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Biomedical subjects

R Nair

Publications and source records attributed to R Nair.

At least 19 recordsLinked to original sources
PubMed2006

Imaging growth dynamics of tumour spheroids using optical coherence tomography.

Optical coherence tomography (OCT) was used to monitor the dynamics of tumour spheroid formation by the hanging drop method. In contrast to microscopy, the estimates obtained using OCT for the volume of the spheroid, were consistent with the measured changes in cell number as a function of time. The OCT images also revealed heterogeneous structures in the spheroids of approximately 200 microm diameter. These corresponded to the necrotic regions identified by fluorescence of propidium iodide stained cells.

Cell Count↗
PubMed2006

Is IgA nephropathy the commonest primary glomerulopathy among young adults in the USA?

Over the past decade, focal segmental glomerulosclerosis (FSGS) has emerged as the most common primary glomerulopathy in adults in the USA. However in our practice, we became aware of increased numbers of patients with IgA nephropathy (IgAN). In order to further examine this, a retrospective analysis of renal biopsy diagnoses from adults was done from our biopsy database. Adult renal biopsies received from 3/1/2001 to 2/28/2005 were analyzed to determine the frequency of common primary glomerulopathies, which included FSGS, IgAN, membranous nephropathy (MN), minimal change disease, and membranoproliferative glomerulonephritis Type I (MPGN). The patients were grouped as all adults (>or=20 years) and young adults (20-39 years). The distribution of common primary glomerulopathies among the two age groups, expressed as a percentage of all non-transplant diagnoses (n = 4,504), was IgAN 6.9/3.4%, FSGS 9.6/3.2%, MN 6.8/1.6%, minimal change disease 2.5/0.9%, MPGN 1.2/0.2%. IgAN was as common as FSGS in young adults in our biopsy population (IgAN/FSGS 154/143 1.08:1). IgAN was the most common primary glomerulopathy in young adult Caucasians (IgAN/FSGS 2.1:1). IgAN was also the most common cause of end-stage renal disease (ESRD) in young adult Caucasians. In contrast, IgAN was rare in African Americans in whom FSGS remains more common (FSGS/IgAN 9.7:1). These findings from a large renal biopsy referral center serving 24 Midwestern and Southern states suggest that IgAN may be the most common primary glomerulopathy and the most common cause of ESRD in young adult Caucasians in the USA.

Adult↗
PubMed2006

Focal segmental glomerulosclerosis: cellular variant and beyond.

The entity of focal segmental glomerulosclerosis (FSGS), oddly, includes several distinct changes involving glomeruli that need not be focal, segmental, or even sclerotic. It is fitting to rethink our nosological approach to FSGS, which has focused on descriptive morphological entities. Rather, we should consider them as 'podocytopathies' - diseases with an etiological commonality involving injury to the podocyte.

Glomerulosclerosis, Focal Segmental↗
PubMed2006

Rituximab (anti-CD20 monoclonal antibody) in lymphoproliferative malignancies: Tata Memorial experience.

Rituximab has been used extensively in lymphoproliferative disorders. We evaluated the results of 64 consecutive patients treated between 2001 and 2004 at our institution. This included 54 males and 10 females. The median age was 54 years (range 17 to 85 years). One-fourth of patients were above 60 years. The histology was aggressive NHL in 35, indolent NHL in 22 and 7 cases were diagnosed as CLL. Among NHL, sixteen were in early stage (I/II) and the remaining forty-one were in advanced stage (III/IV) of disease. B symptoms were present in 47% of cases. A total of 33 were de novo cases and 31 were previously treated. Rituximab monotherapy was used in 17 cases. Rituximab was used in combination with chemotherapy in the other 47 cases. Infusional toxicity included anaphylaxis in one, hypotension in one and minor infusional reactions in four others. The patient who developed anaphylaxis required discontinuation of further Rituximab. Growth factors were used in 25 patients. Febrile neutropenia occurred in 19 patients. The overall RR (CR + PR) was 72%. One patient had stable disease and progressive disease was documented in 17 patients. A total of seven patients died, three due to progressive disease, three due to chemotherapy related toxicity and one due to an unrelated cause. We conclude that Rituximab is a valuable addition to the treatment armamentarium of lymphoproliferative disorders.

Adolescent↗
PubMed2005

Perforated gastric ulcer--reappraisal of surgical options.

