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Biomedical subjects

R H Gelber

Publications and source records attributed to R H Gelber.

At least 37 records · Page 2Linked to original sources
PubMed1991

The activity of amoxicillin plus clavulanic acid against Mycobacterium leprae in mice.

The activity of amoxicillin plus clavulanic acid against logarithmically multiplying Mycobacterium leprae was evaluated by treating mice by gavage five times weekly with various amounts of the compound from day 60 to day 150 after footpad infection. At 25, 50, and 100 mg/kg, it was inactive; at 200-600 mg/kg, multiplication of M. leprae was entirely prevented for 6-11 months after drug discontinuation, consistent with observations of bactericidal activity for M. leprae. In a confirmatory study in mice, five-times-weekly intraperitoneal ticarcillin plus clavulanic acid, 1000 mg/kg, was not bactericidal for M. leprae, while amoxicillin plus clavulanic acid, 400 mg/kg five times weekly, was weakly bactericidal (80% +/- 14%). In addition, activity of amoxicillin plus clavulanic acid, 400 mg/kg, was evaluated in combination with previously established active drugs dapsone, 0.0001% (in diet), rifampin, 20 mg/kg monthly (by gavage), and kanamycin, 25 mg/kg five times weekly (intraperitoneally). All three combinations were active, and the combination with kanamycin was more active than either drug alone.

Amoxicillin↗
PubMed1991

Activities of various macrolide antibiotics against Mycobacterium leprae infection in mice.

We evaluated the activities of several macrolide antibiotics against M. leprae infections in mouse footpads. Erythromycin and azithromycin were inactive, while both roxithromycin and clarithromycin were found to be consistently active and, in fact, bactericidal. By both methods, clarithromycin was found to be superior to roxithromycin, a finding which, at least in part, may be a consequence of the higher levels of clarithromycin at the site of infection.

Animals↗
PubMed1991

Effect of low-level and intermittent minocycline therapy on the growth of Mycobacterium leprae in mice.

We evaluated the minimal concentrations of minocycline in the diet and in serum required to inhibit the growth of seven Mycobacterium leprae isolates in mice. Minocycline concentrations of 0.01 and 0.04% in the diet, which resulted in levels in serum of less than or equal to 0.17 and 0.51 microgram/ml, respectively, were consistently and completely inhibitory. Even 0.004% dietary minocycline (levels in serum, less than or equal to 0.08 microgram/ml) partially inhibited five of these strains, while 0.001% minocycline was consistently inactive. For five of these isolates, minocycline at a concentration of 0.04% in the diet given 3 days (Monday, Wednesday, Friday) and 1 day weekly completely inhibited the growth of M. leprae, and minocycline given even 1 day monthly was partially inhibitory for three of these five M. leprae isolates.

Animals↗
PubMed1991

Effect of dapsone on haemoglobin concentration in patients with leprosy.

Haemolysis and frank anaemia from dapsone therapy of leprosy has been long recognized. However, the frequency and severity of this side-effect have not been well documented. We report herein a retrospective analysis of the effect of daily dapsone (generally 100 mg/day) on the haemoglobin concentration of 100 leprosy patients undergoing initial chemotherapy. The average haemoglobin was found to fall significantly by almost 2 g/dl, from 14.25 +/- 1.27 g/dl to a nadir of 12.31 +/- 1.61 (P less than 0.001). Eighty-three percent of patients had a fall of haemoglobin concentration of 1 g/dl or more, while in 16% of patients the haemoglobin fell greater than or equal to 3 g/dl. Increasing age was found associated with an increased magnitude of dapsone-related haemolysis (P less than or equal to 0.004). Decreasing the daily dose of dapsone was associated with an increased haemoglobin concentration (P less than 0.001%). We have concluded that dapsone commonly results in not only haemolysis but a significant decrease in haemoglobin concentration. This may have serious clinical implications, especially in endemic areas, where, owing to nutrition, malaria, and intestinal parasitism, the haemoglobin concentration is already compromised.

Adolescent↗
PubMed1990

Identification of an immunostimulating protein from Mycobacterium leprae.

Despite the recent identification of a number of Mycobacterium leprae proteins, the major immunogenic determinants of this organism remain obscure. We isolated from M. leprae a potent immunostimulatory preparation, designated the MLP fraction, which contains a major protein of 35 kilodaltons (kDa). This protein was precipitated by monoclonal antibody ML03-A1, which recognizes a 35-kDa protein of M. leprae, and by sera obtained from patients with lepromatous leprosy. Neither sera from healthy controls nor sera from patients with pulmonary tuberculosis recognized the 35-kDa protein, and only one of four serum samples from patients with borderline tuberculoid leprosy reacted with this protein. The MLP fraction stimulated T-cell proliferation in patients with leprosy whose T cells proliferate in response to whole M. leprae cells. Apparently, the T-cell epitope associated with MLP is also expressed on M. tuberculosis and M. bovis BCG, since patients with pulmonary tuberculosis and BCG-vaccinated individuals demonstrated significant responses to the MLP fraction. The 35-kDa M. leprae protein, purified to homogeneity in the laboratory of P. J. Brennan, stimulated T-cell proliferative responses in all MLP-responsive subjects. These findings suggest that the 35-kDa protein present in MLP is an immunostimulatory component of M. leprae. In addition to serving as a useful probe for study of the T-cell anergy associated with lepromatous disease, this protein may ultimately be useful as a component of a vaccine designed to provide protection against infection with M. leprae.

