Spontaneous antepartum uterine artery rupture.
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Journal Article↗
Biomedical subjects
S Agarwal
Publications and source records attributed to S Agarwal.
Role of antioxidant lycopene in cancer and heart disease.
Lycopene, a carotenoid without provitamin-A activity, is present in many fruits and vegetables; however, tomatoes and processed tomato products constitute the major source of lycopene in North American diet. Among the carotenoids, lycopene is a major component found in the serum and other tissues. Dietary intakes of tomatoes and tomato products containing lycopene have been shown to be associated with decreased risk of chronic diseases such as cancer and cardiovascular diseases in several recent studies. Serum and tissue lycopene levels have also been inversely related with the chronic disease risk. Although the antioxidant properties of lycopene are thought to be primarily responsible for its beneficial properties, evidence is accumulating to suggest other mechanisms such as modulation of intercellular gap junction communication, hormonal and immune system and metabolic pathways may also be involved. This review summarizes the background information about lycopene and presents the most current knowledge with respect to its role in human health and disease.
Animals↗
Vesicoureteral reflux and urinary tract infections.
Urinary tract infection is a common problem in children. The combination of vesico-ureteric reflux (VUR) and urinary tract infection may predispose children to pyelonephritis and subsequent complications. This review outlines the modifications suggested in the recent literature in the protocol for investigations and diagnosing VUR. Recent interest has been expressed in studying certain molecular markers to measure non-invasively renal damage in children with VUR. Long term results of comparative trials between medical and surgical management have been published recently.
Child↗
Ascites fluid as a possible origin for hyperfibrinolysis in advanced liver disease.
OBJECTIVES: Advanced liver disease is associated with both exaggerated fibrinolysis and with ascites. This study was undertaken to determine whether fibrinolytic activity exists in the ascites fluid of patients with liver disease and to see whether such activity is associated with evidence of plasma fibrinolysis. METHODS: Both the ascites fluid and plasma from 15 patients with cirrhotic ascites (group A) were evaluated for markers of fibrinolysis: fragment D-dimer, plasminogen, fibrinogen, and fibrin split products. In addition, the euglobulin lysis time, a test highly specific for fibrinolysis, was evaluated in the ascites fluid samples. As a control group, the plasma from 15 cirrhotic patients without ascites (group B) was evaluated for markers of fibrinolysis. RESULTS: In group A, elevated fragment D-dimer and fibrin split products were uniformly found in ascites fluid in concentrations that would be considered pathologically elevated if in plasma. Ascites fluid was also depleted, compared with plasma, of both plasminogen and fibrinogen. These results, along with the short euglobulin lysis time in 83% of the patients, suggest that increased fibrinolytic activity is present in ascites fluid. In 93% of these patients, plasma D-dimer was elevated. The mean plasma plasminogen was also low in these patients. In group B, only 33% of patients had elevated plasma D-dimer. CONCLUSIONS: Ascites fluid has fibrinolytic activity. Because ascites fluid reenters the systemic circulation via the thoracic duct, via a natural peritoneovenous shunt, ascites fluid warrants serious consideration as a pathological fluid that contributes to the systemic fibrinolytic state found in the majority of our patients with ascites.
Ascitic Fluid↗
Type IV phosphodiesterase inhibitor is effective in prevention and treatment of experimental crescentic glomerulonephritis.
BACKGROUND: Tumour necrosis factor alpha (TNF-alpha) has an important role in acute glomerular inflammation. Rolipram, a type IV phosphodiesterase inhibitor, has multiple anti-inflammatory effects including inhibition of TNF-alpha synthesis. METHODS: We investigated the effects of rolipram in prevention and delayed treatment of crescentic glomerulonephritis in Wistar Kyoto rats. Glomerulonephritis was induced by injection of nephrotoxic serum. RESULTS: In the preventive study, rolipram (6.25 mg/kg i.p. twice daily) was started 2.5 h before injection of nephrotoxic serum. Rolipram reduced the expression of TNF-alpha in glomeruli and renal tubules and abrogated glomerular injury on day 4 (99.7% reduction in albuminuria and 96.4% reduction in fibrin deposition). In the delayed-treatment experiment, rolipram was started 4 days after injection of nephrotoxic serum. Rolipram reduced renal excretion of TNF-alpha by 63% on day 7. TNF-alpha was not detected in the sera of treated or control rats. Delayed treatment was effective in crescentic glomerulonephritis, as shown by reduction in albuminuria by 38.1%, fibrin deposition by 60.8%, and crescent formation by 67% on day 7. CONCLUSIONS: Rolipram is effective both in prevention and treatment of experimental crescentic glomerulonephritis. This was associated with a reduction of renal production of TNF-alpha.
