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Biomedical subjects

Sanjay Kumar

Publications and source records attributed to Sanjay Kumar.

At least 109 records · Page 6Linked to original sources
PubMed2004

Infection with cytomegalovirus in patients with inflammatory bowel disease: prevalence, clinical significance and outcome.

Despite frequent use of immunosuppressive drugs in patients with inflammatory bowel disease (IBD) and reports of cytomegalovirus (CMV) infection following post-transplant immunosuppression, data on the frequency and clinical significance of CMV in patients with IBD are scant. Sixty-three patients with IBD (61 ulcerative colitis and two Crohn's disease) were evaluated for CMV using serology (IgM antibody, mu-capture ELISA), PCR for CMV DNA in colonic biopsy and histological assessment of haematoxylin and eosin-stained colonic biopsy. Positive result in any test was considered as CMV infection. Various parameters associated with CMV infection were analysed using univariate and multivariate analysis. Ten of 63 (15.8 %) patients (age 36.0 +/- 11.2 years, 31 female) were infected with CMV (DNA alone in four, IgM antibody alone in two and both in four, inclusion body in one). Patients with CMV infection were more often female (8/10 vs 23/53, P < 0.05), had pancolitis (10/10 vs 33/53, P < 0.05), histological activity (9/10 vs 17/53, P < 0.005) and used azathioprine (5/10 vs 7/53, P = 0.04; Fisher exact test for all). On multivariate analysis, female gender, pancolitis and histological activity were the independent factors associated with infection. Patients with CMV infection more often required surgical treatment for IBD (4/10 vs 4/53, P = 0.01) and had fatal outcome (3/10 vs 0/53, P = 0.003). CMV infection in patients with IBD may be common and is associated with poor outcome. PCR of rectal biopsy was the most sensitive method of detection followed by IgM antibody for diagnosis.

Adolescent↗
PubMed2004

Severe ulcerative colitis: prospective study of parameters determining outcome.

BACKGROUND: One-third of patients with exacerbations of ulcerative colitis (UC) require colectomy and 1% die. Although several studies have reported parameters associated with failure of medical treatment, studies using multivariate analysis of various predictors are scanty. METHODS: Demographic, clinical and laboratory parameters within 48 h of admission of 50 consecutive patients (55 episodes) were prospectively recorded. Each episode was treated with intravenous hydrocortisone, antibiotics and fluid administration. The data of patients who failed to respond, deteriorated, developed complications requiring emergency surgery or died within 7 days of hospitalization, were compared with the data of those who responded during this period using Mann-Whitney U-test or chi-squared tests. Variables found to be significant on univariate analysis were entered into a multivariate model. RESULTS: Medical treatment failed in 10 of 55 episodes; eight had surgery (one died), another died with bowel perforation and peritonitis and one left hospital in a moribund state. Younger age, pedal edema, transverse colonic diameter >5 cm on abdominal radiograph, low hemoglobin, low serum albumin, high C-reactive protein, presence of fibrin degradation product (FDP) in serum, low serum fibrinogen, prolonged prothrombin time, Truelove-Witt's fulminant disease, and high clinical activity index were associated with failure of medical treatment on univariate analysis. All the above variables were significant by multivariate analysis except age, serum albumin level and presence of FDP. CONCLUSION: It may be possible to predict the failure of medical treatment in exacerbations of UC using a scoring system based on clinical parameters and simple laboratory tests.

Adolescent↗
PubMed2004

Growth-inhibitory effect of heparin on Babesia parasites.

We examined the inhibitory effects of three heparins on the growth of Babesia parasites. The multiplication of Babesia bovis, B. bigemina, B. equi, and B. caballi in in vitro cultures and that of B. microti in vivo were significantly inhibited in the presence of heparins, as determined by light microscopy. Treatment with various concentrations of heparin showed complete clearance of the intracellular parasites. Interestingly, a higher percentage of abnormally multidividing B. bovis parasites was observed in the presence of low concentrations of heparin. Furthermore, fluorescein isothiocyanate-labeled heparin was preferably found on the surfaces of extracellular merozoites, as detected by confocal laser scanning microscopy. These findings indicate that the heparin covers the surfaces of babesial merozoites and inhibits their subsequent invasion of erythrocytes.

