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Biomedical subjects

J K John

Publications and source records attributed to J K John.

At least 19 recordsLinked to original sources
PubMed2001

Development of potent non-carbohydrate imidazole-based small molecule selectin inhibitors with antiinflammatory activity.

A novel series of non-carbohydrate imidazole-based selectin inhibitors has been discovered via high-throughput screening using a P-selectin ELISA-based assay system. The initial lead 1 had an IC(50) of 17 microM in the P-selectin ELISA; this potency was significantly improved via an extensive SAR exploration. One of the current lead compounds (29) has an IC(50) of 300 nM in a P-selectin ELISA; it also has good activity in P- and E-selectin cell adhesion assays and shows efficacy in vivo. These compounds represent a novel series of sLe(X) mimetics with antiinflammatory activity. Their unique profile supports our interest in their further evaluation as drug candidates for the treatment of inflammation. Herein we describe the syntheses, optimization, and SAR of this series of novel potent selectin antagonists.

Animals↗
PubMed1996

Reconstruction of mandible and surrounding soft tissues in patient with necrotizing fasciitis.

Necrotizing fasciitis is rare in the orofacial region, with fewer than 20 cases reported in the literature. Extension of the disease process to involve the underlying bone has not been previously reported. A patient is presented in whom destruction of superficial skin and fascia, necrosis of a portion of the mandible, and involvement of the parotid gland complicated reconstruction.

Calcium Hydroxide↗
PubMed1991

Psychiatric morbidity in HIV infected individuals.

Forty six subjects infected with the human immunodeficiency virus (HIV) were followed up, for recording psychiatric morbidity if any, before and after the information regarding their HIV status was revealed to them. Among these, four patients had the AIDS syndrome, while 42 individuals were HIV carriers. The pre-information morbidity in the AIDS group included two individuals who presented with delirium and one with an adjustment disorder. The psychiatric diagnosis among the HIV carriers revealed one patient with major depression, four with adjustment disorders and four with alcohol dependence syndrome. The additional morbidity after the diagnoses was revealed included major depression and adjustment disorders which could be managed by psychological intervention and counselling in most cases. The individual who developed major depression later, committed suicide. The study though preliminary in nature, suggests that it may be beneficial to include psychiatric management as part of the general care of individuals with HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1989

The fear of AIDS: psychiatric symptom or syndrome?

The clinical characteristics of 13 patients who presented with the fear of AIDS are documented. The common features included anxiety traits in premorbid personality, a past history of promiscuous heterosexual behaviour, signs and symptoms of an anxiety state. The current controversies regarding the diagnostic status of patients presenting with the fear of AIDS and its clinical significance are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Factors associated with the course and outcome of schizophrenia in India. Results of a two-year multicentre follow-up study.

The paper describes the two-year follow-up results from 323 out of 386 patients fulfilling a modified version of Feighner's criteria for diagnosis of schizophrenia, in Lucknow, Vellore, and Madras. There was remission in 66% of cases. Short duration of illness, consistent compliance with medication, positive attitudes of relatives and neighbours, absence of economic difficulties, increase in religious activities on the part of patients, a rural background, and a non-schizoid pre-morbid personality were associated with good outcome. Features of depression, dangerous behaviour, and absence of agitation were associated with poor outcome.

Adolescent↗
PubMed1988

Flow cytometric analysis of lymphocyte activation in the mixed lymphocyte response.

Interleukin 2 receptor (IL2R) expression may be a useful parameter for assessing lymphocyte activation in the mixed lymphocyte response (MLR). However, the contribution of irradiated stimulator (S*) cells to the levels of IL2R+ cells recovered must first be defined. We have used a flow cytometric parameter termed the sip count to assess this potential contribution of S* cells. This parameter, which is the number of cells within a defined cell gate, is a reflection of the viable cell number per culture well, since (a) a constant number of cells were plated per well on day 0, (b) cells recovered from a well were resuspended in a constant volume, (c) the flow cytometer aspirated (sipped) a constant volume of cell suspension, and (d) nonviable cells were not included in the gate. Sip count assessment showed that only 5% of S* cells were recoverable by day 4 of culture; in contrast, 70% or more of unstimulated responder cells were recoverable. Sip counts of MLR cultures identified an increase in cell number beginning on day 5, reflecting DNA synthesis and cell division. We then used the sip count to assess changes in the levels of IL2R+ cells in MLR cultures. The number of IL2R+ cells continued to increase up to day 7, even though maximal DNA synthesis occurred on day 5. Further, dual color analysis revealed that the proportion of CD4 cells expressing IL2R was maximal on day 5, whereas the proportion of CD8 cells expressing IL2R continued to increase until day 9. These findings show that flow cytometry can be used to study lymphocyte activation by alloantigens.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

AIDS-Phobia.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Abnormalities of interleukin 2 receptor expression associated with decreased antigen-induced lymphocyte proliferation in patients with AIDS and related disorders.