Animals↗
Evaluation of formalin preserved allogeneic bone graft as a grafting material.
Formalin preserved allogeneic (FPA) bone graft was used in 18 patients with benign bone cavities, nine patients with malignant bone cavities, 12 patients with atrophic nonunion of fractures, seven with gap nonunion and 18 with comminuted fractures. The benign bone cavities were obliterated in 20 weeks and malignant cavities in 24 weeks. Union was obtained in atrophic ununited fractures in 29 weeks, in gap nonunion in 40 weeks and in comminuted fractures in 27 weeks. FPA is a simple, inexpensive and easily available alternative to autologous bone and to deep frozen bone in filling bone defects and enhancing fracture union.
Bone Diseases↗
Activation of knot (kn) specifies the 3-4 intervein region in the Drosophila wing.
Hedgehog (Hh) plays an important role in Drosophila wing patterning by inducing expression of Dpp, which serves to organize the wing globally across the A-P axis. We show here how Hh signalling also plays a direct role in patterning the medial wing through the activation of the Hh-target gene, knot (kn). kn is expressed in Hh-responsive cells near the A-P compartment boundary, where its expression is dependent on fu, a component of Hh signalling. kn is required for the proper positioning of veins 3 and 4 and to prevent ectopic venation between them. Furthermore, the expansion anteriorly of the normal kn expression domain causes an associated anterior shift in the position of vein 3 in the resultant wing. Ectopic expression of kn elsewhere in the wing imaginal disc results in the failure to properly activate the vein initiation genes, rho and Dl. Expression of the gene encoding the EGF-receptor (EGFR), which is required for vein initiation and subsequent differentiation, is normally depressed in the 3-4 intervein region. This downregulation of EGFR in the medial portion of the imaginal disc is dependent on kn activity and ectopic expression of kn inactivates EGFR elsewhere in the wing primordium. We propose kn expression in Hh-responsive cells of the wing blade anlagen during the late third instar creates a zone of cells in the medial wing in which vein primordia cannot be induced. The primordia for veins 3 and 4 are laid down adjacent to the kn-imposed vein-free zone, presumably by a signalling factor (such as Vn) also synthesized in the medial region of the wing.
Animals↗
Carotenoids and chronic diseases.
Chronic diseases such as cancer and cardiovascular diseases are the major causes of deaths in North America. Dietary intake of fruits and vegetables has been suggested to have protective effects against such chronic diseases. Carotenoids are important plant pigments which are thought to contribute towards the beneficial effects of fruit and vegetable consumption. This review focuses on the role of carotenoids and particularly lycopene in chronic diseases.
Animals↗
Geographic and ethnic distribution of beta-thalassemia mutations in Uttar Pradesh, India.
We have studied the geographic and ethnic distribution of mutations in 376 subjects who were carriers of beta-thalassemia, and identified the mutations in 365 chromosomes. The majority of the beta-thalassemia carriers were of Uttar Pradesh (India) origin. Their pattern of mutations differed from the other states of India and from those families who had migrated from Pakistan. The frequency of the IVS-I-5 (G-->C) and 619 bp deletion mutations were 64.3 and 2.5%, respectively, among families originating from Uttar Pradesh, compared to a prevalence of 37.5 and 27.5%, respectively in the population of Pakistani immigrants. Of the 10 common Asian Indian mutations, only eight were observed in subjects studied from different parts of India. By use of the amplification refractory mutation system along with DNA sequencing techniques, the mutations were successfully identified in 97.1% of subjects, while 11 cases (2.9%) still remain to be characterized by single strand conformation polymorphism and sequencing analyses. The application of this knowledge has facilitated the successful implementation of the program of genetic counseling and prenatal diagnosis of beta-thalassemia, thus helping to avoid the birth of an affected child in India.
DNA Mutational Analysis↗
Cyclooxygenase expression in the gallbladder.
