Search PubMed⌕ Search

Biomedical subjects

Ashok Kumar

Publications and source records attributed to Ashok Kumar.

At least 73 records · Page 4Linked to original sources
PubMed2006

Differential regulation of CXCR4 and CCR5 expression by interleukin (IL)-4 and IL-13 is associated with inhibition of chemotaxis and human immunodeficiency Virus (HIV) type 1 replication but not HIV entry into human monocytes.

Chemokine receptors CXCR4 and CCR5 play a key role in Human Immunodeficiency Virus (HIV) entry into CD4+ monocytic cells. Alteration in the expression levels of these receptors by immunoregulatory cytokines may influence viral entry and hence susceptibility to HIV infection, viral tropism, and disease progression. Helper T cell type 2 (Th2) cytokines interleukin (IL)-4 and IL-13, which share a subunit of their receptor components and exhibit similar biological effects, have been shown to play a key role in HIV infection and disease progression. In this study, we investigated the effects of IL-4 and IL-13 on the expression of CXCR4 and CCR5, and the biological implications of alteration of CXCR4 and CCR5 regulation on monocytic cells with respect to their migration in response to chemokines, HIV entry, and its replication. The results suggest that both IL-4 and IL-13 inhibited the expression of CXCR4, in contrast to CCR5, which was inhibited by IL-13 alone. The downregulation of CXCR4 and CCR5 was correspondingly associated with the inhibition of their respective ligand-induced chemotaxis. Although IL-13 inhibited the expression of both CXCR4 and CCR5, this downregulation of chemokine receptor expression was not sufficient to prevent virus entry. Furthermore, both IL-4 and IL-13 inhibited viral replication in monocytic cells, suggesting that inhibition of chemokine receptor expression per se by these cytokines may not be sufficient to prevent virus entry, and indicating these cytokines may be inhibiting viral replication by targeting pathways subsequent to virus entry.

Chemotaxis, Leukocyte↗
PubMed2006

Long-term survival and recurrence patterns in ampullary cancer.

OBJECTIVE: Ampullary cancers are associated with high resectability rates and good long-term survival. However, the small number of patients in various series has hampered survival analysis. METHODS: One hundred thirteen patients with ampullary cancer underwent pancreaticoduodenectomy between 1989 and 2000, with 48% morbidity and 8% mortality. One hundred four patients who survived the operation were analyzed to identify predictors of long-term survival. RESULTS: The overall median survival was 30.1 (1.6-140.0) months with actuarial 1-, 3-, and 5-year survival rates of 79%, 43%, and 33%, respectively. Lymph node metastasis (P = 0.002) and vascular invasion (P = 0.008) were 2 independent factors adversely influencing survival. Perioperative blood transfusion (P = 0.001) and vascular invasion (P = 0.026) were important factors predicting recurrent disease. CONCLUSIONS: Lymph node metastasis and vascular invasion were 2 important factors, which adversely influenced survival in patients with ampullary cancer. Perioperative blood transfusion and vascular invasion were associated with recurrent disease.

Adult↗
PubMed2006

Toll-like receptor 3 agonist poly(I:C)-induced antiviral response in human corneal epithelial cells.

The objective of this study was to examine the expression of Toll-like receptor 3 (TLR3) by human corneal epithelial cells (HCECs) and to determine whether exposure to the TLR3 agonist polyinosinic-polycytidylic acid [poly(I:C)] induces an antiviral response in these cells. Fluorescence-activated cell sorter (FACS) analysis revealed TLR3 to be constitutively expressed and distributed intracellularly in HCECs. Stimulation of HCECs with the TLR3 agonist poly(I:C) induced the activation of nuclear factor (NF)-kappaB and production of the proinflammatory cytokine interleukin (IL)-6 and the chemokine IL-8. Upon exposure to poly(I:C), HCECs initiated a potent antiviral response resulting in an increase of interferon (IFN)-beta mRNA expression (7-fold). Poly(I:C) stimulation also up-regulated mRNA expression of the antiviral chemokine IFN-gamma inducible protein 10 (IP10), myxovirus resistance gene A and 2',5'-oligoadenylate synthetase (5-, 10- and 9-fold, respectively), and secretion of IP10. These responses were also induced by exogenously added type 1 IFNs, but could not be blocked by pretreatment of the cells with anti-TLR3 monoclonal antibody, suggesting that the receptor was not expressed on the cell surface. Furthermore, incubation of HCECs with an endosomal acidification inhibitor, chloroquine, markedly inhibited poly(I:C)-mediated IFN-beta expression in HCECs. These results suggest that corneal epithelial cells are important sentinels of the corneal innate immune system against viral infection, and that stimulation of TLR3 can induce the expression of key proinflammatory cytokines and chemokines and antiviral genes that help in the defence of the cornea against viral infection.

