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Biomedical subjects

K Das

Publications and source records attributed to K Das.

At least 55 records · Page 3Linked to original sources
PubMed2001

Modulation of rat liver mitochondrial antioxidant defence system by thyroid hormone.

In the present study the effect of thyroid hormone (T(3)) on oxidative stress parameters of mitochondria of rat liver is reported. Hypothyroidism is induced in male adult rats by giving 0.05% propylthiouracil (PTU) in drinking water for 30 days and in order to know the effect of thyroid hormone, PTU-treated rats were injected with 20 microg T(3)/100 g body weight/day for 3 days. The results of the present study indicate that administration of T(3) to hypothyroid (PTU-treated) rats resulted in significant augmentation of oxidative stress parameters such as thiobarbituric acid reactive substances and protein carbonyl content of mitochondria in comparison to its control and euthyroid rats. The hydrogen peroxide content of the mitochondria of liver increased in hypothyroid rats and was brought to a normal level by T(3) treatment. Induction of hypothyroidism by PTU treatment to rats also resulted in the augmentation of total and CN-sensitive superoxide dismutase (SOD) activities of the mitochondria, which was reduced when hypothyroid rats were challenged with T(3). Although CN-resistant SOD activity of the mitochondria remained unaltered in response to hypothyroidism induced by PTU treatment, its activity decreased when hypothyroid rats were injected with T(3). The catalase activity of the mitochondria decreased significantly by PTU treatment and was restored to normal when PTU-treated rats were given T(3). Total, Se-independent and Se-dependent glutathione peroxidase activities of the mitochondria were increased following PTU treatment and reduced when T(3) was administered to PTU-treated rats. The reduced and oxidised glutathione contents of the mitochondria of liver increased significantly in hypothyroid rats and their level was restored to normal when hypothyroid rats were injected with T(3). The results of the present study suggest that the mitochondrial antioxidant defence system is considerably influenced by the thyroid states of the body.

Animals↗
PubMed2001

The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance.

Inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (RT) are widely used in the treatment of HIV infection. Loviride (an alpha-APA derivative) and HBY 097 (a quinoxaline derivative) are two potent non-nucleoside RT inhibitors (NNRTIs) that have been used in human clinical trials. A major problem for existing anti-retroviral therapy is the emergence of drug-resistant mutants with reduced susceptibility to the inhibitors. Amino acid residue 103 in the p66 subunit of HIV-1 RT is located near a putative entrance to a hydrophobic pocket that binds NNRTIs. Substitution of asparagine for lysine at position 103 of HIV-1 RT is associated with the development of resistance to NNRTIs; this mutation contributes to clinical failure of treatments employing NNRTIs. We have determined the structures of the unliganded form of the Lys103Asn mutant HIV-1 RT and in complexes with loviride and HBY 097. The structures of wild-type and Lys103Asn mutant HIV-1 RT in complexes with NNRTIs are quite similar overall as well as in the vicinity of the bound NNRTIs. Comparison of unliganded wild-type and Lys103Asn mutant HIV-1 RT structures reveals a network of hydrogen bonds in the Lys103Asn mutant that is not present in the wild-type enzyme. Hydrogen bonds in the unliganded Lys103Asn mutant but not in wild-type HIV-1 RT are observed between (1) the side-chains of Asn103 and Tyr188 and (2) well-ordered water molecules in the pocket and nearby pocket residues. The structural differences between unliganded wild-type and Lys103Asn mutant HIV-1 RT may correspond to stabilization of the closed-pocket form of the enzyme, which could interfere with the ability of inhibitors to bind to the enzyme. These results are consistent with kinetic data indicating that NNRTIs bind more slowly to Lys103Asn mutant than to wild-type HIV-1 RT. This novel drug-resistance mechanism explains the broad cross-resistance of Lys103Asn mutant HIV-1 RT to different classes of NNRTIs. Design of NNRTIs that make favorable interactions with the Asn103 side-chain should be relatively effective against the Lys103Asn drug-resistant mutant.

Acetamides↗
PubMed2001

Posterior fusion of the subaxial cervical spine: indications and techniques.

