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Biomedical subjects

M Moore

Publications and source records attributed to M Moore.

At least 415 records · Page 23Linked to original sources
PubMed1983

Critical aspects of immune complex assays employing polyethylene glycol.

Treatment of artificial immune complexes (ICs) with 2.5% polyethylene glycol (PEG)--conditions under which C1q-binding activity is routinely measured in the fluid phase--produced marked changes in molecular size as determined by Sepharose 6B chromatography. The effect of PEG on the C1q-binding capacity of ICs, was therefore investigated using a solid phase (SP) system. PEG enhanced the binding of aggregated human gammaglobulin (AHG) and artificial ICs to SP-C1q and, in reverse experiments, also increased the binding of C1q to SP-AHG. The degree of enhancement varied according to the Ag:Ab ratio employed; the binding of ICs formed in moderate Ab excess was only modestly enhanced but that of complexes formed at slight Ab excess, equivalence and Ag excess was markedly elevated. The profile of PEG-induced enhancement of binding paralleled that of similar ICs in the C1q fluid phase system, suggesting that C1q binding in the latter may be influenced by PEG. However, the C1q-binding activity of in vivo-formed ICs seemed to be relatively unaffected by PEG since enhanced binding was comparable in control and pathological sera. The results indicate that PEG causes cross-linking and aggregation of ICs (and possibly other serum proteins) which may alter their biological activity and hence influence the results of IC assays that employ this agent.

Antigen-Antibody Complex↗
PubMed1983

Coat protein conformation in M13 filaments, I-forms and spheroids.

Circular dichroism studies of the filamentous coliphage M13 were carried out to determine conformational changes in the major capsid protein (the B protein) that occur during contraction of the filaments to I-forms and spheroids. The alpha-helicity of the B protein is somewhat lower in the I-forms than in filaments and much lower in spheroids. This conformational change may explain the increased detergent and lipid solubility of both I forms and spheroids relative to filaments.

Capsid↗
PubMed1983

Aseptic meningitis and high school football players. 1978 and 1980.

During 1978 and 1980, epidemiologists at the Centers for Disease Control investigated seven outbreaks of aseptic meningitis-like illness (AMLI) occurring in high school football players in four different states. One or more enterovirus types were isolated from affected students at all seven schools. Attack rates were highest among the varsity football teams (range, 21% to 68%), although junior varsity teams were also affected at most schools (range, 5% to 63%). Non-football athletes were relatively spared. The illness was also reported by nonathletes at all three schools where more extensive investigations were undertaken. At one school, the AMLI attack rate was higher among students who were close friends of football players than among students who were not close friends; at the other two schools, these rates were similar. Hospitalization was more likely for football players with AMLI than for affected nonfootball players. Transmission of enteroviruses among football players was probably from person to person, although there was additional evidence to implicate common vehicle transmission at two schools. We conclude that football players may or may not have been more likely to be exposed to the enteroviruses circulating in their communities, but once introduction of a virus into a team occurred, transmission potential may have been enhanced, resulting in a large number of AMLI cases in players.

Disease Outbreaks↗
PubMed1983

Limitations of immune complex measurements in colorectal disease.

Three techniques (Clq, Raji and L1210 binding assays) alleged to measure circulating immune complexes (ICs) were applied to the sera of 101 patients with colorectal disease (54 carcinoma; 23 inflammatory; 13 benign tumour and 11 miscellaneous) at the time of diagnostic or definitive surgery, and 58 healthy adult controls. Elevated levels in the pathological sera were observed by all 3 methods in order of sensitivity: Raji greater than Clq greater than L1210. However, none of them differentiated between benign, inflammatory and neoplastic conditions nor, in the case of colorectal carcinoma, was there any correlation with stage of disease. With the exception of Raji v. L1210 (r = 0.43, P less than 0.001), correlations between the various assays were poor and levels of serum carcinoembryonic antigen (CEA) did not correlate with ICs measured by any of the techniques. Indeed, the IC assays were even less discriminatory than CEA, which was elevated mainly in the serum of carcinoma patients and which was positively correlated with serum gamma-glutamyl transpeptidase (gamma GT) (r = 0.42, P less than 0.005). The data suggest that the lack of concordance between the IC assays is a reflection of heterogeneity among ICs, interfering factors present in pathological sera, or both. Thus the IC assays deployed here have neither diagnostic nor prognostic utility in colorectal disease at this time, and immunochemical characterization of the serum reactive material detected by the different assays is required.