BACKGROUND: The available operative procedures for perforated gastric ulcer are gastrectomy, ulcer excision and omental patch closure. This study analysed the outcome of these operative options in a single institution. PATIENTS AND METHODS: Seventy-two patients (mean age 43 years, 62 males) with perforated gastric ulcers were managed by laparotomy. There were 34 lesser curve (incisural) and 38 antral ulcers. RESULTS: Partial gastrectomy was performed in 27 patients, ulcer excision in 27 and simple patch closure in 18. Two ulcers were malignant. The mortality rate was 18% (26% for gastrectomy, 19% for ulcer excision and 5% for patch closure). Shock on admission (p = 0.006) and Candida (p = 0.020) in the histological specimen were predictive of poor outcome. Hospital stay was similar in the 3 groups. CONCLUSION: Omental patch closure and ulcer excision are as effective as gastrectomy in the management of perforated gastric ulcer and merit consideration as first-line therapy in technically applicable cases.

Adult↗
PubMed2004

Increasing the accuracy of operative coding.

INTRODUCTION: Operative codes provide a readily retrievable record of operative procedures and interventions and are invaluable in performance of clinical audit and research. In most hospitals, coding is performed by coding clerks who depend on legible complete operative notes for coding. In others, coding is by the operator/surgeon. The aim of this audit was to determine the impact of hand-written and typed operative notes on accuracy of coding as well as deciding if the operator is the better coder. METHODS: A total of 200 operations/procedures performed by one surgical firm were randomised, prospectively, into hand-written (HN, 100) and template-based typed (TN, 100) operation notes. Each procedure was coded by the operator/surgeon as well as by the coding clerk. The results were compared for error, incomplete and complete codes. RESULTS: Coding clerks were found to be better coders with 97% of TN and 85% of HN coded completely compared to 48% and 62%, respectively, by operators. There were more incomplete codes for HN compared to TN (15% versus 6% for coders and 62% versus 53% for operators). There were no error codes for both groups. CONCLUSIONS: These results suggest that the quality of coded information is poorer if operation notes are hand-written rather than typed, with template-based mandatory fields in typed notes possibly acting as an aide-memoir in generating complete, accurate notes. In the absence of formal training for clinicians, coding of procedures should probably be left to coding clerks.

Forms and Records Control↗
PubMed2004

Primary non-Hodgkin's lymphoma of the bone: a single institution experience.

UNLABELLED: Primary non-Hodgkin's lymphoma of the bone is an unusual entity. Twenty-five patients with diffuse large cell lymphoma of the bone were registered at the Tata Memorial Hospital (TMH) from August, 1991, to May, 2002. Pain at the local site and soft tissue swelling were the commonest symptoms. Involvement of the bones in the lower half of the body was more frequent than the bones in the upper half. Osteolytic lesions and an associated soft tissue mass were the common radiological findings. Nineteen patients received CHOP chemotherapy and five received COP chemotherapy. Twenty-three patients received involved field radiotherapy. The overall response to therapy was 96%. On follow-up, two patients had a nodal relapse. One patient died of progressive disease, and one patient died of cryptococcal meningitis. There were no deaths due to treatment-related toxicity. The mean progression free survival was 9.39 yr and the overall survival was 11.66 yr. The median overall survival has not been reached. At last follow-up, 21 patients were being following up at TMH and are free of disease. CONCLUSION: Primary bone lymphoma is a malignancy that is highly curable with a combination of chemotherapy and radiotherapy.

Adolescent↗
PubMed2003

Automatic prediction of protein function.

Most methods annotating protein function utilise sequence homology to proteins of experimentally known function. Such a homology-based annotation transfer is problematic and limited in scope. Therefore, computational biologists have begun to develop ab initio methods that predict aspects of function, including subcellular localization, post-translational modifications, functional type and protein-protein interactions. For the first two cases, the most accurate approaches rely on identifying short signalling motifs, while the most general methods utilise tools of artificial intelligence. An outstanding new method predicts classes of cellular function directly from sequence. Similarly, promising methods have been developed predicting protein-protein interaction partners at acceptable levels of accuracy for some pairs in entire proteomes. No matter how difficult the task, successes over the last few years have clearly paved the way for ab initio prediction of protein function.

Computational Biology↗
PubMed2003

A retrospective hospital-based study on congenital hypothyroidism in the Sultanate of Oman.

A retrospective study was conducted on 45 children with congenital hypothyroidism (CH) to estimate the number of missed cases of CH among Omani children per year and compare the intellectual outcome of children diagnosed by neonatal screening (Group A) with those who were diagnosed clinically at a later age (Group B). Our results revealed 14 children in Group A, diagnosed at a mean age of 2.3 +/- 0.8 months and 31 children in Group B diagnosed at a mean age of 9.8 +/- 2.5 months. IQ assessment revealed that 67 per cent of the children in Group A had a normal IQ compared to only 15 per cent of those in Group B. The above results point to a great demand for a national screening programme in the Sultanate of Oman.

