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Biomedical subjects

C K Job

Publications and source records attributed to C K Job.

At least 73 records · Page 4Linked to original sources
PubMed1989

Single lesion subpolar lepromatous leprosy and its possible mode of origin.

Three case reports of patients with a single, nodular, subpolar lepromatous skin lesion, one on the left elbow, another on the posterior aspect of the left leg, and the third on the extensor ulnar aspect of the right forearm, are presented. The lesions, clinically and histopathologically, resemble lepromas which develop at the site of experimental inoculation of Mycobacterium leprae in armadillos. These are sites on the body which are likely to be traumatized. With the distinct possibility of the presence of viable M. leprae in the soil of Louisiana and Texas from wild armadillos with the natural disease, it is suggested that these three patients acquired the infection from the environment and had inoculation lepromas.

Adult↗
PubMed1989

Intracellular parasitism of parenchymal cells by Mycobacterium leprae.

The liver, skeletal muscle, and adrenal gland obtained from two nine-banded armadillos infected with Mycobacterium leprae were studied using an electron microscope. M. leprae were found in varying numbers inside hepatocytes, Kupffer's cells, striated muscle cells, adrenal cortical and adrenal medullary cells, endothelial cells, and macrophages. There was evidence to suggest that M. leprae were actively phagocytosed by the liver and skeletal muscle cells. The inert nature of M. leprae and its behavior as an almost ideal parasite of parenchymal cells are emphasized. The question of whether this unique parasitism of parenchymal cells and the possible processing and presentation of M. leprae antigens by these cells could be responsible for aberrant immune responses is raised.

Adrenal Cortex↗
PubMed1988

Efficacy of a cell-mediated reaction to the purified protein derivative of tuberculin in the disposal of Mycobacterium leprae from human skin.

The purpose of this study was to evaluate the effects of a delayed-type cell-mediated immune response to Mycobacterium tuberculosis antigen on the Mycobacterium leprae load in the skin of leprosy patients. Twelve patients with the lepromatous form of leprosy have been injected intradermally with 5 units of the purified protein derivative of tuberculin (PPD). Ten individuals responded with areas of induration ranging from 12 to 21 mm in diameter, and two were unresponsive (less than 10 mm). Twenty-one days thereafter, the injected and control sites were biopsied, and the histology, number of acid-fast bacilli, nature and phenotype of the emigrant cells, and ultrastructural characteristics of the lesions were evaluated. Eight of the 10 responding patients showed reductions in the number of acid-fast bacilli by factors ranging from 5 to 10,000. Two responders and both nonresponders exhibited no discernible decline in the number of organisms. The reduction in bacillary load was correlated with an intense mononuclear cell infiltrate, the maintenance of a high CD4+ T-cell/CD8+ T-cell ratio, the formation of granulomata, and the extensive destruction of previously parasitized macrophages.

Antigens, Bacterial↗
PubMed1988

Lepromatous meningoencephalitis in the nine-banded armadillo (Dasypus novemcinctus).

The brains from 10 nine-banded armadillos with lepromatous leprosy were studied histopathologically. All of them showed evidence of lepromatous meningitis. In two there was invasion by Mycobacterium leprae into the brain tissue, with neuronal cells and glial cells containing intracellular bacilli. To our knowledge, this is the first report of meningoencephalitis in a lepromatous nine-banded armadillo.

Animals↗
PubMed1987

Surveillance for naturally acquired leprosy in a nine-banded armadillo population.

Samples from 77 nine-banded armadillos (Dasypus novemcinctus) inhabiting a 16.7 km portion of the East Atchafalaya River Levee, Point Coupee Parish, Louisiana, were serologically tested and/or histopathologically examined for evidence of naturally acquired leprosy. Five of 67 (7.5%) armadillos tested sero-positive with ELISA test for IGM class antibodies to the phenolic-glycolipid-1 antigen of Mycobacterium leprae. One of 74 (1.3%) was histopathologically positive as determined by presence of acid-fast bacteria in nerves.

Animals↗
PubMed1987

Purification of the 65 kD protein from Mycobacterium gordonae and use in skin test response to Mycobacterium leprae.

