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Biomedical subjects

S Srinivas

Publications and source records attributed to S Srinivas.

At least 19 recordsLinked to original sources
PubMed2005

Structure, bonding, and magnetism in manganese clusters.

We investigate the structures and magnetic properties of small Mn(n) clusters in the size range of 2-13 atoms using first-principles density functional theory. We arrive at the lowest energy structures for clusters in this size range by simultaneously optimizing the cluster geometries, total spins, and relative orientations of individual atomic moments. The results for the net magnetic moments for the optimal clusters are in good agreement with experiment. The magnetic behavior of Mn(n) clusters in the size range studied in this work ranges from ferromagnetic ordering (large net cluster moment) for the smallest (n=2, 3, and 4) clusters to a near degeneracy between ferromagnetic and antiferromagnetic solutions in the vicinity of n=5 and 6 to a clear preference for antiferromagnetic (small net cluster moment) ordering at n=7 and beyond. We study the details of this evolution and present a picture in which bonding in these clusters predominantly occurs due to a transfer of electrons from antibonding 4s levels to minority 3d levels.

Journal Article↗
PubMed2003

Management of acute diarrhoea in children.

Acute diarrhoeal disease is one of the major killers in children in the developing countries. A management protocol consisting of "Triple A" (assessment, analysis of clinical presentation and action plan protocol) approach has been found to be rewarding in our set-up. The matter has been dealt with by the authors in this article in its proper perspective.

Acute Disease↗
PubMed2002

Bilateral congenital choanal atresia.

Our experience with the diagnosis and management of bilateral choanal atresia is presented. Four patients were treated by endoscopic transnasal approach followed by stenting with portex endotracheal tube for four to six weeks. Meticulous postoperative care particularly stent management is crucial for successful treatment of choanal atresia.

Choanal Atresia↗
PubMed2002

Treatment of simulated Reactive Yellow 22 (azo) dye effluents using Spirogyra species.

The potential of commonly available green algae belonging to Spirogyra species was investigated as viable biomaterials for biological treatment of simulated synthetic azo dye (Reactive Yellow 22) effluents. The results obtained from the batch experiments revealed the ability of the algal species in removing the dye colour and was dependent both on the dye concentration and algal biomass. Maximum dye colour removal was observed on the third day for all the system conditions. Monitoring of ORP values helped to understand the overlying biochemical mechanism of algal-dye system. Based upon the results, the dye-algal treatment mechanism was attributed to biosorption (sorption of dye molecules over the surface of algal cells), bioconversion (diffusion of dye molecules into the algal cells and subsequent conversion) and biocoagulation (coagulation of dye molecules present in the aqueous phase onto the biopolymers released as metabolic intermediates during metabolic conversion of dye and subsequent settlement).

Azo Compounds↗
PubMed2001

Differential activities of the RET tyrosine kinase receptor isoforms during mammalian embryogenesis.

The RET receptor tyrosine kinase has a critical role in kidney organogenesis and the development of the enteric nervous system. Two major isoforms, RET9 and RET51, differ in the amino acid sequence of the C-terminal tail as a result of alternative splicing. To determine the roles of these isoforms in vivo, we used targeted mutagenesis to generate mice that express either RET9 or RET51. Monoisoformic RET9 mice, which lack RET51, are viable and appear normal. In contrast, monoisoformic RET51 animals, which lack RET9, have kidney hypodysplasia and lack enteric ganglia from the colon. To study the differential activities of the two RET isoforms further, we generated transgenic mice expressing ligand-dependent and constitutively active forms of RET9 or RET51 under the control of the Hoxb7 regulatory sequences. Such RET9 transgenes are capable of rescuing the kidney agenesis in RET-deficient mice or causing kidney hypodysplasia in wild-type animals. In contrast, similar RET51 transgenes fail to rescue the kidney agenesis or cause hypodysplasia. Our findings show that RET9 and RET51 have different signaling properties in vivo and define specific temporal and spatial requirements of c-Ret function during renal development and histogenesis of the enteric nervous system.

Alternative Splicing↗
PubMed2001

Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus.