Several parameters of lymphocyte interleukin 2 receptor (IL-2R) expression in response to tetanus toxoid (TT) were monitored using a receptor-specific monoclonal antibody and flow cytometry in patients with acquired immunodeficiency syndrome (AIDS, n = 6), AIDS-related complex (ARC, n = 8), or lymphadenopathy syndrome (LAS, n = 9). These parameters, measured on days 6 and 7 of culture, included (a) the percentage of recovered lymphocytes expressing IL-2R, (b) the number of IL-2R-positive cells/lymphocyte trigger region (a relative measure of the number of IL-2R-positive cells per culture), and (c) mean fluorescence intensity of IL-2R-positive cells. Data were then assessed in relation to DNA synthesis on day 7 of culture. Normal DNA synthesis was observed in nine patients (Pt-N group), and the mean values for all three IL-2R expression parameters in this group did not significantly differ from those of the healthy control group (n = 20). In contrast, 14 patients exhibited low proliferation (Pt-L group) and mean values for all three parameters were significantly lower in this group compared to both the Pt-N and control groups. When considering individual patient values, day 7 IL-2R+ cell number proved the best predictor of DNA synthesis results: all 14 patients in the Pt-L group exhibited low IL-2R+ cell number, while seven of nine patients in the Pt-N group exhibited normal IL-2R+ cell number. Thus, low TT-induced lymphocyte proliferation in AIDS and related disorders is associated with defective IL-2R expression. Further, assessment of IL-2R+ cell number appears to be a valid alternative assay for monitored antigen-induced T cell proliferation in vitro.

AIDS-Related Complex↗
PubMed1986

Cyclosporine inhibits the expression of receptors for interleukin 2 and transferrin on mitogen-activated human T lymphocytes.

The effect of cyclosporine A (CsA) on the mitogen-induced expression of Interleukin 2 receptor (IL2R) and transferrin receptor (TR) was monitored using receptor-specific monoclonal antibodies and flow cytometry. For all mitogens tested (PHA, Con A, OKT3, and Leu 4), expression of IL2R and TR, as well as DNA synthesis (3H-thymidine incorporation), were significantly reduced in the presence of CsA (0.5 microgram/ml). Titration experiments in the OKT3 system, the mitogen system most profoundly affected by CsA, revealed that CsA concentrations as low as 0.05 microgram/ml inhibited IL2R and TR expression and DNA synthesis, and that changes in DNA synthesis reflected changes in IL2R and TR expression. The addition of exogenous IL2 partially abrogated the CsA-mediated inhibition of all three activation parameters (IL2R, TR, DNA synthesis) in response to PHA, OKT3, and Leu 4. In contrast, exogenous IL2 did not reverse CsA-mediated reductions in Con A-stimulated activation parameters. These findings indicate that CsA inhibits mitogen-induced expression of IL2R and TR, and for some mitogen systems, this inhibition appears, at least in part, to be secondary to decreased IL2 production.

Antibodies, Monoclonal↗
PubMed1986

Unique pattern of interleukin 2 receptor expression by lymphocytes in response to anti-Leu 4 monoclonal antibody: relationship to monocyte accessory cell function.

The relationship of early interleukin 2 receptor (IL2R) expression to subsequent DNA synthesis by mitogen-stimulated human mononuclear cells (MC) was studied. For serial dilutions of a given mitogen, the percentage of lymphocytes expressing IL2R after 1 day of culture was plotted vs 3H-thymidine incorporation on day 3, and the IL2R value associated with a proliferative response of 50,000 counts per minute (IL2R-50K) determined. A mean IL2R-50K value of 7 characterized PHA, Con A, and OKT3 responses, while a higher mean value of 29 characterized anti-Leu 4(L4) responses. As tested in OKT3 and L4 systems, the addition of exogenous IL2 did not alter IL2R-50K values. Because both OKT3 and L4 recognize the lymphocyte CD3 antigen but react with different monocyte Fc receptors, the role of monocytes in producing elevated L4 IL2R-50K values was explored. MC from healthy L4 nonresponders (NR), induced to proliferate with L4 in the presence of responder (R) monocytes, also yielded an elevated mean IL2R-50K value of 31. In contrast, direct stimulation of R-MC, NR-MC, or NR-MC plus R monocytes by L4-coated sepharose beads produced lower mean IL2R-50K values of 12 or 13. Two-color cytofluorescence studies measuring IL2R and transferrin receptor (TR) on day 2 of culture revealed that most of the increase in IL2R+ cells in response to L4 was attributable to IL2R+TR-cells. These findings suggest that crosslinking of lymphocyte-bound soluble L4 by R monocytes leads to a uniquely elevated pattern of IL2R expression involving a disproportionate increase in the level of IL2R+TR-cells.

Antibodies, Monoclonal↗
PubMed1986

Early activation marker expression to detect impaired proliferative responses to pokeweed mitogen and tetanus toxoid: studies in patients with AIDS and related disorders.

