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Biomedical subjects

S Sen

Publications and source records attributed to S Sen.

At least 145 records · Page 8Linked to original sources
PubMed1998

Increased protein kinase C activity in myotrophin-induced myocyte growth.

Myotrophin, a novel protein that has been shown to stimulate myocyte growth, has been isolated, purified, and sequenced from the hearts of spontaneously hypertensive rats and dilated cardiomyopathic human tissue. Recently, the cDNA clones encoding myotrophin have been isolated and expressed in Escherichia coli, and the recombinant myotrophin was found to be as biologically and immunologically active as natural myotrophin. The mechanism by which myotrophin stimulates protein synthesis and initiates myocardial hypertrophy is not known. To evaluate the involvement of protein kinase C (PKC) in myotrophin-induced hypertrophy, PKC activity and its distribution in the subcellular fraction were determined in cultured neonatal and adult myocytes. PKC activity was determined by measuring the incorporation of 32P into histone type III-S and PKCepsilon substrate peptide (epsilon(pep)) from [gamma-32P]ATP in neonatal myocytes. Myotrophin significantly stimulated PKC activity in neonatal myocytes and was associated with a significant increase in protein synthesis. The effect of myotrophin on the stimulation of PKC activity and [3H]leucine incorporation was abolished by pretreatment with either staurosporine or H-7, two selective, pharmacological PKC inhibitors. Pretreatment of myocytes with staurosporine also reduced the myotrophin-induced mRNA levels of c-fos and beta-myosin heavy chain. To evaluate the subcellular events whose occurrence was due to myotrophin and translocation of PKC, we studied the effect of genistein, a tyrosine kinase inhibitor, on myotrophin-induced neonatal myocyte growth. Genistein attenuated the [3H]leucine incorporation induced by myotrophin. To define the specificity of the PKC isoform(s) involved in myotrophin-stimulated myocyte growth, both neonatal and adult myocytes were treated with myotrophin, and Western blot analyses were performed by using the antibodies of different PKC isoforms. Results showed that both PKCalpha and PKCepsilon isoforms participated in the myotrophin-induced neonatal myocyte growth, whereas only the PKCepsilon isoform was involved in myotrophin-induced adult myocyte hypertrophy. PKCdelta and PKCzeta do not seem to participate in either neonatal or adult myocyte growth induced by myotrophin. Treatment with antisense oligonucleotides specific for PKCalpha and PKCepsilon isoforms further supported this result. PKCalpha is the major PKC isoform in neonatal myocytes and needs Ca2+ and phospholipids for its activation, and PKCepsilon (the Ca2+-independent PKC isoform) is present in both neonatal and adult myocytes; the 15-mer antisense oligodeoxynucleotides of each were used for this study. Treatment of neonatal myocytes with the PKCalpha and PKCepsilon antisense oligodeoxynucleotides for 5 days significantly reduced Ca2+-dependent and Ca2+-independent PKC activity, respectively, as well as the [3H]leucine incorporation induced by myotrophin. Furthermore, myotrophin-induced PKC activity was primarily located in the particulate fraction and did not result in a concomitant decrease in the cytosolic fraction. Myotrophin does not change PKC isoform expression (both Ca2+ dependent and independent PKC isoforms used in this study) in rat neonatal cardiac fibroblasts. Our data suggest that myotrophin exerts its action on protein synthesis, possibly through a tyrosine kinase-coupled pathway and translocation of PKC from the cytosol to the cell membrane.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

The structural basis of ankyrin-like repeat function as revealed by the solution structure of myotrophin.