2',5'-Oligoadenylate Synthetase↗
PubMed2006

Herpes simplex virus 1 infection induces the expression of proinflammatory cytokines, interferons and TLR7 in human corneal epithelial cells.

Herpetic epithelial and stromal keratitis is a sight-threatening ocular infection. To study the role of the epithelium in the innate response to herpes simplex virus 1 (HSV-1) infection of the cornea, we used a telomerase-immortalized human corneal epithelial cell (HCEC) line, HUCL, and primary HCECs as a model and infected the cells with HSV-1 (KOS strain). HSV-1 infection of HCECs resulted in a two-phase activation of nuclear factor-kappaB (NF-kappaB), JNK and p38, with the first peak at 1-4 hr and a second peak at 8 hr. Concomitant with the first peak of activation, transcriptional expression of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF)-alpha and interferon (IFN)-beta was rapidly induced in HSV-1-infected cells. HSV-1 infection also induced the production of IL-6, IL-8, and TNF-alpha in both HUCL cells and primary HCECs. Coincident with the second phase of NF-kappaB activation in HSV-1-infected HCECs, the expression of Toll-like receptor 7 (TLR7) was induced, whereas the level of TLR3 was greatly down-regulated. Thus, in response to HSV-1 infection, HCECs produce proinflammatory cytokines, leading to infiltration, and IFNs to enhance the antiviral activity in the cornea, probably through sequential activation of TLRs.

Cells, Cultured↗
PubMed2006

Evaluation of desmoglein enzyme-linked immunosorbent assay (ELISA) in Indian patients with pemphigus vulgaris.

OBJECTIVE: To evaluate the role of the enzyme-linked immunosorbent assay (ELISA) test for the detection of antibodies to desmoglein 1 (dsg1) and desmoglein 3 (dsg3) in the diagnosis of pemphigus vulgaris (PV), and its correlation with disease severity and clinical presentation (mucosal PV, cutaneous PV, mucocutaneous PV). METHODS: Twenty-seven active PV patients and 26 controls with other dermatologic disorders were included in the study. The severity of oral and cutaneous involvement was assessed and recorded. ELISA test for the measurement of anti-dsg1 and anti-dsg3 antibodies was performed (Medical and Biological Laboratories Co. Ltd., Nagoya, Japan). The cut-off ELISA value for both anti-dsg1 and anti-dsg3 was taken as 20. RESULTS: Of the 27 patients, 26 were ELISA positive for anti-dsg1 antibodies and 23 for anti-dsg3 antibodies. Of the controls, two were positive for anti-dsg1 and none for anti-dsg3 antibodies. The sensitivity and specificity of ELISA for anti-dsg1 in the diagnosis of PV were 96.3% and 92.3%, respectively. For anti-dsg3, they were 85.2% and 100%, respectively. The different morphologic types of PV could not be differentiated on the basis of antibody profile; however, a direct correlation between anti-dsg3 titers and the severity of oral disease was noted, and also between anti-dsg1 titers and the severity of cutaneous disease. CONCLUSIONS: ELISA (dsg1 and dsg3) is an efficient tool for confirming the diagnosis of PV. Specific antibody titers correlate with disease severity; however, desmoglein testing cannot differentiate between the various morphologic subtypes of PV.

Autoantibodies↗
PubMed2006

Redefining the role of splenectomy in patients with idiopathic splenomegaly.

