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Biomedical subjects

K Das

Publications and source records attributed to K Das.

At least 109 records · Page 6Linked to original sources
PubMed1998

No evidence for significant linkage between bipolar affective disorder and chromosome 18 pericentromeric markers in a large series of multiplex extended pedigrees.

Bipolar affective disorder (BP) is a major neuropsychiatric disorder with high heritability and complex inheritance. Previously reported linkage between BP and DNA markers in the pericentromeric region of chromosome 18, with a parent-of-origin effect (linkage was present in pedigrees with paternal transmission and absent in pedigrees with exclusive maternal inheritance), has been a focus of interest in human genetics. We reexamined the evidence in one of the largest samples reported to date (1,013 genotyped individuals in 53 unilineal multiplex pedigrees), using 10 highly polymorphic markers and a range of parametric and nonparametric analyses. There was no evidence for significant linkage between BP and chromosome 18 pericentromeric markers in the sample as a whole, nor was there evidence for significant parent-of-origin effect (pedigrees with paternal transmission were not differentially linked to the implicated chromosomal region). Two-point LOD scores and single-locus sib-pair results gave some support for suggestive linkage, but this was not substantiated by multilocus analysis, and the results were further tempered by multiple test effects. We conclude that there is no compelling evidence for linkage between BP and chromosome 18 pericentromeric markers in this sample.

Adolescent↗
PubMed1998

Irving S. Cooper (1922-1985): a pioneer in functional neurosurgery.

Irving S. Cooper (1922-1985), the son of a salesman, worked his way through high school, college, and medical school to become one of the pioneers in functional neurosurgery. He developed several novel techniques for the surgical management of Parkinson's disease and other crippling movement disorders. A keen interest in the physiology of movement disorders was kindled by his doctoral research and continued during his neurosurgical training. He began to apply this knowledge to surgical practice in 1952 when he began his faculty career as Assistant Professor of Surgery at New York University. At the time, surgical treatment of parkinsonian tremor focused on various techniques used to interrupt the pyramidal tract. During a subtemporal approach for a cerebral pedunculotomy, he inadvertently injured and, subsequently, was forced to occlude the anterior choroidal artery. Much to Cooper's surprise, following emergence from anesthesia the patient's tremor and rigidity were abolished without any residual hemiparesis. This serendipitous observation, together with Meyer's earlier work on the role of the basal ganglia in motor control, helped focus surgical efforts on targets within the basal ganglia and, subsequently, within the thalamus to alleviate the movement disorders associated with Parkinson's disease. While at New York University, Cooper developed chemopallidectomy and, later at St. Barnabas Hospital in the Bronx (1954-1977), he used cryothalamectomy as a surgical technique for primary control of tremor in patients with Parkinson's disease. Cooper authored many original papers on surgical techniques and several textbooks on the lives of patients afflicted with Parkinson's disease and other crippling movement disorders. Although considered controversial, this fascinating and complex neurosurgeon made significant contributions to this field.

Cryosurgery↗
PubMed1998

Clinicopathologic study of lupus nephritis.

Needle biopsies of kidney were done in 35 cases of systemic lupus erythematosus (SLE) with renal lesions. The lupus nephritis were classified according to WHO classification and were correlated with response to therapy and prognosis. Detailed clinical features, routine haematological, biochemical tests (e.g., serum urea, creatinine, total protein and albumin, cholesterol, etc), examination of urine (degree of proteinuria and cells) and occurrence of various auto-antibodies e.g., antinuclear antibody (ANA), anti double stranded DNA (anti DsDNA) by enzyme immunoassay (EIA) method, LE cells and rheumatoid factor (RF) were studied in all cases. Clinically hypertension was present in 19 (54.3%) cases and nephrotic range of proteinuria was detected in 20 (57.2%) cases. ANA was found in 31 (88.5%) cases, anti DsDNA 24 (68.5%) and LE cells were detected in 25 (71.5%) cases. RF was detected in 2 (5.7%) cases. Histologically the most frequent lesions were class IV occurring in 15 cases (42.8%) with initial complete remission achieved only 4 cases by immunosuppressive therapy. Active lesions were also most frequent in this class. Class III lesions were found in 8 (22.8%) cases with 6 cases had complete remission. The best prognosis was noted in class II cases with 4 out of 5 (14.3%) cases had complete remission. Class V lesions were found in 6 (17.2%) cases with complete remission achieved in 3 cases. Only one patient presented with class VI lesion. RF positive cases had milder renal lesions.