The biomechanical stability of the subaxial cervical spine (C3-7) can be compromised by numerous pathological processes, and the restoration of stability may ultimately require fusion and placement of rigid internal fixation devices. A posterior fusion and stabilization procedure is often used to treat cervical instability secondary to traumatic injury, rheumatoid arthritis, ankylosing spondylitis, neoplastic disease, infections, and previous laminectomy. Numerous techniques and advances in spinal instrumentation have evolved over the last 30 years. The authors review the indications and the various methods for stabilizing and fusing the subaxial cervical spine via posterior approaches.

Cervical Vertebrae↗
PubMed2001

Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA.

We have determined the 3.0 A resolution structure of wild-type HIV-1 reverse transcriptase in complex with an RNA:DNA oligonucleotide whose sequence includes a purine-rich segment from the HIV-1 genome called the polypurine tract (PPT). The PPT is resistant to ribonuclease H (RNase H) cleavage and is used as a primer for second DNA strand synthesis. The 'RNase H primer grip', consisting of amino acids that interact with the DNA primer strand, may contribute to RNase H catalysis and cleavage specificity. Cleavage specificity is also controlled by the width of the minor groove and the trajectory of the RNA:DNA, both of which are sequence dependent. An unusual 'unzipping' of 7 bp occurs in the adenine stretch of the PPT: an unpaired base on the template strand takes the base pairing out of register and then, following two offset base pairs, an unpaired base on the primer strand re-establishes the normal register. The structural aberration extends to the RNase H active site and may play a role in the resistance of PPT to RNase H cleavage.

Crystallography↗
PubMed2001

Chromosomal localization, expression pattern, and promoter analysis of the mouse gene encoding adipocyte-specific secretory protein Acrp30.

Acrp30 is an abundantly expressed secretory protein exclusively synthesized in adipose tissue. Due to the dysregulation in various forms of obesity in humans and mice and its strong structural similarity to TNFalpha, it is currently under study as an important molecule involved in whole body energy homeostasis. Here we describe the sequence of mouse Acrp30 locus, define the intron/exon boundaries and map the gene to the telomere of mouse chromosome 16, syntenic to the human chromosomal locus 3q27. We demonstrate that alternative polyadenylation gives rise to two distinct mRNA species. We also show that Acrp30 expression is induced only at the late stages of mouse embryonic development. Finally, we have characterized the mouse Acrp30 promoter in tissue culture cells. We propose that Acrp30 promoter has the potential to drive strong adipocyte specific heterologous gene expression in transgenic mice.

3T3 Cells↗
PubMed2001

Effect of amino acids on goat cauda epididymal sperm cryopreservation using a chemically defined model system.

Studies were carried out to analyze the cryoprotecting efficacy of several amino acids by use of a chemically defined synthetic medium (modified Ringer's solution) and goat cauda epididymal sperm as the model system. Motile goat cauda sperm dispersed in the synthetic medium were subjected to a freezing protocol in a computer-controlled bio-freezer, cooling 0.25 degrees C x min(-1) to 5 degrees C, 5 degrees C x min(-1) to -20 degrees C, and 20 degrees C x min(-1) to -100 degrees C, prior to being plunged into liquid nitrogen. In the absence of amino acids, sperm cells completely lost their flagellar motility. Of all the amino acids tested, l-alanine showed maximal cryoprotection potential. l-Alanine at 135 mM offered optimum cryoprotection potential: recovery of sperm forward motility and total motility were 14 +/- 2% and 19 +/- 2%, respectively. l-Glutamine, l-proline, and glycine at optimum concentration (100-150 mM) cryopreserved approx. 11-17% total motility of the sperm cells, whereas amino acids such as l-arginine, l-lysine, and l-histidine offered little cryoprotection (0-5%) to the cells. Increasing the amino acid concentration beyond the optimum level sharply decreased the recovery of the sperm motility, which therefore showed a biphasic cryoprotection profile. Addition of amino acids enhanced (approx. 7-10%) the cryoprotection efficacy of the well-known cryoprotectants glycerol and a combination of glycerol and dimethyl sulfoxide. The presence of glycerol caused a marked reduction (from 100-150 mM to 20-70 mM levels) in the optimal cryoprotective concentration of the amino acids. The combined cryoprotecting action of glycerol, dimethyl sulfoxide, and amino acids provided motility recovery as high as 52%. The observation that amino acids and dimethyl sulfoxide had an additive effect in augmenting the cryoprotecting potential of glycerol suggests that the mechanism of their action is different from that of glycerol. This cocktail of cryoprotectants may be useful for cryopreservation of semen of various species.