Adult↗
PubMed1983

Native and inducible levels of natural cytotoxicity in lymph nodes draining mammary carcinoma.

Lymphocytes isolated from axillary nodes draining breast carcinoma possess variable natural cytotoxic capacity. Augmentation of lymph node cell (LNC) cytotoxicity by interferon (IFN) is also variable, with only some populations displaying potentiated lysis following exposure to either IFN-a or gene-cloned IFN-a2. Where present the IFN-induced augmentation of LNC cytotoxicity was invariably weaker than that observed following similar treatment of autochthonous peripheral blood mononuclear cells (PBMC). Irrespective of their responsiveness to IFN the cytotoxic activity of all LNC preparations examined was significantly increased following pre-incubation with either staphylococcal enterotoxin A (SEA) or factors elaborated by lectin-pulsed allogeneic LNC. THe induction or amplification fo LNC-mediated natural cytotoxicity by lymphokines may provide a local potentiation of natural immune function at the host : tumour interface.

Breast Neoplasms↗
PubMed1983

Postmastectomy adjuvant chemotherapy with or without radiation therapy in women with operable breast cancer and positive axillary lymph nodes: the Southeastern Cancer Study Group experience.

Between September 1976 and June 1982, 308 patients with operable breast cancer with 1-3 involved axillary nodes were stratified according to institution, type of mastectomy, and time from surgery to protocol entry, and then randomized to receive either six or 12 months of adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). With a median time of follow-up of 33 months, relapse rates among 181 reviewed and evaluable patients are 20/85 (23.5%) for pre- and 23/96 (24%) for postmenopausal patients. Results for premenopausal women, while better than historical controls at a similar time interval, appear inferior to other published adjuvant studies (e.g., NSABP and Milan). Although total relapse rates were 23/100 (23%) for six months and 20/81 (25%) for 12 months of therapy, suggestive differences were encountered by menopausal status with early trends favoring 12 months of treatment for premenopausal patients and six months of treatment for postmenopausal patients. During this same period, 283 patients with four or more involved axillary nodes were randomized to 1-3 treatment arms: six months of CMF, six months of CMF preceded by local-regional x-ray therapy (XRT), or 12 months of CMF. The latter arm was closed in February 1980 while the two six-month chemotherapy arms remain open as of January 1983. Relapse rates for 174 reviewed and evaluable patients on the three arms include: 27/76 (36%) for six months CMF, 15/54 (28%) for XRT and CMF, and 24/44 (45%) for 12 months CMF. Local-regional relapse rates were 12/120 (10%) for the combined two non-XRT arms and 3/54 (6%) for the XRT treatment arm (p = 0.34). Thus, at this early stage of follow-up there are still no statistically significant differences between six or 12 months of adjuvant CMF therapy and neither definite beneficial nor detrimental effects of prechemotherapy adjuvant radiation therapy. Longer follow-up will be needed to provide definitive conclusions.

Adenocarcinoma↗
PubMed1983

Intakes of copper, zinc, cadmium, tin, iron, nickel and arsenic in a population exposed to lead from water.

Adult diets obtained from a population in Ayr, Scotland, U.K., known to be exposed to lead from water were analysed for arsenic, cadmium, copper, iron, nickel, tin and zinc to assess the intake of these elements. With few exceptions, the concentration of each element varied little from diet to diet, and therefore the range of intakes varied only in proportion to the weights of the diets. With the exception of nickel, the difference between the observed average dietary intakes of the metals studied and those expected on the basis of a nationwide Total Diet Study is largely accounted for on the basis of the differences between the weights of the duplicate diet and the weight for the Total Diet Study.

Adult↗
PubMed1983

Southeastern Cancer Study Group: breast cancer studies 1972-1982.

