Abacus VAS in burn pain assessment.
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Burns↗
Biomedical subjects
P Kumar
Publications and source records attributed to P Kumar.
Correlation of T-cell response and lymphokine profile with RESA peptides of Plasmodium falciparum containing a universal T-cell epitope and an immunopotentiator, polytuftsin.
Two RESA repeat sequences, (EENVEHDA)2 and (DDEHVEEPTVA)2, were chemically linked to a universal T-cell epitope, CS.T3 and polytuftsin, and a natural immunopotentiator, was physically mixed with these conjugates. The immunogens were studied for in vitro antigen-induced T-cell proliferation, and cytokine levels were measured in the culture supernatants. The RESA peptide(s)-CS.T3 conjugate containing polytuftsin showed the highest stimulation index (SI) as compared to the RESA peptide-CS.T3 conjugates or RESA peptides alone. Spleen cells from mice primed with either RESA peptide(s)-CS.T3 conjugate or RESA peptide-CS.T3 conjugate containing polytuftsin, when pulsed in vitro with the respective RESA peptide, showed a higher proliferation index as compared to spleen cells primed and pulsed in vitro with the respective RESA peptides. This observation has an important relevance during natural reinfection for boosting the immune response. The culture supernatants from the cells primed and pulsed in vitro with RESA peptide-CS.T3 conjugate and RESA peptide-CS.T3 conjugate containing polytuftsin showed higher IL-2 and IFN-gamma levels as compared to the RESA peptides alone. Very low IL-4 levels were detected with the above formulations. The cytokine profile is suggestive of a CD4+ TH1 type of immune response, which is ideal for the killing of intracellular pathogens like the malarial parasite.
Adjuvants, Immunologic↗
Potentiation of immune response against the RESA peptides of Plasmodium falciparum by incorporating a universal T-cell epitope (CS.T3) and an immunomodulator (polytuftsin), and delivery through liposomes.
Synthetic peptides representing repeat sequences of ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum have shown poor immunogenicity and protection. In this study, the RESA peptides [(EENVEHDA)2 and (DDEHVEEPTVA)2] were chemically linked to a universal T-cell determinant, CS.T3, derived from the CS protein of P. falciparum. Polytuftsin (TKPR)40, a polymer of naturally occurring immunomodulator "tuftsin," was physically mixed with these conjugates. These preparations in alum and liposomes were immunized in four inbred strains of mice with different genetic backgrounds to study the humoral response. In the case of liposome-entrapped preparations, a 10 microg dose of antigen showed the optimum antibody response. Mice immunized with liposome containing RESA peptide(s)-CS.T3 conjugate along with polytuftsin showed the highest antibody levels in all the strains, whereas the RESA peptide(s) alone, adsorbed on alum or entrapped in liposomes, showed either poor or moderate antibody levels. The antibodies raised against liposome-entrapped preparations in both high-responder strain (SJL/J H-2s) and low-responder strain (FVB/J H-2q) showed 2 4-fold lower Kd values as compared to the alum adsorbed preparations, suggestive of high affinity antibodies. All the antigen preparations predominantly induced IgG2a and IgG2b isotype response, suggesting that the T-helper response involved is of the CD4 Thl type. The in vitro merozoite reinvasion inhibition assay showed 50-92% inhibition with sera raised against different antigen formulations. The highest percentage inhibition was observed with the RESA peptide-CS.T3 conjugate containing polytuftsin in liposomes. Thus, the incorporation of peptide antigens inside liposomes not only reduced the antigen dose by 5-fold but also elicited a high titre with high affinity antibodies and the inhibition of merozoites to RBC in vitro. Therefore, we conclude that the incorporation of these synthetic constructs in liposomes could be a useful strategy for the development of a subunit immunogen against malaria.
Adjuvants, Immunologic↗
Irradiation induces upregulation of CD31 in human endothelial cells.