BACKGROUND: Several Cre reporter strains of mice have been described, in which a lacZ gene is turned on in cells expressing Cre recombinase, as well as their daughter cells, following Cre-mediated excision of a loxP-flanked transcriptional "stop" sequence. These mice are useful for cell lineage tracing experiments as well as for monitoring the expression of Cre transgenes. The green fluorescent protein (GFP) and variants such as EYFP and ECFP offer an advantage over lacZ as a reporter, in that they can be easily visualized without recourse to the vital substrates required to visualize beta-gal in living tissue. RESULTS: In view of the general utility of targeting the ubiquitously expressed ROSA26 locus, we constructed a generic ROSA26 targeting vector. We then generated two reporter lines of mice by inserting EYFP or ECFP cDNAs into the ROSA26 locus, preceded by a loxP-flanked stop sequence. These strains were tested by crossing them with transgenic strains expressing Cre in a ubiquitous (beta-actin-Cre) or a cell-specific (Isl1-Cre and En1-Cre) pattern. The resulting EYFP or ECFP expression patterns indicated that the reporter strains function as faithful monitors of Cre activity. CONCLUSIONS: In contrast to existing lacZ reporter lines, where lacZ expression cannot easily be detected in living tissue, the EYFP and ECFP reporter strains are useful for monitoring the expression of Cre and tracing the lineage of these cells and their descendants in cultured embryos or organs. The non-overlapping emission spectra of EYFP and ECFP make them ideal for double labeling studies in living tissues.

Animals↗
PubMed2001

Varicella-zoster virus (VZV) ORF65 virion protein is dispensable for replication in cell culture and is phosphorylated by casein kinase II, but not by the VZV protein kinases.

The unique short region of varicella zoster virus (VZV) encodes four genes. One of these, ORF65, is predicted to encode an 11-kDa protein. Antibody to ORF65 protein immunoprecipitated a 16-kDa protein from the membrane fraction of VZV-infected cells. ORF65 protein was shown to be phosphorylated by casein kinase II. The VZV ORF47 or ORF66 protein kinases were not required for phosphorylation of ORF65. VZV with a large deletion in ORF65 was constructed and was shown to be dispensable for replication of virus in cell culture. The herpes simplex virus homolog of VZV ORF65 has been reported to be located in the nucleus of infected cells and in virions as a tegument protein, whereas the pseudorabies virus homolog is located in the Golgi apparatus of infected cells and in virions as a type II membrane protein. The ORF65 protein localized to the Golgi apparatus in virus-infected cells and was located in virions, most likely as a type II membrane protein. Thus, VZV ORF65 more closely resembles its pseudorabies virus homolog in its localization in infected cells and virions.

Animals↗
PubMed2001

Progressive decrease in bone density over 10 years of androgen deprivation therapy in patients with prostate cancer.

OBJECTIVES: Several reports suggest an increased incidence of osteoporosis and concomitant fractures in men receiving androgen deprivation therapy (ADT) for prostate cancer. We sought to estimate the longitudinal effects of ADT on loss of bone density in this cross-sectional study. METHODS: Hip and spine bone mineral density (BMD) studies were performed by dual-energy x-ray absorptiometry on 36 patients with prostate cancer. The year 0 cohort (n = 8) consisted of patients who had not yet begun planned ADT. These men were compared to patients receiving ADT who underwent BMD evaluation at year 2 (n = 6), year 4 (n = 7), year 6 (n = 5), year 8 (n = 5), and year 10 (n = 5) of therapy. All BMD values for the patients with prostate cancer were compared to age-matched control subjects. RESULTS: Hip BMD was significantly lower in patients on ADT (mean BMD 0.802 g/cm(2)) compared with those not on ADT (mean BMD 0.935 g/cm(2)). Patients at year 0 had hip and spine BMD similar to age-matched control subjects. There was a significant trend for decreased hip BMD with increasing years of ADT (r = 0.46, P = 0.00008). This relationship was more dramatic when hip BMD at each time point was compared to age-matched control subjects (r = 0.55, P = 0.5 x 10(-16)). This bone loss was evident even up to year 10. BMD loss was more dramatic in patients who had undergone surgical castration than those receiving medical ADT (P = 0.08). Patients on intermittent ADT had similar BMD loss as patients on continuous ADT at year 2 and year 4 but demonstrated less bone loss at year 6 (P = 0.07) despite equivalently low testosterone levels. CONCLUSIONS: There is diminished BMD with increasing duration of ADT. Continuous ADT and surgical castration may be more deleterious than medical therapy, particularly when the medical therapy is given in an intermittent fashion.

Aged↗
PubMed2001

Vitamin A controls epithelial/mesenchymal interactions through Ret expression.