Adjuvants, Immunologic↗
PubMed1990

Effective vaccination of mice against leprosy bacilli with subunits of Mycobacterium leprae.

Model vaccines against leprosy bacilli have consisted of nonvirulent, live, attenuated Mycobacterium bovis BCG and irradiated, heat-killed, or autoclaved intact M. leprae. We report that immunization with various cell wall fractions of M. leprae, progressively depleted of lipids, carbohydrates, and soluble proteins, as well as a partially purified protein(s) derived from a pellet fraction of sonicated M. leprae, conferred significant protection against subsequent infection with live leprosy bacilli. Moreover, lymphocytes from regional lymph nodes and spleens of mice immunized with these M. leprae-derived subunits responded by proliferation when stimulated with M. leprae in vitro. Our results provide the first evidence that vaccination with M. leprae-derived fractions protects mice against leprosy bacilli.

Animals↗
PubMed1990

Rapid and sensitive detection of Mycobacterium leprae using a nested-primer gene amplification assay.

By using a set of four nested oligonucleotide primers, a two-step polymerase chain reaction assay for the detection and identification of Mycobacterium leprae that does not require the use of radioactivity labeled hybridization probes was developed. The nested-primer procedure amplified a 347-base-pair product from M. leprae genomic DNA. No amplification products were produced from DNAs of 19 other Mycobacterium species, 19 non-Mycobacterium species, mouse cells, or human cells. Minor amplification products were observed with three additional Mycobacterium species, i.e., "M. lufu", M. simiae, and M. smegmatis. These products were easily distinguished from the M. leprae product by size and restriction enzyme cleavage patterns. The assay could amplify the 347-base-pair product from samples containing as little as 3 fg of M. leprae genomic DNA--the amount of DNA in a single bacillus. The assay also amplified target sequences in crude lysates of M. leprae bacilli isolated from tissue biopsy specimens from infected animals and humans. The entire assay, from sample preparation to data analysis, can be completed in less than 8 h.

Animals↗
PubMed1990

Primary dapsone-resistant Hansen's disease in California. Experience with over 100 Mycobacterium leprae isolates.

We found that in the years 1978 through 1981 only one of 54 previously untreated patients with Hansen's disease was found to harbor dapsone-resistant Mycobacterium leprae. That single strain was only partially resistant, ie, it was resistant to 0.0001% dapsone in a mouse diet but not to higher concentrations. During the years 1983 through 1988, M leprae from 47 previously untreated patients presenting to clinics in San Francisco, Calif, and Los Angeles, Calif, grew in mice. None of these strains was found to be dapsone resistant. Thus, from 1978 through 1988 only one of 101 M leprae isolates obtained from skin biopsy specimens from patients with leprosy was found to be resistant to dapsone. We have concluded that primary dapsone resistance still does not appear to be a significant problem in California. Owing to the fact that our single resistant case and those reported from international sources are, in general, partially resistant, the potential importance of partial dapsone resistance is discussed.

Adolescent↗
PubMed1990

Intraocular pressure and iris denervation in Hansen's disease.

We retrospectively analyzed 255 Hansen's disease patients and found low intraocular pressure (less than 7 mm Hg) in 12% of them. We showed a correlation between low intraocular pressure and avascular keratitis and iritis. We also found that patients with low intraocular pressures had abnormally large postural changes in intraocular pressure. We speculate that abnormalities in the autonomic innervation of the anterior segment of the eye may be related to the intraocular pressure abnormalities. Further investigations along this line may increase our understanding not only of the pathophysiology of Hansen's disease but also of the mechanisms regulating homeostasis of intraocular pressure.

Autonomic Nervous System↗
PubMed1989

Low intraocular pressure and postural changes in intraocular pressure in patients with Hansen's disease.

We found intraocular pressures of less than 7 mm Hg in 11 of 72 patients (15%) with early Hansen's disease. Furthermore, significant postural changes in intraocular pressure (greater than 30%) occurred in 43 of 72 patients (60%). This loss of intraocular pressure homeostasis, which results from reduced aqueous humor production or increased uveoscleral outflow with reduced local adrenergic control in the ciliary body-iris-trabecular meshwork region, suggests that early autonomic neuropathy of the eye may occur in Hansen's disease. The only predictive value for significant postural change in intraocular pressure was the presence of immunologically unstable disease.

Homeostasis↗
PubMed1989

Serum antibodies to defined carbohydrate antigens during the course of treated leprosy.

Sequential monitoring of 724 sera for antibodies to a neoantigen based on phenolic glycolipid-I (PGL-I) and native lipoarabinomannan (LAM) in 90 leprosy patients undergoing therapy in San Francisco was conducted. Untreated lepromatous patients frequently (91%) had significant antibodies to both moieties. Antibodies were less frequently found in tuberculoid patients (74% to neoantigen and 37% to LAM). In the first 3 years of treatment, average serum antibodies to both moieties fell significantly. Antibodies to LAM fell during each of the first 4 years of therapy, but decreasing antibody levels to the PGL-I neoantigen did not appear to fall consistently after the third year of treatment. A wide variation in the rate of fall of serum antibodies was noted. Sequential changes in the amounts of serum antibodies to the neoantigen and LAM in general paralleled one another but were at times discrepant. Both in San Francisco and Malaysia, skin-smear negative, long-term treated, lepromatous leprosy patients frequently harbored significant antibodies to both PGL-I and LAM.

Antibodies, Bacterial↗