Radiation-induced vascular injury is believed to be a major factor contributing to parenchymal atrophy, fibrosis and necrosis in normal tissue after radiotherapy. In this study irradiation of human umbilical vein endothelial cells (HUVECs) significantly increased adherence of U-937 cells in a time-dependent manner. Given the potential multifunctional role of CD31 in the vasculature we have examined the possible effects of irradiation on levels of CD31 expression in HUVECs. Irradiation upregulated CD31 expression on HUVECs, independently of initial plating density and radiation-induced changes such as cell number, cell cycle stage, or cell size. CD31 mRNA levels were raised in irradiated HUVECs relative to controls. Both CD31 mRNA and surface protein showed similar changes, suggesting that the increase in mRNA in irradiated HUVECs is responsible for the elevation in cell surface protein. A semi-quantitative study of tissue specimens from patients who had received radiotherapy indicated that CD31 staining in the blood vessels from irradiated tissues was increased compared with controls. Endothelial CD31 is important in the transmigration of leukocytes. We have demonstrated that the incorporation of monoclonal antibody to CD31 significantly inhibited the transmigration of human peripheral blood leukocytes through a monolayer of irradiated HUVECs. Taken together these data strongly suggest that irradiation induces a marked increase in CD31 expression on endothelial cells as part of a general response to irradiation. Its upregulation may play an important role in the development of radiation-induced normal tissue damage and thus is a possible target for therapeutic intervention.
Alternative Splicing↗
Erythropoietin and iron therapy for preterm infants.
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Blood Transfusion↗
Vascular endothelial growth factor and its receptor, KDR, in human brain tissue after ischemic stroke.
Ischemic stroke results from a reduction in cerebral blood flow to a focal region of the brain after the occlusion of an artery, causing damage to nervous tissue. There is a region of cerebral ischemic tissue (penumbra) surrounding an acute cerebral infarct that is dysfunctional but potentially viable. Restoration of perfusion in the penumbra may ameliorate the tissue damage. The identity and the role of growth factors that control the extent of tissue damage and its repair are poorly understood. Angiogenesis has been demonstrated to occur in brain tissues of patients surviving an acute ischemic stroke. In this paper we have investigated the status of a potent angiogenesis factor, vascular endothelial growth factor (VEGF), in patients after acute ischemic brain stroke. Western blotting and immunohistochemistry were used to determine protein expression, and in situ hybridization was used to quantify and localize mRNA synthesis. The expression of VEGF protein was increased in the penumbra compared with infarcted brain and contralateral hemisphere. Neurones, endothelial cells, and astrocytes in the penumbra in all patients studied had significant up-regulation of both VEGF165 and VEGF189 mRNA (p < 0.01, Wilcoxon Matched-Pairs Signed-Ranks Test) compared with infarcted tissue and the normal looking contralateral hemisphere that was used as a control. Immunohistochemistry demonstrated that kinase insert domain receptor was present in blood vessels within the infarct/penumbra and absent from the normal contralateral hemisphere. VEGF, which is important in angiogenesis, may also influence long term neuronal survival, and possibly its modulation may prove to be of therapeutic value for patients with ischemic stroke.
Aged↗
Kala-azar epidemic in Varanasi district, India.
Reports at the Sir Sunder Lal Hospital, Banaras Hindu University, of a large number of kala-azar cases from one particular village in Varanasi district, Uttar Pradesh, led us to carry out an epidemiological study of the situation using standard techniques. The overall prevalence and case fatality of the disease were 12.9% and 10.5%, respectively. A history of fever and hepatosplenomegaly was noted for all the cases. The case definition was the presence of parasites in bone marrow or splenic aspirate smears. The disease was more prevalent among adults, but occurred also among children. However, there was no clear linear relationship between the prevalence of the disease and age group. Kala-azar occurred among males and females, and its prevalence did not correlate significantly with income. Since the disease vector continues to be present in the study area, the health authorities should take strong steps to control the disease.
Adolescent↗
Contribution of the MHC region to the familial risk of coeliac disease.