Adolescent↗
PubMed1997

Specific interaction of eukaryotic translation initiation factor 5 (eIF5) with the beta-subunit of eIF2.

Eukaryotic translation initiation factor 5 (eIF5) interacts with the 40 S initiation complex (40 S.mRNA. eIF3.Met-tRNAf.eIF2.GTP) and mediates hydrolysis of the bound GTP. To characterize the molecular interactions involved in eIF5 function, we have used 32P-labeled recombinant rat eIF5 as a probe in filter overlay assay to identify eIF5-interacting proteins in crude initiation factor preparations. We observed that eIF5 specifically interacted with the beta subunit of initiation factor eIF2. No other initiation factors including the gamma subunit of eIF2 tested positive in this assay. Furthermore, both yeast and mammalian eIF5 bind to the beta subunit of either mammalian or yeast eIF2. Binding analysis with human eIF2beta deletion mutants expressed in Escherichia coli identified a 22-amino acid domain, between amino acids 68 and 89, as the primary eIF5-binding region of eIF2beta. These results along with our earlier observations that (a) eIF5 neither binds nor hydrolyzes free GTP or GTP bound as Met-tRNAf.eIF2.GTP ternary complex, and (b) eIF5 forms a specific complex with eIF2 suggests that the specific interaction between eIF5 and the beta subunit of eIF2 may be critical for the hydrolysis of GTP during translation initiation.

Amino Acid Sequence↗
PubMed1997

Costs of an emergency department-based accelerated diagnostic protocol vs hospitalization in patients with chest pain: a randomized controlled trial.

CONTEXT: More than 3 million patients are hospitalized yearly in the United States for chest pain. The cost is over $3 billion just for those found to be free of acute disease. New rapid diagnostic tests for acute myocardial infarction (AMI) have resulted in the proliferation of accelerated diagnostic protocols (ADPs) and chest pain observation units. OBJECTIVE: To determine whether use of an emergency department (ED)-based ADP can reduce hospital admission rate, total cost, and length of stay (LOS) for patients needing admission for evaluation of chest pain. DESIGN: Prospective randomized controlled trial comparing admission rate, total cost, and LOS for patients treated using ADP vs inpatient controls. Total costs were determined using empirically measured resource utilization and microcosting techniques. SETTING: A large urban public teaching hospital serving a predominantly African American and Hispanic population. PATIENTS: A sample of 165 patients was randomly selected from a larger consecutive sample of 429 patients with chest pain concurrently enrolled in an ADP diagnostic cohort trial. Eligible patients presented to the ED with clinical findings suggestive of AMI or acute cardiac ischemia (ACI) but at low risk using a validated predictive algorithm. MAIN OUTCOME MEASURES: Primary outcomes measured for each subject were LOS and total cost of treatment. RESULTS: The hospital admission rate for ADP vs control patients was 45.2% vs 100% (P<.001). The mean total cost per patient for ADP vs control patients was $1528 vs $2095 (P<.001). The mean LOS measured in hours for ADP vs control patients was 33.1 hours vs 44.8 hours (P<.01). CONCLUSIONS: In this trial, ADP saved $567 in total hospital costs per patient treated. Use of ED-based ADPs can reduce hospitalization rates, LOS, and total cost for low-risk patients with chest pain needing evaluation for possible AMI or ACI.

Adult↗
PubMed1997

An evaluation of a chest pain diagnostic protocol to exclude acute cardiac ischemia in the emergency department.