The COX expressions were evaluated separately in the epithelium and in the stroma of gallbladder cancer, chronic cholecystitis, xanthogranulomatous cholecystitis (XGC) and the normal gallbladder. In normal gallbladder COX-2 expression rate was significantly higher in the epithelium than in the stroma. The COX-2 expression rate in the epithelium of non-cancerous adjacent epithelium to cancerous lesion was significantly lower than those not only of cancer, but also chronic cholecystitis, XGC and normal gallbladder. In stroma, the COX-2 expression rate in cancer, chronic cholecystitis and XGC were significantly higher than that of the normal gallbladder. The rate in non-cancerous adjacent stroma to cancer is significantly lower than that of cancer and XGC. However, the difference of rate between of normal and of chronic cholecystitis was not significant. The COX-2 expression rates were significantly higher in both the epithelium and the stroma in the well and moderately differentiated cancer group than in the poorly and undifferentiated cancer group. Our results suggest that COX-2 expression in the gallbladder may be regulated by various factors and not directly related to carcinogenesis. The significance of its repression in the non-cancerous adjacent tissue to cancer lesion should be re-evaluated.
Cholecystitis↗
Association between polymorphism in p21(Waf1/Cip1) cyclin-dependent kinase inhibitor gene and human oral cancer.
The cyclin-dependent kinase inhibitor gene p21(Waf1/Cip1) plays a central role in inducing cellular growth arrest, terminal differentiation, and apoptosis. Alterations in this gene may adversely affect regulation of these processes and increase susceptibility for cancer. We have recently reported a novel polymorphism in the p21(Waf1/Cip1) gene in the Indian population and its association with esophageal cancer. An A-->G transition at codon 149 resulted in amino acid substitution from aspartate to glycine in the proliferating cell nuclear antigen binding COOH-terminal domain of p21(Waf1/Cip1) that may affect PCNA-p21(Waf1/Cip1) interactions, thereby affecting regulation of cellular proliferation, and may increase susceptibility for development of cancer. In a parallel study in our laboratory, we searched for putative p21(Waf1/Cip1) mutations in oral premalignant and malignant lesions. No somatic mutation was detected in exon 2 of p21(Waf1/Cip1). Interestingly, a codon 149 polymorphism variant (A-->G) was identified in 11 of 30 (37%) premalignant lesions (7 of 19 hyperplastic lesions and 4 of 11 dysplastic lesions) and 11 of 30 (37%) squamous cell carcinomas (SCCs). This codon 149 variant was also identified in paired lymphocytes of all of the patients with premalignant lesions and SCCs harboring the variant allele, suggesting the occurrence of a polymorphism. Lymphocyte DNA isolated from 50 unrelated age- and gender-matched healthy subjects was screened for this polymorphism. Seven of 50 (14%) normal controls harbored the A-->G codon 149 variant allele. Immunohistochemical analysis of p21(Waf1/Cip1) protein expression showed immunoreactivity in 19 of these 30 (63%) oral premalignant lesions and 16 of 30 (53%) SCCs. The most intriguing features of the study were: (a) the significant increase in frequency of this polymorphism not only in patients with oral SCCs (P = 0.038), but also in patients with premalignant lesions (P = 0.038), compared with normal controls; and (b) the significantly higher frequency of p21(Waf1/Cip1) variants (codon 149) in oral premalignant lesions (10 of 11 cases) and SCCs (11 of 11 cases) with wild-type p53 (P = 0.045) than in lesions with p53 mutations, suggesting that this polymorphism affects the p53 pathway and may play a vital role in oral tumorigenesis. Furthermore, overexpression of p21 protein in oral lesions harboring missense mutations in the p53 gene suggest a p53-independent role for p21 in the pathogenesis of oral cancer.
Adult↗
Dandy Walker Syndrome associated with unusual congenital anomalies.
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Abnormalities, Multiple↗
Interaction of strain and interleukin-1 in articular cartilage: effects on proteoglycan synthesis in chondrocytes.
