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Biomedical subjects

R K Saxena

Publications and source records attributed to R K Saxena.

At least 19 recordsLinked to original sources
PubMed1992

Acid pH-induced changes in the immunoreactivity of specific antigen and antibody in circulating immune complexes from tuberculosis sera.

The effect of acid pH treatment of circulating immune complexes (CIC) derived from tuberculosis sera was studied on the relative titers of specific antibody (CIC Ab) and mycobacterial antigen (CIC Ag) in the complexes. While the specific antibody titers increased, the titers of CIC Ag declined as a result of acid pH treatment of CIC, both changes being highly significant statistically. Direct exposure of TB sera to pH 2.8 also resulted in significant enhancements in the titers of antibodies directed against Mycobacterium tuberculosis (M.tb.). Competition experiments indicated that the acid pH-treated antibodies retained their antigen specificity. TB sera treated with pH 2.8 for 30 min and then neutralized back to pH 7.4 retained the enhanced antibody reactivity even after 7 days of storage at 4 degrees C. Our results indicate that acid pH treatment induces higher antigen binding ability in anti-M.tb. antibodies, present in free or complexed form in TB sera. These changes appear to be irreversible. Dissociation of CIC and analyzing the titers of released antibody and antigen components offered no advantage with respect to the immunodiagnosis of tuberculosis, as compared to the levels of undissociated CIC components or the serum antibody.

Antibodies, Bacterial↗
PubMed1992

Immune status of children suffering from minimal change nephrotic syndrome.

Twenty five children suffering from minimal change nephrotic syndrome were studied for immunological alterations at different stages of this disease i.e., onset, relapse and remission. Changes were found mainly at onset and during relapse in the form of altered helper and suppressor cell ratio, depressed delayed cutaneous hypersensitivity reaction, decreased S-IgG bearing lymphocytes with low serum IgG concentration, and increased S-IgM bearing lymphocytes with high serum IgM concentration. Majority of these parameters returned to normal values during remission. Serum IgE was found high at all stages of this. These alterations suggest defects in cell mediated immunity resulting in secretion of some substance which modifies the glomerular anionic charges.

Adrenal Cortex Hormones↗
PubMed1991

Antigenic epitopes on Mycobacterium tuberculosis recognized by antibodies in tuberculosis and mouse antisera.

The effect of sodium periodate and proteolytic enzyme treatments on the antibody binding capacity of Mycobacterium tuberculosis antigen (Ag) was studied by ELISA. Treatment with sodium periodate resulted in a marked decrease in the capacity of M. tuberculosis Ag to bind antibodies in human TB sera, but had no effect on the reactivity with antibodies in mouse. In contrast, treatment with proteolytic enzymes (trypsin and chymotrypsin) had no effect on the reactivity of M. tuberculosis Ag with human TB sera but reduced substantially the reactivity to antibodies in mouse antisera. These results indicate that anti-M. tuberculosis antibodies in human TB sera react predominantly with carbohydrate determinants and not with protein epitopes sensitive to trypsin and chymotrypsin. The bulk of murine antibodies on the other hand were directed against protein determinants and not the carbohydrate epitopes.

Animals↗
PubMed1991

Analysis of circulating immune complexes (CIC) in tuberculosis: levels of specific antibody and antigens in CIC and relationship with serum antibody.

Eighty sera from tuberculosis (TB) patients, 16 Indian and 10 American control sera were analyzed by ELISA for relative titres of antibody against mycobacterial antigens. Levels of specific antibody and mycobacterial Ag in circulating immune complexes (CIC) isolated from these sera were also studied. All these parameters were found to be elevated in TB sera as compared to control sera. Maximum increase was however noted in CIC specific antibody titres. A good correlation was observed between serum and CIC levels of specific antibody (r = 0.72) and between specific antigen (Ag) and antibody (Ab) levels within CIC (r = 0.64). In a few of the TB sera examined, CIC specific Ab contributed less than 1% to the Ab titres in sera. In order to examine the differences between different subgroups within TB patients, a statistical analysis of variance was performed. Sex of the patients had no effect on any parameter. Sputum-positive patients had significantly higher levels of CIC Ag and Ab than the sputum-negative patients, although no significant difference occurred in respect to serum Ab. All three parameters were significantly higher in patients on chemotherapy as compared to fresh untreated cases. The relevance of these observations to the development of a CIC-based immunodiagnostic assay for TB is discussed.