Amino Acids↗
PubMed2001

Hirschsprung's disease, associated rare congenital anomalies.

OBJECTIVE: Hirschsprung's disease may be associated with a number of congenital anomalies of which Down's syndrome and intestinal atresias are commonly encountered. The study aimed to assess the impact of rare associated anomalies on the diagnosis and management of Hirschsprung's disease. METHODS: A retrospective review of the clinical presentation, diagnosis and outcome of thirty five consecutive newly diagnosed cases of Hirschsprung's disease encountered over two years was performed. RESULTS: Besides Down's syndrome (two), intestinal atresia (one) and pigmentary ocular defects (two), three rare anomalies (Occipital meningocele, Calcific meconium cyst with anal stenosis, Malrotation) were encountered in four of thirty five cases. The clinical features, radiologic anatomy and gross morphology of the bowel were unconventional and the diagnosis was supported by intraoperative acetylcholinesterase staining of biopsies. Though the diagnosis was relatively delayed in these cases, the outcome has been comparable to the rest. The dilemma in their diagnosis and management and their possible pathoembryology is discussed. CONCLUSION: Awareness of such associations and a specific investigative protocol is imperative for timely diagnosis and minimal morbidity in complex presentations of Hirschsprung's disease.

Abnormalities, Multiple↗
PubMed2001

Silo construction from a sterile adhesive film and polypropylene mesh in the repair of gastroschisis and omphalocele.

A simple technique of constructing a silo for the treatment of gastroschisis (GS) and omphalocele (OMP) is described. A polypropylene mesh covered on both sides with a sterile transparent adhesive film (incise drape) was used; both these items are freely available in the operating room. The resultant silo is sterile, soft, flexible, sturdy, internally smooth, provides a reasonable barrier, and allows enough visibility of the bowel. This silo was used in the treatment of 25 cases of GS and 13 cases of OMP with acceptable results. Survival was better in patients in whom primary closure could be achieved in both OMP and GS. Silo treatment was associated with higher mortality from septic causes.

Gastroschisis↗
PubMed2001

Emergency department admissions to inpatient cardiac telemetry beds: a prospective cohort study of risk stratification and outcomes.

PURPOSE: Little is known about physicians' use of inpatient cardiac telemetry units among emergency department patients at risk for cardiac complications. We therefore studied the outcomes of patients admitted to inpatient telemetry beds to identify a subset of patients from whom cardiac monitoring could be withheld safely. SUBJECTS AND METHODS: We conducted a prospective cohort study of 1, 033 consecutive adult patients admitted to an inpatient telemetry unit from the emergency department of a 700-bed urban public teaching hospital. Subjects with or without chest pain were risk-stratified using a prediction rule and observed for in-hospital cardiac complications, acute myocardial infarction, and transfer to an intensive care unit (ICU). RESULTS: There were no significant differences between patients with (n = 677) or patients without chest pain (n = 356) in the rates of major cardiac complications, myocardial infarctions, or transfers to an ICU. Among 318 patients with chest pain who were classified as being very low risk, none suffered major complications (negative predictive value 100%; 95% confidence interval [CI]: 98.8% to 100%). Among 214 very low risk patients without chest pain, 1 (0.5%) had a major complication (negative predictive value 99.5%; 95% CI: 97.4% to 99.9%). CONCLUSIONS: The prediction rule accurately identified patients with or without chest pain who were at very low risk of major complications, identifying a subset from whom cardiac monitoring could be withheld safely.

Adolescent↗
PubMed2001

Symptomatic subdural hygroma and temporal lobe edema after translabyrinthine removal of acoustic neuroma.