During the past 10 years, the Southeastern Cancer Study Group (SECSG) has been engaged in one major adjuvant study and three major advanced disease studies for patients with adenocarcinoma of the breast. The adjuvant study is demonstrating that six months of adjuvant CMF is the therapeutic equivalent of 12 months and that post-operative irradiation is of no added therapeutic benefit. In patients with advanced disease, a low dose 5 drug combination of CMFVP induces more objective responses than single agent 5FU, but improves survival only for those patients with liver metastases when compared to the sequential use of the same 5 single agents. The three drug combination, CAF, utilizing doxorubicin, induces more objective responses than low dose CMFVP, but it does not improve overall survival. The subsets of patients with bone-only metastases, with local chest wall recurrence and with nodular lung metastases benefit from CAF in terms of a longer duration of disease control and longer duration of unmaintained remission, but have only a marginal improvement in survival. The addition of a phase active combination, CAMELEON, (i.e., sequentially alternating therapy) to CAF has not improved the duration of disease control and survival for patients with liver metastases, lymphangitic and nodular lung metastases compared to CAF. Aggressive combination chemotherapeutic approaches to patients with advanced disease provide better and longer disease and tumor control but only marginal improvements in overall survival. Adding additional agents to a maximally tolerable regimen has not improved the therapeutic outcome.

Adult↗
PubMed1983

Epidemiologic investigations of dengue infection in Mexico, 1980.

A binational investigation was conducted in two Mexican cities in 1980 to study epidemiologic characteristics of dengue. Two study areas were selected in each of the cities (Merida and Tampico); in each area, in February and in September, sanitarians recorded information concerning abundance of Aedes aegypti, and public health nurses obtained blood specimens and clinical information from residents. Ninety-nine individuals (24% of the study population) showed serologic evidence of recent dengue 1 infection by hemagglutination inhibition or complement fixation. Infection rates in the four study areas (9%-51%) increased with age in three of the four areas and were higher in females in all four areas. These differences in rates may be related to exposure to infectious mosquitoes in the home; A. aegypti feed most actively during daylight hours, and both females (p less than 0.001) and older individuals (p less than 0.001) were more likely than males or younger persons to be in the home when the study was conducted. A positive correlation was found between infection rates and the container index (number of potential A. aegypti breeding sites per premise--Pearson correlation coefficient 0.95, p = 0.05), suggesting that this index may be a useful predictor of neighborhoods at high risk of dengue transmission. Pending additional studies, public cleanup campaigns should be targeted to neighborhoods in which container indices are highest when an outbreak of dengue is likely to occur.

Adolescent↗
PubMed1983

Naturally cytotoxic tonsillar lymphocytes: a manifestation of heterogeneity among human NK cells.

Lymphocytes isolated from human tonsils are capable of lysing cells of the natural killer (NK)-susceptible line K562. Although weak compared with that of autochthonous peripheral lymphocytes, cytotoxicity is invariably manifest at high effector-to-target ratios. Like peripheral NK cells, tonsillar cytotoxic lymphocytes possess a low buoyant density, which makes possible their partial enrichment from non-cytotoxic cells by centrifugation on discontinuous Percoll gradients. However, examination of cytotoxic fractions indicates that, unlike blood lymphocyte-mediated cytotoxicity, effector function is not associated with the presence of large granular lymphocytes. Furthermore, a functional distinction from classical NK cells is apparent since, although tonsillar cytotoxicity is significantly enhanced after exposure to supernatants from polyclonally activated allogeneic tonsils, pretreatment with lymphoblastoid (Namalva) interferon (IFN-alpha) at doses shown to potentiate maximally the cytotoxicity of peripheral blood lymphocytes fails to influence reactivity. These data provide preliminary evidence for the existence of, at least limited, heterogeneity among human NK cells.

Cell Separation↗
PubMed1983

Ranitidine in the prevention of gastric and duodenal ulcer relapse.

