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Biomedical subjects

R Agarwal

Publications and source records attributed to R Agarwal.

At least 91 records · Page 5Linked to original sources
PubMed2001

Elevated levels of interleukin-13 and IL-18 in patients with dengue hemorrhagic fever.

Interleukin (IL)-13 is produced by T helper 2 (Th2)-type cells and inhibits the production of proinflammatory cytokines by activated monocytes, while IL-18 is a pleiotropic cytokine that induces interferon-gamma and plays an important role in the development of Th1-type cells. Role of the shift from a Th1-type response to Th2-type has been suggested in the pathogenesis of dengue hemorrhagic fever (DHF). This study was undertaken to investigate the possible protective/pathogenic role of IL-13 and IL-18 in patients with DHF. Sera were collected from a total of 84 patients with various grades of dengue illness and 21 normal healthy controls and tested for IL-13 and IL-18 levels using commercial enzyme-linked immunosorbent assay kits. The results showed that very low levels of IL-13 (4+/-3 pg ml(-1)) and IL-18 (15+/-4 pg ml(-1)) were detected in the sera of healthy controls. In dengue patients, the levels of IL-13 and IL-18 were the highest in the patients with DHF grade IV (205+/-103 pg ml(-1) and 366+/-155 pg ml(-1), respectively) and the lowest in patients with dengue fever (22+/-12 pg ml(-1) and 76+/-50 pg ml(-1), respectively). Both the cytokines appeared (IL-13=20+/-11 pg ml(-1) and IL-18=70+/-45 pg ml(-1)) during the first 4 days of illness and reached peak levels (IL-13=204+/-96 pg ml(-1) and IL-18=360+/-148 pg ml(-1)) by day 9 onwards. The presence of high levels of IL-13 and IL-18 during severe illness and late phases of the disease suggests that both of these cytokines may contribute to the shift from a Th1- to Th2-type response and thus to the pathogenesis of DHF.

Humans↗
PubMed2001

Differential responses of skin cancer-chemopreventive agents silibinin, quercetin, and epigallocatechin 3-gallate on mitogenic signaling and cell cycle regulators in human epidermoid carcinoma A431 cells.

Silibinin, quercetin, and epigallocatechin 3-gallate (EGCG) have been shown to be skin cancer-preventive agents, albeit by several different mechanisms. Here, we assessed whether these agents show their cancer-preventive potential by a differential effect on mitogenic signaling molecules and cell cycle regulators. Treatment of human epidermoid carcinoma A431 cells with these agents inhibited the activation of the epidermal growth factor receptor and the downstream adapter protein Shc, but only silibinin showed a marked inhibition of mitogen-activated protein kinase-extracellular signal-regulated kinase-1 and -2 activation. In terms of cell cycle regulators, silibinin treatment showed an induction of Cip1/p21 and Kip1/p27 together with a significant decrease in cyclin-dependent kinase (CDK)-4, CDK2, and cyclin D1. Quercetin treatment, however, resulted in a moderate increase in Cip1/p21 with no change in Kip1/p27 and a decrease in CDK4 and cyclin D1. EGCG treatment also led to an induction of Cip1/p21 but no change in Kip1/27, CDK2, and cyclin D1 and a decrease in CDK4 only at low doses. Treatment of cells with these agents resulted in a strong dose- and time-dependent cell growth inhibition. A high dose of silibinin and low and high doses of quercetin and EGCG also led to cell death by apoptosis, suggesting that a lack of their inhibitory effect on mitogen-activated protein kinase-extracellular signal-regulated kinase-1 and -2 activation possibly "turns on" an apoptotic cell death response associated with their cancer-preventive and anticarcinogenic effects. Together, these results suggest that silibinin, quercetin, and EGCG exert their cancer-preventive effects by differential responses on mitogenic signaling and cell cycle regulators.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Neuropathy in rheumatoid arthritis.

