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Biomedical subjects

V D Ramanathan

Publications and source records attributed to V D Ramanathan.

At least 19 recordsLinked to original sources
PubMed2002

Biochemical and histochemical changes pertaining to active and healed cutaneous tuberculosis.

BACKGROUND: Fibrosis is one of the major causes of post-treatment morbidity in tuberculosis. The molecular basis of fibrosis in active and healed tuberculous lesions is yet to be fully characterized. OBJECTIVES: To measure the tissue levels of collagen, elastin, fibronectin, transforming growth factor-beta (TGF-beta) and zinc in active and healed lesions of cutaneous tuberculosis. PATIENTS AND METHODS: Biopsy lesions obtained from 17 patients with active cutaneous tuberculosis and 12 patients after a 6-month regimen of antituberculous chemotherapy were examined. Collagen, elastin and zinc were estimated biochemically. In addition, the presence of collagen IV, TGF-beta and fibronectin were determined immunohistochemically. RESULTS: It was found that collagen, elastin, fibronectin and TGF-beta levels were higher in the active lesions. The levels of zinc were similar in both active and healed lesions. Clinically, scar tissue or keloid formation was not seen in any of the healed lesions. CONCLUSIONS: Effective antituberculous chemotherapy will lead to a substantial reduction of fibrosis and the consequent disability that can arise in patients with tuberculosis.

Antitubercular Agents↗
PubMed1999

A histological spectrum of host responses in tuberculous lymphadenitis.

A total of 446 lymph node biopsy specimens showing histological evidence of tuberculosis were classified into four groups based on the organization of the granuloma, the type and numbers of participating cells and the nature of necrosis. These were, hyperplastic (22.4%)--a well-formed epithelioid cell granuloma with very little necrosis, reactive (54.3%)--a well-formed granuloma consisting of epithelioid cells, macrophages, lymphocytes and plasma cells with fine, eosinophilic caseation necrosis, hyporeactive (17.7%)--a poorly organized granuloma with macrophages, immature epithelioid cells, lymphocytes and plasma cells and coarse, predominantly basophilic caseation necrosis and nonreactive (3.6%)--unorganized granuloma with macrophages, lymphocytes, plasma cells and polymorphs with non caseating necrosis. Though the number of bacilli in the sections differed in each group, there were no differences in culture positivity, Mantoux reaction or the clinical features. It is likely that the spectrum of histological responses seen in tuberculous lymphadenitis is the end result of different pathogenic mechanisms underlying the disease.

Adolescent↗
PubMed1999

Biochemical & histochemical changes relating to fibrosis following infection with Mycobacterium tuberculosis in the guinea pig.

Guinea pigs infected with M. tuberculosis were studied for parameters relating to fibrosis following infection. The infected animals were followed up to a period of 44 wk and the changes that occurred in the lung, liver and spleen were studied. Corresponding tissues from animals injected with bleomycin, an anti-mitotic drug which has the ability to produce pulmonary fibrosis, served as positive controls. Tissue collagen, elastin and hexosamines were estimated biochemically. The presence of granuloma and stainable collagen in paraffin sections of these tissues was also studied. Establishment of the infection was assessed bacteriologically by culturing the viable organisms from the spleen. It was observed that a self-limiting infection was established in the guinea pigs and none of the animals died of the infection. In the infected animals, collagen, elastin and hexosamines showed an initial decrease followed by an increase. While the elastin and the hexosamine levels returned to the basal levels in all the three organs, collagen levels increased in the lung and were comparable to those of the bleomycin control. Collagen stainable by Van Gieson's method was found to be increased in the lung from the 4th wk onwards. The present report indicates the potential of adopting this system for studying mechanisms of fibrogenesis in tuberculous infection.

Animals↗
PubMed1999

The clearance of tubercle bacilli & mycobacterial antigen vis a vis the granuloma in different organs of guinea pigs.

In the present study, an attempt was made to define the relationship of intact tubercle bacilli and/or their antigenic fragments to a granuloma in the guinea pig in order to distinguish an active from a resolving granuloma. In one set of animals, granuloma was induced in the skin by injecting heat-killed Mycobacterium tuberculosis intradermally and in another set, granuloma was produced in the lung and spleen by injecting live M. tuberculosis intramuscularly. The animals were sacrificed at various time points and skin, lung and spleen from the two groups were subjected to histological examination for the presence of granuloma, bacilli and antigenic fragments. In the dermal lesion, intact acid fast bacilli were cleared first by day 42 followed by the removal of their antigenic fragments by day 63 and finally by day 84, the granuloma had resolved completely. In the guinea pigs infected with live M. tuberculosis, removal of the bacilli followed by the clearance of antigen was observed. Though the granuloma itself did not subside completely in these animals, it was found that there was a reduction in congestion and oedema of the granulomatous area. It is concluded from the results that the demonstration of antigen at the site of lesion may be potentially useful to discriminate between a persisting and a resolving tuberculous granuloma.