We tested the premise that measurement of interleukin 2 receptor (IL2R) and transferrin receptor (TR) can be used to assess proliferative responses to pokeweed mitogen (PWM) and tetanus toxoid (TT). Our study group consisted of patients with Human Immunodeficiency Virus (HIV) infection, including patients with acquired immunodeficiency syndrome (AIDS, n = 10), AIDS-related complex (n = 14), lymphadenopathy syndrome (n = 7), or homosexual men seropositive for HIV (n = 6). Controls were 40 healthy seronegative blood donors. IL2R and TR expression by stimulated mononuclear cells were assessed using specific monoclonal antibodies and flow cytometry, and results were analyzed using the 3H-thymidine assay for DNA synthesis as a standard for comparisons. For identifying low PWM responses, both the IL2R+ cell percent and the IL2R+ cell number (no.) per lymphocyte trigger region (a relative measure of IL2R+ cell no. per culture) on day 3 (72 h) were sensitive (greater than 90%) and specific (80%); day 3 TR+ cell no. was also sensitive (92%) and specific (100%). For detecting low TT-induced responses, day 7 IL2R+ cell no. proved the most sensitive (100%) and specific (78%) parameter. These findings indicate that cytofluorometric analysis of IL2R and/or TR expression is a reliable method for detecting impaired proliferative responses to PWM and TT in these patients. Such a method offers an attractive alternative to the regulatory and disposal problems associated with radioactivity in the conventional DNA synthesis assay, as well as providing insight to the mechanism(s) responsible for impaired proliferation.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Social and personality factors in dapsone resistant patients.

A preliminary study in which a sample of 25 patients registered with SLR and TC, Karigiri, with proved secondary DDS-resistant leprosy were compared, with 25 patients not suspected to be DDS-resistant, for social and personality factors, which could have lead to non-compliance in treatment. A structured interview schedule enquiring into factors leading to irregular treatment and the psycho-social background of the patient was used. The Eysank's Personality Inventory (EPI) and Personality traits assessment on a linear analogue was also administered to them. Statistical analysis showed that DDS-resistant leprosy patients were as a group more irregular for treatment, showed personality traits of being casual and uncontrolled and scored high on the neuroticism scale of the EPI.

Adult↗
PubMed1980

ATP-dependent activation of glucocorticoid receptor from rat liver cytosol.

The glucocorticoid--receptor complex from freshly prepared rat liver cytosol is in a non-activated form, with very little affinity to bind to isolated nuclei. When such preparations were incubated with 5--10 mM-ATP at 4 degrees C, the receptor complex acquired the properties of an 'activated' transformed form, which readily bound to nuclei, ATP--Sepharose, phosphocellulose and DNA--cellulose. This transformation was comparable with the activation achieved by warming the steroid--receptor complex at 23 degrees C. The effect of ATP was specific, as it was more effective than ADP, whereas AMP had no such effect on activation. The process of receptor activation was sensitive to the presence of 10 mM-sodium molybdate; the latter blocked activation by both ATP and heat. Bivalent cations had no observable effect on the receptor activation at low temperature, but they decreased the extent of activation by ATP. The steroid-binding properties of glucocorticoid receptor remained intact under the above conditions. However, a significant increase in steroid binding occurred when ATP was preincubated with cytosol receptor before the addition of [3H]triamcinolone acetonide. ATP also stabilized the glucocorticoid--receptor complexes at 23 degrees C. These results suggest a role for ATP in receptor function and offer a convenient method of studying the activation process of glucocorticoid receptor under mild assay conditions.

Adenosine Triphosphate↗
PubMed1980

Interaction of rat liver glucocorticoid receptor with adenosine 5'-triphosphate. Characterization of interaction by use of ATP-sepharose affinity chromatography.

An interaction between rat liver glucocorticoid--receptor complex and immobilized ATP was identified. Rat liver cytosol preparations were incubated with [3H]triamcinolone acetonide for 4 h at 4 degrees C and partially purified by precipitation with (NH4)2SO4 before use. The resulting glucocorticoid--receptor complex could be selectively adsorbed on to columns of ATP--Sepharose. The freshly prepared cytosol [3H]triamcinolone acetonide--receptor complex had very little affinity for binding to the ATP--Sepharose column, but acquired this ability on temperature- or salt-activation. The presence of 10 mM-sodium molybdate during this salt- or temperature-dependent activation blocked the binding of the receptor complex to ATP--Sepharose. The interaction is reversible, since it can be disrupted by high-salt conditions. A competitive binding assay, using free nucleotides in samples to be chromatographed, revealed a preferential interaction between ATP and the glucocorticoid--receptor complex. Buffer containing ATP was also used to elute the glucocorticoid--receptor complex from ATP--Sepharose columns successfully. When ATP was added to the preparations containing [3H]triamcinolone acetonide--receptor complexes, the steroid specificity or sedimentation properties of the complex remained unaltered. Our results demonstrate an interaction between rat liver glucocorticoid--receptor complex and immobilized ATP and suggest a role of this nucleotide in receptor function.

Adenosine Triphosphate↗