Mutations or rearrangements in the gene encoding the receptor tyrosine kinase RET result in Hirschsprung disease, cancer and renal malformations. The standard model of renal development involves reciprocal signaling between the ureteric bud epithelium, inducing metanephric mesenchyme to differentiate into nephrons, and metanephric mesenchyme, inducing the ureteric bud to grow and branch. RET and GDNF (a RET ligand) are essential mediators of these epithelial-mesenchymal interactions. Vitamin A deficiency has been associated with widespread embryonic abnormalities, including renal malformations. The vitamin A signal is transduced by nuclear retinoic acid receptors (RARs). We previously showed that two RAR genes, Rara and Rarb2, were colocalized in stromal mesenchyme, a third renal cell type, where their deletion led to altered stromal cell patterning, impaired ureteric bud growth and downregulation of Ret in the ureteric bud. Here we demonstrate that forced expression of Ret in mice deficient for both Rara and Rarb2 (Rara(-/-)Rarb2(-/-)) genetically rescues renal development, restoring ureteric bud growth and stromal cell patterning. Our studies indicate the presence of a new reciprocal signaling loop between the ureteric bud epithelium and the stromal mesenchyme, dependent on Ret and vitamin A. In the first part of the loop, vitamin-A-dependent signals secreted by stromal cells control Ret expression in the ureteric bud. In the second part of the loop, ureteric bud signals dependent on Ret control stromal cell patterning.

Animals↗
PubMed2001

Student leadership and activism for social change in the US.

As the US health-care system continues on a path toward greater patient and provider dissatisfaction and decreasing access to primary health services, there is a growing need for leadership among tomorrow's health professionals. Students of today must acquire the skills to lead the United States toward solutions that will offer universal access and eliminate disparities. As examined in the US, there are two main modes for students to learn these meaningful skills; curriculum- and institution-based leadership development and organization-based leadership development. In this paper we review these two methods from an American perspective and discuss ways that educational institutions can support student leadership development. In addition, we address ways in which non-governmental organizations can provide opportunities to foster student leadership. Lastly, we offer recommendations for US policy change at institutional, local, state, and national levels to help achieve the goals stated above.

Journal Article↗
PubMed2000

Comparison of FDG-PET and Bone Scans for Detecting Skeletal Metastases in Patients with Non-small Cell Lung Cancer.

Purpose: Positron Emission Tomography (PET) with F18-fluorodeoxyglucose has been proven useful for staging non-small cell lung cancer. Bone scans are frequently performed for suspected skeletal metastases. The purpose of this study was to evaluate if bone scans compared to PET scans provide additional information that changes the stage of disease.Procedures: Nineteen patients with non-small cell lung cancer had PET and bone scans done for staging of the malignancy. The results of both studies were compared.Results: Bone and PET scans agreed on the presence or absence of skeletal metastases in all nineteen patients. The addition of a bone scan to a PET scan did not change the stage of the disease or the management in any of the patients. Bone scans allowed for more precise localization of the lesions in some patients.Conclusions: Bone scans do not change the stage of disease when performed in addition to PET scans, but provide more precise localization of skeletal abnormalities.

Journal Article↗
PubMed2000

Spontaneous pneumothorax in malignancy: a case report and review of the literature.

BACKGROUND: Pneumothorax occurring in the absence of obvious lung disease is defined as spontaneous pneumothorax. Spontaneous pneumothorax occurs in a variety of settings in patients with malignancies. PATIENTS AND METHODS: We present a case report of spontaneous pneumothorax in malignancy and review the literature. RESULTS: No correlation was found between the occurrence of pneumothorax with age, sex or smoking history. Pneumothorax occurred with a variety of primary tumors. However it was always associated with lung metastases or lung involvement with tumor. In certain cases the metastases were detected after the occurrence of pneumothorax. CONCLUSIONS: The occurrence of pneumothorax in a patient with malignancy should prompt a search for lung metastases.

Diagnosis, Differential↗
PubMed2000

Structural basis of the recognition of the dishevelled DEP domain in the Wnt signaling pathway.

The DEP domain of Dishevelled (Dvl) proteins transduces signals to effector proteins downstream of Dvl in the Wnt pathway. Here we report that DEP-containing mutants inhibit Wnt-induced, but not Dvl-induced, activation of the transcription factor Lef-1. This inhibitory effect is weakened by a K434M mutation. Nuclear magnetic resonance spectroscopy revealed that the DEP domain of mouse Dvl1 comprises a three-helix bundle, a beta-hairpin 'arm' and two short beta-strands at the C-terminal region. Lys 434 is located at the tip of the beta-hairpin 'arm'. Based on our findings, we conclude that DEP interacts with regulators upstream of Dvl via a strong electric dipole on the molecule's surface created by Lys 434, Asp 445 and Asp 448; the electric dipole and the putative membrane binding site are at two different locations.

3T3 Cells↗
PubMed2000

High-dose chemotherapy in poor-risk germ-cell tumors.

Testicular cancer is a highly curable cancer. However, 30% of patients are refractory to standard therapy and will need additional therapy. This article focuses on the use of high-dose chemotherapy in germ-cell tumors. High-dose chemotherapy use is discussed both in the refractory setting and as either first-salvage or first-line therapy. Various criteria for risk assessment are also discussed.

