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Biomedical subjects

R K Saxena

Publications and source records attributed to R K Saxena.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1987

A spleen cell derived factor imparts resistance to NK cell mediated lysis in a mouse lymphoma cell line.

The effect of interleukin-2 (IL-2) preparations on the susceptibility of YAC cells to mouse natural killer (NK) cells was examined. Crude IL-2 preparations induced a significant decrease in the susceptibility of YAC cells. Highly purified IL-2 preparations, however, did not have a similar effect. Since the IL-2 preparations used in this study were purified from the culture supernatant of Con A activated spleen cells (Con A Sup.), our results indicated the presence in Con A Sup. of a lysis resistance inducing factor (LRIF), distinct from IL-2. We were able to purify LRIF from Con A Sup. by preparative isoelectric focusing and determined its isoelectric pH to be 4.8.

Animals↗
PubMed1986

Early electrocardiographic diagnosis of left ventricular hypertrophy in hypertensive patients.

This study included 25 hypertensive patients with "normal" standard 12-lead scalar electrocardiogram and an equal number of age- and sex-matched controls. We recorded routine twelve leads, posterior chest leads, ensiform lead, right-sided precordial leads, lead CM5 and oesophageal electrocardiogram at different levels in all individuals. In addition we recorded an unconventional unipolar lead with the chest electrode placed on the thoracic seven spine. We also recorded some unconventional bipolar leads, in each instance using V5 as the positive electrode and the T7 spine, or the oesophageal electrode as negative. We observed that the T wave height of 20% or less of R wave amplitude in lead I was highly specific (92%) and sensitive (76%) in detecting early left ventricular hypertrophy in hypertensive patients, with the standard 12-lead electrocardiogram considered "normal" by conventional criteria. The T wave amplitude of 15% or less of the accompanying QRS in lead V6 was nearly equally diagnostic (specificity 88% and sensitivity 68%). An S wave of 0.3 mV or more in the bipolar lead recorded with the positive electrode at V5 and the negative electrode on T7 spine was also highly specific (80%) and sensitive (72%). Isoelectric or inverted T wave in lead V8, ST segment depression and T wave inversion in lead CM5 and ST segment depression in the bipolar lead recorded with the positive electrode at the V5 position and negative electrode at the atrial level of the oesophagus were highly specific (100%) but had a low sensitivity (40, 36, 16, and 28%, respectively). Combined lead V8 and lead I further improved the sensitivity to 96% without decreasing the specificity.

Adult↗
PubMed1984

Effect of feeding a diet with half of the recommended levels of all vitamins on the natural and inducible levels of cytotoxic activity in mouse spleen cells.

Groups of 6-week-old female C57Bl/6 mice were fed a normal diet with recommended levels of all vitamins or a vitamin-deficient (VD) diet containing half of the recommended level of each vitamin. At different time periods (1-11 weeks) after the initiation of diets, basal natural killer (NK) activity, interleukin-2 (IL-2) and concanavalin A (Con A)-induced cytotoxic activity, Con A-induced IL-2 production and levels of allospecific cytotoxic T cell activity generated in a mixed lymphocyte culture (MLC), were studied in spleen cells derived from control and VD mice. Results indicated that: (i) spleen NK activity remained normal until 2 weeks after the initiation of VD diet, fell steeply to low levels at the 4 and 5 week time points and remained depressed thereafter; (ii) IL-2- and Con A-induced levels of cytotoxic activity in spleen cells derived from VD mice declined at 4 weeks after the institution of VD diet, and then remained low throughout the study; (iii) the capacity of spleen cells from VD mice to generate IL-2 in response to Con A and cytotoxic T cells in response to allogeneic spleen cells, was normal at 1 and 4 weeks after initiation of the VD diet and was markedly depressed at the 6 and 9 week time points. These results suggest that partial combined deficiencies of dietary vitamins strongly influence assays of immune function.

Animals↗
PubMed1984

Effect of protein calorie malnutrition on the levels of natural and inducible cytotoxic activities in mouse spleen cells.

Six-week-old C57B1/6 female mice were fed a normal (24% protein) or an isocaloric but protein-deficient (4% protein) diet. At different time periods after the initiation of diets, basal natural killer (NK) activity, interleukin-2 (IL-2) and concanavalin-A (Con-A)-induced cytotoxic activity, Con-A-induced IL-2 production and levels of allospecific cytotoxic T cell activity generated in a mixed lymphocyte culture (MLC), were studied in spleen cells derived from control and protein deficient (PD) mice. Results indicated that (a) levels of spleen NK activity increased initially in PD mice, but after 7 weeks on PD diet declined to normal and subnormal levels, (b) IL-2 generation in response to Con-A as well as IL-2 activation of NK activity were comparable in spleen cells of control and PD mice at all time points tested, (c) Con-A-induced cytotoxic activity was significantly greater in spleen cells from PD mice, the difference being greater at higher doses of Con-A, and (d) generation of alloimmune cytotoxic T cells in a MLC reaction was normal in PD mouse spleen cells until 4 weeks after the beginning of PD diet, but declined markedly thereafter. Relevance of these observations to other related findings in protein calorie malnutrition are discussed.

