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Biomedical subjects

M A Neill

Publications and source records attributed to M A Neill.

27 records · Page 2Linked to original sources

The effect of phenolic glycolipid-1 from Mycobacterium leprae on the antimicrobial activity of human macrophages.

Purified PGL-1 and dPGL from M. leprae can prevent bacterial killing by intact phagocytes and cell-free antimicrobial systems. Both glycolipids completely abolished the antimicrobial effect of the acetaldehyde-XO-Fe2+ system. Because the cytotoxicity of this system is inhibited by catalase, SOD, mannitol, and ethanol, but not by heated SOD or catalase, these data suggest that toxicity is due to OH. generated by the Haber-Weiss reaction. That the antimicrobial killing in the XO system is completely blocked by the addition of PGL-1 or dPGL suggests that these glycolipids can act as OH. scavengers. A modest protective effect against the cytotoxicity of the MPO-H2O2-halide system by both PGL-1 and dPGL was also observed. The antimicrobial activity of the MPO system was abolished with chloride, but not iodide, as the halide. The effect of the M. leprae-derived glycolipid on bacterial killing by intact phagocytes was examined. Two linking antibodies were used to bind the dPGL to a rapidly growing test organism, S. aureus, a murine IgM mAb specific for the terminal glycoside of PGL-1, and a rabbit IgG anti-mouse IgM which bound the staphylococcal protein A via its Fc region. Examination by transmission EM of human monocyte-derived macrophages which had ingested staphylococci either coated with both antibodies and dPGL, or coated only with the IgG and IgM antibodies, demonstrated the presence of bacteria in phagosomes of control and IFN-gamma-activated macrophages. Activation of the macrophage monolayers by pretreatment with IFN-gamma markedly increased their staphylocidal activity. When dPGL coated staphylococci were ingested, killing by both control and IFN-gamma-activated macrophages was completely blocked. These results, suggesting that PGL-1 can scavenge reactive oxygen species and prevent microbial death within the phagosome, may in part explain the intracellular survival of M. leprae in certain cell types.

Antigens, Bacterial↗

Escherichia coli O157:H7 as the predominant pathogen associated with the hemolytic uremic syndrome: a prospective study in the Pacific Northwest.

During a 12-month period, 14 patients with the hemolytic uremic syndrome were identified in a prospective study of enteric pathogens associated with this disorder. Of the 12 patients with a diarrheal illness preceding the onset of hemolytic uremic syndrome, fecal Escherichia coli O157:H7 was detected in seven (58%), all of whom had bloody diarrhea. Half of the siblings of these patients had concurrent nonbloody diarrhea. No source for infection with this organism was identified. Enteric infection with E coli O157:H7 occurs in the majority of cases of hemolytic uremic syndrome following diarrheal illness in the Pacific Northwest and may represent a previously overlooked cause of hemolytic uremic syndrome in other locales. Evaluation of all cases of hemolytic uremic syndrome for enteric pathogens should routinely include cultures for E coli O157:H7 until results of additional studies clarify the distribution of agents associated with hemolytic uremic syndrome in different geographic regions. These findings may provide new opportunities for the design of therapeutic and preventive strategies in this disorder.

Adolescent↗

Oxidative degradation of leukotriene C4 by human monocytes and monocyte-derived macrophages.

Freshly isolated 2-h adherent normal human monocytes, when stimulated, degrade added leukotriene C4 (LTC4) by a myeloperoxidase (MPO) and H2O2-dependent mechanism. Among the stimuli effective in this regard are phorbol myristate acetate (PMA), the calcium ionophore A23187, opsonized zymosan, and N-formyl-methionine-leucine-phenylalanine (FMLP) when combined with cytochalasin B. The predominant products formed are the all-trans isomers of LTB4, 5-(S), 12-(R)-6-trans-LTB4 and 5-(S),12-(S)-6-trans-LTB4. Degradation is inhibited by azide and catalase, but not by superoxide dismutase. LTC4 degradation does not occur when MPO-deficient monocytes are used, unless MPO is added. Stimulated monocytes from patients with chronic granulomatous disease also are unable to degrade LTC4 under these conditions. Normal monocytes maintained in culture lose their ability to degrade LTC4. The addition of MPO to monocyte-derived macrophages increases degradation, particularly when the monolayers are pretreated with gamma-interferon. The oxidative degradation of LTC4 is a capacity shared by neutrophils, eosinophils, and mononuclear phagocytes, and may be an important mechanism for the modulation of leukotriene activity in inflammatory lesions.

Calcimycin↗

Nosocomial legionellosis, Paris, France. Evidence for transmission by potable water.