Congenital Hypothyroidism↗
PubMed2003

Spontaneous improvement of severe neonatal hyperparathyroidism after failed total parathyroidectomy.

We report an interesting case of severe neonatal hyperparathyroidism (SNHP) treated by sub-total parathyroidectomy, as her fourth parathyroid gland could not be identified. The clinical course changed over time to a more benign course resembling familial hypocalciuric hypercalcemia. This indicates that the natural course of SNHP is probably gradual spontaneous improvement, if patient survives the first few months of life.

Female↗
PubMed2002

Influence of polyethylene glycol and povidone on the polymorphic transformation and solubility of carbamazepine.

PURPOSE: Influence of polymers on the polymorphic transition of drugs has received limited attention in the literature. The main objective of this study was to gain an understanding of the influence of polyethylene glycol and povidone on the crystalline modification and subsequently the solubility of carbamazepine in solid dispersions. METHODS: The physical state of the drug within the dispersions was determined using DSC and powder X-ray diffractometer. DSC and optical microscopy was used to study the kinetics and morphology of dihydrate formation, respectively. RESULTS: Both the polymeric dispersions showed an improved dissolution profile for carbamazepine. Carbamazepine was present in an amorphous form within the povidone dispersions. In contrast, the PEG dispersions showed the presence of crystalline drug. Higher ratios of drug/PEG resulted in the metastable form I of carbamazepine. Dihydrate formation from both the polymeric dispersions was higher compared with pure carbamazepine. The physical state of the drug and the amount of drug in solution accounted for the higher dihydrate formation from these dispersions. CONCLUSIONS: Knowledge of the factors contributing to enhanced solubility is critical to the stability of solid dispersions. Additionally, influence of polymers like povidone on the crystalline transitions of polymorphic drugs may be crucial during its use as a binder in granulation.

Calorimetry, Differential Scanning↗
PubMed2001

Influence of various drugs on the glass transition temperature of poly(vinylpyrrolidone): a thermodynamic and spectroscopic investigation.

PURPOSE: To determine the influence of hydrogen bonding and solubility parameter on the glass transition temperature (T(g)) of various drug-poly(vinylpyrrolidone) blends. METHODS: The T(g) of PVP films containing either acetaminophen, naproxen, salicylamide, carbamazepine, griseofulvin or propranolol hydrochloride were measured using differential scanning calorimetry. Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction was used to characterize the specific interactions between the drug-PVP blends and the physical state of the films, respectively. The total solubility parameter and its individual components were calculated using the method of Van Krevelen. RESULTS: Salicylamide displayed the greatest plasticizing effect, depressing the T(g) to the minimum. This was consistent with the FTIR data, which indicated the presence of hydrogen bonding with PVP. Griseofulvin showed the least plasticizing effect due to lack of interaction with PVP. All the drugs except griseofulvin were amorphous within the film up to 30% (w/w) drug composition. The correlation between the various components of the solubility parameters and the plasticizing effect of drugs was very poor. CONCLUSIONS: Spectroscopic investigation for the presence of interaction between the drugs and PVP proved to be extremely predictive of the plasticizing effect of various drugs. In contrast, solubility parameters appeared to be far less sensitive indicators of drug-PVP miscibility.

Chemistry, Pharmaceutical↗
PubMed2001

Transformation nonresponsive cells owe their resistance to lack of p65/nuclear factor-kappaB activation.