Animals↗
PubMed1984

Interleukin-2-induced activation of natural killer activity in spleen cells from old and young mice.

Generation of natural killer (NK) activity in response to a partially purified preparation of rat interleukin-2 (IL-2) was compared in spleen cells derived from young (8-10 weeks old) and old (greater than 2 years old) female C57BL/6 mice. Significant NK activation was observed in both young and old mouse spleen cells incubated with 100 U IL-2/ml for 1-4 days, but the levels of cytotoxic activity generated in old mouse spleen cells was always lower than those of similarly treated young mouse spleen cells. Differences in IL-2-induced NK activation in old and young mouse spleen cells was obtained irrespective of the concentration of IL-2 used (25-400 U/ml). Quantitative comparisons indicated that old spleen cells activated by 3 day incubation with IL-2 acquired about two-fold higher NK activity than fresh young mouse spleen cells but still had only one-fourth of the levels of NK activity attained by IL-2-activated young mouse spleen cells. Cytotoxic activity of IL-2-activated young or old mouse spleen cells were totally abrogated by anti-asialo GM-1 antiserum + C but not by anti-Ly-2 + C treatment, indicating that the activated cytotoxic cells fell in the NK cell category. An analysis of NK precursor (NK-p) frequency by limiting dilution assay indicated that the NK-p frequency was about 4-fold higher in young as compared to old mouse spleen cells. The level of cytotoxic activity attained per NK-p cell was not significantly different for NK-p cells of old or young mice.

Aging↗
PubMed1983

Immunodiagnosis of Bancroftian filariasis by enzyme linked immunosorbent assay using Litomosoides carinii and Setaria cervi antigens.

An ELISA was developed using cross-reacting antigens of Litomosoides carinii and Setaria cervi to detect antibodies in filarial patients. The diagnostic potential of the test was investigated in 80 symptomatic cases of filariasis, 40 asymptomatic carriers and 50 normal subjects of an area around Lucknow endemic for Bancroftian filariasis. By the criteria laid down for ELISA positivity for filariasis, 86.2% of the symptomatic cases could be detected by this test. Only four of 40 asymptomatic carriers and one of 50 normal subjects gave a positive ELISA response. Purified antigenic fractions of S. cervi are also promising for detecting asymptomatic carriers.

Antibodies↗
PubMed1982

Regulation of natural killer activity in vivo. III. Effect of hypophysectomy and growth hormone treatment on the natural killer activity of the mouse spleen cell population.

Spleen natural killer (NK) activity against YAC tumor cells was reduced in female C57BL/6J mice hypophysectomized at 3 weeks and sacrificed 4-8 weeks later. Proportions of null cells and of target binding cells in spleens from hypophysectomized and sham operated mice were significantly different. Administration of ovine growth hormone (GH) (100 microgram/day, i.p. for 10 days) resulted in a marked recovery of NK activity in hypophysectomized mice. NK activity by spleen cells from hypophysectomized or sham operated mice (with or without GH treatment) was mediated by non-T, non-B lymphocytes.

Animals↗
PubMed1982

Identity of effector cells participating in the reverse antibody-dependent cell-mediated cytotoxicity.

Our previous work has shown that antibody-coated mouse spleen cells express enhanced cytotoxic activity against some Fc-receptor-bearing target tumour cells by a mechanism which appears to be similar to an antibody-dependent cell-mediated cytotoxicity (ADCC) reaction with reversed polarity of the antibody bridge (R-ADCC). In this report we have shown that (i) the levels of basal natural killer (NK), ADCC and R-ADCC cytotoxic activities in mouse spleen cells are strongly correlated with each other, (b) simultaneous induction of ADCC and R-ADCC reactions does not result in an additive cytotoxic response, and (iii) YAC cells which do not bear Fc receptors and are highly sensitive to lysis by NK cells, can specifically and competitively inhibit the ADCC and R-ADCC reactions. These results suggest that the R-ADCC reaction may be mediated by the same effector cell population as mediates NK and ADCC reactions against tumour target cells.

Animals↗