Biomedical subjects

H C Meeker

Publications and source records attributed to H C Meeker.

28 records · Page 2Linked to original sources

PubMed1989

Analysis of human antibody epitopes on the 65-kilodalton protein of Mycobacterium leprae by using synthetic peptides.

In order to study antibody reactivity to the Mycobacterium leprae 65-kilodalton (kDa) antigen, peptides representing overlapping sequences of the 65-kDa protein were synthesized, and a recombinant protein expression system for r65-kDa was constructed. Mouse monoclonal antibodies and leprosy patient seroreactivity to peptides and r65-kDa were tested by an enzyme-linked immunosorbent assay. All seven of the monoclonal antibodies used in this study reacted with their previously defined epitopes when tested against peptides. All monoclonal antibodies also reacted with r65-kDa. Leprosy patient seroreactivity to peptides and r65-kDa was seen in about one-third of active multibacillary cases. Specimens from patients positive for antibodies to peptides were seen to recognize different epitopes than did mouse monoclonal antibodies used in this study. It is concluded that substantial differences exist between mouse monoclonal antibodies and human leprosy patient reactivity to the 65-kDa antigen and that human seroreactivity to the 65-kDa antigen is indicative of a highly elevated bacillary load.

Amino Acid Sequence↗

PubMed1989

Testicular dysfunction in leprosy: relationships of FSH, LH and testosterone to disease classification, activity and duration.

Luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone levels were determined by radioimmunoassay (RIA) in leprosy patients and analysed for effect of disease classification, disease activity and duration of disease. LH and FSH levels were found to be significantly elevated in lepromatous patients compared to borderline-lepromatous, midborderline and borderline-tuberculoid patients. A positive correlation was seen between LH and FSH and a negative correlation was seen between testosterone and both LH and FSH. No correlation was seen between hormone levels and measures of disease activity: bacillary index and IgM to phenolic glycolipid I, a Mycobacterium leprae antigen. A significant correlation was seen between duration of disease and FSH when age was taken into account, indicating that testicular dysfunction is probably cumulative and irreversible. It is recommended that LL patients be routinely screened for hypogonadism using FSH, LH and testosterone levels.

Follicle Stimulating Hormone↗

PubMed1987

Mycobacterial carbohydrate antigens for serological testing of patients with leprosy.

To determine whether quantitation of antibodies to mycobacterial carbohydrate determinants would be valuable in serodiagnosis and monitoring of leprosy, we tested serum IgM antibody to Mycobacterium leprae phenolic glycolipid I and IgM and IgG antibodies to Mycobacterium tuberculosis and M. leprae lipoarabinomannan (LAM) by enzyme-linked immunosorbent assay. Seventy-one percent of patients with paucibacillary disease and 85.5% of patients with multibacillary disease were positive for at least one of the three antibodies. The 15% of antibody-negative patients with multibacillary disease were mostly long-term-treated patients, with inactive disease by biopsy. There was excellent agreement between M. tuberculosis LAM and M. leprae LAM in detection of antibodies. Bacillary index and levels of both IgG and IgM antibodies to LAM were positively correlated when all patients were analyzed. When patients with a history of erythema nodosum leprosum (ENL) were analyzed separately, there was no correlation between IgM or IgG antibody to LAM and bacillary index, a result suggesting a possible role for LAM in the pathogenesis of ENL.

Antibodies, Bacterial↗

PubMed1987

Defective monocyte chemotaxis in active lepromatous leprosy.

This study of monocyte chemotaxis in leprosy patients showed a significant inverse correlation (p less than 0.05) of chemotaxis and the bacterial index (BI) (N = 22). In addition, there was a significant inverse correlation (p less than 0.05) between chemotaxis and the serum levels of anti-phenolic glycolipid-I IgM antibodies (N = 20). Patients taking thalidomide who had a BI greater than or equal to 1 had a significantly greater (p less than 0.001) chemotaxis response than that of patients with the same BI who were not taking thalidomide. No significant decrease in chemotaxis of monocytes from healthy donors was observed when the cells were pre-incubated with serum from 18 leprosy patients. We conclude that monocytes from patients with active lepromatous leprosy not receiving thalidomide have an intrinsic abnormality when assessed by chemotaxis.

Antibodies, Bacterial↗

PubMed1986

IgM and IgG antibodies to phenolic glycolipid I from Mycobacterium leprae in leprosy: insight into patient monitoring, erythema nodosum leprosum, and bacillary persistence.

Serum IgM and IgG antibodies against Mycobacterium leprae-derived phenolic glycolipid I (PG) were determined in leprosy patients, contacts, and controls by enzyme-linked immunosorbent assay (ELISA). Anti-PG IgM levels increased from the tuberculoid (TT) to the lepromatous (LL) pole of the disease spectrum. There was a positive linear correlation between anti-PG IgM and bacillary index (BI). Patients with erythema nodosum leprosum (ENL) had lower levels of serum anti-PG IgM than non-ENL patients of comparable BI, suggesting that anti-PG IgM is involved in the pathogenesis of ENL. Initial observations indicate that high anti-PG IgM levels in bacillary-negative patients might reflect bacillary persistence. A study of 2 different substrate reagents in the ELISA [2,2'-azino-di(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), 0.1 mM H2O2, serum diluted 1:20, and o-phenylenediamine (OPD), 5 mM H2O2, serum diluted 1:300] showed generally good correlation in detection of anti-PG IgM. However the OPD system detected more paucibacillary disease (BT), while the ABTS system detected the significant effect of ENL on the relationship between BI and anti-PG IgM. Anti-PG IgM was clearly dominant over anti-PG IgG. However, certain patients, including several patients who had upgraded from LL and borderline lepromatous leprosy (BL), showed high levels of anti-PG IgG. Since studies have shown that LL patients are selectively deficient in cell-mediated immunity, T-cell products may be required for the IgM to IgG isotype switch. We conclude that anti-PG IgM is useful for monitoring the bacillary load in individual patients and should prove useful for leprosy control strategies.