BACKGROUND: Despite extensive work-up to establish the cause of splenomegaly, splenectomy may be required for diagnosis in certain situations. The aim of this study was to find out the role of diagnostic splenectomy in the current era. METHODS: Between January 1989 and June 2004, 211 patients underwent splenectomy for indications other than trauma. In 41 (19%) patients, splenectomy was carried out for diagnostic purposes. Retrospective analysis of these patients was done for the purpose of the study. RESULTS: All patients who underwent diagnostic splenectomy had a complete haemogram, biochemical tests for liver and renal function, bone marrow biopsy and abdominal ultrasonography before splenectomy. There were 28 (68%) men and 13 (32%) women with median age of 37 years (range, 6-62 years). The median duration of symptoms was 12 months (range, 1-180 months). Common presentations were fever (n = 27; 66%), malaise (n = 26; 63%), pallor (n = 33; 80%) and gross splenomegaly (n = 27; 66%). Thirty-two (78%) patients had hypersplenism. Splenic lesions were shown in 14 (34%) patients on ultrasonogram and in 16 (39%) patients on contrast-enhanced computed tomography scan of the abdomen. Open splenectomy was carried out in all patients. Seventeen (41%) patients had postoperative complications. Among these, three (7%) patients had postoperative bleeding. One patient died because of acute respiratory distress syndrome. Final histopathology of the spleen showed lymphoma in 15 (37%), tuberculosis in five (12%) and other lesions in five (12%) patients. Sixteen (39%) patients had only congestive splenomegaly. CONCLUSION: A high proportion of patients presenting with idiopathic splenomegaly will have underlying haematological malignancies even in tropical countries. The clinical presentation, laboratory profile and imaging findings were not helpful in differentiating between patients with haematological malignancies and non-malignant conditions. Splenectomy still has an important role in establishing the pathology in patients presenting with idiopathic splenomegaly.

Adolescent↗
PubMed2006

Structural and optical properties of tin oxide branched nanostructures.

Branched nanostructures of tin oxide (SnO2) have been synthesized by Vapor-Liquid-Solid (VLS) mechanism using a gold catalyst in the temperature range of 800-850 degrees C under an ambient gas flow of 200 sccm. The microstructural and the optical properties of the as prepared products have been studied by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), micro-Raman, and photoluminescence (PL) studies. SnO2 branches with a rutile phase are found to have a preferential orientation along (101). Typical lengths of these branches are found to be approximately 3-5 microm and diameters in the range of 50-100 nm. Selected area electron diffraction (SAED) pattern shows that the SnO2 branches have a tetragonal cross section with [101] crystal direction. A Raman line at 631 cm(-1) (Sn-O bond) is obtained in the micro Raman spectra. Low temperature PL spectrum shows a strong green emission band near 506 nm.

Crystallization↗
PubMed2006

Toll-like receptors and corneal innate immunity.

The ocular surface is constantly exposed to a wide array of microorganisms. The ability of the cornea to recognize pathogens as foreign and eliminate them is critical to retain its transparency, hence preservation of sight. In the eye, as in other parts of the body, the early response against invading pathogens is provided by innate immunity. Corneal innate immune system uses a series of pattern recognition receptors to detect the presence of pathogens thus allowing for rapid host defense responses to invading microbes. A key component of such receptors is the "Toll-like receptors" (TLRs), which have come to occupy the center stage in innate immunity against invading pathogens. An increasing number of studies have shown that TLRs are expressed by a variety of tissues and cells of the eye and play an important role in ocular defense against microbial infection. Here in this review we summarize the current knowledge about TLR expression in human eye with main emphasis on the cornea, and discuss the future directions of the field.

Animals↗
PubMed2006

Frequency and comparative analysis of hapatitis D in petients seeking treatment for hepatitis B.