The translabyrinthine approach is familiar to most neurosurgeons and neuro-otologists and is frequently used to remove acoustic neuromas. Some of the complications associated with this surgery include cerebrospinal fluid (CSF) leaks, meningitis, and rarely fat graft prolapse. The authors report a 60-year-old woman who underwent a translabyrinthine approach and microsurgical resection of a right-sided 1-cm acoustic neuroma. Initially, she was discharged home after an uneventful postoperative course. Four days later, she sought treatment in the emergency room complaining of headaches, dizziness, and lethargy. A computed tomographic (CT) scan showed a large right-sided subdural hygroma and right temporal lobe edema. The patient underwent burr hole evacuation of the collection and placement of a subdural drain, after which the edema in the temporal lobe and hygroma resolved. We speculate that the underlying mechanism was the result of inadvertant damage to the venous drainage and an arachnoid tear that was not appreciated during surgery. Neurosurgeons and neuro-otogists should be aware of this unusual complication of translabyrinthine surgery and its possible underlying mechanisms.

Case Reports↗
PubMed2001

Molecular modeling and biochemical characterization reveal the mechanism of hepatitis B virus polymerase resistance to lamivudine (3TC) and emtricitabine (FTC).

Success in treating hepatitis B virus (HBV) infection with nucleoside analog drugs like lamivudine is limited by the emergence of drug-resistant viral strains upon prolonged therapy. The predominant lamivudine resistance mutations in HBV-infected patients are Met552IIe and Met552Val (Met552Ile/Val), frequently in association with a second mutation, Leu528Met. The effects of Leu528Met, Met552Ile, and Met552Val mutations on the binding of HBV polymerase inhibitors and the natural substrate dCTP were evaluated using an in vitro HBV polymerase assay. Susceptibility to lamivudine triphosphate (3TCTP), emtricitabine triphosphate (FTCTP), adefovir diphosphate, penciclovir triphosphate, and lobucavir triphosphate was assessed by determination of inhibition constants (K(i)). Recognition of the natural substrate, dCTP, was assessed by determination of Km values. The results from the in vitro studies were as follows: (i) dCTP substrate binding was largely unaffected by the mutations, with Km changing moderately, only in a range of 0.6 to 2.6-fold; (ii) K(i)s for 3TCTP and FTCTP against Met552Ile/Val mutant HBV polymerases were increased 8- to 30-fold; and (iii) the Leu528Met mutation had a modest effect on direct binding of these beta-L-oxathiolane ring-containing nucleotide analogs. A three-dimensional homology model of the catalytic core of HBV polymerase was constructed via extrapolation from retroviral reverse transcriptase structures. Molecular modeling studies using the HBV polymerase homology model suggested that steric hindrance between the mutant amino acid side chain and lamivudine or emtricitabine could account for the resistance phenotype. Specifically, steric conflict between the Cgamma2-methyl group of Ile or Val at position 552 in HBV polymerase and the sulfur atom in the oxathiolane ring (common to both beta-L-nucleoside analogs lamivudine and emtricitabine) is proposed to account for the resistance observed upon Met552Ile/Val mutation. The effects of the Leu528Met mutation, which also occurs near the HBV polymerase active site, appeared to be less direct, potentially involving rearrangement of the deoxynucleoside triphosphate-binding pocket residues. These modeling results suggest that nucleotide analogs that are beta-D-enantiomers, that have the sulfur replaced by a smaller atom, or that have modified or acyclic ring systems may retain activity against lamivudine-resistant mutants, consistent with the observed susceptibility of these mutants to adefovir, lobucavir, and penciclovir in vitro and adefovir in vivo.

Acyclovir↗
PubMed2001

Approaches to the sellar and parasellar region: anatomic comparison of endonasal-transsphenoidal, sublabial-transsphenoidal, and transethmoidal approaches.