Animals↗
PubMed2004

Molecular epidemiological survey of benign Theileria parasites of cattle in Japan: detection of a new type of major piroplasm surface protein gene.

Benign Theileria species of cattle are found in most parts of the world. The major piroplasm surface protein (MPSP), a conserved protein in all Theileria species, has been used as a maker for epidemiological and phylogenetical studies of benign Theileria species. Parasites with Ikeda- or Chitose-type MPSP genes are dominant in Japan, but we report here mixed infection cases of Theileria parasites with an additional MPSP type parasite infecting cattle in Abashiri District, Hokkaido. The MPSP gene sequence found in the additional type was closely related to MPSP genes of Theileria parasites found in Southeast Asian countries, including Thailand (Narathiwat) and Indonesia (Java). Theileria parasites from the blood sample were also distinguishable from the Ikeda or Chitose type parasites by the small subunit (SSU) rRNA gene sequence analysis, and they are grouped into the SSU rRNA types C/D found in Korea, North America, and Spain. The present finding of mixed infections of cattle with three different types of Theileria makes epidemiological feature of bovine theileriosis in Japan more complex. We have designed a set of primers specific to this MPSP type in order to conduct further epidemiological study.

Animals↗
PubMed2004

Molecular characterization of Theileria orientalis piroplasm protein encoded by an open reading frame (To ORF2) in a genomic fragment.

In the present study, a novel antigenic protein expressed in the piroplasm stage of Theileria orientalis was characterized. A 4,707 bp genomic fragment amplified by PCR contained two open reading frames (ORFs). The deduced amino acid sequence of the first ORF showed significantly high similarlity to the ubiquitin carboxy terminal hydrolases/proteases while the second ORF (To ORF2) showed homology to several surface antigens of plasmodia. To ORF2 was expressed to determine whether the protein product is expressed by the parasite. In western blot analysis, bovine antiserum from a T. orientalis-infected calf recognized the recombinant protein containing a C-terminal part of the ORF expressed by baculovirus system. Western blot analysis with the anti-To ORF2 mouse serum recognized a 48 kDa protein in T. orientalis piroplasm lysates. Indirect immunofluorescence antibody test by confocal scanning laser microscopic analysis showed that antisera against the recombinant protein recognized T. orientalis piroplasm in the infected erythrocyte. The results from this study indicate that To ORF2 protein is expressed at the piroplasm stage and is immunogenic. This novel antigenic To ORF2 protein could be exploited for vaccine development against bovine piroplasmosis.

Amino Acid Sequence↗
PubMed2004

Periprosthetic humeral fractures after shoulder arthroplasty.

BACKGROUND: Currently, there is little information concerning periprosthetic humeral fractures after shoulder arthroplasty. Therefore, we reviewed our experience with these fractures to determine the results of treatment, the risk factors for periprosthetic fracture, and the rates of reoperation. METHODS: Between 1976 and 2001, nineteen postoperative periprosthetic humeral fractures occurred among 3091 patients who had undergone shoulder arthroplasty at our institution. Sixteen patients had a complete series of radiographs and were included in this study. The average time from the arthroplasty to the fracture was forty-nine months. Seven patients had severe osteopenia. Twelve fractures occurred at the tip of the prosthesis; of these, six extended proximally (type-A fractures) and six did not (type-B fractures). Three fractures occurred distal to the implant and extended into the distal humeral metaphysis (type-C fractures). One fracture occurred in the proximal metadiaphyseal region because of osteolysis. RESULTS: Six fractures healed after an average of 180 days of nonoperative treatment. Five fractures were treated operatively after an average of 123 days of unsuccessful nonoperative treatment. The remaining five fractures had immediate operative treatment. All sixteen fractures healed. One patient required multiple operations over a period of three years before union was achieved. With the exclusion of this patient and one other patient who received a custom prosthesis, the average time between the first operative procedure and union was 278 days. CONCLUSIONS: Our data do not clearly indicate the need for operative treatment of type-A fractures unless the humeral component is loose. A trial of nonoperative treatment may be considered for well-aligned type-B fractures that are associated with a well-fixed humeral component; however, operative intervention should be considered for type-B fractures that have not progressed toward union by three months. If the component is well fixed, open reduction and internal fixation may be performed. If the component is loose, revision with a long-stem component is recommended. For type-C fractures, a trial of nonoperative treatment is recommended.