BACKGROUND: Myotrophin is a 12.5 kDa protein that appears to have a key role in the initiation of cardiac hypertrophy, a central process in many heart diseases. Myotrophin primarily comprises ankyrin-like (ANK) repeats, the 33 amino acid motifs involved in a wide range of protein-protein interactions. As a first step in the structure-based search for cardiac hypertrophy antagonists and in order to gain insight into the molecular basis of action of the ubiquitous and multifunctional ANK repeat motif, we have determined the solution structure of myotrophin using multidimensional heteronuclear NMR spectroscopy. RESULTS: The myotrophin structure determination was based on 2786 experimental NMR restraints, and the precision of the coordinates for the final 45 simulated-annealing structures is 0.43 A for the backbone atoms and 0.87 A for all atoms. The structure of myotrophin is well defined and is ellipsoidal: approximately 46 A long and 21 A wide. The ANK repeats, which constitute the main part of the myotrophin structure, are characteristic of a hairpin-like protruding tip followed by a helix-turn-helix motif. The V-shaped helix-turn-helix of the ANK repeats stack sequentially in bundles and are stabilized by compact hydrophobic cores, whereas the protruding tips are less ordered. This arrangement is quite different to the continuous beta-sheet topology observed in the corresponding regions of another ANK protein, 53BP2, the structure of which was determined in complex with p53. CONCLUSIONS: The solution structure of myotrophin provides important insights into the structural and dynamic features of the ANK motif, and suggests that the protruding tips with highly variable sequences may be critical to facilitate diverse protein-protein recognition. The present structure also provides a molecular basis for the further functional characterization of myotrophin and the development of therapeutics for hypertrophy-related heart diseases.

Amino Acid Sequence↗
PubMed1998

Alfalfa Saponins and Their Implication in Animal Nutrition.

Alfalfa (Medicago sativa L.) is of immense importance as livestock fodder for both developed and lesser developed countries as it contains a high amount of protein, and yield of dry matter is also very high. The main antinutritional components present in this plant are saponins, and their unfavorable effects on animal performance have restricted the optimum use of this high-protein plant as an animal feed. The occurrence, chemistry, analysis, and consequences of intake of alfalfa saponins are reviewed. The information synthesized may lead to planning of more detailed studies on isolation and characterization of saponins and sapogenins to gain a better understanding of the biological activities of the aglycon and carbohydrate moieties of saponins.

Journal Article↗
PubMed1998

Results of Wilms' tumour management in two tertiary-care hospitals in Asia.

In the period 1985-1995, 87 children underwent surgery for Wilms' tumour; 16 were lost to follow-up. Of the remaining children, 27 presented with stage I disease, 11 with stage II, 12 with stage III, 14 with stage IV, and 6 with stage V. One child was not staged. The histology was favourable Wilms' tumour in 44, anaplastic in 12, unclassified in 8, clear-cell sarcoma in 4, and rhabdoid tumour in 3. Although a total nephrectomy was generally performed, partial renal surgery was performed for 6 bilateral and 4 unilateral tumours, the latter including 2 fused kidneys. Preoperative chemotherapy was employed with benefit in massive tumours, tumour in fused kidneys, bilateral tumours, and preoperatively diagnosed inferior vena caval tumour thrombi. Postoperative chemotherapy, employed in all cases, consisted of actinomycin D and vincristine with the addition of adriamycin in anaplastic and advanced-stage tumours. Ten children underwent second-line chemotherapy for disease unresponsive to the above management, but only 1 of these is currently free of disease. Postoperative tumour-bed radiotherapy, used in selected cases, prevented local recurrence in stage I and II disease. However, 20% of stage I and II patients not receiving radiotherapy developed tumour-bed recurrence. Twenty-three children have died and 5 with advanced disease and incomplete follow-up are presumed to be dead. Nine children are currently on treatment; 34 have successfully completed treatment, the disease-free survival in stages I-V being 81%, 75%, 42%, 14%, and 50%, respectively. Overall disease-free survival was 69% for Wilms' tumour of favourable histology and 50% for anaplastic tumours. The 3 patients with rhabdoid tumours and 3 of 4 with clear-cell sarcomas have died. Wilms' tumour management in the developing world is compromised by cases lost to follow-up and late presentation with massive tumours and advanced stage. Preoperative chemotherapy is advantageous in a number of cases, and postoperative radiotherapy should be deployed more frequently.

Adolescent↗
PubMed1998

Surgical management of complete ureteric duplication abnormalities.