BACKGROUND: Paucity of Indian literature on rheumatoid neuropathy creates a lacuna in the critical evaluation and discussion of the subject. We did this study to find out the incidence and pattern of neuropathy and to correlate it with disease parameters and other extra-articular involvement. MATERIAL AND METHODS: We studied 31 patients of rheumatoid arthritis (RA) classified by ACR criteria. Electromyography and nerve conduction studies (EMG/NCV) were done in all the patients apart from routine laboratory and radiological investigations. Electrocardiograph (ECG), pulmonary function tests (PFT) and ophthalmological examination were also carried out to ascertain extra-articular involvement. RESULTS: Ten out of 31 RA patients had neuropathy of which five each were overt and subclinical respectively. Only one patient had entrapment neuropathy. Four of the ten patients had pure motor neuropathy whereas the other six were sensori-motor neuropathies. Four patients had mononeuritis multiplex and five had symmetrical peripheral neuropathy. Nine of the ten neuropathic patients had RA for more than 2 years. Seven patients had other extra-articular features along with neuropathy. CONCLUSIONS: One-third of patients with RA have evidence of neuropathy. Disease parameters such as activity, rheumatoid factor and functional and radiological grade do not correlate with neuropathy. Non-entrapment sensori-motor type of neuropathy is the most common type.

Adult↗
PubMed2001

Neurotrophin and neurotrophin receptor expression by cells of the human lamina cribrosa.

PURPOSE: To determine whether cells and tissue from the human lamina cribrosa (LC) express neurotrophin and tyrosine kinase (trk) receptor mRNA and protein and whether these cells secrete neurotrophins. METHODS: Synthesis of cDNA and the reverse transcription-polymerase chain reaction (RT-PCR) were conducted using total RNA obtained from well-characterized cell lines from the human LC and human optic nerve head (ONH) tissue. Immunofluorescent localization and Western blot analysis were used to evaluate neurotrophin and trk protein expression in cells and tissue from the human LC. Immunoassay systems (ELISAs) were used to detect the secretion of neurotrophins. RESULTS: Two morphologically distinct cell types (LC cells and ONH astrocytes) were isolated and characterized from the human LC. Messenger RNA for each of the neurotrophins, three full-length trk receptors and two truncated trk receptors were detected in both cell types and in human ONH tissue. Protein for the neurotrophins and trk receptors were detected in LC cells, ONH astrocytes, and ONH tissue. Neither cell type expressed mRNA or protein for the low-affinity neurotrophin receptor p75. The secretion of neurotrophins was observed in both cell types. CONCLUSIONS: Cells from the human LC express mRNA and protein of neurotrophins and trk receptors. In addition, cells from the LC secrete neurotrophins, which suggests that there is paracrine and/or autocrine signaling within the LC. Neurotrophin signaling within this region of the ONH may play important roles in the maintenance of the normal LC and in such diseases as glaucoma.

Blotting, Southern↗
PubMed2001

Pseudomyxoma peritonei of hernial sac--a case report.

A rare presentation of Pseudomyxoma Peritonei of hernial sac is described. The patient was admitted for repair of an inguinal hernia. During herniorraphy large amount of mucinous material was found in hernial sac. Microscopy revealed epithelial glandular cells with bland appearance within mucinous pools. A search for primary remained fruitless.

Diagnosis, Differential↗
PubMed2000

Cell signaling and regulators of cell cycle as molecular targets for prostate cancer prevention by dietary agents.

