergistic rather than an additive action in combination with rIFN gamma. The addition of 600 U/ml rTNF alpha to low dose rIFN gamma (10 U/mL) enhanced class II expression by 50%, as quantified by RIA. We also demonstrated that normal thyrocytes possess distinct receptors for the two cytokines and that rTNF alpha probably augments IFN gamma binding, since it increased when the cells were first incubated with rTNF alpha. This increased binding provides an explanation for the synergistic action of rTNF alpha in enhancing class II molecule expression by rIFN gamma. We conclude that the presence of receptors for these cytokines on human thyroid cells gives a direct demonstration of their potential biological action on cells normally not involved in the immunological circuit. The phenomenon might also explain their direct or indirect involvement in vivo, such as in influencing inappropriate HLA class II molecule expression in epithelial cells affected by autoimmunity.

Binding Sites

Gastric cell c-AMP stimulating autoantibodies in duodenal ulcer disease.

Gastric cell c-AMP stimulating antibodies (GCS-Ab) were studied in 30 patients with duodenal ulcer (DU) disease. Semipurified immunoglobulin (Ig) preparations from 13/30 patients stimulated c-AMP production in parietal cell enriched gastric cell suspensions obtained from male guinea pig stomachs. Maximum stimulation (varying between 260 and 547%) was reached after four hours incubation with 2 and 4 mg/ml Ig concentrations. The 13 patients with gastric cell stimulating antibodies (GCS-Ab), all male patients, developed the disease at a younger age (nine of 13 under the age of 30), had a longer duration of symptoms (mean 18.4 years), and had a higher incidence of DU in their families (61%). Eight of 13 (61%) in the GCS-Ab+ group did not respond to anti-H2-R drugs, whereas in the negative patients only three of 17 (18%) were classified as 'non-responders'. Remarkably few conventional autoantibodies were detected in our series. Gastric cell stimulating antibodies are a new addition to the growing list of receptor antibodies in human diseases and the described in vitro test should provide an easier tool for screening large populations.

Adult

Prostatitis.

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Humans

Preoperative cervical dilatation: a trial of laminaria tents and prostaglandin F2 alpha gel.

Surgical damage to the cervix in patients undergoing termination of pregnancy may be responsible for serious complications in subsequent pregnancies. Sixty nulliparous women undergoing first trimester termination of pregnancy were randomly allocated to 3 treatment groups, one using laminaria tents preoperatively, one using intracervical PGF2 alpha gel preoperatively and one using no pretreatment. Results showed clear benefits in the laminaria group, in terms of achieving preoperative cervical dilatation and ease of further operative dilatation. Laminaria tents were superior to PGF2 alpha gel which was, in turn, superior to no pretreatment. There were no differences in blood loss or postoperative complications among the 3 groups. Laminaria tents provide a cheap, effective and safe method of reducing the risk of cervical damage in women undergoing surgical termination of pregnancy.

Abortion, Induced

Characterization of monoclonal antibodies directed towards the microsomal/microvillar thyroid autoantigen recognized by Hashimoto autoantibodies.

Monoclonal antibodies reacting with thyroid microsomes have been described. In this report, we present evidence that some of these monoclonal antibodies (MoAb) MAH C3 and perhaps MAH C6 are directed towards the thyroid microsomal antigen towards which microsomal autoantibodies from Hashimoto patients are directed. Immunofluorescence on cryostat sections with MAH C3 and MAH C6 on thyroid gland gave cytoplasmic staining patterns that were comparable to those obtained with autoantibodies. By western blotting, reactivity of MAH C3 was shown to be directed towards a 105,000 mol. wt component, comparable to that recognized by autoantibodies by immunoprecipitation. Double immunofluorescence with MAH C3 and autoantibodies on cultured, viable thyroid monolayers revealed a large number of comparable binding sites; in contrast, binding sites for asioloagalactothyroglobulin were different of binding of MAH C3 by the autoantibodies suggesting that the epitopes recognized were different. This was confirmed with the use of a rat thyroid cell line FRTL-5 and fluorescence activated cell sorter analysis which showed binding to the rat microsomal component with autoantibodies but negligible binding with MAH C3 and MAH C6. It therefore appears that the monoclonal antibodies recognize species specific determinants while the autoantibodies recognize species cross reactive determinants. These monoclonal antibodies will be useful for purification and immunochemical analysis of this autoantigen in human thyroid disease.

Animals

Structural features of the autoantigens involved in thyroid autoimmune disease: the thyroid microsomal/microvillar antigen.

The microsomal/microvillar antigen of the human thyroid gland which provokes thyroid autoimmunity was characterised by immunoprecipitation studies. Sera from patients with Hashimoto's thyroiditis, primary myxoedema or Graves' disease containing autoanti-microsomal antibody specifically precipitated a component, which under reducing conditions migrates with a mol. wt of 105,000 on SDS-polyacrylamide gel electrophoresis. This protein was absent in auto- or xeno-anti-thyroglobulin precipitates, which under reducing conditions display four polypeptides of Mr 260,000, 230,000, 180,000 and 142,000. Under non-reducing conditions, the microsomal/microvillar antigen displayed a small shift in mobility to a mol. wt of 117,000 suggesting the presence of intrachain disulphide bonds. In contrast, under these conditions, anti-thyroglobulin precipitated components displaying polypeptides of approx. mol. wts in the region of 240,000-260,000, 170,000-180,000 and 140,000. Absorption of thyroiditis sera on thyroglobulin-Sepharose followed by immunoprecipitation abolished the anti-thyroglobulin components without affecting the binding of the 105,000-dalton polypeptide, if the sera contained antimicrosomal antibody. No comparable material was identified in microsomal membrane preparations prepared from the stomach which is also commonly involved in organ-specific autoimmunity. The 105,000-dalton component does not bind to a Lens culinaris lectin affinity column. We conclude that the epitopes of the microsomal/microvillar antigen are presented on a poorly glycosylated peptide of mol. wt 105,000, which is probably stabilised by intrachain disulphide bonds and which does not share serological reactivity with membrane-bound thyroglobulin.

Antigens