In temporomandibular joint disorders, the release of proinflammatory cytokines such as interleukin-1 (IL-1) initiates an inflammatory process disrupting cartilage homeostasis, ultimately leading to cartilage destruction. Additionally, mechanical stimuli affect articular chondrocyte metabolism. While articular chondrocytes generate nitric oxide (NO) in the presence of IL-1 proteoglycan synthesis is consecutively suppressed. The purpose of this study was to assess the effects of proinflammatory cytokines and mechanical strain in the form of cyclic tensile stretch on proteoglycan synthesis in chondrocytes, as compared to the NO competitive inhibitor L-N-monomethyl arginine (LMA), and to assess whether this effect is secondarily related to the activity of growth factors such as transforming growth factor beta (TGF-beta). Lapine articular chondrocytes were exposed to one of four different treatment regimens: no cyclic tensile stretch, IL-1, cyclic tensile stretch, or IL-1 plus cyclic tensile stretch. NO production was determined as medium nitrite accumulation. TGF-beta-bioactivity in chondrocyte conditioned medium was measured with the mink-lung epithelial cell bioassay. Proteoglycan synthesis was measured as the incorporation of 35-[S]-sodium sulfate into macromolecules separated from unincorporated label by gel filtration on PD-10 columns. In resting chondrocyte cultures, only baseline levels of NO were measured and the application of stretch for 24 h did not affect NO production. Addition of IL-1 provoked a large increase in NO synthesis which was abrogated in the presence of LMA. Application of stretch decreased the IL-1 induced NO synthesis, but did not modify the effect of LMA (being a competitive inhibitor of the inducible NO synthase) inhibiting IL-1 induced NO production. Glucosaminoglycan production was noted as proteoglycan synthesis showing almost no effect of cyclic stretch alone in comparison to the control condition, which correlates with the missing NO production in control and stretch conditions. Addition of IL-1 strongly inhibited proteoglycan synthesis, which was partly restored in the presence of LMA. However, cyclic stretch acted as a stronger restorer of proteoglycan synthesis in IL-1 treated conditions in the absence, and even more in the presence, of LMA. It was concluded that motion in the form of cyclic tensile stretch is a remarkable anti-inflammatory stimulus reversing the IL-1 induced suppression of proteoglycan synthesis in chondrocytes. These findings have therapeutic implications for the treatment of temporomandibular joint disorders, supporting early onset of postoperative and post-traumatic continuous passive motion therapy.
Animals↗
Impact of the integrated child development services (ICDS) on maternal nutrition and birth weight in rural Varanasi.
OBJECTIVE: To evaluate the impact of ICDS on maternal nutrition and birth weight. SETTING: 28 ICDS and 21 non-ICDS villages in two adjoining blocks of Varanasi. METHODS: 5289 pregnancies were registered during 1987-1993 in these two blocks. In the ICDS block 916 and 1453 nutrition supplemented and unsupplemented, respectively and 1748 of the non-ICDS live births with weight recorded within 48 h formed the study subjects. RESULTS: The ICDS supplemented mothers gained 100g more in pregnancy and birth weight was higher by 58 g (p < 0.05) as compared to unsupplemented ICDS mothers. Birth weight in unsupplemented ICDS areas was 25g higher as compared to non ICDS area. ICDS supplemented women had a significantly smaller proportion of low birth weight babies (14.4%) compared to ICDS unsupplemented (20.4%) and non-ICDS women (26.3%). The corresponding prevalence of preterm births was 2.0, 2.4 and 4.3%, respectively (P < 0.001). Multiple regression analysis showed that increased wight gain in pregnancy, length of gestation, caloric intake and term hemoglobin were significantly associated with birth weight. However, the length of gestation was not influenced by factors improving the birth weight. CONCLUSION: Undernourished pregnant women are benefitted by late pregnancy nutrition supplement
Adult↗
Fine needle aspiration of bone tumors.
Fine needle aspiration cytology (FNAC) was performed in 226 cases of bone tumors and the cytohistologic correlation was calculated to assess the technique's diagnostic efficacy aided by immunocytochemistry, considering histopathology as the gold standard. Of the 226 cases, 136 were malignant and 72 cases were benign tumors. In the remaining 18 cases, cytohistopathologic examination revealed no bony lesion. There were 178 evaluable cases, but the specific morphologic diagnosis on FNAC was possible only in 159 cases with one false positive and 29 false negatives. Giant cell tumor (32%) and Ewing's sarcoma (22%) were the most common bony tumors encountered in this series. The diagnostic indices were calculated by a decision matrix comparison. The overall sensitivity and specificity were 86.0 (confidence interval [CI], 80.3-90.3) and 94.7 (CI, 71.9-99.7), respectively. The positive predictive value (PPV) was as high as 99.4 (CI, 96.5-100), while the negative predictive value (NPV) was 38.3 (CI, 24.9-53.6) with positive and negative likelihood ratios of 16.338 and 0.147, respectively. Diagnosis of malignant tumors was more accurate with a PPV of 99.2 (CI, 94.8-100.0) and specificity of 94.7 (CI, 71.9-99.7), while the sensitivity was 89.0 (CI, 82.2-93.5) and NPV was 54.5 (CI, 36.6-71.5). This study highlights the usefulness of FNAC along with the use of immunocytochemistry in the rapid diagnosis of bone tumors.