Susceptibility to coeliac disease is genetically determined by possession of specific HLA-DQ alleles, acting in concert with one or more non-HLA linked genes. The pattern of risk seen in sibs and twins in coeliac disease is most parsimonious with a multiplicative model for the interaction between the two classes of genes. Based on a sib recurrence risk for coeliac disease of 10% and a population prevalence of 0.0033, the sib relative risk is 30. To evaluate the contribution of the MHC region to the familial risk of coeliac disease, we have examined haplotype sharing probabilities across this region in 55 coeliac disease families. Based on these probabilities the sib relative risk of coeliac disease associated with the MHC region is 3.7. Combining these results with published data on allele sharing at HLA, the estimated sib relative risk associated with the MHC region is 3.3. Therefore, the MHC genes contribute no more than 40% of the sib familial risk of coeliac disease and the non-HLA linked gene (or genes) are likely to be the stronger determinant of coeliac disease susceptibility.
Celiac Disease↗
Monoclonal antibodies against bovine growth hormone.
A number of mouse x mouse hybridomas producing monoclonal antibodies (MAbs) against bovine growth hormone (bGH) were prepared by fusion of spleen cells from bGH-primed mice (Balb/c) with non-secretory mouse myeloma cells (PAIOP3) and characterized. MAbs obtained from three fusion experiments belonged to IgM, IgG1 and IgG2b class/subclass of antibodies. Cross-reaction studies indicated that generated antibodies were against three different epitopes of bGH. VIA6E8 (IgG1) and VIIB2E11C9 (IgM) did not cross-react with ovine prolactin (oPRL), ovine leutinizing hormone (oLH) and porcine follicle stimulating hormone. Antibody VIB3C9E8 (IgM) exhibited cross-reaction with oPRL and oLH. Antibody VIC1F9 (IgG2b) cross reacted with oPRL. All MAbs were against conformational epitopes of bGH.
Animals↗
Growth and morbidity patterns of exclusively breast-fed preterm babies.
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Analysis of Variance↗
Impact of a multi-method promotional package on awareness and knowledge about STD and AIDS among the trainees of an industrial training institute in a resettlement colony of Delhi, India.
To design and apply a multi-method promotional package for enhancing awareness and knowledge on STD and AIDS among ITI trainees, and evaluate its impact, an intervention study, using pre and post assessment of the subjects for comparison was carried out. The study was carried out in the Industrial Training Institute (ITI), in a resettlement colony of Delhi. Urethral/vaginal discharge, genital ulcer and pain on micturition were identified as symptoms of STD by a significantly higher number of respondents in the post package sample. A sizable number of subjects included inguinal swelling and lower abdominal pain also as STD symptoms. The IEC intervention showed a significant improvement in knowledge about all four major routes of transmission of HIV/AIDS. Using condoms and avoiding sex with Commercial Sex Workers were reported as measures to prevent STD/AIDS by a significantly higher number of subjects after the intervention. A sizable number of subjects also included other measures (using safe blood/not sharing needles etc.) as well. There was a significant decline in the subjects preferring self treatment or treatment from a chemist shop in case one suffered with an STD. A significant increase was observed in those preferring treatment from govt. facilities or private allopathic doctors. However, the intervention did not seem to result in preference for alternative systems of medicine. The study demonstrated that exposure to intensive promotional intervention, even for a brief period can significantly raise awareness and knowledge of young people even on sensitive topics like STD and AIDS.
Acquired Immunodeficiency Syndrome↗
Cost of medications for elderly in a nursing home.
The rising cost of medical care, particularly for elderly patients in nursing homes, is receiving increasing attention. The purpose of this study was to investigate the cost of and the average number of medications taken per patient in a nursing home. The study included 116 residents of a nursing home in New Orleans, Louisiana. Relevant information about the number of medications taken by each patient on a regular basis was obtained by chart review. The cost of medications was calculated from the Red Book (which represents the cost of drugs to the pharmacy), because the medication prices charged by the nursing home were not available. The number of medications used per patient per day expressed as mean +/- S.D. was 8.1 +/- 4.1. The cost of medications per patient per month expressed as mean +/- S.D. was $182 +/- 141. The estimated annual cost of medications per patient was $2,184. It is highly likely that the cost to the patient is higher than the cost shown here. This preliminary study shows that elderly patients take several medications associated with significant expense.