In 2 decades (1974-1993), the senior author (S.A.) managed 148 patients with various abnormalities associated with complete ureteric duplication. Included were 72 patients with primary vesicoureteric reflux, 50 with ureteroceles, and 26 with upper-pole ectopic ureters. The majority of the patients were female, and the common clinical presentations included urinary tract infection (UTI), UTI with septicemia, and urinary incontinence. Ten cases were diagnosed after recognition of a renal abnormality on prenatal ultrasonography, an avenue that has provided new challenges, new opportunities, and new dilemmas. This review article is based on the authors' experience together with an analysis of current emphasis on early diagnosis, minimal surgery, and maximum preservation of renal function.

Female↗
PubMed1998

Varied presentations of unilateral lung hypoplasia and agenesis: a report of four cases.

Unilateral lung hypoplasia or agenesis can be asymptomatic or present with recurrent respiratory symptoms. The latter may be amenable to surgical treatment in selected cases. Of four children in this report, two are being managed without surgery. A third was relieved of his symptoms by pneumonectomy. The fourth presented with acute foreign-body inhalation into the healthy right main bronchus, and coexistent left pulmonary agenesis was discovered at bronchoscopy. Bronchoscopy and computed tomography were found to be the most useful investigations in management.

Child, Preschool↗
PubMed1998

The relationship between circadian patterns of salivary cortisol and endogenous inhibitor of monoamine oxidase A.

The circadian pattern of free cortisol, measured in saliva, was monitored in normal healthy adults (N=41) for the first half hour immediately after awakening and in a smaller group (N=8) at timed intervals throughout the day. The endogenous inhibitor of monoamine oxidase A (MAO-AI) was measured in the same saliva samples in order to explore the relationship between circadian activation of the hypothalamic-pituitary-adrenocortical (HPA) axis and MAO-AI. A marked elevation of salivary cortisol was recorded in the first half hour immediately after awakening resulting in a two to three fold increase from the first awakening level. By contrast MAO-AI was highest immediately upon awakening and fell subsequently. Hence the cortisol response to awakening is preceded by heightened MAO-AI. Moreover those subjects who showed more persistently elevated MAO-AI were characterised by a more pronounced cortisol response. An association between MAO-AI and cortisol was also manifest in the diurnal pattern recorded at timed intervals throughout the day. The decline of salivary cortisol from the morning acrophase to the evening nadir was paralleled by MAO-AI. Both patterns of decline were significant (P< 0.01). Taken together with previously reported psychological stress studies these findings suggest a possible relationship between MAO-AI and HPA activity.

Adult↗
PubMed1998

Identification of antibodies directed against O-acetylated sialic acids in visceral leishmaniasis: its diagnostic and prognostic role.

A significantly increased O-acetylated sialic acid (O-AcSA) binding fraction was purified from serum of visceral leishmaniasis (VL) patients by affinity chromatography on immobilized bovine submaxillary mucin (BSM) and found to be immunoglobulin in origin. The serodiagnostic and prognostic potential of BSM as a capture antigen was established by ELISA with no cross reactivity with coendemic diseases like malaria, tuberculosis, leprosy, chagas disease and cutaneous leishmaniasis; however, a strong cross reactivity was present with trypanosomiasis patients. In 56 clinically diagnosed VL patients, the BSM-ELISA was compared with diagnosis by microscopy using Giemsa stained tissue smears and direct ELISA using crude parasite antigen (parasite-ELISA); 49/56(87.5%) and 5/56(9.0%) were positive and negative respectively by all 3 methods. The BSM-ELISA failed to diagnose 2/56(3.5%) patients which were biopsy and parasite-ELISA positive. The prognostic potential of the BSM-ELISA in 18 longitudinally monitored VL patients before and after conventional antimonial treatment showed a significant decrease in anti O-AcSA titres in drug responsive patients whereas anti O-AcSA levels persisted in drug unresponsive patients. The IgG subclass distribution of antibodies directed against O-AcSA showed increased IgG2 levels in VL patients as compared to healthy controls. The BSM-based ELISA holds great promise as a serodiagnostic and prognostic assay for VL.

Acetylation↗
PubMed1998

Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation.