Antibodies, Bacterial↗

PubMed1986

Serodiagnosis of leprosy: relationships between antibodies to Mycobacterium leprae phenolic glycolipid I and protein antigens.

Sera from leprosy patients and controls were assayed for immunoglobulin M (IgM) and IgG antibodies to the Mycobacterium leprae-specific phenolic glycolipid I antigen (PG) by enzyme-linked immunosorbent assay, for IgG antibodies to M. leprae protein antigens by Western immunoblot, and for antibodies to a 65-kilodalton (kDa) protein antigen of M. leprae by a competition antibody binding assay. Elevated levels of anti-PG IgM were seen in lepromatous and borderline lepromatous patients, and elevated levels of anti-PG IgG were seen in borderline lepromatous patients. There was a significant correlation between the bacillary index (BI) and anti-PG IgM whether all leprosy patients or only multibacillary patients were analyzed. A significant correlation was seen between anti-PG IgG and BI when all leprosy patients were used for analysis, but not when only multibacillary patients were used. IgG antibodies to protein antigens of M. leprae, as detected by Western immunoblot, were more prevalent in lepromatous and borderline lepromatous patients than in borderline tuberculoid patients, while one of eight controls showed one weak band. There were significant correlations between the number of M. leprae protein antigens detected by the sera of patients and both BI and the level of anti-PG IgM. The 65-kDa competition antibody binding assay detected active multibacillary leprosy. Patients positive for antibody to the 65-kDa antigen had a significantly higher BI and levels of anti-PG IgM and anti-PG IgG than did patients that were negative. In addition, the level of antibody to the 65-kDa antigen correlated with both the BI and anti-PG IgM. We conclude that testing for antibodies to protein antigens of M. leprae may provide a useful adjunct to testing for antibodies to PG.

Animals↗

PubMed1986

ELISA detection of IgM antibodies against phenolic glycolipid-I in the management of leprosy: a comparison between laboratories.

IgM antibodies to the phenolic glycolipid-I (PGL-I) antigen of Mycobacterium leprae were detected by different ELISA techniques in three laboratories (in New York, Colorado, Seattle, U.S.A.). The agreement on seropositivity and overall correlation between techniques was excellent. A positive linear correlation between the bacterial index (BI) and anti-PGL-I IgM, previously reported by the New York laboratory, was detected by all techniques. The role of erythema nodosum leprosum in decreasing the relationship of BI versus anti-PGL-I IgM was seen by the New York laboratory with sera diluted 1:20 and ABTS substrate solution and by the Colorado laboratory but not by New York with sera at 1:300 and OPD substrate or by the Seattle laboratory.

Antibodies, Bacterial↗

PubMed1985

Antioxidant effects on cell-mediated immunity.

Experiments were performed to determine the effects of dietary selenium and/or vitamin E deficiency on cell-mediated cytotoxicity in the mouse. Natural killer cell-mediated cytotoxicity (NKCC) was depressed after 8 wk on diets deficient in selenium and/or vitamin E. In contrast, antibody-dependent cell-mediated cytotoxicity (ADCC) was not affected by 8 wk of dietary deficiency of selenium and/or vitamin E. T-lymphocyte-mediated cytotoxicity (TCMC) was found to be depressed by combined selenium-vitamin E deficiency after 7 weeks on diets.

Animals↗

PubMedDate not supplied

Titers of murine leukemia virus are higher in brains of SAMP8 than SAMR1 mice.

To elucidate possible causes of premature aging seen in a strain of senescence-accelerated prone (SAMP8) mice, levels of murine leukemia virus (MuLV) were quantitated in various tissues of SAMP8 by an SC-1/UV plaque assay. MuLV levels in SAMP8 tissues were compared to those seen in the closely related SAMR1 strain, which is resistant to premature aging. MuLV titers were found to be higher in blood and spleen and much higher in brain of SAMP8 than in the same tissues of SAMR1. MuLV levels were seen to increase in SAMP8 brain with increasing age. Virus typing experiments indicated that the MuLV from SAMP8 brain is N-tropic, as is the MuLV seen in the AKR strain, one of the SAM progenitor strains. MuLV from SAMP8 brain was able to grow well in SAMR1 mouse embryo cells, indicating that it may be possible to infect SAMR1 mice with the SAMP8 MuLV to determine the effects of the virus on aging of SAMR1 mice.

Aging↗

PubMedDate not supplied

IgM antibodies against phenolic glycolipid I from Mycobacterium leprae in leprosy sera: relationship to bacterial index and erythema nodosum leprosum.

Serum IgM antibodies against Mycobacterium leprae-derived phenolic glycolipid I (PG) were determined in 121 leprosy patients, in contacts and controls by an enzyme-linked immunosorbent assay technique. Anti-PG IgM levels correlated with disease classification, increasing from the tuberculoid towards the lepromatous pole of the disease spectrum. There was a linear correlation between serum IgM PG-antibody levels and bacillary index (BI), a measure of bacterial load. Elevated anti-PG IgM in bacillary negative patients was usually indicative of active disease, undetected by BI. We conclude that anti-PG IgM levels are valuable for monitoring the degree of disease activity. Serum anti-PG IgM levels were significantly lower in patients with erythema nodosum leprosum (ENL) as compared to those without ENL, suggesting that IgM PG-antibodies are also involved in the pathogenesis of ENL.

Antibodies, Bacterial↗