Aged↗
Role of transforming growth factor beta3 in lymphatic metastasis in breast cancer.
Transforming growth factor-betas (TGFbetas) play a prominent role in tumour growth and metastasis by enhancing angiogenesis and suppressing immune surveillance. Despite the increased interest in the effect of TGFbetas on tumour progression, little is known about the importance of TGFbeta3 and its receptor CD105 in breast cancer. In the present study, we measured the plasma levels of TGFbeta3, CD105-TGFbeta3 complexes and TGFbeta1 in 80 patients with untreated early-stage breast cancer using an enhanced chemiluminescence ELISA method. Of the 80 patients, 14 were histologically confirmed as having axillary lymph node metastases, while the remainder had no evidence of lymph node involvement. The results showed that levels of both TGFbeta3 and CD105-TGFbeta3 complex were significantly elevated in patients with positive lymph nodes compared to those without node metastasis. Furthermore, the levels of both TGFbeta3 and CD105-TGFbeta3 complex correlated with lymph node status. The only patient who died of the disease had very high plasma levels of TGFbeta3 and CD105-TGFbeta3 complex and positive lymph nodes; this patient developed lung metastases within 2 years of diagnosis. No significant correlation was seen between either TGFbeta3 or CD105-TGFbeta3 complex levels and tumour stage, size or histological grade. Plasma TGFbeta1 levels were not correlated with node metastasis, tumour stage, grade or size. Our data suggest that plasma levels of TGFbeta3 and CD105-TGFbeta3 complex may be of prognostic value in the early detection of metastasis of breast cancer.
Adult↗
Insulin-like growth factor II and PAX3-FKHR cooperate in the oncogenesis of rhabdomyosarcoma.
The mouse myoblast C2C12 cell line transfected singly with cDNA for Pax-3, PAX3-FKHR, or insulin-like growth factor (IGF) II or cotransfected with IGF-II plus Pax-3 or with IGF-II plus PAX3-FKHR genes showed an altered morphology, a lack of differentiation, and higher proliferation rates in vitro. On s.c. injection into nude mice, tumors grew from transfected cell lines but not from cells transfected with the empty vector. Tumors derived from IGF-II/PAX3-FKHR- and IGF-II-transfected cells grew most rapidly. Cotransfection of IGF-II plus Pax-3 induced tumors comprised highly differentiated striated muscle cells; Pax-3, PAX3-FKHR, or IGF-II transfection produced tumors at varying stages of differentiation. Tumors derived from IGF-II plus PAX3-FKHR-cotransfected cells were composed of undifferentiated cells. This was the only tumor type to infiltrate the underlying muscle. The most angiogenesis and the least apoptosis were observed in the latter tumors. These results support the hypothesis that PAX3-FKHR interacts with IGF-II to play a critical role in the oncogenesis of rhabdomyosarcoma.
Animals↗
Absence of effect of glutamic acid hydrochloride on the bioavailability of oral ganciclovir in AIDS patients with cytomegalovirus disease.
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AIDS-Related Opportunistic Infections↗
Acute oral gallium arsenide exposure and changes in certain hematological, hepatic, renal and immunological indices at different time intervals in male Wistar rats.
Male albino rats were given a single oral dose of gallium arsenide (GaAs) (100, 200 or 500 mg/kg). Erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity was inhibited in all the three GaAs-exposed groups accompanied by elevated urinary excretion of ALA. A significant increase in serum aspartate aminotransferase (AST) activity, and gamma-glutamyltranspeptidase (gamma-GT) was observed. A significant increase in hepatic malondialdehyde (MDA) and a decrease in hepatic glutathione contents were also noted. Renal alkaline phosphatase activity, urinary ALA and protein excretion increased significantly on GaAs exposure. These changes were accompanied by significant alterations in almost all the immunological variables, with an increase in gallium and arsenic concentration in blood and soft tissues. While most of the above biochemical alterations were prominent at day 7 following single exposure to 200 and 500 mg/kg GaAs, most of the immunological indices altered with all the three doses and remained high even at day 21. The results suggest only a moderate effect of GaAs on renal and hepatic tissues. By contrast, immunological and haematological systems are the most vulnerable to the toxic effects of GaAs.