During a five-week period in 1981, six cases of legionellosis due to Legionella pneumophila serogroup 1 were recognized in a hospital in Paris, France. Four cases were clearly nosocomial in origin. There was a direct association between development of disease and exposure to potable hot water (p = 0.003). The entire hot water system was contaminated with L. pneumophila serogroup 1; monoclonal antibody testing demonstrated that the case isolate and the potable water isolates belonged to the same subgroup. Although serogroup 1 was isolated from both the cooling tower and its drift, the cooling tower isolate was antigenically distant from the case isolate. In other nosocomial outbreaks of legionellosis, multiple sources have been found within the hospital environment, but an epidemiologic association of disease with potable water had not been shown. The significant association of cases with exposure to the potable hot water supply, and the identification of case and potable water isolates of the same subtype, suggest that the potable hot water was responsible for transmission of disease in this outbreak.

Adult↗

Interaction between the posterior pituitary and LHRH in the control of LH secretion.

We have recently reported that the posterior lobe of the pituitary differentially inhibits the secretion of prolactin (PRL) and luteinizing hormone (LH), but not follicle stimulating hormone (FSH) throughout the estrous cycle. Removal of the posterior pituitary (posterior pituitary lobectomy) results in elevations of plasma LH on all days of the cycle except on diestrus-day-2. In the present study we examined: whether the control of LH release involves an interaction between the posterior pituitary and hypothalamic luteinizing hormone-releasing hormone (LHRH), and whether the elevation of LH seen following posterior lobectomy is due to the removal of a posterior pituitary substance(s) which alters anterior pituitary sensitivity to LHRH. In order to block the action of hypothalamic LHRH, a potent LHRH inhibitory analog (50 micrograms) was injected SC two hours prior to removal of the posterior pituitary in estrous rats. Administration of the inhibitory analog completely eliminated the elevation of plasma LH seen following posterior lobectomy, but did not alter the posterior lobectomy-induced rise of plasma PRL, or plasma FSH concentrations. In order to test whether anterior pituitary sensitivity to LHRH is altered by posterior lobectomy, a moderate dose of LHRH (15 ng) was administered to both posterior lobectomized and sham lobectomized estrous rats. The time-course and magnitude of the LH response to LHRH was similar in both groups. The results are consistent with the hypothesis that LH secretion is controlled by an interaction between hypothalamic LHRH and the posterior lobe of the pituitary, but this interaction does not appear to involve lobectomy-induced changes in anterior pituitary responsiveness to LHRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Leprosy in the United States, 1971-1981.

In the period 1971-1981, 1,835 cases of leprosy were reported in the United States; only 10% of these cases were indigenous. Since 1977, the number of new cases reported each year has risen because of an increase in imported cases of disease, a situation reflecting the increased number of refugees and immigrants who have entered the United States from areas endemic for leprosy. Forty-five of the 50 states reported cases. In only 25% of the imported cases were the patients known to have had leprosy at the time of immigration; the remaining 75% were diagnosed in this country. The highest rate of disease onset for this latter group occurred within 12 months after entry into the United States, but cases continued to be reported 10 years after entry. Active refugee resettlement programs have widely distributed persons with leprosy, contacts of diseased persons, and persons from endemic areas throughout the 50 states, a situation necessitating the development of expertise by medical professionals and public health officials in the diagnosis, treatment, and long-term follow-up of patients with leprosy.

Adolescent↗

Hemorrhagic colitis with Escherichia coli O157:H7 preceding adult hemolytic uremic syndrome.

Escherichia coli serotype O157:H7 is a rarely identified organism that has recently been associated with hemorrhagic colitis in all age groups and with the hemolytic uremic syndrome (HUS) in children. We now report the development of HUS in two young women following enteric infection with E coli O157:H7. Both patients were hospitalized because of the severity of their colitis. They later developed major hemolysis requiring transfusion and significant renal failure requiring, in one case, hemodialysis. One patient underwent laparotomy, where sterile ascites, marked right colonic edema, and intraserosal hemorrhage were noted. Both women survived and are currently improving. Fecal E coli serotype O157:H7 was sought only after routine cultures were negative and features of HUS were recognized. The search for the E coli was facilitated by the continued availability of stool cultures obtained early in the course of the illness. The source of infection was not ascertained, but ingestion of untreated water was a feature of both cases. The HUS is a potential complication of the hemorrhagic colitis associated with E coli serotype O157:H7 and may develop in adults as well as children following enteric infection with this organism.

Adult↗

Risk factors for development of toxic shock syndrome. Association with a tampon brand.

In September 1980, we interviewed by telephone 50 patients with menstrually associated toxic shock syndrome (TSS) who had onset of illness in July or August 1980. These women were asked to provide information about the type of menstrual sanitary products used during the menstrual period associated with their illness. We also interviewed 150 age-matched control subjects, who were asked the same questions for the menstrual period that occurred in the same month as the illness of the matched case. All 50 cases, but only 125 of 150 controls, used tampons. Among women using tampons, cases were more likely to have used Rely brand tampons when compared with controls. No differences were found between cases and controls in the absorbency of tampon products used. No other factors studied through analysis of a follow-up questionnaire mailed five months after the first study were found to be significantly associated with the development of menstrually associated TSS.

Female↗