Analysis of Variance↗
PubMed1991

Morphological changes in the bovine articular cartilage subjected to moderate and high loadings.

This study aims at examining the morphological changes in the cartilage structure of the bovine knee joint when the amputated joints are subjected to (a) a moderate load of 150 kg and (b) a high load of 300 kg and fitted on a knee joint articulating machine at 45 cycles/min for 2 h. The scanning-microscopic study of the surface structure of the experimental and control cartilage shows no appreciable change in the surface morphology of the cartilage when subjected to the moderate load of 150 kg. However, in the case of the high load (300 kg) there is appreciable change in the fibrillary structural pattern of the surface morphology. Histologically too, no appreciable change was noticed when subjected to moderate loadings, but in the case of high loading the cartilage develops roughness of the surface with occasional small clefts.

Animals↗
PubMed1991

Shear properties of articular cartilage of a bovine knee joint subjected to moderate and high loads: an experimental study.

Freshly excised bovine knee joints were subjected to oscillation under constant load on a specially designed knee joint articulating machine with the joints subjected to moderate and high loadings of 1471.5 and 2943 N respectively. Instantaneous and equilibrium shear moduli of the articular cartilage obtained from the experimental knee joints were measured on a mechanical indentor (DuPont 943 TMA) and compared with the corresponding values of the shear moduli of the cartilage obtained from the control knee joints. At moderate load, both the instantaneous and the equilibrium shear moduli exhibit significant increase in their values. However, at high load the constant shear moduli showed a decrease in its value whereas the value of the equilibrium shear modulus was observed to increase slightly.

Animals↗
PubMed1990

Necessity for interaction between adherent and non-adherent rat spleen cells for the generation of a suppressor factor of NK activation.

Whole rat spleen cell populations in culture release constitutively a factor which suppresses the NK activation in response to interleukin-2. Culture supernatants derived from adherent (AD) and non-adherent (NAD) cell preparations obtained from rat spleen cells, did not have a suppressor activity comparable to that present in the culture supernatants of whole spleen cells. When reconstituted mixtures of the AD and NAD cells were cultured, high levels of suppressor activity could again be demonstrated in the culture supernatants, indicating that some kind of co-operation between AD and NAD cells was needed for efficient generation of the suppressor. Non-suppressive culture supernatants derived from NAD cells became suppressive when AD cells were cultured in them. On the other hand, relatively little suppressor activity was generated when NAD cells were cultured in non-suppressive culture supernatants from AD cells. Our results seem to indicate that NAD cells may release some agent which is not itself a suppressor but either (a) induces the generation of suppressor activity from AD cells, or (b) is "processed" into a suppressor agent by AD cells.

Animals↗
PubMed1990

Quantitative estimation of major histocompatibility complex antigens on live tumour cells.

Quantitation of major histocompatibility complex (MHC) antigens on cells can accurately be done by using a flowcytometer. Since flowcytometer is not freely accessable an alternate, simple method for relative quantitation of MHC antigens has been devised. In this procedure, YAC lymphoma cells were first treated with a monoclonal anticlass I MHC antibody and then with a rabbit anti mouse Ig-antibody coupled to peroxidase, followed by colour development using a substrate of peroxidase enzyme. Various assay parameters have been optimized. The validity of the procedure was examined by assessing the enhanced MHC expression on YAC cells treated with a soluble rat spleen derived factor, by the new procedure as well as by the flowcytometer. Comparable results were obtained by using both techniques.