BACKGROUND: Although accelerated diagnostic protocols are being increasingly used in emergency departments to diagnose acute cardiac ischemia, there have been no prospective evaluations of a chest pain diagnostic protocol with serial determinations of creatine kinase MB isoenzyme and mandatory exercise electrocardiography (ExECG). METHODS: Prospective cross-sectional study in which chest pain protocol results were compared with final (reference) diagnoses of acute cardiac ischemia (including acute myocardial infarction and unstable angina). Patients in need of hospital admission but at low probability (by a validated algorithm) for acute myocardial infarction were examined for exclusions: known coronary artery disease, cardiac complications, severe comorbidities, or inability to perform exercise testing. A 12-hour diagnostic protocol included serial measurements of creatine kinase MB, ECG, and clinical assessments followed by ExECG for those with negative initial serial testing. Reference diagnoses were established during hospitalization and diagnostic accuracy was assessed. RESULTS: The study group of 317 patients was 54% male and 65% black, and had a mean age of 46.6 years; 9.5% had a final diagnosis of acute cardiac ischemia. For this diagnosis, the protocol had a sensitivity of 90.0% (95% confidence interval, 72.3%-97.4%); specificity, 50.5% (95% confidence interval, 44.6%-56.4%); positive predictive value, 16.0%; and negative predictive value, 98.0%. Creatine kinase MB, serial ECGs, and ExECG each made a contribution to improved sensitivity and accuracy, whereas clinical reassessments were less discriminating, as indicated by protocol's receiver operating characteristic curve. CONCLUSIONS: A chest pain diagnostic protocol achieved high sensitivity and improved specificity over the standard emergency department workup. There were no adverse advents associated with early ExECG.

Algorithms↗
PubMed1997

Extensive DNA deletion associated with severe disease alleles on spinal muscular atrophy homologues.

Spinal muscular atrophy (SMA) is a motor neuron disease presenting with a wide spectrum of phenotypic variations. The primary cause of most, if not all, forms of childhood-onset spinal muscular atrophy appears to be the homozygous loss of the telomeric copy of the survival motor neuron (SMNT) gene. It is interesting that approximately half of all affected patients are likewise homozygous nulls for the neuronal apoptosis inhibitory protein (NAIP) gene and a somewhat lesser fraction for the basal transcription factor, p44 subunit (BTF2p44) gene. It has been proposed that homozygous loss of SMNT is the primary cause of spinal muscular atrophy while the loss of NAIP and perhaps other genes primarily affects the severity of disease manifestation. We explored this hypothesis by evaluating the extent of gene deletions in three multigenerational families with spinal muscular atrophy exhibiting dramatic intrafamilial phenotypic variation. Using somatic cell hybrid lines to sequester individual spinal muscular atrophy homologues, we show that homologues missing several contiguous genes correlate with "severe" disease alleles and homologues missing only SMNT correlate with "mild" disease alleles. These observations support the hypothesis that phenotypic severity among the childhood-onset spinal muscular atrophies is directly correlated with the extent of disease-specific deletions.

Adult↗
PubMed1997

Perinodular hydropic degeneration of a uterine leiomyoma: a diagnostic challenge.

Perinodular hydropic degeneration of a uterine leiomyoma is a rare form of the more common hydropic change observed in leiomyomas. With minimal discussion in the surgical pathology literature, appropriate evaluation may be challenging because the differential diagnosis includes other uncommon uterine disorders such as intravenous leiomyomatosis, diffuse leiomyomatosis, myxoid leiomyosarcoma, endometrial stromal sarcoma, angiofibroma, and angiomyxoma. We describe such a diagnostic challenge in a 42-year-old woman with a left adnexal mass discovered during an annual examination. With only three cases of perinodular hydropic degeneration previously reported, this case is the first with extrauterine extension and was initially concerning for a more aggressive process.

Adult↗
PubMed1997

Feasibility of a rapid diagnostic protocol for an emergency department chest pain unit.

STUDY OBJECTIVE: To evaluate the applicability of a short-stay protocol for exclusion of acute ischemic heart disease without hospital admission and to analyze these results in the context of a conceptual model. METHODS: An observational study of patients who presented with chest pain to the emergency department of an 886-bed inner-city municipal hospital and who needed hospital admission to rule out acute myocardial infarction (AMI). Patients were assessed by ED attending physicians to determine eligibility for an alternative, 12-hour protocol in an ED chest pain observation unit (CPOU) followed by immediate exercise testing. Outcome measures were proportion of patients eligible for the short-stay protocol, risk factor profile, and reasons for exclusion. RESULTS: Of 500 patients screened, 446 had sufficient data points to determine protocol eligibility. Of these, 238 (53.3%; 95% confidence interval [CI], 48.7% to 57.9%) were found to have low probability for AMI. After study exclusion criteria were applied to the patient cohort, 63 patients (14.1%; 95% CI, 10.9% to 17.3%) were eligible for the protocol. The most common reasons for exclusion were history of coronary artery disease (46%) and inability to perform an interpretable exercise tolerance test (42%). CONCLUSION: Although most admitted patients with chest pain (53%) were at low probability for AMI, only a minority (14%) were eligible for a short-stay protocol that required patients to be free of known coronary artery disease and able to perform an exercise tolerance test. Factors affecting the operations and efficiency of a CPOU include clinical characteristics of the target patient population, protocol tests used, and hospital occupancy and reimbursement patterns.