The cell wall-associated protein of Mycobacterium gordonae (Mr = 65,000) was purified by affinity chromatography using a murine monoclonal antibody produced in response to the crossreactive 65 kD protein of M. leprae. The affinity-purified material was analyzed for purity by protein and carbohydrate analyses, SDS-PAGE, and immunoblotting. The final preparation contained a major protein band on SDS-PAGE analysis (Mr = 65,000) with no detectable carbohydrates. The affinity fraction was prepared at 250 micrograms/ml (protein) in sterile saline and 0.1 ml injected intradermally into guinea pigs immunized 30 days earlier. Gross changes at 48 hr were consistent with the characteristics of a delayed hypersensitivity skin reaction measuring 2.5 mm, 3.4 mm, and 2.7 mm in animals which had been immunized with M. leprae, M. gordonae, or M. bovis (BCG), respectively. Histologically, all 65 kD protein skin-test sites showed marked edema and infiltration by numerous lymphocytes, macrophages, and scattered neutrophils. Animals injected with Freund's incomplete adjuvant showed a minimal or no reaction (1.8 mm) to the purified protein. These results further define the immunogenicity of the 65 kD protein of M. gordonae and by inference M. leprae, and demonstrate the ability of crossreactive epitopes of the 65 kD protein to sensitize lymphocytes involved in delayed-type hypersensitivity reaction to M. leprae, M. gordonae, and M. bovis (BCG).

Animals↗
PubMed1987

Cellular responses to the intradermal injection of recombinant human gamma-interferon in lepromatous leprosy patients.

The local response to a single intradermal injection of 10 micrograms recombinant gamma-interferon (rIFN gamma) has been studied in 17 patients with lepromatous leprosy. Of these, 2 patients additionally received two intradermal injections of 10 micrograms rIFN gamma at another site. The results were compared with those of 3 patients who received three injections of the same dose at a single site in an earlier study. One to 7 days after lymphokine administration 4-mm punch biopsies were obtained and examined for cellular alterations in the dermis and epidermis. This allowed a kinetic analysis of mononuclear cell infiltration, keratinocyte proliferation and differentiation, and Langerhans cell redistribution. At 24 hours, the migration of large numbers of helper T cells and monocytes was already prominent and associated with induration. Mononuclear cell accumulation peaked at 72 hours but then persisted for 5-7 days. Only small numbers (one-third or less of total T cells) of suppressor/cytotoxic T cells were present at any time, and granulocytes were absent. Two daily injections of rIFN gamma led to a more intense accumulation of cells. Ten micrograms of rIFN gamma resulted in enhanced keratinocyte proliferation, Ia expression, and thickening of the epidermis. At 24-48 hours major histocompatibility Class II (Ia) antigen was first noted on the dividing cells of the basal layer. By 72-96 hours the entire epidermis exhibited strong expression of Ia antigen on cell surfaces. Repeated doses of lymphokine accentuated these changes and resulted in a more prompt keratinization and sloughing of this layer. Whereas a single dose of rIFN gamma resulted in the upward movement of T6+ Langerhans cells (LCs) in the epidermis, two injections led to a 50% reduction in their numbers and three doses were associated with an almost total loss of detectable T6+ LCs from the epidermis. These are probably sloughed along with keratinocytes. In contrast to the situation with a delayed immune response in the skin (purified protein derivative), no LCs accumulated in the dermis in association with helper T cells.

Animals↗
PubMed1987

Ability of the phenolic glycolipid-I antigen of M. leprae to elicit a positive Mitsuda response in the armadillo (Dasypus novemcinctus).

Three lepromin-positive armadillos and three lepromin-negative armadillos were tested intradermally with 100 micrograms of phenolic glycolipid-I (PGL-I) in 0.1 ml of normal saline. Positive delayed-hypersensitivity granulomas at 21 days in the lepromin-positive animals and negative responses in the lepromin-negative animals were obtained. These observations suggest that purified PGL-I is capable of eliciting cell-mediated immune or delayed-hypersensitivity responses in animals sensitized to Mycobacterium leprae.

Animals↗
PubMed1987

Adoptively transferred reactivity to M. leprae in nude mice infected with M. leprae.

Reversal reactions are manifestations of delayed hypersensitivity to M. leprae and are thought to be usually accompanied by manifestations of effective cell-mediated immunity (CMI) as measured by bacterial clearing. These experiments were designed to study the induction of reversal reactions in M. leprae-infected, congenitally athymic nude mice using adoptive transfer of CMI. Splenic cell suspensions derived from unimmunized heterozygous nu/+ mice, and those vaccinated with heat-killed M. leprae, viable BCG and a mixture of the two antigens were diluted to contain 10(4), 10(5), 10(6), 10(7) lymphocytes/0.1 ml and infused intravenously into multibacillary nude mice. The production of reversal reactions in leprous nude mice in response to adoptively transferred CMI was studied in a quantitative fashion. Dose responsive induction of reversal reactions, apparent by footpad inflammation and swelling, decreased morphological indices (MI) of the bacteria and mononuclear cell infiltrations, histopathologically, were observed. For nude mice receiving cells primed with 3.9 X 10(5) living BCG alone, the effective dose 50% (ED50) was 1.0 x 10(6) lymphocytes to induce reversal reactions. For those receiving cells primed with 10(7) M. leprae the ED50 was 3.7 x 10(5) lymphocytes. For nude mice receiving cells primed with a mixture consisting of 1/2 the above dose of BCG + 1/2 the above dose of M. leprae, the ED50 was 6.8 x 10(4) lymphocytes.

