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Biomedical subjects

T Das

Publications and source records attributed to T Das.

At least 37 records · Page 2Linked to original sources
PubMed2001

Studies on central nervous system function in diabetes mellitus.

Fifty-seven insulin dependent (IDDM) and non-insulin dependent (NIDDM) diabetic patients and 25 controls were studied. Patients with history of strokes, hypoglycaemia, hearing impairment, diabetic retinopathy, etc, were excluded. Clinical examination of central nervous system (CNS) and computerised tomography scan of brain were absolutely normal in all cases. Neuroelectrophysiological tests done were the visual evoked potential (VEP), brainstem auditory evoked response (BAER) and somatosensory evoked potential (SEP). The mean VEP latency was significantly raised in both NIDDM and IDDM compared with controls. The mean BAER and SEP latencies were both significantly raised in NIDDM but not in IDDM. The percentage of cases with abnormally raised CNS latencies were as follows: In NIDDM, VEP-16.7%, BAER-50% and SEP-26.7%; in IDDM, VEP-11.1%, BAER-14.8% and SEP-18.5%. Thus, subclinical CNS dysfunction is common in diabetes mellitus particularly in NIDDM and this can be reliably detected by measuring the CNS latencies, specially VEP.

Adolescent↗
PubMed2000

Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acids.

The Saccharomyces cerevisiae protein ELO2p is involved in the elongation of saturated and monounsaturated fatty acids. Among several sequences with limited identity with the S. cerevisiae ELO2 gene, a consensus cDNA sequence was identified from the LifeSeq(R) database of Incyte Pharmaceuticals, Inc. Human liver cDNA was amplified by PCR using oligonucleotides complementary to the 5' and 3' ends of the putative human cDNA sequence. The resulting full-length sequence, termed HELO1, consisted of 897 bp, which encoded 299 amino acids. However, in contrast with the ELO2 gene, expression of this open reading frame in S. cerevisiae demonstrated that the encoded protein was involved in the elongation of long-chain polyunsaturated fatty acids, as determined by the conversion of gamma-linolenic acid (C(18:3, n-6)) into dihomo-gamma-linolenic acid (C(20:3, n-6)), arachidonic acid (C(20:4, n-6)) into adrenic acid (C(22:4, n-6)), stearidonic acid (C(18:4, n-3)) into eicosatetraenoic acid (C(20:4, n-3)), eicosapentaenoic acid (C(20:5, n-3)) into omega3-docosapentaenoic acid (C(22:5, n-3)) and alpha-linolenic acid (C(18:3, n-3)) into omega3-eicosatrienoic acid (C(20:3, n-3)). The predicted amino acid sequence of the open reading frame had only 29% identity with the yeast ELO2 sequence, contained a single histidine-rich domain and had six transmembrane-spanning regions, as suggested by hydropathy analysis. The tissue expression profile revealed that the HELO1 gene is highly expressed in the adrenal gland and testis. Furthermore, the HELO1 gene is located on chromosome 6, best known for encoding the major histocompatibility complex, which is essential to the human immune response.

Acetyltransferases↗
PubMed2000

Identification and characterization of an enzyme involved in the elongation of n-6 and n-3 polyunsaturated fatty acids.

The enzymes that are involved in the elongation of fatty acids differ in terms of the substrates on which they act. To date, the enzymes specifically involved in the biosynthesis of polyunsaturated fatty acids have not yet been identified. In an attempt to identify a gene(s) encoding an enzyme(s) specific for the elongation of gamma-linolenic acid (GLA) (18:3n-6), a cDNA expression library was made from the fungus Mortierella alpina. The cDNA library constructed in a yeast expression vector was screened by measuring the expressed elongase activity [conversion of GLA to dihomo-GLA (20:3n-6)] from an individual yeast clone. In this report, we demonstrate the isolation of a cDNA (GLELO) whose encoded protein (GLELOp) was involved in the conversion of GLA to dihomo-GLA in an efficient manner (60% conversion). This cDNA contains a 957-nucleotide ORF that encodes a protein of 318 amino acids. Substrate specificity analysis revealed that this fungal enzyme acted also on stearidonic acid (18:4n-3). This report identifies and characterizes an elongase subunit that acts specifically on the two Delta6-desaturation products, 18:3n-6 and 18:4n-3. When this GLELO cDNA was coexpressed with M. alpina Delta5-desaturase cDNA in yeast, it resulted in the conversion of GLA to arachidonic acid (20:4n-6) as well as the conversion of stearidonic acid to eicosopentaenoic acid (20:5n-3). Thus, this GLELO gene may play an critical role in the bio-production of both n-6 and n-3 polyunsaturated fatty acids.

Acetyltransferases↗
PubMed2000

High-level expression of biologically active human prolactin from recombinant baculovirus in insect cells.