Acute Disease↗
PubMed1997

Identification and analysis of mutations in the Wilson disease gene (ATP7B): population frequencies, genotype-phenotype correlation, and functional analyses.

Wilson disease (WD) is an autosomal recessive disorder characterized by toxic accumulation of copper in the liver and subsequently in the brain and other organs. On the basis of sequence homology to known genes, the WD gene (ATP7B) appears to be a copper-transporting P-type ATPase. A search for ATP7B mutations in WD patients from five population samples, including 109 North American patients, revealed 27 distinct mutations, 18 of which are novel. A composite of published findings shows missense mutations in all exons-except in exons 1-5, which encode the six copper-binding motifs, and in exon 21, which spans the carboxy-terminus and the poly(A) tail. Over one-half of all WD mutations occur only rarely in any population sample. A splice-site mutation in exon 12 accounts for 3% of the WD mutations in our sample and produces an in-frame, 39-bp insertion in mRNA of patients homozygous, but not heterozygous, for the mutation. The most common WD mutation (His1069Glu) was represented in approximately 38% of all the WD chromosomes from the North American, Russian, and Swedish samples. In several population cohorts, this mutation deviated from Hardy-Weinberg equilibrium, with an overrepresentation of homozygotes. We did not find a significant correlation between His1069Glu homozygosity and several clinical indices, including age of onset, clinical manifestation, ceruloplasmin activity, hepatic copper levels, and the presence of Kayser-Fleischer rings. Finally, lymphoblast cell lines from individuals homozygous for His1069Glu and 4 other mutations all demonstrated significantly decreased copper-stimulated ATPase activity.

Adenosine Triphosphatases↗
PubMed1997

Multiple biological roles associated with the Rous sarcoma virus 5' untranslated RNA U5-IR stem and loop.

The 5' untranslated region of Rous sarcoma virus (RSV) RNA is a highly ordered structure involved in multiple processes in the viral replication cycle. One of these structures, referred to as the U5-IR stem, is located immediately upstream of the 5' end of the primer binding site. Disruption of its base pairing results in a decrease in initiation of reverse transcription (D. Cobrinik, A. Aiyar, Z. Ge, M. Katzman, H. Huang, and J. Leis, J. Virol. 65:3864-3872, 1991). In the present study, the length of the U5-IR stem structure has been extended by insertions of different sequences which decrease the efficiency of reverse transcription, in vivo and in vitro. Reverse transcription is rescued partially by placing single-stranded bulges into the middle of the extended duplexes. Nucleotide substitutions or insertions into the loop region of the U5-IR stem also decrease the efficiency of reverse transcription, suggesting that these sequences may specifically interact with reverse transcriptase. Surprisingly, all of the extended stem mutations cause significant RNA packaging defects. In contrast, nucleotide insertions or base substitutions in the U5-IR loop do not affect RNA packaging. These data indicate that the reverse transcription initiation complex and RNA packaging apparatus are influenced by the same region of RSV RNA and that each process is differentially sensitive to changes in sequence and/or secondary structure.

Animals↗
PubMed1997

MR imaging, MR angiography, and MR spectroscopy of the brain in eclampsia.

PURPOSE: To compare the MR imaging and MR angiographic changes with in vivo proton MR spectroscopic findings and to determine the spectral differences between edema and ischemia in patients with eclampsia. METHODS: Spin-echo MR imaging, MR angiography, and single-voxel proton MR spectroscopy were performed in 10 patients with eclampsia. MR studies were obtained within 3 to 5 days of diagnosis and repeated after 2 weeks with identical parameters. RESULTS: Multifocal subcortical/cortical hyperintensities were noted in all 10 patients on T2-weighted images; in two patients, hyperintensities were seen in both cerebral hemispheres. In nine patients, MR angiograms showed narrowing of the major vessels constituting the circle of Willis that resolved after 2 weeks. In one patient with subtle imaging changes, MR angiography showed mild bilateral narrowing of the proximal middle and posterior cerebral arteries that did not change after 2 weeks, whereas imaging abnormalities worsened. Findings at single-voxel MR spectroscopy of the reversible T2 hyperintense lesions were significantly different from findings in the control group for N-acetylaspartate (NAA)/creatine ratios. One patient with mild abnormalities at MR imaging and MR angiography had lactate and decreased creatine and NAA, and on a follow-up study had a further decrease of NAA and creatine as well as a decrease in lactate. CONCLUSION: In vivo proton MR spectroscopy may help to differentiate cerebral edema from ischemia in patients with eclampsia and thus may help to determine the prognosis for these patients.