OBJECTIVE: To find the frequency of hepatitis 'D' in patients of hepatitis 'B' seeking treatment and to compare clinical and biochemical features in patients harboring HDV with those who are not. DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Medical Unit-IV, Civil Hospital Karachi, Medical Unit-VI and Surgical Unit-VII, Lyari General Hospital, Dow University of Health Sciences, Karachi; from July 2003 to June 2005. PATIENTS AND METHODS: HBsAg positive patients seeking treatment were enrolled in the study. Anti-HDV was done in all. Patients were split into two groups according to their anti-HDV status into HDV positive and HDV negative groups. Liver biochemistries and viral profile for HCV, anti-HBc IgM and HBeAg were done and compared between the two groups. RESULTS: A total of 246 patients were selected. HDV was positive in 66 (26.8%) patients. No significant difference was observed in the frequency and stages of cirrhosis between the two groups while significant differences were observed in the mean SGPT (95% CI: -381.09 to -110.74; P = 0.001) and albumin levels (95% CI: 1.87 to 7.73; P = 0.007) and in the frequency of HBeAg (P = 0.001), anti-HBc IgM (P = 0.02) and HBV DNA (P<0.001). CONCLUSION: HDV infection was common in patients with HBV in this cohort of patients. All patients of HBV should be screened for HDV before treatment decision for the former is taken.

Adult↗
PubMed2005

Supermacroporous cryogel matrix for integrated protein isolation. Immobilized metal affinity chromatographic purification of urokinase from cell culture broth of a human kidney cell line.

A new type of supermacroporous, monolithic, cryogel affinity adsorbent was developed, allowing the specific capture of urokinase from conditioned media of human fibrosarcoma cell line HT1080. The affinity adsorbent was designed with the objective of using it as a capture column in an integrated perfusion/protein separation bioreactor setup. A comparative study between the utility of this novel cryogel based matrix and the conventional Sepharose based affinity matrix for the continuous capture of urokinase in an integrated bioreactor system was performed. Cu(II)-ion was coupled to epoxy activated polyacrylamide cryogel and Sepharose using iminodiacetic acid (IDA) as the chelating ligand. About 27-fold purification of urokinase from the conditioned culture media was achieved with Cu(II)-IDA-polyacrylamide cryogel column giving specific activity of about 814 Plough units (PU)/mg protein and enzyme yields of about 80%. High yields (95%) were obtained with Cu(II)-IDA-Sepharose column by virtue of its high binding capacity. However, the adsorbent showed lower selectivity as compared to cryogel matrix giving specific activity of 161 PU/mg protein and purification factor of 5.3. The high porosity, selectivity and reasonably good binding capacity of Cu(II)-IDA-polyacrylamide cryogel column make it a promising option for use as a protein capture column in integrated perfusion/separation processes. The urokinase peak pool from Cu(II)-IDA-polyacrylamide cryogel column could be further resolved into separate fractions for high and low molecular weight forms of urokinase by gel filtration chromatography on Sephacryl S-200. The selectivity of the cryogel based IMAC matrix for urokinase was found to be higher as compared to that of Cu(II)-IDA-Sepharose column.

Acrylamides↗
PubMed2005

Role of HCV coinfection towards disease progression and survival in HIV-1 infected children: a follow-up study of 10 years.

The present study was taken up to evaluate the pattern of disease progression and survival in a group of HIV-1 positive children, coinfected with HCV infection (n=25) in comparison to those without such coinfection (n=23). There was a significant negative correlation between the rate of decline of the CD4 + T cell percentage and the duration of the AIDS-free interval in most (80.0 per cent) of the HCV seropositive children showing such decline (r=-0.588; p=0.005). The HCV seropositive children had twofold higher risk of progression to development of AIDS than HCV seronegatives (RR=2.51; 95 per cent CI:1.34-4.69; p=0.004). There was a significant negative correlation between the rate of decline of CD4 + T cell percentage and overall survival duration for HCV seropositive group (r=-0.609; p=0.003). Moreover, children coinfected with HCV had more than twofold higher risks of death than those without HCV (RR=2.39; 95 per cent CI:1.17-4.89; p<0.01). It appears that HCV infection may be an important contributor to the rapid disease progression and increase in mortality in HCV-HIV-1 coinfected children of thalassemia major.