Clonal variants of mouse epidermal JB6 cells that are genetically susceptible (P+) or resistant (P-) to tumor promoter-induced neoplastic transformation exhibit differential activator protein-1 (AP-1) response. Transactivation of AP-1 appears to be necessary but not sufficient to promote transformation in JB6 cells. Inhibition of AP-1 is invariably accompanied by inhibition of nuclear factor-kappaB (NF-kappaB) when transformation is suppressed, suggesting that NF-kappaB may also play a role in neoplastic transformation. We report here that transactivation of NF-kappaB is inducible by tumor promoters in P+ but not in P- JB6 cells. Inhibition of NF-kappaB using a nondegradable mutant of IkappaBalpha suppressed inducible anchorage-independent transformation of P+ JB6 cells, suggesting that NF-kappaB activation is required for tumor promotion. Induced degradation of IkappaBalpha occurred in both P+ and P- JB6 cells, indicating that failure to activate NF-kappaB in P- JB6 cells cannot be attributed to failure to degrade IkappaBalpha. Slightly higher levels of nuclear p65 were seen in P+ than in P- JB6 cells. The p65-specific DNA binding activity was also higher in P+ cells upon induction by tumor necrosis factor-alpha, suggesting that differential NF-kappaB activation may be attributable to changes in p65 activity. Transactivation of p65 protein was substantially higher in P+ than in P- JB6 cells, as determined by assay of Gal4-p65 fusion constructs. Thus activated, p65 may be a limiting factor for NF-kappaB activation and transformation responses. Stable expression of p65 in P- JB6 cells conferred not only inducible NF-kappaB and AP-1 activation but also transformation response to tumor promoters. Therefore, p65/NF-kappaB appears to be not only necessary for but also sufficient to confer tumor promotion response. Although stable expression of p65 in P- cells produced p65 increases in whole cell extracts, only the transfectants exhibiting increased nuclear p65 showed transformation response. Thus, elevation of nuclear p65 appears to be a necessary step for a transformation response. The P-/p65 transfectants showing acquired transformation response also showed elevated p65-specific transactivation response, thus recapitulating the NF-kappaB phenotypes seen in P+ cells. Expression of a transactivation-deficient mutant of Jun or dominant-negative extracellular signal-regulated kinase suppressed both AP-1 activation and p65-specific transactivation in JB6 cells, suggesting that AP-1 activity is needed for p65 transactivation and consequently for NF-kappaB activation. Thus, the transformation nonresponsive P- JB6 cells owe their resistance to lack of NF-kappaB activation and p65 transactivation that appears in turn to be attributable to insufficient AP-1 activation.

Animals↗
PubMed2001

Effect of butyl benzyl phthalate on reproduction and zinc metabolism.

Butyl benzyl phthalate (BBP) has been shown to be teratogenic. One mechanism contributing to the teratogenicity of several developmental toxicants, is chemical-induced changes in maternal zinc (Zn) metabolism which result in an increased synthesis of maternal liver metallothionein (Mt), and a subsequent reduction in Zn delivery to the conceptus. We investigated the effects of maternal BBP exposure on maternal-fetal Zn metabolism in Wistar rats. In study I, dams were gavaged with BBP (0,250,1000,1500 or 2000 mg/kg) on gestation days (GD) 11 through 13, and killed on GD 20. Maternal toxicity was evident in the three highest dose groups. Embryo/fetal death and small pup weights and lengths were noted in the 2000 mg BBP/kg group. Fetuses in the 1500 and 2000 mg/kg groups were characterized by poor skeletal ossification, and a high frequency of cleft palate. Rib anomalies were observed in the three highest dose groups. Maternal liver Mt concentrations were only slightly elevated in the 1500 and 2000 mg/kg groups. In study II, dams treated as above, were gavaged with 65Zn and killed 18 h later. While the 2000 mg/kg group had high percentages of 65Zn in some maternal tissues, sequestration of 65Zn in maternal liver was not evident. Thus, BBP is not a strong inducer of Mt, and the teratogenicity of BBP does not appear to be due to alterations in maternal and/or embryonic Zn metabolism.

Abnormalities, Drug-Induced↗
PubMed2001

A novel transformation suppressor, Pdcd4, inhibits AP-1 transactivation but not NF-kappaB or ODC transactivation.

Pdcd4 is a novel transformation suppressor that is highly expressed in promotion-resistant (P-) mouse epidermal JB6 cells but not in susceptible (P+) cells. Overexpression of pdcd4 cDNA in stably transfected P+ cells rendered cells resistant to tumor promoter-induced transformation, indicating that elevated expression of Pdcd4 protein is sufficient to suppress neoplastic transformation. To determine whether Pdcd4 suppresses neoplastic transformation through inhibiting known transformation required events, we examined the possibility that pdcd4 inhibited the activation of AP-1 or NF-kappaB dependent transcription or of ornithine decarboxylase (ODC) activity. Activation of AP-1-dependent transcriptional activity was inhibited by pdcd4 expression in a concentration dependent manner. In contrast, Pdcd4 slightly increased NF-kappaB-dependent transcription and did not alter ODC enzymatic activity. Previous studies suggested that activation of AP-1 was required for P+ cell transformation as well as for tumor promotion in vivo. These results indicate that Pdcd4 functions as a transformation suppressor, possibly through inhibiting AP-1 activation in combination with other factors such as enhancing NF-kappaB activation. Pdcd4 may thus constitute a useful molecular target for cancer prevention.

Animals↗
PubMed2001

Fluorescence in situ hybridization: a highly efficient technique of molecular diagnosis and predication for disease course in patients with myeloid leukemias.