Adolescent↗
PubMed1997

Intravenous cyclosporine therapy in the treatment of pyoderma gangrenosum secondary to Crohn's disease.

Pyoderma gangrenosum is a destructive, ulcerative skin condition often associated with systemic illnesses such as inflammatory bowel disease, myeloproliferative disorders, and the inflammatory arthritides. We present a patient with long-standing pyoderma gangrenosum associated with Crohn's disease. Multiple deep leg ulcerations were unresponsive over the course of several years to treatment with azathioprine, systemic corticosteroids, 6-mercaptopurine, and dapsone. The patient was hospitalized and treated with a ten-day course of intravenous cyclosporine therapy followed by outpatient oral cyclosporine and showed significant improvement.

Adult↗
PubMed1997

Metallic ion concentration during menstrual cycle in normally menstruating women.

Plasma concentration of metallic ions levels during menstrual cycle of twenty normally menstruating women were observed in four phases i.e. menses, follicular, ovulatory and luteal. The concentration of magnesium, zinc, selenium and manganese was highest during menses and lowest at ovulatory phase. There was rise in ionic levels of magnesium and selenium, while fall in zinc and manganese during luteal phase. Findings demonstrate changes in metallic ions (Magnesium, zinc, selenium and manganese) level in relation to hormonal status during menstrual cycle in women.

Adult↗
PubMed1997

Ultrastructure of intermediate trophoblast cells during morphogenesis of syncytiotrophoblast in early human pregnancy.

During human embryonic development the process of differentiation begins in the cells covering the blastocyst, resulting in the formation of outer syncytial and inner cytotrophoblastic cell layers. Although the outer syncytial layer is known to be derived from the underlying layer of mononuclear cytotrophoblasts, the cellular mechanism involved in its morphogenesis is not clear. Furthermore, there is another type of cells, designated as intermediate trophoblasts, which play a vital role in syncytium formation. Using early first-trimester (6-10 weeks' gestation) human chorionic villi, a study was carried out to illustrate the ultrastructural features of these cells. It was observed that while there was a large number of coated vesicles, vacuoles, lysosomes and dense granules in the syncytiotrophoblast, in cytotrophoblasts there was a relatively smaller number. In intermediate cells, however, these organelles were more abundant. Moreover, a discontinuity in the plasma membrane along with gap junctions was frequently observed in these cells. Since these features represent the transitional stage of a differentiating cell, it is possible that the syncytiotrophoblast is in fact formed by the differentiation of intermediate trophoblasts.

Cell Membrane↗
PubMed1996

Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant.