Adult↗
PubMed2004

Gene therapy for osteoinduction.

Various disorders of bone and mineral metabolism are diagnosed to be defective in genes related to cellular growth and differentiation. Gene therapy to introduce normal copy of defective genes into cells and tissues to compensate for silent, minimally expressed or mutated genes can be accomplished by multiple approaches. Although each bone disease/disorder would require a case-wise evaluation of potential strategies for best possible outcome, considerations for the gene therapy approaches are: 1) introduction of a therapeutic gene into cells without changing any of its native biological properties, 2) minimal or total absence of immunogenic and toxic effects from introduced vectors, genetically-modified cells or conditionally-expressed proteins, while achieving a therapeutic effect, 3) cell-type or tissue-specific, regulated expression of a therapeutic protein, and 4) restricting or abolishing the expression of disease triggering genes at the RNA or DNA levels. Although most of the currently available therapies for osteoinduction are pharmacological in nature, molecular understanding of biologically-driven factors provides greater opportunity to test their potential as therapeutic proteins. Strategies of gene therapy complement this approach through efficient delivery of genes encoding therapeutic proteins to target sites. The present review will attempt to give a comprehensive account of existing therapies for osteoinduction and discuss the potential and limitation of vector-mediated gene therapy for bone diseases.

Bone Diseases↗
PubMed2004

Anti-angiogenic gene therapy for cancer (review).

Angiogenesis is a prerequisite for the growth and metastasis of solid tumors. Studies have confirmed that in the absence of angiogenesis, tumors rarely have the ability to develop beyond a few millimeters in diameter. Tumor-associated endothelium is activated by the production of soluble factors by tumor and stromal cells. Tumor-associated endothelial cells are physiologically homogeneous and divide more frequently. Thus, targeting the proliferation of tumor neovasculature will form an effective anti-cancer therapy. With the identification of drug and biological molecules that inhibit the growth of tumor endothelium, several attempts have been made in preclinical and clinical research to evaluate the potential of anti-angiogenic therapy. Although several drugs and purified proteins have shown promise, their wide-spread application is limited by half-life, side effects and cost involved. Gene therapy approaches, on the other hand, have the potential to overcome these limitations. Further, genetic transfer of anti-angiogenic genes can be combined with other treatments including radiation therapy or chemotherapy for synergistic effects. In this review, we provide a comprehensive account of factors and mechanisms underlying tumor angiogenesis, the potential and limitations of available gene therapy vectors for anti-angiogenesis and current status of preclinical and clinical gene therapy studies targeting tumor angiogenesis.

Clinical Trials as Topic↗
PubMed2004

Papillary carcinoma thyroid: FNAC diagnosis.

Thyroid carcinoma in children is currently assuming greater importance due to increase incidence in the recent times. In carcinoma thyroid, the age at the time of diagnosis is an important prognostic factor and children in particular are considered to have an excellent prognosis. We came across 3 cases of papillary carcinoma thyroid involving both the lobes and having lymph node metastasis in children, the youngest being 4 years of age at the time of diagnosis. All these cases were diagnosed on aspiration cytology.

Biopsy, Fine-Needle↗
PubMed2004

Leaching study of trace elements from coal ashes: A case study of Bokaro Thermal Power Station "B".

Electricity generation has been increasing at a rapid rate due to rapid industrialization and changing life styles. In our Country coal is the major source of energy since India has vast reserves of thermal power grade coal. Nearly every naturally occurring element is likely to be present in coal and these get entertained in the resultant coal ash. Indian coals contain high ash coupled with low calorific value and consequently resulting huge amount of coal ashes. This ash accumulates in on site piles and ponds thereby resulting in serious environmental problems particularly trace elements contamination of ground and surface waters. This study envisages the environmental assessment of coal ashes from Bokaro Thermal Power Station- Leaching study of coal ashes was made through analysis of leachates from open percolation leaching column experiments over a period of 300 days. Trace elements were observed within the regulatory limits. Many of the trace elements evaluated viz. Ni., Co, Se, Al, As, B, Ba, Sb, Hg, were observed at below detection limits of AAS. Na, K, Ca, Fe, Pb, Cd and other dissolved ions leached at significant concentration levels. This study suggests low cost high volume utilisation of bottom ash as fill material for reclaiming surrounding abandoned mined out areas in an environmentally acceptable manner.