The centrosomes are thought to maintain genomic stability through the establishment of bipolar spindles during cell division, ensuring equal segregation of replicated chromosomes to two daughter cells. Deregulated duplication and distribution of centrosomes have been implicated in chromosome segregation abnormalities, leading to aneuploidy seen in many cancer cell types. Here, we report that STK15 (also known as BTAK and aurora2), encoding a centrosome-associated kinase, is amplified and overexpressed in multiple human tumour cell types, and is involved in the induction of centrosome duplication-distribution abnormalities and aneuploidy in mammalian cells. STK15 amplification has been previously detected in breast tumour cell lines and in colon tumours; here, we report its amplification in approximately 12% of primary breast tumours, as well as in breast, ovarian, colon, prostate, neuroblastoma and cervical cancer cell lines. Additionally, high expression of STK15 mRNA was detected in tumour cell lines without evidence of gene amplification. Ectopic expression of STK15 in mouse NIH 3T3 cells led to the appearance of abnormal centrosome number (amplification) and transformation in vitro. Finally, overexpression of STK15 in near diploid human breast epithelial cells revealed similar centrosome abnormality, as well as induction of aneuploidy. These findings suggest that STK15 is a critical kinase-encoding gene, whose overexpression leads to centrosome amplification, chromosomal instability and transformation in mammalian cells.

Aneuploidy↗
PubMed1998

Effect of Quillaja saponaria saponins and Yucca schidigera plant extract on growth of Escherichia coli.

Escherichia coli K-12 was exposed to Quillaja saponaria saponins from various commercial firms (Sigma, Roth and Nor-feed) and to an extract of Yucca schidigera plant powder (DK Sarsaponin 30) at different concentrations (0.05-1.0% w/v). A concentration-dependent response was observed. Quillaja saponaria saponins from Sigma increased growth up to 0.1% (w/v) level, whereas Nor-feed and Roth saponins produced maximum growth at a much higher level (0.5 and 0.75%, w/v, respectively). These results suggest that quillaja saponins from various sources differ in their biological activity, although all three saponins had the same content of vanillin-sulphuric acid reactive moieties. The lyophilized water extract from the DK Sarsaponin powder showed maximum growth at 0.1% (w/v) level. The levels at which maximum growth was observed did not change on subjecting the quillaja or yucca saponins to heat treatment in an autoclave (121 degrees C for 30 min). All the saponins and the plant extract increased growth of Escherichia coli up to a certain concentration and thereafter decreased growth. In spite of the decreased growth at higher levels of saponins, it was higher compared to the control (without saponin) up to levels of 1% (w/v) for all saponins except Quillaja saponins from Sigma, for which the growth was lower at levels of 0.25% (w/v) and higher. Saponins have the potential to modulate microbial growth in natural and artificial fermenters.

Anti-Bacterial Agents↗
PubMed1998

Buckling of redundant expansile stent distal to an oesophageal cancer: endoscopic management.

This report describes a complication that occurred as a result of deploying an Ultraflex stent too low in relation to a stenosing carcinoma of the gastro-oesophageal junction. Intermittent kinking of the redundant lower end of the stent caused frequent episodes of total dysphagia. A percutaneous endoscopic gastrostomy was deployed to anchor the redundant portion of the stent within the stomach, allowing it to be shortened with endoscopic stitch cutters. This procedure relieved the episodic dysphagia, and was well tolerated.

Adenocarcinoma↗
PubMed1998

IFN-beta partially counteracts inhibition of natural killer activity induced by some antitumor agents.