Prostate cancer (PCA) is the most common invasive malignancy and leading cause (after lung) of cancer deaths in males. Since PCA is initially androgen-dependent, strategies are targeted toward androgen depletion for its control. However, tumor re-growth mostly occurs following this modality, and is androgen-independent. A loss of functional androgen receptor and an enhanced expression of growth factor receptors (e.g. erbB family members) and associated ligands have been shown to be the causal genetic events in PCA progression. These genetic alterations lead to an epigenetic mechanism where a feed-back autocrine loop between membrane receptor (e.g. epidermal growth factor receptor [erbB1] and associated ligand (e.g. transforming growth factor-alpha) results in an enhanced activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) as an essential component of the uncontrolled growth of PCA at an advanced and androgen-independent stage. Together, we rationalized that inhibiting these epigenetic events would be useful in controlling advanced PCA growth. Dietary polyphenolic flavonoids and isoflavones are being studied extensively as cancer-preventive and interventive agents. Therefore, we focused our attention on silymarin, genistein, and epigallocatechin 3-gallate (EGCG), present in milk thistle, soy beans, and green tea, respectively. The effect of these agents was assessed on the erbB1-Shc-ERK1/2 signal transduction pathway, cell cycle regulatory molecules, and cell growth and death. In androgen-independent human prostate carcinoma DU145 cells, silymarin, genistein, and EGCG resulted in a significant to complete inhibition of transforming growth factor-alpha-caused activation of membrane receptor erbB1 followed by inhibition of downstream cytoplasmic signaling target Shc activation and a decrease in its binding with erbB1, without an alteration in their protein expression. Silymarin and genistein also inhibited ERK1/2 activation, suggesting that these agents impair the activation of erbB1-Shc-ERK1/2 signaling in DU145 cells. In the case of EGCG, a further increase in ERK1/2 activation was observed that was related to its pro-oxidant and apoptotic activities. Silymarin, genistein, and EGCG also resulted in a significant induction of Cip1/p21 and Kip1/p27 and a decrease in cyclin-dependent kinase (CDK) 4, but a moderate inhibition of CDK2, cyclin D1, and cyclin E was observed. An enhanced level of Cip1/p21 and Kip1/27 also led to an increase in their binding to CDK4 and CDK2. Treatment of cells with silymarin, genistein, and EGCG also resulted in strong cell growth inhibition at lower doses, and complete inhibition at higher doses. In contrast to silymarin, higher doses of genistein also showed cell death. A more profound cytotoxic effect was observed in the case of EGCG, with strong cell death at lower doses and complete loss of viability at higher doses. Together, these results suggest that cell signaling and regulators of cell cycle are potential epigenetic molecular targets for prostate cancer prevention by dietary agents. More studies, therefore, are needed with these agents to explore their anticarcinogenic potential against human prostate cancer.

Anticarcinogenic Agents↗
PubMed2000

Silibinin up-regulates insulin-like growth factor-binding protein 3 expression and inhibits proliferation of androgen-independent prostate cancer cells.

Silibinin, a naturally occurring flavonoid antioxidant found in the milk thistle, has recently been shown to have potent antiproliferative effects against various malignant cell lines, but the underlying mechanism of action remains to be elucidated. We investigated the effect of silibinin on androgen-independent prostate cancer PC-3 cells. At pharmacologically achievable silibinin concentrations (0.02-20 microM), we observed increased insulin-like growth factor-binding protein 3 (IGFBP-3) accumulation in PC-3 cell conditioned medium and a dose-dependent increase of IGFBP-3 mRNA abundance with a 9-fold increase over baseline at 20 microM silibinin. An IGFBP-3 antisense oligodeoxynucleotide that attenuated silibinin-induced IGFBP-3 gene expression and protein accumulation reduced the antiproliferative action of silibinin. We also observed that silibinin reduced insulin receptor substrate 1 tyrosine phosphorylation, indicating an inhibitory effect on the insulin-like growth factor I receptor-mediated signaling pathway. These results suggest a novel mechanism by which silibinin acts as an antiproliferative agent and justify further work to investigate potential use of this compound or its derivatives in prostate cancer treatment and prevention.

Androgens↗
PubMed2000

Anti-angiogenic potential of a cancer chemopreventive flavonoid antioxidant, silymarin: inhibition of key attributes of vascular endothelial cells and angiogenic cytokine secretion by cancer epithelial cells.

In recent studies, we have shown that silymarin, a naturally occurring flavonoid antioxidant, exhibits anti-cancer effects against several epithelial cancers. Here, we assessed its potential as an anti-angiogenic agent employing human umbilical vein endothelial cells (HUVEC) and human prostate and breast cancer epithelial cells. When sub-confluent HUVEC were treated for 48 h, adherent cell number decreased by 50 and 90% at 50 and 100 microg/ml doses, respectively. Apoptotic cell death principally accounted for cell loss at >50 microg/ml doses. In biochemical analysis, silymarin treatment of HUVEC for 6 h resulted in a concentration-dependent decrease in the secretion and cellular content of matrix metalloproteinase (MMP)-2/gelatinase A. Silymarin also inhibited HUVEC tube formation (in vitro capillary differentiation) on a reconstituted extracellular matrix, Matrigel. In other studies, 5 to 6 h exposure of DU145 prostate, and MCF-7 and MDA-MB-468 breast cancer cells to silymarin resulted in a dose-dependent decrease in the secreted vascular endothelial growth factor (VEGF) level in conditioned media without any visible change in cell morphology. The inhibitory effect of silymarin on VEGF secretion occurred as early as 1 h. These observations indicate a rapid inhibitory action of silymarin on the secretion of this primary angiogenic cytokine by cancer epithelial cells. Taken together, the results of this study support the hypothesis that silymarin possesses an anti-angiogenic potential that may critically contribute to its cancer chemopreventive efficacy.