The accuracy of cytogenetic diagnosis in the management of hematological malignancies has improved significantly over the past 10 years. Fluorescence in situ hybridization (FISH), a technique of molecular cytogenetics, has played a pivotal role in the detection of unique sub-microscopic chromosomal rearrangements that helped in the identification of chromosomal loci, which contain genes involved in leukemogenesis. We studied the feasibility and sensitivity of the FISH technique for molecular analysis of translocations markers, t(9;22) and t(15;17) for accurate molecular diagnosis and for monitoring the disease in 21 patients with chronic myeloid leukemia (CML) who received interferon-alpha and/or chemotherapy (7 patients), bone marrow transplantation (14 patients), and 14 patients with acute promyelocytic leukemia (APL) who received all-trans-retinoic acid (ATRA) and/or chemotherapy. We also applied conventional karyotyping (CK) for identification of t(9;22) and t(15;17) at diagnosis. All CML cases had a Ph; t(9;22) and except for two cases all APL had t(15;17). The FISH studies on CML marrows in complete cytogenetic remission (CCR) (100% Ph- by CK) achieved by IFN-alpha, showed 0-2.5% of cells with BCR-ABL fusion in first cytogenetic remission (Controls, range 0.5-1.5%). Repeat follow-up FISH studies could be done in two cases in remission, which demonstrated 0-10% of cells with BCR-ABL fusion. Evaluation of Ph positive status of CML marrow at diagnosis by CK (100% Ph+ cells) and FISH (80-92% BCR-ABL fusion) pointed the existence of dormant clone of normal residual hematopoietic cells along with actively proliferating clones of Ph positive cells. Fluorescence in situ hybridization analysis of post-BMT CML marrows in CCR (0% Ph+ mitoses) could detect MRD with range of 1-6%. Among 14 patients, 9 who showed percentage of BCR-ABL positive cells (0.0-1.5%) almost similar to normal controls, 6 patients had comparatively good prognosis (disease-free survival 7-14 months). Of five patients with residual leukemic cells in the range of 2-6%, 4 relapsed within a period of 3-24 months. Fourteen APL patients in CCR [100% t(15;17) negative cells by CK] were evaluated by FISH to check the presence of residual leukemic cells. In these patients FISH could efficiently detect 1-14.5% of residual cells with PML-RARA (patients mean MRD 5%, controls mean MRD 3.5%, P=.02). Since the time of FISH analysis, 5 to 7 patients with higher fraction of leukemic cells (5-11%) relapsed within a short period (1-7 months). On the contrary, 5 of 7 patients with either absence or low percentage of PML-RARA positive cells remained in complete remission for 11-24 months. Our data show that FISH has a potential to detect and measure the fraction of aberrant malignant cells in remission marrows, induced by BMT in CML and chemotherapy in APL. These findings encourage the investigations on a large scale to merit its potential for identification of patients at high risk. In the present studies, FISH on interphase cells also demonstrated its efficiency in the molecular diagnosis by its ability to detect BCR-ABL and PML-RARA fusion in CML with masked/variant Ph and t(15;17) negative APL, respectively. The efficiency of technique in molecular diagnosis was also proved in one of the CML patients who progressed to myeloid blastic phase where interphase FISH could identify an extra BCR-ABL fusion on both chromosomes 9 indicating insertion of BCR into ABL and its duplication.

Adolescent↗
PubMed2001

Genetic analysis of the chromosome segregation protein Spo0J of Bacillus subtilis: evidence for separate domains involved in DNA binding and interactions with Soj protein.

Spo0J and Soj belong to the ParB/ParA family of proteins involved in chromosome and plasmid segregation in bacteria. In Bacillus subtilis, Spo0J protein binds to several specific sites, parS, located on both sides of the origin of DNA replication, oriC, and apparently self-associates to form large discrete foci visible by fluorescence microscopy. Soj protein forms large 'patches' probably associated with the nucleoid, which can undergo dynamic, co-operative jumping from nucleoid to nucleoid in the presence of Spo0J. Patches of Soj protein somehow help to bring about the condensation of Spo0J foci. Soj is also a negative regulator of transcription. In the absence of Spo0J, Soj is statically distributed on each of the nucleoids in the cell and blocks the transcription of several sporulation genes. To analyse the functional interaction between Spo0J and Soj further, we have constructed and studied a collection of spo0J mutants. Most of the mutants completely prevent Spo0J from interacting with DNA. One mutation impairs the formation of compact Spo0J foci and simultaneously results in loss of Soj movement. We also isolated one spo0J mutant, in which the frequency of Soj internucleoid oscillation is highly increased. Both mutations affecting the interaction with Soj lie in the N-terminal coding part of spo0J, whereas the substitutions affecting DNA binding lie in the mid- to C-terminal coding region.

Alleles↗