We investigated whether recombinant human (rHu-IFN-beta) (IFN-beta) could counteract the inhibition of natural killer (NK) activity caused by antitumor agents. Peripheral blood lymphocytes (PBL) were incubated with different antitumor agents alone or in combination with IFN-beta for 3 days and then tested in a cytotoxicity assay against the K562 cell line. The following drugs were used, all of which caused a dose-dependent inhibition of NK activity: etoposide, camptothecin, doxorubicin, cis-DDP, tallimustine, and L-PAM. Concomitant treatment with (1000 U/ml) IFN-beta counteracted the inhibitory effect of etoposide and camptothecin but had no consistent effect on the inhibition mediated by the other drugs. Mean values of inhibition of NK activity at 1 microM camptothecin was 48%+/-3.4% and with IFN-beta was 10%+/-4.9%. With 100 microM etoposide, mean value of inhibition was 78%+/-3.3%, and with IFN-beta, it was 18%+/-1.5%. Cell viability, assessed by vital dye exclusion, and drug uptake, assessed with radiolabeled etoposide, were similar in cells treated with or without IFN-beta. The protective effect of IFN-beta on NK function was rather selective, as IFN-beta did not counteract the drug-mediated inhibition of PBL proliferation when stimulated by phytohemagglutinin (PHA). Other cytokines, IFN-alpha, IFN-gamma, and interleukin-2 (IL-2), had similar protective effect, although IFN-beta, was slightly more potent. On the other hand, IL-6, a cytokine sharing some properties with IFNs was ineffective. Camptothecin inhibited the expression of mRNA for granzyme B, a lytic protein involved in lymphoid-mediated cytotoxicity. Combined treatment with IFN-beta restored-at least in part-the transcription of granzyme B mRNA. These results show that the immunosuppressive effect of some antitumor agents could be partly counteracted by treatment with IFN-beta.

Antineoplastic Agents↗
PubMed1998

Cardiac disorders and stroke.

Cardiac disorders are increasingly recognised as an important source of cerebral embolism. Atrial fibrillation is the most common cardiac dysrrhythmia that can predispose to stroke. Recent advances have significantly increased the identification of clinical, hematological and echocardiographic risk factors that predict the occurrence of atrial fibrillation related stroke. Also, clinical risk stratification has been used to determine medical therapy (aspirin or warfarin) for prevention of atrial fibrillation related brain embolization. Among the various structural heart diseases causing stroke, the role of patent foramen ovale remains controversial. Strides have been made in the use of ultrasonographic techniques such as transesophageal echocardiography and contrast transcranial doppler to detect patent foramen ovale. Coronary artery bypass grafting is often performed in patients with concomitant aortic atheroma and carotid stenosis that may predispose to stroke in the perioperative period. It is now possible to identify perioperatively significant aortic atherosclerosis (using transesophageal echocardiography and aortic ultrasound) and significant carotid disease (using carotid ultrasound) and make appropriate modifications in surgical technique to reduce the incidence of coronary artery bypass grafting related stroke. Because of shared risk factors it is not surprising that coronary artery disease is frequently found in stroke patients. Recent studies suggest that more than one-third of stroke patients have asymptomatic coronary artery disease. Conversely, the brain damaged by infarction may itself be responsible for the production of cardiac structural and electrical abnormalities. Both these factors may contribute to the finding that cardiac events are the leading cause of death in stroke patients on long term follow-up. Recognition of these correlations has enhanced our ability to treat and prevent stroke related mortality.

Animals↗
PubMed1998

The Mitrofanoff procedure in paediatric urinary tract reconstruction.

BACKGROUND: Urinary tract reconstruction is required in many congenital and some acquired urological conditions in childhood. The majority are managed by clean intermittent catheterization (CIC), for which purpose the appendix or other tubular structure may be used to provide a continent catheterizable abdominal stoma. METHODS: Between 1991 and 1996, 23 children underwent urinary tract reconstruction of varying complexity together with a continent diversion according to the Mitrofanoff principle. The appendix was used in 14 patients and the ureter in seven. Two patients had previously had an appendicectomy and the ureters were not suitable. One had a catheterizable channel made from an isolated segment of colon and the other had a detrusor tube constructed. RESULTS: Twelve patients with an appendix conduit, six with a ureteric conduit, and one with a colonic tube are continent, although the latter has had some problems with stomal stenosis. All manage CIC with comfort, the older children doing the procedure themselves. One appendix conduit has stomal incontinence and another was inadvertently divided during renal transplantation. The detrusor tube strictured and was removed. CONCLUSIONS: A continent abdominal stoma using the Mitrofanoff principle gives reliable results in children and is well tolerated. It should be considered in the management of children undergoing urinary tract reconstruction when CIC is necessary. The appendix is eminently suitable for this purpose but the ureter provides a satisfactory alternative in selected cases. When neither is available, alternative techniques for constructing a catheterizable continent channel may be considered.

Adolescent↗