Administration, Oral↗
The role of interleukin-converting enzyme in Fas-mediated apoptosis in HIV-1 infection.
Apoptosis of CD4+ lymphocytes is partially responsible for the depletion of these cells in HIV-infected individuals. CD4+ lymphocytes from HIV-1-infected patients express higher membrane levels of the Fas receptor, and are particularly susceptible to apoptosis after Fas triggering. IL-1beta- converting enzyme (ICE) is a key enzyme of the apoptotic machinery involved in Fas-mediated apoptosis of normal lymphocytes. The role of ICE in mediating the increased susceptibility of CD4+ lymphocytes from HIV-1-infected patients to apoptosis has not been examined. In this study, we found that ICE mRNA was present in T cells from both HIV-1-infected patients and controls. Active ICE proteins, p10 and p20, were demonstrated by immunoblot in lymphocytes from HIV-1-infected patients and in normal lymphocytes after treatment with Fas agonist, CH11 mAb. Cocultivation of lymphocytes from HIV-1-infected persons with Fas antagonist, antibody ZB4, resulted in decreased expression of ICE protein in lymphocytes from HIV-infected patients, and decreased apoptosis. Similar effects were obtained when cells were treated with synthetic ICE inhibitors, which blocked apoptosis in response to Fas triggering. When CD4+ and CD8+ cells were sorted by flow cytometry and analyzed by reverse transcriptase PCR, ICE mRNA was present in both CD8+ and CD4+ cells. However, flow cytometric analysis of lymphocytes with intracellular staining for ICE demonstrated ICE protein in the CD4+ but not the CD8+ cell fraction derived from blood of HIV-1-infected patients. These data suggest that activation of ICE occurs in vivo in CD4+ lymphocytes from HIV-1-infected individuals, and may account for the increased susceptibility of CD4+ cells to apoptosis.
Apoptosis↗
Eating and weight changes following chemoradiation therapy for advanced head and neck cancer.
OBJECTIVE: To describe the functional outcomes of weight loss and eating following a targeted chemoradiation protocol consisting of a selective supradose of intra-arterial cisplatin (150 mg/m2 per week for 4 weeks) with parenteral sodium thiosulfate and external-beam irradiation (1.8-2.0 Gy per fraction per day for 35 days). SUBJECTS AND DESIGN: Forty-seven patients with advanced head and neck cancer treated with a targeted chemoradiation protocol were monitored for weight and eating status before treatment and as long as 18 months after treatment. RESULTS: A statistically significant weight loss (P<.001) occurred during the targeted chemoradiation protocol, with a mean weight ratio of 90% of the starting weight. The ability to eat also declined, with an increase in reported swallowing difficulties and a need for percutaneous endoscopic gastrostomy tubes from 4 (9%) to 12 (26%). There were no significant changes in weight after the initial weight loss. Tumor stage and nodal involvement had no effect on weight loss. At the start of treatment, 18 patients (38%) reported normal eating and 4 (8%) required a feeding tube. By 18 months after treatment, 41 (87%) were eating normally, 34 (72%) reported normal eating, and 6 (13%) required a percutaneous endoscopic gastrostomy tube. CONCLUSIONS: Patients undergoing a targeted chemoradiation protocol for head and neck cancer lost about 10% of their pretreatment weight and had a decline in eating ability. Difficulty swallowing during the treatment may be due to adverse effects such as mucositis and nausea. By 18 months after therapy, most were able to eat normally and maintain their weight.
Adult↗