Coal↗
PubMed2003

Identification, characterization, and inhibition of Plasmodium falciparum beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ).

The emergence of drug-resistant forms of Plasmodium falciparum emphasizes the need to develop new antimalarials. In this context, the fatty acid biosynthesis (FAS) pathway of the malarial parasite has recently received a lot of attention. Due to differences in the fatty acid biosynthesis systems of Plasmodium and man, this pathway is a good target for the development of new and selective therapeutic drugs directed against malaria. In continuation of these efforts we report cloning and overexpression of P. falciparum beta-hydroxyacyl-acyl carrier protein (ACP) dehydratase (PffabZ) gene that codes for a 17-kDa protein. The enzyme catalyzes the dehydration of beta-hydroxyacyl-ACP to trans-2-acyl-ACP, the third step in the elongation phase of the FAS cycle. It has a Km of 199 microM and kcat/Km of 80.4 m-1 s-1 for the substrate analog beta-hydroxybutyryl-CoA but utilizes crotonoyl-CoA, the product of the reaction, more efficiently (Km = 86 microM, kcat/Km = 220 m-1 s-1). More importantly, we also identify inhibitors (NAS-91 and NAS-21) for the enzyme. Both the inhibitors prevented the binding of crotonoyl-CoA to PfFabZ in a competitive fashion. Indeed these inhibitors compromised the growth of P. falciparum in cultures and inhibited the parasite fatty acid synthesis pathway both in cell-free extracts as well as in situ. We modeled the structure of PfFabZ using Escherichia coli beta-hydroxydecanoyl thioester dehydratase (EcFabA) as a template. We also modeled the inhibitor complexes of PfFabZ to elucidate the mode of binding of these compounds to FabZ. The discovery of the inhibitors of FabZ, reported for the first time against any member of this family of enzymes, essential to the type II FAS pathway opens up new avenues for treating a number of infectious diseases including malaria.

Amino Acid Sequence↗
PubMed2003

A rapid protocol for the prevention of contrast-induced renal dysfunction: the RAPPID study.

OBJECTIVES: This study was designed to test a rapid protocol of intravenous acetylcysteine for prevention of radiocontrast-induced nephropathy (RCIN). BACKGROUND: Oral acetylcysteine (NAC) may provide better prophylaxis against RCIN than intravenous (i.v.) hydration alone. Current protocols preclude prophylaxis of same-day or emergency patients owing to the need for prolonged pretreatment. METHODS: We prospectively randomized 80 patients with stable renal dysfunction undergoing cardiac catheterization/intervention to a rapid protocol of i.v. NAC (150 mg/kg in 500 ml N/saline over 30 min immediately before contrast followed by 50 mg/kg in 500 ml N/saline over 4 h, n = 41, 67 +/- 10 years, 90% men) or i.v. hydration (1 ml/kg/h N/saline for 12 h pre- and post-contrast, n = 39, 71 +/- 8.8 years, 85% men). RESULTS: Radiocontrast-induced nephropathy occurred in 2 of the 41 patients in the NAC group (5%) and in 8 of the 39 patients in the hydration group (21%; p = 0.045; relative risk: 0.28; 95% confidence interval 0.08 to 0.98). In the NAC group, mean serum creatinine fell from 1.85 +/- 0.59 to 1.77 +/- 0.73 and 1.79 +/- 0.73 mg/dl 48 h and four days post-contrast (p = 0.02 and 0.023 vs. baseline, respectively). In the hydration group, serum creatinine increased from 1.75 +/- 0.41 to 1.81 +/- 0.6 48 h and 1.80 +/- 0.50 mg/dl four days post-contrast (p = 0.99 and 0.23, respectively). NAC infusion was ceased after the bolus in three patients (7%) due to flushing, itching, or a transient rash. CONCLUSIONS: Administration of i.v. NAC should be considered in all patients at risk of RCIN before contrast exposure when time constraints preclude adequate oral prophylaxis, provided the patient is able to tolerate this degree of volume loading.

Acetylcysteine↗