Animals↗
PubMed1997

Regional lymphadenitis following antileprosy vaccine BCG with killed Mycobacterium leprae.

Phase-II and extended Phase-II studies were conducted in three different sets of the population in Thiruthani Taluk, Chengalpattu District, South India, involving BCG and killed Mycobacterium leprae (KML) combination vaccines to ascertain the acceptability of the vaccines. In the Phase-II study, 997 healthy volunteers were vaccinated on individual randomization with one of the vaccines arms: BCG 0.1 mg + 6 x 10(8) KML, BCG 0.1 mg + 5 x 10(7) KML, BCG 0.1 mg + 5 x 10(6) KML, BCG, 0.1 mg or normal saline. Blood samples were taken and the serum was tested for antibody levels against phenolic glycolipid-I (PGL-I) and the 35-kDa protein of M. leprae. In this study, we observed regional suppurative adenitis in 6% (6 out of 100), 3% (3 out of 100), and 3% (3 out of 100) of the vaccinees in the BCG 0.1 mg + 6 x 10(8) KML, BCG 0.1 mg + 5 x 10(7) KML, and BCG 0.1 mg + 5 x 10(6) KML vaccine arms, respectively, in the 13-70 year age group. Earlier BCG scar status, skin-test reactions to lepromin-A, Rees' MLSA, and serum antibody levels against PGL-I and the 35-kDa protein did not help to identify the group at risk of developing suppurative adenitis. Suppurative adenitis appears to have a different relationship between the age of the subject and the dose of the vaccine. In order to overcome the problem of regional suppurative adenitis and to know the mechanism involved, an extended Phase-II study was conducted in similar groups of the population by reducing the BCG and KML doses, i.e., with BCG 0.05 mg + 6 x 10(8) KML, BCG 0.05 mg + 5 x 10(7) KML, and BCG 0.01 mg + 5 x 10(7) KML. Biopsy specimens were collected from lymph nodes of the suppurative adenitis cases and were subjected for culture and histopathological examination. The observations showed that regional suppurative adenitis could be reduced to 1% in the BCG 0.05 + 6 x 10(8) KML group, 0.5% in the BCG 0.05 + 5 x 10(7) KML group, and 0.5% in the BCG 0.01 + 5 x 10(7) KML group. This phenomenon of suppurative adenitis appears to be related to the total dose of mycobacterial antigens. Suppurative adenitis was seen by weeks 18 and 20 post-vaccination in the latter two lower doses; whereas it was seen by week 8 in the higher dose of the combination vaccines. No case of suppurative adenitis was observed in the BCG 0.1 mg group. Culture and histopathology ruled out the possibilities of progressive BCG infection and superadded infection. Considering the above results, BCG 0.05 mg + 6 x 10(8) KML was acceptable for a large-scale vaccine trial in South India.

Adolescent↗
PubMed1992

A study on viability of mycobacteria after treating them with complement system.

The effect of complement system on viability of mycobacteria (Mycobacterium vaccae and Mycobacterium bovis-BCG, as models) was studied by using 3H-uracil uptake method. The results showed no killing effect on these mycobacteria. Pretreatment of these mycobacteria with antimycobacterial antibodies also did not result in making them susceptible to complement. These observations were confirmed electronmicroscopically where no ultrastructural changes indicative of cell destruction were seen after treatment with complement in the presence and absence of antibody.

Antibodies, Bacterial↗
PubMed1991

Persistent reduced solubilization of immune complexes in lepromatous leprosy patients with reactions.

It is held that immune complexes (IC) play a vital role in the pathogenesis of some of the reactions in leprosy. The complement system is known to solubilize and render IC innocuous. We have previously shown that patients undergoing lepra reactions had lowered complement-mediated IC solubilization (CMS). We, therefore, undertook a prospective study of untreated multibacillary leprosy patients and monitored their CMS levels sequentially while on therapy. In addition, the concentrations of the complement component C3d, immunoglobulins G, A and M, and circulating immune complexes (CIC) were also estimated. A total of 26 patients were included in the study and were investigated at 3-month intervals for 3 years. Thirteen of the 14 patients who did not develop reactions at all had normal CMS values, although all of them showed elevated CIC. From the inception of treatment, 10 of the 12 patients who developed lepra reactions had low CMS values which remained below normal levels even after evidence of complement activation disappeared and long after the subsidence of reaction. It is suggested that this defective CMS acts as a predisposing cause of lepra reactions.