Antioxidants↗
PubMed2000

mu-Calpain activation, DNA fragmentation, and synergistic effects of caspase and calpain inhibitors in protecting hippocampal neurons from ischemic damage.

The differentiated cells seem to share the ability to induce their own death by the activation of an internally encoded suicide program. When activated, this suicide program initiates a characteristic form of cell death called apoptosis. A central challenge in apoptosis research is understanding the mechanisms by which apoptotic cascades are initiated and affected. We tested a potential role for calpain in the programmed cell death under ischemic conditions and found that calpain is (1) activated at a time preceding morphological changes, DNA fragmentation and death, (2) that calpain is translocated to the nucleus before DNA laddering, (3) pretreatment with caspase inhibitors and/or calpain inhibitors block not only the proteolytic actions of the enzyme, but also the cell death process itself in the CA1 subfield after transient global ischemia in a synergistic manner. In conclusion, the present results contribute additional evidence that proteases may play a functional role in apoptotic cell death and extend them to include the possibility that endogenous proteases are capable of inducing the striking DNA fragmentation and chromatin condensation, which are the principle criteria currently used to define apoptotic death. Moreover, the synergistic effect of caspase and calpain inhibitors in protecting neurons form ischemic damage suggests that there is a cross-talk between caspase and calpain during apoptosis.

Amino Acid Chloromethyl Ketones↗
PubMed2000

Anticarcinogenic effect of a polyphenolic fraction isolated from grape seeds in human prostate carcinoma DU145 cells: modulation of mitogenic signaling and cell-cycle regulators and induction of G1 arrest and apoptosis.

There is an increasing interest in identifying potent cancer preventive and therapeutic agents against prostate cancer (PCA). In a recent study, we showed that a polyphenolic fraction isolated from grape seeds (hereafter referred to as GSP) that is substantially rich in antioxidant procyanidins exerts exceptionally high preventive effects against tumorigenesis in a murine skin model. In the present study, we investigated the anticarcinogenic effect of GSP against PCA by employing DU145 human prostate carcinoma cells. GSP treatment (10-100 microg/mL doses for 2-6 d) of cells resulted in a highly significant (P < 0.01-0.001) inhibition of cell growth in both dose- and time-dependent manner. Compared with the vehicle, 2 d of GSP treatment resulted in 27, 39, and 76% growth inhibition at 50, 75, and 100 microg/mL doses, respectively, whereas 28-97% and 12-98% inhibition was evident at 10-100 microg/mL doses of GSP after 4 and 6 d of treatment, respectively. These doses of GSP also resulted in dose- and time-dependent cell death (6-50%, P <0.1-0. 001) that was later characterized as apoptotic death. In molecular mechanistic studies, treatment of DU145 cells with GSP at 25-75 microg/mL doses for 24, 48, and 72 h resulted in 77-88%, 65-93%, and 38-98% reduction, respectively (P < 0.001), in phospho-extracellular signal-regulated protein kinase (ERK) 1 and 78%, 19-76%, and 63-71% reduction (P < 0.1-0.001) in phospho-ERK2 levels, respectively. In other studies, similar doses of GSP showed up to 1.9-fold increases in Cip1/p21 and a significant (P < 0.001) decrease in cyclin-dependent kinase (CDK) 4 (up to 90% decrease), CDK2 (up to 50% decrease), and cyclin E (up to 60% decrease). GSP treatment of DU145 cells also resulted in a significant (P < 0.001) G1 arrest in cell-cycle progression in a dose-dependent manner. The growth-inhibitory and cell-death effects of GSP were also observed in another human PCA line, LNCaP. Together, these results suggest that GSP may exert strong anticarcinogenic effect against PCA and that this effect possibly involves modulation of mitogenic signaling and cell-cycle regulators and induction of G1 arrest, cell-growth inhibition, and apoptotic death. Mol. Carcinog. 28:129-138, 2000.

Adenocarcinoma↗
PubMed2000

Ultrasonic parameters and relationship between compressive strength, microstructure of gall bladder stones.