Various surgical approaches have been described for treating lesions which arise in the sellar region. The popular transnasal-transsphenoidal and transethmoidal-transsphenoidal approaches avoid the morbidity associated with transcranial operations while allowing enough exposure to successfully remove most lesions that arise in and around the sella. The goal of the present study was to accurately quantify the amount of exposure to the sellar and suprasellar region that the transethmoidal-transsphenoidal, endonasal-transphenoidal, and sublabial-transsphenoidal approaches provide. Each of the three approaches was performed on 14 formalin fixed heads with the aid of the operative microscope. The distances of relevant surgical landmarks, and the amount of exposure superior and anterior to the dorsum sella as well as the lateral exposure obtained through each of these approaches was carefully recorded. The mean distances were then used to calculate the volume of exposure offered by each approach. It was found that the sublabial-transsphenoidal approach afforded the greatest volume of exposure superior and anterior to the dorsum sella. The endonasal-transsphenoidal and the transethmoidal approaches were both found to offer less suprasellar volume exposure, with the transethmoidal approach offering the least. The authors believe the information obtained through this study illustrates some important anatomical relationships which can be used to advantage by the surgeon to tailor the most appropriate approach, depending upon the precise location of the lesion either within the sella or suprasellar region.

Brain Neoplasms↗
PubMed2001

The history and evolution of transsphenoidal surgery.

Initial attempts at transcranial approaches to the pituitary gland in the late 1800s and early 1900s resulted in a mortality rate that was generally considered prohibitive. Schloffer suggested the use of a transsphenoidal route as a safer, alternative approach to the sella turcica. He reported the first successful removal of a pituitary tumor via the transsphenoidal approach in 1906. His procedure underwent a number of modifications by interested surgeons, the culmination of which was A. E. Halstead's description in 1910 of a sublabial gingival incision for the initial stage of exposure. From 1910 to 1925, Cushing, combining a number of suggestions made by previous authors, refined the transsphenoidal approach and used it to operate on 231 pituitary tumors, with a mortality rate of 5.6%. As he developed increasing expertise with transcranial surgery, however, Cushing reduced his mortality rate to 4.5%. With the transcranial approach, he was able to verify suprasellar tumors and achieve better decompression of the optic apparatus, resulting in better recovery of vision and a lower recurrence rate. As a result he and most other neurosurgeons at the time abandoned the transnasal in favor of the transcranial approaches. Norman Dott, a visiting scholar who studied with Cushing in 1923, returned to Edinburgh, Scotland, and continued to use the transsphenoidal procedure while others pursued transcranial approaches. Dott introduced the procedure to Gerard Guiot, who published excellent results with the transsphenoidal approach and revived the interest of many physicians throughout Europe in the early 1960s. Jules Hardy, who used intraoperative fluoroscopy while learning the transsphenoidal approach from Guiot, then introduced the operating microscope to further refine the procedure; he thereby significantly improved its efficacy and decreased surgical morbidity. With the development of antibiotic drugs and modern microinstrumentation, the transsphenoidal approach became the preferred route for the removal of lesions that were confined to the sella turcica. The evolution of the transsphenoidal approaches and their current applications and modifications are discussed.

History, 19th Century↗
PubMed2001

Use of cylindrical titanium mesh and locking plates in anterior cervical fusion. Technical note.

After performing anterior cervical corpectomy or discectomy for cervical spondolytic myelopathy or radiculopathy, iliac crest bone graft and fibular auto- or allograft is often used to achieve arthrodesis in the cervical spine. The purpose of this study was to evaluate the use of a cylindrical titanium mesh and locking plate system as an alternative technique in achieving anterior cervical fusion and maintaining lordosis. Hospital records and radiographs of 38 patients who underwent anterior cervical discectomies (28 patients) or corpectomies (10 patients) from 1995 to 1997 were reviewed retrospectively. All patients had undergone arthrodesis in which autograft and a cylindrical titanium mesh and anterior locking plate fixation were used after discectomy or corpectomy. There were 20 men and 18 women (mean age 46.1 years; range 34-72 years). Presenting symptoms included radiculopathy (61%), myelopathy (37%), and neck pain (2%). Preoperative and postoperative radiographs were studied, and data were obtained on the following: overall lordosis or kyphosis of the cervical spine, segmental lordosis or kyphosis at each surgically treated level, and evidence of fusion. In all of the patients in whom lordosis was present preoperatively, lordosis was maintained during the follow-up period. The overall fusion rate was 100%. The average change in overall lordosis or kyphosis related to the fixation devices was 1.2 degrees (range 1-5 degrees) the average segmental change was 2.3 degrees (range 0-5 degrees); and the mean follow up was 16 months (range 12-36 months). Anterior cervical fusion with cylindrical titanium mesh and cervical locking plate system is an effective method of achieving arthrodesis and maintaining alignment in the cervical spine. The construct may provide additional load-sharing function, and it avoids the use of cadaveric bone or the need for harvesting tricortical iliac crest autograft.