Adolescent↗
Percussion of Traube's space--a useful index of splenic enlargement.
OBJECTIVE: To evaluate the sensitivity and specificity of palpation and percussion for splenic enlargement, as the accuracy of many of the clinical maneuvers we perform remains largely unstudied. METHODS: One hundred cases were selected at random from medical wards, and splenic enlargement was assessed by palpation and percussion of the Traube's space (Barkuns method), which was confirmed by the ultrasonography of the abdomen. The results of the various tests were tabulated and assessed statistically. RESULTS: 1) Performance of Traube's space percussion shows 24 true positive and 48 true negative cases, the test thus had an overall sensitivity of 67% and specificity of 75%. It was also found that the BMI of the false negative cases was significantly higher (29.43 Kg/m2). 2) Palpation as a diagnostic maneuver had a high specificity of 96.87% along with high false negative rate with overall low sensitivity of 44.44%. 3) Interpolation of findings of Traube's space percussion and palpation showed that maximum clinical utility could be achieved when both percussion and palpation were positive. CONCLUSION: Percussion of the Traube's space is a useful clinical screening test for splenomegaly, with a sensitivity of 67% and specificity of 75%, as compared to palpation (sensitivity of 44.44% and specificity of 96.87%). And maximum clinical utility is achieved when both percussion and palpation are combined.
Adult↗
Large-scale analysis of the yeast genome by transposon tagging and gene disruption.
Economical methods by which gene function may be analysed on a genomic scale are relatively scarce. To fill this need, we have developed a transposon-tagging strategy for the genome-wide analysis of disruption phenotypes, gene expression and protein localization, and have applied this method to the large-scale analysis of gene function in the budding yeast Saccharomyces cerevisiae. Here we present the largest collection of defined yeast mutants ever generated within a single genetic background--a collection of over 11,000 strains, each carrying a transposon inserted within a region of the genome expressed during vegetative growth and/or sporulation. These insertions affect nearly 2,000 annotated genes, representing about one-third of the 6,200 predicted genes in the yeast genome. We have used this collection to determine disruption phenotypes for nearly 8,000 strains using 20 different growth conditions; the resulting data sets were clustered to identify groups of functionally related genes. We have also identified over 300 previously non-annotated open reading frames and analysed by indirect immunofluorescence over 1,300 transposon-tagged proteins. In total, our study encompasses over 260,000 data points, constituting the largest functional analysis of the yeast genome ever undertaken.
Algorithms↗
Cyclic tensile stress exerts antiinflammatory actions on chondrocytes by inhibiting inducible nitric oxide synthase.
Continuous passive motion manifests therapeutic effects on inflamed articular joints by an as-yet-unknown mechanism. Here, we show that application of cyclic tensile stress (CTS) in vitro abrogates the catabolic effects of IL-1beta on chondrocytes. The effects of CTS are mediated by down-regulation of IL-1beta-dependent inducible NO production, and are directly attributed to the inhibition of inducible NO synthase (iNOS) mRNA expression and protein synthesis. The inhibition of iNOS induction by CTS is paralleled by abrogation of IL-1beta-induced down-regulation of proteoglycan synthesis. Furthermore, CTS inhibits iNOS expression and up-regulates proteoglycan synthesis at concentrations of IL-1beta frequently observed in inflamed arthritic joints, suggesting that the actions of CTS may be clinically relevant in suppressing the sustained effects of pathological levels of IL-1beta in vivo. These results are the first to demonstrate that mechanisms of the intracellular actions of CTS in IL-1beta-activated chondrocytes are mediated through inhibition of a key molecule in the signal transduction pathway that leads to iNOS expression.
Animals↗