We examined the feasibility of high-level production of recombinant human prolactin, a multifunctional protein hormone, in insect cells using a baculovirus expression system. The human prolactin cDNA with and without the secretory signal sequence was cloned into pFastBac1 baculovirus vector under the control of polyhedrin promoter. Prolactin was produced upon infection of either Sf9 or High-Five cells with the recombinant baculovirus containing the human prolactin cDNA. The production of recombinant prolactin varied from 20 to 40 mg/L of monolayer culture, depending on the cell types. The prolactin polypeptide with its own secretory signal was secreted into the medium. N-terminal amino acid sequence analysis of the recombinant polypeptide purified from the culture medium indicated that the protein was processed similar to human pituitary prolactin. Carbohydrate analysis of the purified protein indicated that a fraction of the recombinant prolactin made in insect cells appeared to be glycosylated. Also, both secreted and nonsecreted forms of the recombinant prolactin in insect cells were biologically equivalent to the native human prolactin (pituitary derived) in the Nb2 lymphoma cell proliferation assay.

Animals↗
PubMed2000

[(186/188)Re] rhenium-ethylene dicysteine (Re-Ec): preparation and evaluation for possible use in endovascular brachytherapy.

188ReO(4)(-), (188)Re-MAG(3), and (188)Re-DTPA are currently under investigation as radiation sources in liquid-filled balloons for prevention of restenosis following coronary angioplasty. Because (99m)Tc-labeled ethylene dicysteine (EC) is a well-established agent for renal tubular function imaging, the use of [(188)Re] rhenium-labeled EC as a potential agent for prevention of restenosis after angioplasty is worth evaluation. In this article, the preparation and pharmacological behavior of [(188/186)Re]Re complex of EC are reported. The yield of the Re complex was optimized by varying the parameters of complexation. The complex prepared under the optimized conditions was found to be stable over a period of 7 days when stored at pH 2 and at 4 degrees C. The pharmacological behavior of [(188/186)Re]Re-EC confirms its similarity to (188)Re-MAG(3) and its superiority over (188)ReO(4)(-) for use in endovascular brachytherapy.

Animals↗
PubMed2000

Protection of apoptotic cell death by protein A.

The word "Apoptosis" or pragrammed cell death is described as the ultimate end of multiple cellular events converging from numerous initiating events to the ultimate death of a cell or organism. Several processes, such as initiation of death signals at the plasma membrane, expression of pro-apoptotic oncoproteins, activation of death proteases, endonucleases etc., that ultimately coalesce to a common irreversible execution phase, lead to cell demise. Counteracting the death signals are cell survival factors. A balance between the cell death and cell survival factors plays a major role in the decision making process as to whether a cell should die or must live. It is, therefore, hypothesized that if the balance can be shifted in favor of cell survival, one might be able to arrest the aging process, save the injured cells or else if the balance is shifted toward cell-kill it might help destroy tumors and other undesirable cells. Protein A (PA) of Staphylococcus aureus has been found to have multifarious biological response modifying properties. It has been shown to possess anti-tumor, antitoxic, anti-parasitic and antifungal activities. It also acts as a potent immunostimulator. PA can protect bone marrow progenitor cells from zidovudin(AZT)-induced apoptosis and can stimulate immunocyte proliferation, thereby helping to replenish/restore the depleted hematopoietic cell pool. Such ability to replenish hematopoietic cells is a common property of PA observed against a number of toxic drugs/chemicals, such as cyclophosphamide, benzene, aflatoxin, salmonella endotoxin, etc. Interestingly, it was further demonstrated in our laboratory that PA can selectively kill tumor cells without affecting normal cells of the host. A search for the mechanisms of PA action revealed that this bacterial protein could shift the balance between pro- and anti-apoptotic proteins in favor of survival in normal cells, but in favor of cell death in tumor cells at a particular dose level. This unique property of PA suggests that controlled use of such type of Biological Response Modifier might help in controlling both cell growth and death phenomena.

Animals↗
PubMed2000

Case-control and qualitative study of attrition in a community epilepsy programme in rural India.

Dropout from epilepsy programmes is a serious problem in developing countries and has not been systematically studied before. We set up a community-based programme for children with epilepsy in rural India. The aim of this study was to assess reasons for dropout. We assessed medical and sociodemographic variables for their effect on dropout at 12 months using an unmatched case-control design on 32 cases and 62 controls. We also interviewed the parents of 32 children who dropped out of treatment, using a topic schedule. Two-thirds of the dropouts occurred within the first 6 months of treatment. Severely impaired children were more likely to drop out (odds ratio 4.60, 95% CI: 1.0-21.0) and families who had tried AEDs before were less likely to do so (odds ratio 0.12, 95% CI: 0.015-0.88). Denial of diagnosis, access problems and symptom resolution were the other main reasons underlying attrition. Active ascertainment methods should be reconsidered in community programmes. Very poor families without a male head or with long journey times are at high risk of dropout. People with severe impairments need appropriate integrated rehabilitation.