Antineoplastic Agents↗
PubMed1999

Expression of green fluorescent protein in the ureteric bud of transgenic mice: a new tool for the analysis of ureteric bud morphogenesis.

The growth and branching of the ureteric bud is a complex process that is ultimately responsible for the organization of the collecting duct system as well as the number of nephrons in the metanephric kidney. While the genes involved in the regulation of this process have begun to be elucidated, our understanding of the cellular and molecular basis of ureteric bud morphogenesis remains rudimentary. Furthermore, the timing and sequence of branching and elongation that gives rise to the collecting system of the kidney can only be inferred from retrospective staining or microdissection of fixed preparations. To aid in the investigation of these issues, we developed strains of transgenic mice in which a green fluorescent protein (GFP) is expressed in the ureteric bud under the control of the Hoxb7 promoter. In these mice, GFP is expressed in every branch of the ureteric bud throughout renal development, and in its derivative epithelia in the adult kidney. As GFP fluorescence can be easily visualized in living tissue, this allows the dynamic pattern of ureteric bud growth and branching to be followed over several days when the kidneys are cultured in vitro. Using confocal microscopy, branching of the ureteric bud in all three dimensions can be analyzed. These mice represent an extremely powerful tool to characterize the normal patterns of ureteric bud morphogenesis and to investigate the response of the bud to growth factors, matrix elements, and other agents that regulate its growth and branching.

Animals↗
PubMed1999

Oximetry of retinal vessels by dual-wavelength imaging: calibration and influence of pigmentation.

A method for noninvasive measurement of Hb O2 saturation (SO2) in retinal blood vessels by digital imaging was developed and tested. Images of vessels were recorded at O2-sensitive and O2-insensitive wavelengths (600 and 569 nm, respectively) by using a modified fundus camera with an image splitter coupled to an 18-bit digital camera. Retinal arterial SO2 was varied experimentally by having subjects breathe mixtures of O2 and N2 while systemic arterial SO2 was monitored with a pulse oximeter. Optical densities (ODs) of vascular segments were determined using a computer algorithm to track the path of reflected light intensity along vessels. During graded hypoxia the OD ratio (ODR = OD600/OD569) bore an inverse linear relationship to systemic SO2. Compensation for the influence of choroidal pigmentation significantly reduced variation in the arterial SO2 measurements among subjects. An O2 sensitivity of 0.00504 +/- 0.00029 (SE) ODR units/%SO2 was determined. Retinal venous SO2 at normoxia was 55 +/- 3.38% (SE). Breathing 100% O2 increased venous SO2 by 19.2 +/- 2.9%. This technique, when combined with blood flow studies in human subjects, will enable the study of retinal O2 utilization under experimental and various disease conditions.

Adolescent↗
PubMed1999

Dominant effects of RET receptor misexpression and ligand-independent RET signaling on ureteric bud development.

During kidney development, factors from the metanephric mesenchyme induce the growth and repeated branching of the ureteric bud, which gives rise to the collecting duct system and also induces nephrogenesis. One signaling pathway known to be required for this process includes the receptor tyrosine kinase RET and co-receptor GFR(&agr;)-1, which are expressed in the ureteric bud, and the secreted ligand GDNF produced in the mesenchyme. To examine the role of RET signaling in ureteric bud morphogenesis, we produced transgenic mice in which the pattern of RET expression was altered, or in which a ligand-independent form of RET kinase was expressed. The Hoxb7 promoter was used to express RET throughout the ureteric bud branches, in contrast to its normal expression only at the bud tips. This caused a variable inhibition of ureteric bud growth and branching reminiscent of, but less severe than, the RET knockout phenotype. Manipulation of the level of GDNF, in vitro or in vivo, suggested that this defect was due to insufficient rather than excessive RET signaling. We propose that RET receptors expressed ectopically on ureteric bud trunk cells sequester GDNF, reducing its availability to the normal target cells at the bud tips. When crossed to RET knockout mice, the Hoxb7/RET transgene, which encoded the RET9 isoform, supported normal kidney development in some RET-/- animals, indicating that the other major isoform, RET51, is not required in this organ. Expression of a Hoxb7/RET-PTC2 transgene, encoding a ligand-independent form of RET kinase, caused the development of abnormal nodules, outside the kidney or at its periphery, containing branched epithelial tubules apparently formed by deregulated growth of the ureteric bud. This suggests that RET signaling is not only necessary but is sufficient to induce ureteric bud growth, and that the orderly, centripetal growth of the bud tips is controlled by the spatially and temporally regulated expression of GDNF and RET.

Animals↗