Prophylactic maintenance therapy for one year using ranitidine 150 mg at night or a placebo was assessed in 68 patients whose gastric or duodenal ulcers had previously healed after therapy with ranitidine 150 mg twice daily or placebo. Gastroscopy was carried out on symptomatic relapse and at the end of the year. Of the duodenal ulcer group, seven out of 20 relapsed on ranitidine compared with 15 out of 17 on placebo (p less than 0.001). Of the gastric ulcer group one of 15 patients relapsed on ranitidine compared with 11 of 16 patients on placebo (p less than 0.005). There were no adverse effects from ranitidine during the trial period. Ranitidine in low dose maintenance therapy is therefore reasonably effective in the prevention of relapse of duodenal ulcers and appears to be particularly effective in preventing relapse of gastric ulcers at least for one year. As gastric ulcers occur more frequently in the older patients in whom there are often medical contraindications to surgery, maintenance treatment may be appropriate for many such patients.

Adult↗
PubMed1983

Human K cell-mediated haemolysis: determination of the cytotoxic capacity and antibody sensitization requirements of T lymphocyte enriched and depleted populations.

We have examined the cytotoxic activity of unfractionated peripheral blood lymphocytes (PBL) and T cell-enriched and depleted populations for human red blood cells (HRBC) sensitized with anti-D. Although K cell function was frequently enriched in non-sheep red blood cell (SRBC) rosetting (E-) fractions in some cases cytotoxic activity was equivalent in SRBC rosetting (E+) and non-rosetting cells or greater in E+ populations. The distribution of antibody induced haemolytic activity was similar, but not identical, to that of natural killer (NK) cell-mediated lysis. The sensitization requirements of E- and E+ populations measured as the concentration of anti-D capable of inducing 50% of maximum lysis (Ab50) were similar or identical. In addition it was apparent that the differences in cytolytic potential of E- and E+ are quantitative rather than qualitative since E+ cells exhibited lytic profiles equivalent to E- populations following increase of the effector cell concentration. Despite the similar antibody requirements of E- and E+ effectors these populations exhibited markedly different sensitivity to inhibition of haemolysis by heat-aggregated gammaglobulin (HAG). We conclude that functional K cells are variably distributed between E- and E+ populations and that differences in cytotoxic activity are a reflection of the relative number of effector cells in each fraction. The differences in the sensitivity of E- and E+ K cells to HAG do not influence the apparently identical sensitization requirements of the 2 populations, possibly because receptors for aggregated IgG are independent of those involved in the induction of ADCC.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1983

The relationship between antibody concentration and target cell number in the induction of K cell-mediated haemolysis: evidence for asymmetry among reactants.

The cytotoxic capacity of peripheral blood mononuclear cells for anti-D sensitized human O Rh(D) + ve (R1R2) erythrocytes was measured under conditions where antibody concentrations and target cell number were varied with respect to each other. It was observed that where sensitization was limiting, due either to target cell excess or increased antibody dilution, the relationship between lysis and antibody concentration was non-linear, and that the end-point dilution of anti-D at which measurable cytotoxicity occurred was dependent upon the source or concentration of effector cells. The asymmetrical relationship between cytotoxic activity and the degree of sensitization suggests that, in this system at least, there is extensive heterogeneity either among target erythrocytes in terms of their degree of sensitization and consequent susceptibility to lysis, and/or among effector cells in terms of their sensitization requirements for induction of cytotoxicity.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1983

Reactivity of low molecular weight material in cellular immune complex assays.

A major difference in molecular size of material reactive in the C1q binding assay and two cellular assays (Raji and L1210) for immune complexes, is reported. Elevated C1q binding of pathological sera was associated with material in the range 7-19S, as determined by Sepharose 6B chromatography of sera from patients with chronic inflammatory and neoplastic lung diseases. By contrast, reactivity of identical sera in the Raji and L1210 assays was linked predominantly with material of molecular size 7S. Dissociation of immune complexes on storage and/or in consequence of the chromatographic procedure was effectively discounted. Furthermore, differential binding of 7S IgG fractions tested at a standard concentration indicated that reactivity in either test was not attributable to non-specific binding of IgG. In a previous study, saturation of FcR (on L1210 and Raji) and C3R (on Raji only) by heat-aggregated IgG failed to distinguish whether binding directly involved these receptors or other cell surface components. In the present investigation, no firm correlations emerged between reactivity in the two tests and possible candidate antibodies reactive with cell surface components such as anti-lymphocyte and anti-nuclear antibodies. It is therefore suggested that low molecular weight binding may be attributable to more than one factor including 7S IgG (immune complex dissociated, or otherwise), autoantibodies, IgG-C3 complexes and possibly very small immune complexes (Ag1, Ab1). The assumption that Raji and L1210 and possibly other cellular assays detect only high molecular weight immune complexes is questionable and the need for further characterization of other reactive material is emphasized.