Animals↗
PubMed1987

Prevalence and significance of positive Mitsuda reaction in the nine-banded armadillo (Dasypus novemcinctus).

One hundred two armadillos captured from the wild were lepomin tested. Nine of them (8.8%) showed a positive Mitsuda reaction. The histopathological appearance of the reaction had a spectrum showing tuberculoid, borderline tuberculoid, borderline lepromatous, and lepromatous histology. It is possible that armadillos can develop all the different types of leprosy seen in humans. The armadillo is a good animal model to test protective vaccines against leprosy.

Animals↗
PubMed1987

Unusual histological lesions in the eye of a leprosy patient.

A pathological study of an eye from a leprosy patient is reported. In addition to the granulomatous lesions in the anterior aspect of the eye, microgranulomas are demonstrated in the retina of this patient, a very uncommon finding in leprosy.

Adult↗
PubMed1987

Lepromatous placentitis and intrauterine fetal infection in lepromatous nine-banded armadillos (Dasypus novemcinctus).

Three pregnant lepromatous armadillos along with the three sets of four fetuses and their placentae were studied histopathologically. Mycobacterium leprae were present in the decidual tissue, trophoblastic cells which line the chorionic villi, and in the cells that form the internal structure of the villi. Acid-fast organisms were also seen in the spleens of three fetuses. Congenital infection is clearly possible in leprosy in the armadillo and may also occur in humans.

Animals↗
PubMed1986

Local and systemic effects of intradermal recombinant interferon-gamma in patients with lepromatous leprosy.

Evidence that interferon-gamma may be a physiologic macrophage-activating factor, and that macrophage activation may be defective in lepromatous leprosy, led us to test the effects of intradermal injection of low doses of recombinant interferon-gamma in six patients with this disease. Interferon-gamma, 1 or 10 micrograms, was administered daily by jet gun for three days into a single cutaneous lesion. A biopsy specimen was taken from the injection site on the sixth study day and compared with specimens obtained previously from a site where no injection had been made or where excipient alone had been injected in the same way as the interferon. Interferon-gamma elicited local effects similar to certain features of delayed-type hypersensitivity reactions or tuberculoid leprosy, including induration, T-cell and monocyte infiltration, keratinocyte proliferation, diminution of epidermal Langerhans cells, and dermal and epidermal cell HLA-DR (Ia) antigen expression. At some of the sites of interferon-gamma injection, there was also an apparent decrease in acid-fast bacilli. Before treatment, monocytes from patients with lepromatous leprosy released 48 percent as much hydrogen peroxide as did monocytes from controls in response to phorbol myristate acetate, and 36 percent as much as those from controls in response to Mycobacterium leprae. When recombinant interferon-gamma was injected, these responses became normal. No toxic effects were observed. These observations suggest that interferon-gamma can mediate certain manifestations of delayed-type hypersensitivity or cell-mediated immunity in vivo, and that recombinant interferon-gamma should be tested for possible therapeutic effects in certain nonviral infectious diseases.

Adult↗
PubMed1986

A random survey of leprosy in wild nine-banded armadillos in Louisiana.

On the basis of the finding that lepromatous granulomas were almost always seen in the ears of armadillos with disseminated leprosy, a random survey of the prevalence of the disease among wild armadillos in the state of Louisiana, U.S.A., was conducted by examining histopathologically both ears of armadillos killed on the roads by automobiles. Ten (2%) of the 494 animals examined had disseminated leprosy. If a killed lepromatous armadillo releases up to 10 Mycobacterium leprae into the environment, the importance of the event to the epidemiology of leprosy must be considered.

Animals↗
PubMed1986

Thorns in armadillo ears and noses and their role in the transmission of leprosy.

Both ears from 494 wild nine-banded armadillos (Dasypus novemcinctus) and nose specimens from 224 animals were collected and histopathologically studied. Lepromatous granulomas were present in the ear specimens of ten of 494 animals. There were thorns in the ears of 22.5% of animals, and in 36.6% of the nose specimens. In one armadillo, there was evidence to suggest that Mycobacterium leprae entered the tissue through the thorn pricks. In the normal habitat of the armadillo in Louisiana there are thorny bushes consisting mostly of the green briar and the southern dewberry. Thorn pricks as a means of transmission of leprosy in the wild armadillos is suggested.

Animals↗