Patients with symptomatic stones are at a great risk for complications and these complications are a major cause of morbidity. The gall bladder stones may have a complex structure and variable composition. In the present investigation stones have been grouped into three categories namely cholesterol, bilirubinate and mixed, and a correlation between the surface structure, ultrasonic parameters and compressive strength is estimated. A double-probe through-transmission technique was used for the ultrasonic parameters study, a universal testing instrument for hardness and a scanning electron microscope (SEM) for microstructure study. Gall bladder stones of mixed type with higher ultrasonic velocity, less attenuation and higher crushing strength were found to be more difficult to break in comparison to other types of stones. SEM of mixed type stones showed rough surface as compared to bilirubinate and cholesterol stones. The results obtained as well as the relationship might be useful in the design of a focussed ultrasonic 0lithotripter.

Cholelithiasis↗
PubMed2000

Studies of renal injury III: lipid-induced nephropathy in type II diabetes.

UNLABELLED: Studies of renal injury III: Lipid-induced nephropathy in type II diabetes. BACKGROUND: Nephrotoxicity from elevated circulating lipids occurs in experimental and clinical situations. We tested the hypothesis that lipid-induced nephropathy causes advanced renal failure in rats with type II diabetes and dyslipidemia. METHODS: First generation (F1) hybrid rats derived from the spontaneous hypertensive heart failure rat (SHHF/Gmi-fa) and the LA/NIH-corpulent rat (LA/N-fa) were studied for 41 weeks while being on specific diets. Group 1 (14 rats) ingested 11.5% protein, 47.9% fat, and 40.6% carbohydrate. Group 2 (8 rats) ingested 26.9% protein, 16.7% animal fat, and 56.4% carbohydrate, and group 3 (20 rats) ingested 20.2% protein, 40.4% soy and coconut oil, and 39.4% carbohydrate. RESULTS: Hyperglycemia was more severe in rat groups 1 and 2 than in group 3. In contrast, circulating cholesterol and hydroperoxide levels were highest in group 3, intermediate in group 2, and lowest in group 1. Group 3 had severe renal failure secondary to glomerulosclerosis and tubulointerstitial disease, with striking deposition of the lipid peroxidation stress biomarker 4-hydroxynonenal in glomeruli and renal microvessels. Moreover, in group 3, increased arterial wall thickness also connoted vascular injury. In contrast, the glycoxidation stress biomarkers pentosidine and carboxymethyl-lysine were preferentially localized to renal tubules of hyperglycemic rats in groups 1 and 2 and did not segregate with the most severe renal injury. Glomerular and interstitial fibrosis was accompanied by proportional increases in renal transforming growth factor-beta1 levels, which were threefold higher in the hypercholesterolemic rats of group 3 than in the hyperglycemic rats of group 1. CONCLUSIONS: Acquisition of non-nodular glomerular sclerosis and tubulointerstitial disease is dependent on lipoxidation stress in rats with type II diabetes. On the other hand, in the absence of hypercholesterolemia, prolonged glycoxidation stress does not appear to be uniquely nephrotoxic.

Animals↗
PubMed2000

Increased expression of interleukin 6 in term compared to the first trimester human placental villi.

Cytokines and their specific receptors expressed at the feto-maternal interface are known to play a critical role in regulating various placental functions. Interleukin 6 (IL-6) has been shown to be produced by both decidua and the trophoblast cells of the placenta. The aim of the present study was to examine the expression profile of placental IL-6 protein and mRNA at early and late stages of gestation. Placental villi were obtained from women undergoing first trimester pregnancy termination or elective Cesarean section at term. Functionally active placental explant culture system was used to study the release of IL-6 by these tissues. IL-6 was detected in placental conditioned media of all the samples from first trimester and term group. The mean levels of IL-6 produced by term villi were found to be 5.5, 7.5 and 5-fold higher at term when compared with the first trimester at 24 h, 48 h and 72 h of culture, respectively. Expression of IL-6 mRNA was demonstrated by RT-PCR performed on total RNA isolated from these tissues. IL-6 mRNA expression was detected in both early and late gestational placental tissues. Moreover, the level of IL-6 mRNA was found to be approximately 4-fold higher at term compared with first trimester. These data are consistent with the hypothesis that levels of IL-6 production by the placenta are developmental stage-specific and suggest that expression of IL-6 in the placenta could be subjected to transcriptional regulation.

Cells, Cultured↗