Adult↗
PubMed1990

Activation of the human complement system by phenolic glycolipid 1 of Mycobacterium leprae.

The activation of the complement system by phenolic glycolipid 1 (PGL) from Mycobacterium leprae was studied. It was found that PGL consumed haemolytic complement through both the classical and the alternative pathways. This was further studied at the level of C3. Although the activation was independent of anti-PGL antibodies present in normal human serum, the addition of antibody augmented the activation of complement by PGL. The uptake of C3 through the classical pathway was enhanced predominantly by IgM antibody whereas, IgG antibody against PGL was responsible for the augmentation of the alternative pathway activation. Furthermore, it was found that both the disaccharide and trisaccharide components of PGL were able to activate the complement system.

Antigens, Bacterial↗
PubMed1990

Activation of complement by circulating immune complexes isolated from leprosy patients.

Circulating immune complexes isolated from different types of leprosy sera as polyethylene glycol (PEG) precipitates were found to be efficient activators of the alternative pathway of complement. PEG precipitates from BL/LL leprosy patients and those with erythema nodosum leprosum were found to activate both the classical pathway and the alternative pathway of complement efficiently, while PEG precipitates from TT/BT leprosy patients and borderline tuberculoid patients in reaction were found to active the alternative pathway of complement but not the classical pathway. No significant differences were observed between the PEG precipitates from reactional and nonreactional TT/BT and BL/LL patients in their complement activating ability.

Antigen-Antibody Complex↗
PubMed1985

In vitro inhibition of the activation of the human complement and coagulation systems by chloroquine.

The ability of chloroquine to inhibit the activation of the complement and coagulation systems was investigated. The activation of the classical pathway of complement by antibody coated sheep erythrocytes and aggregated IgG was blocked by chloroquine. Similarly, it prevented normal rabbit erythrocytes and zymosan from activating the the alternative pathway of complement. The activation of C3 by immune complexes of different solubilities also was inhibited by this drug. In addition, it abrogated the clotting of plasma by calcium chloride and thrombin. This effect could be reversed by the addition of excess thrombin but not of calcium chloride. It is suggested that the inhibition of these two important phlogistic mediator systems of inflammation may contribute to the anti-inflammatory property of chloroquine.

Animals↗
PubMed1985

Reduced complement-mediated immune complex solubilization in leprosy patients.

The ability of sera from leprosy patients to solubilize immune precipitates in vitro through the complement system was studied. The solubilizing capacity of sera from patients who did not have any reactions during 2 years or more after starting chemotherapy was comparable with that of normal laboratory volunteers. On the other hand, sera from borderline tuberculoid and lepromatous leprosy patients in reaction had markedly decreased levels of solubilization. Their total and the alternative pathway haemolytic levels did not show a corresponding decrease. Although the circulating immune complexes and serum C3d of these patients came down after the subsidence of reaction, their solubilization remained consistently low during a 3 month follow-up period.

Antigen-Antibody Complex↗
PubMed1984

Isolation and analysis of circulating immune complexes in leprosy.

Circulating immune complexes (CIC) were isolated by two antigen nonspecific methods from 60 leprosy patients belonging to borderline tuberculoid (BT) and lepromatous (LL) types with and without reactions. CIC were elevated in both BT and LL reactions. CIC from BT in reaction (BTR) were found to consist largely of IgG and C3, whereas, C-reactive protein could be found in CIC from LL reactions (LR). In addition, IgM and rheumatoid factor were demonstrated in the complexes of LR patients who had mainly arthritis. Antimycobacterial antibody was seen in the complexes of two-thirds of LR patients who had predominantly skin manifestations as part of their reaction. The relevance of these findings to the clinical manifestations of different types of reactions is discussed.

Animals↗
PubMed1980

Activation of the alternative pathway of complement by mycobacteria and cord factor.

The ability of a number of mycobacteria and some of their components to activate complement was examined. Mycobacterium bovis BCG (Glaxo strain), Mycobacterium leprae, Mycobacterium lepraemurium, and cord factor activated the alternative pathway of complement in normal human serum and normal and C4-deficient guinea pig sera and generated biologically active products. BCG (Pasteur strain) and muramyl dipeptide did not activate complement. The relevance of activation of complement by mycobacteria to their induction of granulomas is discussed.

Acetylmuramyl-Alanyl-Isoglutamine↗