Animals↗
PubMed1989

Lack of optimal activation of natural killer levels by interleukin-2 in rat spleen cells: evidence for suppression.

The effect of human recombinant IL-2 on the levels of natural killer (NK) activity in spleen cells derived from BALB/c mice and different strains of rats was studied. Enhancement of murine NK activity in response to IL-2 was readily demonstrable. Levels of NK activity in control as well as IL-2-treated spleen cells from Wistar, Sprague-Dawley, Fischer, and Long-Evans rats increased initially and peaked on Day 1 or 2 of culture. No significant differences between the control and the IL-2-treated cultures was found in this duration. The subsequent fall in NK activity was slower in IL-2-treated cultures of Fischer and Long-Evans rat spleen cells resulting in a significant difference between the NK levels in control and IL-2-treated cells on Day 5 and Day 7 of the culture. In the case of Wistar and Sprague-Dawley rats, the boosting effect of IL-2 on NK levels was either poor or nonexistent. Even though NK activation was poor, spleen cells of all strains of rats did proliferate in response to IL-2, indicating that the IL-2 preparation used was biologically active on rat spleen cells. Rat spleen cells cultured alone or with IL-2 released a factor(s) in the culture supernatant which could suppress the IL-2-induced NK activation in mouse spleen cells. Indomethacin could block the release of suppressor factor by cultured rat spleen cells. Moreover the NK levels in rat spleen cells could be augmented by IL-2 in the presence of indomethacin. These results indicate that the subdued IL-2-induced NK activation in bulk cultures of rat spleen cells could be due to spontaneous release of prostaglandins by the cultured cells.

Animals↗
PubMed1989

Numerical simulation of systemic O2 and CO2 exchange in a hyperbaric environment.

The process of gas exchange in systemic capillaries and its surrounding tissue is simulated numerically in a hyperbaric environment, taking into account the molecular diffusion, convection, saturation of haemoglobin with O2 and CO2, and the metabolic activity in the tissue. Krogh tissue-cylinder is used as a geometrical representation of the capillary-tissue system. The resulting system of non-linear governing equations together with the physiologically relevant boundary conditions is solved numerically. It is found that the concentration of oxygen decreases from the axis of the capillary to the tissue periphery whereas the concentration of carbon dioxide increases. It is shown that very little CO2 is transported radially. The location of the vulnerable region from the point of view of CO2 accumulation is found to be the rim (r = R2, z = L) situated at the periphery of the tissue near the venous end of the capillary. It is also found that accumulation of O2 decreases whereas that of CO2 increases in a hyperbaric environment. Finally, it is surmised that one of the reasons in causing discomfort among divers could be excessive accumulation of CO2 in the tissue.

Biological Transport↗
PubMed1989

Interleukin-2-induced decrease in the buoyant density of cytotoxic cells and its relationship with proliferation.

Interleukin 2 (IL-2) is known to induce an augmentation of natural killer activity. In the present study we have used discontinuous Percoll density gradients to investigate the changes in the buoyant density of killer effector cells generated in response to IL-2. In all systems examined (mouse and rat spleen cells and human peripheral blood mononuclear cells), the cytolytic effectors generated in response to IL-2 have markedly lower buoyant densities compared to fresh natural killer cells. Our results also suggest that if a single layer of 44.2% (v/v) Percoll is used, almost all IL-2-induced cytolytic activity can be enriched in the cells which float on this layer whereas the heavier cells from the pellet are devoid of cytotoxic activity. The contribution of proliferative activity to (a) the generation of cytotoxicity and (b) the decrease in the buoyant density of the IL-2-induced killer cells was also studied in the mouse system. Natural killer levels in mouse spleen cells treated with mitomycin C could be significantly augmented by IL-2. Moreover, the effector cells generated in control as well as mitomycin-C-treated spleen cells in response to IL-2 had the same low buoyant densities. These results indicate that proliferation is not a prerequisite for the activation of killer activity and a reduction in buoyant density in response to IL-2.