CD4 Lymphocyte Count↗
PubMed2005

Cyclophosphamide pulses with oral prednisolone in the treatment of pemphigus: a pilot study.

An open labeled clinical trial aimed at assessing the efficacy and safety of pulse intravenous cyclophosphamide with daily oral prednisolone in the treatment of pemphigus was carried out. Twenty-six patients (12 men, 14 women; mean age, 48.4 years), comprising 25 cases with pemphigus vulgaris and 1 with pemphigus vegetans (< 10% body surface area involvement) who did not achieve adequate control on corticosteroids with or without other adjuvants were included. After baseline evaluation, monthly intravenous boluses of cyclophosphamide (15 mg/kg) along with daily oral prednisolone (starting dose 1 mg/kg/day, tapered according to clinical response) were administered. Patients were assessed monthly for clinical activity and side-effects. All patients experienced significant clinical improvement within 1 month of starting treatment. Healing of skin and mucosal lesions occurred respectively at mean durations of 2.1 and 3.6 months. Three weeks to 8 months later, 9 patients had recurrences of activity on tapering/withdrawal of prednisolone, mainly in the oral mucosa. Side effects of treatment included amenorrhea (3 patients), microscopic hematuria (3) which cleared with co-administration of mesna, vomiting (1), weight gain (10), gastritis (1), and cataract (2). It is concluded that treatment with monthly intravenous cyclophosphamide boluses along with daily oral prednisolone clears lesions of pemphigus with < 10 percent body surface involvement, and this may be an alternative regimen for pemphigus. Monitoring for adverse effects is essential.

Administration, Oral↗
PubMed2005

A haplotype of angiotensinogen gene that is associated with essential hypertension increases its promoter activity in adipocytes.

Obesity is associated with hypertension and other cardiovascular diseases especially in the African-American population. Human angiotensinogen (AGT) gene has seven single nucleotide polymorphisms (SNPs) in 1.2 kb region of its promoter. Recent studies have shown that variant -217A is associated with hypertension in African-American and Chinese population. Nucleotide sequence of the hAGT gene has shown that variant -217A almost always occurs with variants -532T, -793A and -1074T (forming haplotype AAT) and variant -217G almost always occurs with variants -532C, -793G and -1074G (forming haplotype GGG). Since hAGT gene is expressed in the adipose tissue and its expression in this tissue may play a role in hypertension, we have analyzed the role of haplotypes AAT and GGG on the expression of this gene in adipocytes. We show here that a reporter construct with haplotype AAT of the hAGT gene has increased promoter activity on transient transfection in pre-adipocytes and differentiated adipocytes as compared to the reporter construct containing GCGG haplotype. Increased expression of the AGT gene containing haplotype AAT in the liver and adipocytes may be a contributing factor for hypertension.

3T3-L1 Cells↗
PubMed2005

Synthesis, anti-inflammatory and analgesic activities evaluation of some mono, bi and tricyclic pyrimidine derivatives.

3-Aminobenzonitrile and 2-amino-4-phenyl thiazole on condensation with 4-isothiocyanato-4-methyl pentane-2-one gave condensed monocyclic pyrimidine derivatives 1 and 2, 3, respectively. Condensation of 3-aminopropyl imidazole with 3-isothiocyantobutanal gave condensed monocyclic pyrimidine derivative 4. Bicyclic pyrimidine derivatives 5a and 5b have been synthesized by the condensation of diaminomaleonitrile with 4-isothiocyanto-4-methylpentane-2-one and 3-isothiocyanatobutanal, respectively. Condensation of 4-isothiocyanato-4-methyl pentane-2-one with 2,3-diaminopropionic acid hydrochloride yielded another bicyclic compound 7. 4-Isothiocyanato-4-methyl pentane-2-one, 3-isothiocyanatobutanal and 4-isothiocyanatobutan-2-one on condensation with 2-amino-4-nitro phenol gave tricyclic pyrimidine derivatives 8a, 8b and 8c, respectively. Structures of all the synthesized pyrimidine derivatives are supported by correct IR, 1H NMR and mass spectral data. The anti-inflammatory activity evaluation was carried out using carrageenin-induced paw oedema assay, and compounds 1, 3 and 5b exhibited good anti-inflammatory activity, that is, 27.9, 34.5 and 34.3% at 50 mg/kg po, respectively. Analgesic activity evaluation was carried out using phenylquinone writhing assay and compounds 5a, 5b and 8b showed good analgesic activity, that is, 50, 70 and 50% at 50 mg/kg po, respectively.