Adult↗
PubMed2001

HIV-1 reverse transcriptase mutations found in a drug-experienced patient confer reduced susceptibility to multiple nucleoside reverse transcriptase inhibitors.

HIV-1 reverse transcriptase (RT) genotypes were obtained from 13 patients treated with stavudine. No previously-reported mutations indicative of stavudine resistance were found in these patients and no novel mutations occurred in more than two patients. One patient, treated with stavudine for 1 month and treated previously with zidovudine, zalcitabine and lamivudine, carried a mutation at codon 75 of the RT (V75M). A chimeric virus, including the patient's RT sequence from codon 25 to codon 220, which carried the resistance mutations M41 L, D67N, T69D, K70R, L210W and T215Y in addition to V75M, displayed reduced susceptibility to multiple nucleoside RT inhibitors (NRTIs). Removal of V75M from this RT background resulted in a return of susceptibility to didanosine and lamivudine. Our data are in agreement with previous studies demonstrating the rarity of stavudine resistance mutations in stavudine-treated patients. However, we describe a new set of mutations, found in the RT of a heavily-treated patient, that can confer reduced susceptibility to multiple NRTIs. These results underscore the importance of increased vigilance for possible multiple-drug resistance in patients who have been heavily treated with NRTIs.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Caveolin-3 directly interacts with the C-terminal tail of beta -dystroglycan. Identification of a central WW-like domain within caveolin family members.

Caveolin-3, the most recently recognized member of the caveolin gene family, is muscle-specific and is found in both cardiac and skeletal muscle, as well as smooth muscle cells. Several independent lines of evidence indicate that caveolin-3 is localized to the sarcolemma, where it associates with the dystrophin-glycoprotein complex. However, it remains unknown which component of the dystrophin complex interacts with caveolin-3. Here, we demonstrate that caveolin-3 directly interacts with beta-dystroglycan, an integral membrane component of the dystrophin complex. Our results indicate that caveolin-3 co-localizes, co-fractionates, and co-immunoprecipitates with a fusion protein containing the cytoplasmic tail of beta-dystroglycan. In addition, we show that a novel WW-like domain within caveolin-3 directly recognizes the extreme C terminus of beta-dystroglycan that contains a PPXY motif. As the WW domain of dystrophin recognizes the same site within beta-dystroglycan, we also demonstrate that caveolin-3 can effectively block the interaction of dystrophin with beta-dystroglycan. In this regard, interaction of caveolin-3 with beta-dystroglycan may competitively regulate the recruitment of dystrophin to the sarcolemma. We discuss the possible implications of our findings in the context of Duchenne muscular dystrophy.

3T3 Cells↗
PubMed2000

Thoracoscopic surgery: historical perspectives.

Recent technical advances have revolutionized the fields of surgical endoscopy, laparoscopy, thoracoscopy, and microsurgical spinal endoscopy. The authors discuss the rich history and recent evolution of these techniques. Thoracoscopy had been widely used for the treatment of pleural conditions associated with tuberculosis. It was largely abandoned in the 1950s when effective antituberculosis medications were introduced. In the 1980s the development of video-assisted endoscopic procedures in the fields of general surgery, orthopedics, and otolaryngology provided new impetus to revive thoracoscopy. As a result of these advances thoracoscopy replaced open thoracotomy in many cardiothoracic procedures. These improvements led to the application of these techniques to treat disorders of the spine. By the mid-1990s microsurgical endoscopy was being used effectively to treat thoracic disc disease, perform anterior surgical release procedures for scoliosis, resect tumors, and even to conduct complex spinal fusions and reconstructions. As technology continues to improve, there is no doubt that thoracoscopic surgery will find a permanent place in the armamentarium of techniques used to treat pathological entities of the spine.

Animals↗