Animals↗
PubMed1989

Clinical profile and electrodiagnostic study of peripheral neuropathy.

A clinical analysis and electrophysiological study was performed in 40 cases of peripheral neuropathy. Motor nerve conduction velocity (MNCV) and electromyography (EMG) were also recorded in 20 healthy volunteers. Twelve cases were of diabetic neuropathy (DN), nine of Guillain-Barre syndrome (GBS), eight of idiopathic, six of leprous, three of toxic neuropathy and one each of acute intermittent porphyria (AIP) and carcinomatous neuropathy. The onset was insidious in a majority of the cases (70%), the presenting symptom being paraesthesia (27.5%). A variable sensory loss was the commonest finding (77.5%). Two patients each had evidence of cranial nerve involvement and affection of urinary bladder and bowel. In both DN and GBS there was a significant reduction in the MNCV especially in the peroneal nerves. In DN 41.6% had evidence of decreased motor unit potentials and 16.6% showed spontaneous fibrillatory activity. For GBS these figures were 77.7% and 8.3% respectively. The peripheral nerve involvement was variable in leprosy and the EMG was normal in all, but one case.

Adult↗
PubMed1989

Modulation of major histocompatibility complex antigens and inhibition of proliferative activity of YAC lymphoma cells by a natural killer lysis resistance-inducing factor (NK-LRIF).

Concanavalin-A-activated rat spleen cells secrete a natural killer lysis resistance-inducing factor (NK-LRIF) distinct from interleukin-2 and interferon, which induces resistance to NK-cell-mediated lysis in YAC tumor cells. In order for NK-LRIF to have an effect on YAC cells, several hours of incubation is required. When NK-LRIF-treated YAC cells are washed and cultured in the absence of NK-LRIF, normal NK susceptibility is regained. YAC cells treated with NK-LRIF show a significant decrease in the rate of proliferation as judged by changes in cell numbers and rate of thymidine incorporation. Cell cycle studies indicate that the proportion of G0/G1 phase cells increases in YAC preparations treated with NK-LRIF. Major histocompatibility complex (MHC) class I antigen expression is markedly enhanced on YAC cells incubated with NK-LRIF but the expression of MHC class II antigens and Thy-1 antigen remains unchanged. No effect of NK-LRIF treatment on the capacity of YAC cells to bind effector spleen cells could be demonstrated.

Animals↗
PubMed1989

Relapses in paucibacillary patients after treatment with three short-term regimens containing rifampin.

Three multidrug regimens all containing rifampin and dapsone have been tried for the treatment of 278 cases of paucibacillary leprosy. Regimen I was the one recommended by the WHO Study Group. Regimen II was the same as Regimen I with depsone alone continued for a further 6 months. Regimen III was the same as Regimen II but rifampin was given daily for the first 7 days. The patients were comparable with regard to disease classification, lepromin status, bacteriological status, and number of lesions. As reported earlier, the disease inactivity rates by 1 year of treatment were much greater with Regimens II and III than with Regimen I (94% and 97% vs 76%). Early reaction was seen in 6% of those in Regimen III and in none in Regimens I and II. Late reaction was observed in 9% of those in Regimen I and none in Regimens II and III. During 3 1/2 years of follow up, 13% of the cases in Regimen I, 1% in Regimen II, and 2% in Regimen III relapsed. Since the patients in the three regimens were otherwise comparable, it is concluded that the high inactivity rate, low relapse rate (1%-2%), and no early or late reaction as observed in Regimen II patients were because of adequate treatment.

Adult↗
PubMed1988

Properties and characterization of a rat spleen cell-derived factor that induces resistance to natural killer cell lysis in YAC lymphoma cells.