Analgesics↗
PubMed2005

Regulation of B7.1 costimulatory molecule is mediated by the IFN regulatory factor-7 through the activation of JNK in lipopolysaccharide-stimulated human monocytic cells.

The engagement of CD28 or CTLA-4 with B7.1 provides the essential second costimulatory signal that regulates the development of immune responses, including T cell activation, differentiation, and induction of peripheral tolerance. The signaling molecules and the transcription factors involved in B7.1 regulation are poorly understood. In this study we investigated the role of MAPKs in the regulation of LPS-induced B7.1 expression in human monocytes and the promonocytic THP-1 cells. Our results show that LPS-induced B7.1 expression in monocytic cells did not involve the activation of either p38 or ERKs. Using the JNK-specific inhibitor SP600125, small interfering RNAs specific for JNK1 and JNK2, and agents such as dexamethasone that inhibit JNK activation, we determined that LPS-induced B7.1 expression was regulated by JNK MAPK in both monocytes and THP-1 cells. In addition, we identified a distinct B7.1-responsive element corresponding to the IFN regulatory factor-7 (IRF-7) binding site in the B7.1 promoter responsible for the regulation of LPS-induced B7.1 transcription. Furthermore, SP600125 and dexamethasone inhibited LPS-induced IRF-7 activity. Taken together, these results suggest that LPS-induced B7.1 transcription in human monocytic cells may be regulated by JNK-mediated activation of the IRF-7 transcription factor.

Anthracenes↗
PubMed2005

Transcriptional signaling from membrane raft-associated glucocorticoid receptor.

The contribution of plasma membrane-associated glucocorticoid receptor (GR) to transcriptional signaling is unclear. We observed GR in low-density detergent-resistant membrane (DRM) rafts derived from human hepatoma Hep3B cells in complexes with caveolin-1, HSP90, and STAT3. In transient transfection assays, GR-stimulated transcriptional signaling was reversibly inhibited by membrane-raft disrupters filipin III and progesterone. These data provide clear evidence for a functional contribution of DRM-associated GR to transcriptional signaling.

Base Sequence↗
PubMed2005

Gene therapy restores vision-dependent behavior as well as retinal structure and function in a mouse model of RPE65 Leber congenital amaurosis.

Retinal pigment epithelium-specific protein 65 kDa (RPE65) is a protein responsible for isomerization of all-trans-retinaldehyde to its photoactive 11-cis-retinaldehyde and is essential for the visual cycle. RPE65 mutations can cause severe, early onset retinal diseases such as Leber congenital amaurosis (LCA). A naturally occurring rodent model of LCA with a recessive nonsense Rpe65 mutation, the rd12 mouse, displays a profoundly diminished rod electroretinogram (ERG), an absence of 11-cis-retinaldehyde and rhodopsin, an overaccumulation of retinyl esters in retinal pigmented epithelial (RPE) cells, and photoreceptor degeneration. rd12 mice were injected subretinally at postnatal day 14 with rAAV5-CBA-hRPE65 vector. RPE65 expression was found over large areas of RPE soon after treatment. This led to improved rhodopsin levels with ERG signals restored to near normal. Retinyl ester levels were maintained at near normal, and fundus and retinal morphology remained normal. All parameters of restored retinal health remained stable for at least 7 months. The Morris water maze behavioral test was modified to test rod function under very dim light; rd12 mice treated in one eye performed similar to normally sighted C57BL/6J mice, while untreated rd12 mice performed very poorly, demonstrating that gene therapy can restore normal vision-dependent behavior in a congenitally blind animal.

Animals↗