Adolescent↗
PubMed2000

188Re-ethylene dicysteine: a novel agent for possible use in endovascular radiation therapy.

Several agents, such as 188ReO4-, 188Re-MAG3 and 188Re-DTPA are currently under investigation as radiation sources in liquid-filled balloons for prevention of restenosis following coronary angioplasty. Bearing in mind the risk factor associated with leakage of radioactivity in the event of balloon rupture, the criteria sought in selecting suitable agents for endovascular radiation therapy (EVRT) are rapid clearance and low dose to vital organs. Since 99Tcm labelled ethylene dicysteine (EC) is a well established agent for renal tubular function imaging, the use of 186Re-ethylene dicysteine as a potential agent for prevention of restenosis after angioplasty has been evaluated previously. Therefore, it was of interest to evaluate the applicability of the more potential isotope of rhenium, 188Re, a high energy beta-emitter (Ebetamax = 2.12 MeV) with a suitable T 1/2 = 16.9 h, obtainable carrier-free from the 188W-188Re generator, as an attractive and alternative radionuclide for labelling with L,L-EC. In this paper, the preparation and pharmacological behaviour of the 188Re complex of ethylene dicysteine are reported. The complex can be prepared in high yields (99.5%) under optimized conditions of pH 2-3, at a ligand concentration of 15 mM, 50 microg (0.18 mM) carrier rhenium and using 2 mg x mL(-1) stannous chloride. On storage at 4 degrees C, the RC purity was more than 97% after 48 h when prepared under optimum conditions. Biodistribution studies in Wistar rats showed the desired characteristics of fast blood clearance and low retention of activity in the vital organs (< 2% in intestine, < 1% in stomach, < 0.5% in liver) with a high renal excretion (90.65+/-0.6%) at 3 h post-injection. These results confirm the advantages of using the 188Re-EC complex compared with perrhenate and other rhenium radiopharmaceuticals currently being used in balloons for EVRT.

Angioplasty, Balloon, Coronary↗
PubMed2000

Protein A-activated rat splenic lymphocyte proliferation involves tyrosine kinase-phospholipase C-protein kinase C pathway.

Protein A (PA) of Staphylococcus aureus was long been known for its affinity towards the Fc domain of immunoglobulin G. It is now well established that PA is a potent biological response modifier showing simultaneously antitumor, antitoxic, and anticarcinogenic properties. This bacterial protein was also observed to stimulate production of cytokines. But the molecular mechanism(s) of immunocyte activation by PA still remained essentially unknown. In this report, we demonstrate a hitherto undescribed role of PA as a signal inducer in rat splenic lymphocytes. Our studies describe that PA induces transition of G0/G1 to S and G2/M phases of cell cycle, thus ultimately stimulating splenic lymphocyte proliferation. It has also been revealed that PA binds to rat splenic lymphocytes in a dose dependent manner and stimulates proliferation via tyrosine kinase-phospholipase C (PLC)-Ca2+-dependent protein kinase C (PKC) pathway. These observations will be of valid help in correlating the immunostimulatory activities of PA with the molecular mechanism(s) of its action.

Animals↗
PubMed2000

An unusual case of double outlet right ventricle.

A 17-year-old unmarried girl was admitted with the complaints of breathlessness on exertion, swelling of upper and lower limbs and intermittent fever for last 21 days. Past history revealed bluish discolouration of nails and tongue since birth along with recurrent dyspnoea. After thorough general and cardiovascular examination, a provisional diagnosis of tetralogy of Fallot was made. Chest x-ray revealed cardiomegaly and absent main pulmonary artery segment. ECG revealed gross right axis deviation and right ventricular hypertrophy. Echocardiogram showed features of double outlet right ventricle.

Adolescent↗
PubMed2000

Polyunsaturated fatty acid-specific elongation enzymes.

We have isolated a novel gene (GLELO) from Mortierella alpina and its homologue (CEELO1) from Caenorhabditis elegans and demonstrate the involvement of their encoded proteins in the elongation of C(18) polyunsaturated fatty acids.

Acetyltransferases↗
PubMed2000

New approaches in the management of choroidal neovascular membrane in age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly population. The prevalence is reported to be 1.2-1.4% in several population-based epidemiological studies. Currently 25-30 million people worldwide are blind due to AMD. With the aging world population it is bound to increase significantly, and could become a significant public health problem in next two decades, with serious socio-economic implications. Several strategies are today available to treat the wet form of AMD, which is responsible for significant visual loss. These were until recently confined to laser photocoagulation, and subretinal surgery, but today two other modalities, namely, radiation and photodynamic therapy, are available. These treatment modalities however, are aimed at preservation of vision only, and not at reversing the process of the disease. Further research on antiangiogenic drugs and gene therapy could significantly help AMD patients.

Blindness↗