Supernatants of Con A-stimulated rat spleen cell cultures contain a factor that induces relative resistance to NK cell-mediated cytotoxicity in the YAC cell line, a line that is otherwise highly susceptible to murine NK cell-mediated lysis. This NK-lysis resistance-inducing factor (LRIF) has a Mr of 12,600 Da, as determined by gel filtration chromatography, and an isoelectric pH of 4.8. NK-LRIF is heat labile and is de-activated by treatment with proteolytic enzymes. Unlike immune-IFN (IFN-gamma), NK-LRIF is not inactivated by pH 2 treatment, and antibodies capable of neutralizing IFN-alpha and IFN-gamma do not abrogate the effect of NK-LRIF. Highly purified IL-2 preparations lack NK-LRIF activity. NK-LRIF does not induce a general resistance to lysis in YAC cells, because control and NK-LRIF-treated YAC cells were equally susceptible to alloimmune cytotoxic T cells. YAC cells treated with NK-LRIF showed a marked enhancement (5- to 10-fold) in the expression of class I MHC Ag. This observation supports the proposition that the NK susceptibility of target cells could be inversely related to the expression of class I MHC Ag.

Animals↗
PubMed1988

Lectin-induced cytotoxic activity in spleen cells from young and old mice. Age-related changes in types of effector cells, lymphokine production and response.

Concanavalin A (Con A)-induced cytotoxic activity, interferon (IFN) and interleukin-2 (IL-2) levels in cultures of spleen cells from young (2-3 months) and old (22-24 months) C57BL/6 female mice were studied. Con A-activated spleen cells from old mice attained significantly higher cytotoxic activity compared with activated spleen cells from young mice. Activated spleen cells from old and young mice showed differences in their ability to lyse different types of target cells. Both could lyse P-815 cells, neither could lyse K562 cells, and only activated cells from old mice could lyse EL-4 cells. Cytotoxic spleen cells from the old mice were more sensitive to anti-asialo-GM-1 and anti-Lyt-2.2 plus complement (C) treatment. While levels of IL-2 produced by spleen cells from young mice were higher, the addition of exogenous IL-2 had no effect on cytotoxic activity of the spleen cells from old mice. Exogenous IL-2, however, could lower cytotoxic activity of Con A-activated spleen cells from young mice. Activated spleen cells from old mice generated higher levels of IFN-gamma while the addition of an anti-IFN-gamma antibody boosted the level of cytotoxicity by Con A-activated spleen cells from young mice. These results suggest that IFN-gamma may act as a feedback inhibitory signal regulating the levels of cytotoxicity induced in spleen cells from young mice in response to Con A. The cytotoxic activity generated in Con A-activated spleen cells from old mice reflects a defect in this feed-back regulation.

Aging↗
PubMed1988

Interleukin-2 induced activation of natural killer cells in rats and mice: a comparative study.

Effects of interleukin-2 (IL-2) on the natural killer (NK) activities of BALB/c mouse and Wistar rat spleen cells were compared. While mouse spleen cells cultured alone rapidly lost NK activity, co-culture with IL-2 resulted in a marked enhancement of NK activity. In contrast, the levels of NK activity of rat spleen cells cultured alone increased and remained high for 3 days and declined thereafter. Addition of human recombinant IL-2 or purified rat IL-2 did not influence the NK levels in rat spleen cell bulk cultures. Both IL-2 preparations were however biologically active as shown by their capacities to induced proliferation in rat spleen cells. Rat spleen cells suppressed the IL-2 activation of mouse spleen cells in a dose dependent manner, indicating a suppressor influence generated by rat spleen cells. Culture supernatants of rat spleen cells cultured with or without IL-2 for 3 or 5 days could also suppress the mouse spleen NK activation in response to IL-2. The suppressor activity could be concentrated on a 5K MW cut-off Amicon filter indicating that the molecular weight of the factor is more than 5000. These results indicate that a suppressor of IL-2 induced NK activation of mouse spleen cells is released by cultured rat spleen cells.

Animals↗