Antibodies, Antinuclear↗
PubMed1983

Regulation of natural and antibody-dependent cellular cytotoxicity by staphylococcal enterotoxin A.

The capacity of staphylococcal enterotoxin A (SEA), a potent T cell mitogen and inducer of interferon-gamma (IFN-gamma), to modulate human lymphocyte cytotoxic function has been examined and compared with the influence of purified and/or gene cloned IFN-alpha. While the natural killer (NK) cell function of peripheral blood lymphocytes is significantly augmented after exposure to IFN-alpha, levels of cytotoxicity were even greater following pre-treatment with optimal concentrations (0 X 1 microgram/ml) of SEA. Moreover lymphocyte (K cell)-mediated antibody-dependent cellular cytotoxicity (ADCC), which is uninfluenced by exposure to IFN-alpha, was, in most instances, potentiated by SEA. However the efficacy with which SEA augmented natural cytotoxic function was most apparent from experiments utilizing extravascular lymphoid effectors in which basal NK activity is weak and the response to IFN-alpha variable (in the case of lymph node cells) or undetectable (in the case of tonsillar lymphocytes). Co-fractionation on Percoll gradients of lymphocytes responding to SEA with native NK cells suggested that SEA affects NK cells or their non-cytolytic precursors possibly by elaboration of soluble mediators rather than by the induction of a ligand binding mechanism analogous to lectin-dependent cytotoxicity. This system could have important implications for the regulation of NK cell function by lymphocyte stimulatory factors, particularly in lymphoid tissues where indigenous NK activity is low and relatively unaffected by IFN-alpha.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1983

Effect of simple sugars on natural killing: evidence against the involvement of a lectin like mechanism in target recognition.

The spontaneous lysis of target cells sensitive to natural killer (NK) activity is accomplished in two distinct phases: (i) binding between target and effector cells and (ii) post-binding events leading to target cell destruction. To test the hypothesis that cell surface carbohydrate(s) might be involved in recognitive and/or lytic events, the binding and cytotoxicity of peripheral blood lymphocytes (PBL) towards NK sensitive K-562 targets was studied in the presence of simple sugars and after treatment of the targets with the antibiotic, tunicamycin. Lysis by peripheral blood lymphocytes was found to be inhibited by N-acetyl glucosamine, N-acetyl galactosamine and alpha-methyl mannoside in a dose-dependent manner under conditions where neither these sugars nor those (fucose, galactose) which had little effect on lysis inhibited the binding of effector cells to targets. Further, growth of K-562 in tunicamycin (which inhibits N-linked glycosylations occurring through the lipid intermediate pathway) with or without subsequent treatment with the enzyme neuraminidase, markedly reduced cell surface expression of sugars monitored by lectin binding. Treated cells showed no loss of NK susceptibility and were frequently more sensitive to lysis. Sugar inhibition profiles were the same as for untreated cells. These data suggest that carbohydrates are not the target sites of NK recognition but that simple sugars may have an inhibitory action at a later stage of the lytic process.

Acetylgalactosamine↗
PubMed1982

Healing of gastric ulcers after one, two, and three months of ranitidine.

Ranitidine (150 mg twice daily) was compared with placebo in 42 patients with gastric ulcer. The study was conducted as a double-blind trial for one month, followed by an open assessment of one, two, and three months of ranitidine in the patients with persistent ulceration. Thirty-eight patients completed the double-blind trial. Repeat endoscopy confirmed complete healing in 16 of the 21 who had received ranitidine and five of the 17 who had received placebo (p less than 0.01). The remaining 17 patients with persistent ulceration participated in the open assessment. The combined cumulative healing rates of ranitidine at four, eight, and 12 weeks were 73%, 88%, and 97%. There were no adverse effects or unusual reasons for withdrawal from the study (four patients). Ranitidine appears to be a safe and highly effective treatment of gastric ulceration, with about 90% of ulcers healed after eight weeks.

Adolescent↗