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is an important target for chemotherapeutic agents used in the treatment of AIDS; the TIBO compounds are potent non-nucleoside inhibitors of HIV-1 RT (NNRTIs). Crystal structures of HIV-1 RT complexed with 8-Cl TIBO (R86183, IC50 = 4.6 nM) and 9-Cl TIBO (R82913, IC50 = 33 nM) have been determined at 3.0 A resolution. Mutant HIV-1 RT, containing Cys in place of Tyr at position 181 (Tyrl81Cys), is highly resistant to many NNRTIs and HIV-1 variants containing this mutation have been selected in both cell culture and clinical trials. We also report the crystal structure of Tyrl81Cys HIV-1 RT in complex with 8-Cl TIBO (IC50 = 130 nM) determined at 3.2 A resolution. Averaging of the electron density maps computed for different HIV-1 RT/NNRTI complexes and from diffraction datasets obtained using a synchrotron source from frozen (-165 degrees C) and cooled (-10 degrees C) crystals of the same complex was employed to improve the quality of electron density maps and to reduce model bias. The overall locations and conformations of the bound inhibitors in the complexes containing wild-type HIV-1 RT and the two TIBO inhibitors are very similar, as are the overall shapes and volumes of the non-nucleoside inhibitor-binding pocket (NNIBP). The major differences between the two wild-type HIV-1 RT/TIBO complexes occur in the vicinity of the TIBO chlorine substituents and involve the polypeptide segments around the beta5-beta6 connecting loop (residues 95 to 105) and the beta13-beta14 hairpin (residues 235 and 236). In all known structures of HIV-1 RT/NNRTI complexes, including these two, the position of the beta12-beta13 hairpin or the "primer grip" is significantly displaced relative to the position in the structure of HIV-1 RT complexed with a double-stranded DNA and in unliganded HIV-1 RT structures. Since the primer grip helps to position the template-primer, this displacement suggests that binding of NNRTIs would affect the relative positions of the primer terminus and the polymerase active site. This could explain biochemical data showing that NNRTI binding to HIV-1 RT reduces efficiency of the chemical step of DNA polymerization, but does not prevent binding of either dNTPs or DNA. When the structure of the Tyr181Cys mutant HIV-1 RT in complex with 8-Cl TIBO is compared with the corresponding structure containing wild-type HIV-1 RT, the overall conformations of Tyr181Cys and wild-type HIV-1 RT and of the 8-Cl TIBO inhibitors are very similar. Some positional changes in the polypeptide backbone of the beta6-beta10-beta9 sheet containing residue 181 are observed when the Tyr181Cys and wild-type complexes are compared, particularlty near residue Val179 of beta9. In the p51 subunit, the Cys181 side-chain is oriented in a similar direction to the Tyr181 side-chain in the wild-type complex. However, the electron density corresponding to the sulfur of the Cys181 side-chain in the p66 subunit is very weak, indicating that the thiol group is disordered, presumably because there is no significant interaction with either 8-Cl TIBO or nearby amino acid residues. In the mutant complex, there are slight rearrangements of the side-chains of other amino acid residues in the NNIBP and of the flexible dimethylallyl group of 8-Cl TIBO; these conformational changes could potentially compensate for the interactions that were lost when the relatively large tyrosine at position 181 was replaced by a less bulky cysteine residue. In the corresponding wild-type complex, Tyr181 iin the p66 subunit has significant interactions with the bound inhibitor and the position of the Tyr181 side-chain is well defined in both subunits. Apparently the Tyr181 --> Cys mutation eliminates favorable contacts of the aromatic ring of the tyrosine and the bou

Antiviral Agents↗
PubMed1996

Structure of unliganded HIV-1 reverse transcriptase at 2.7 A resolution: implications of conformational changes for polymerization and inhibition mechanisms.

BACKGROUND: HIV-1 reverse transcriptase (RT) is a major target for anti-HIV drugs. A considerable amount of information about the structure of RT is available, both unliganded and in complex with template-primer or non-nucleoside RT inhibitors (NNRTIs). But significant conformational differences in the p66 polymerase domain among the unliganded structures have complicated the interpretation of these data, leading to different proposals for the mechanisms of polymerization and inhibition. RESULTS: We report the structure of an unliganded RT at 2.7 A resolution, crystallized in space group C2 with a crystal packing similar to that of the RT-NNRTI complexes. The p66 thumb subdomain is folded into the DNA-binding cleft. Comparison of the unliganded RT structures with the DNA-bound RT and the NNRTI-bound RT structures reveals that the p66 thumb subdomain can exhibit two different upright conformations. In the DNA-bound RT, the p66 thumb subdomain adopts an upright position that can be described as resulting from a rigid-body rotation of the p66 thumb along the "thumb's knuckle' located near residues Trp239 (in strand beta 14) and Val317 (in beta 15) compared with the thumb position in the unliganded RT structure. NNRTI binding induces an additional hinge movement of the p66 thumb near the thumb's knuckle, causing the p66 thumb to adopt a configuration that is even more extended than in the DNA-bound RT structure. CONCLUSIONS: The p66 thumb subdomain is extremely flexible. NNRTI binding induces both short-range and long-range structural distortions in several domains of RT, which are expected to alter the position and conformation of the template-primer. These changes may account for the inhibition of polymerization and the alteration of the cleavage specificity of RNase H by NNRTI binding.

Anti-HIV Agents↗