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Biomedical subjects

M Prasad

Publications and source records attributed to M Prasad.

At least 19 recordsLinked to original sources

Chromosome 6p amplification and cancer progression.

Chromosomal imbalances represent an important mechanism in cancer progression. A clear association between DNA copy-number aberrations and prognosis has been found in a variety of tumours. Comparative genomic hybridisation studies have detected copy-number increases affecting chromosome 6p in several types of cancer. A systematic analysis of large tumour cohorts is required to identify genomic imbalances of 6p that correlate with a distinct clinical feature of disease progression. Recent findings suggest that a central part of the short arm of chromosome 6p harbours one or more oncogenes directly involved in tumour progression. Gains at 6p have been associated with advanced or metastatic disease, poor prognosis, venous invasion in bladder, colorectal, ovarian and hepatocellular carcinomas. Copy number gains of 6p DNA have been described in a series of patients who presented initially with follicle centre lymphoma, which subsequently transformed to diffuse large B cell lymphoma. Melanoma cytogenetics has consistently identified aberrations of chromosome 6, and a correlation with lower overall survival has been described. Most of the changes observed in tumours to date map to the 6p21-p23 region, which encompasses approximately half of the genes on all of chromosome 6 and one third of the number of CpG islands in this chromosome. Analyses of the genes that cluster to the commonly amplified regions of chromosome 6p have helped to identify a small number of molecular pathways that become deregulated during tumour progression in diverse tumour types. Such pathways offer promise for new treatments in the future.

Chromosome Aberrations↗

Genetic mapping and BAC assignment of EST-derived SSR markers shows non-uniform distribution of genes in the barley genome.

A set of 111,090 barley expressed sequence tags (ESTs) was searched for the presence of microsatellite motifs [simple sequence repeat (SSRs)] and yielded 2,823 non-redundant SSR-containing ESTs (SSR-ESTs). From this, a set of 754 primer pairs was designed of which 525 primer pairs yielded an amplicon and as a result, 185 EST-derived microsatellite loci (EST-SSRs) were placed onto a genetic map of barley. The markers show a uniform distribution along all seven linkage groups ranging from 21 (7H) to 35 (3H) markers. Polymorphism information content values ranged from of 0.24 to 0.78 (average 0.48). To further investigate the physical distribution of the EST-SSRs in the barley genome, a bacterial artificial chromosomes (BAC) library was screened. Out of 129 markers tested, BAC addresses were obtained for 127 EST-SSR markers. Twenty-seven BACs, forming eight contigs, were hit by two or three EST-SSRs each. This unexpectedly high incidence of EST-SSRs physically linked at the sub-megabase level provides additional evidence of an uneven distribution of genes and the segmentation of the barley genome in gene-rich and gene-poor regions.

Chromosomes, Artificial, Bacterial↗

Expression genetics and haplotype analysis reveal cis regulation of serine carboxypeptidase I (Cxp1), a candidate gene for malting quality in barley (Hordeum vulgare L.).

Using a cDNA array-based functional genomics approach in barley, several candidate genes for malting quality including serine carboxypeptidase I (Cxp1) were previously identified (Potokina et al. in Mol Breed 14:153, 2004). The gene was mapped as a single nucleotide polymorphism (SNP) marker on chromosome 3H using the Steptoe (feeding grade)xMorex (malting grade) mapping population. Subsequently, the relative level of Cxp1 expression was determined by real-time RT-PCR for each of the 134 progeny lines and mapped as a quantitative trait. Only one quantitative trait locus (QTL) could be identified that significantly influenced the level of the Cxp1 expression. The expressed QTL maps to the same region on chromosome 3H as does the structural gene and corresponds to a QTL for "diastatic power," one among several traits measured to assess malting quality. An analysis of 90 barley cultivars sampled from a worldwide collection revealed six SNPs at the Cxp1 locus, three of which display complete linkage disequilibrium and define two haplotypes. The Cxp1 expression level in a set of barley accessions showing haplotype I was significantly higher than that of accessions displaying haplotype II. The data provide evidence that (1) the expression of Cxp1 is regulated in cis and that (2) the level of diastatic power in the barley seed is influenced by the level of Cxp1 expression.

Cathepsin A↗

Self-aggregation of binary mixtures of alkyltriphenylphosphonium bromides: a critical assessment in favor of more than one kind of micelle formation.

The micellization behavior of binary combinations of alkyltriphenylphosphonium bromides (ATPBs) with alkyl chain carbons 10, 12, 14, and 16 has been studied by conductometry and calorimetry. The combinations C(10)-C(12), C(10)-C(14), C(10)-C(16), C(12)-C(14), C(12)-C(16), and C(14)-C(16) were found to form two cmc's by both the methods, with good agreement, except C(14)-C(16)TPB, which has evidenced only a single cmc by calorimetry for all combinations. The combinations C(10)-C(12) (for both cmc(1) and cmc(2)) and C(10)-C(14)TPB (for cmc(2)) formed ideal mixtures, whereas the rest were nonideal. In the nonideal binary mixtures, the ATPB components showed antagonistic interaction with each other. The cmc, interaction parameter (beta), mixed micellar composition, extent of counterion binding, and thermodynamic parameters for the micellization process have been reported and discussed. The enthalpy of mixed micelle formation has been found to have a fair correlation with a Clint-type relation applicable to ideal binary mixtures of surfactants.

Journal Article↗

Proximal migration of a lumboperitoneal unishunt system.

Proximal migration of a lumboperitoneal (LP) shunt is a rare complication associated with unishunt systems. We report three cases with a hypothesis that raised intra-abdominal pressure may be a factor responsible for the proximal migration of a LP unishunt. A rare case of proximal migration of LP shunt into the quadrigeminal cistern is also reported.

Adult↗

Povidone iodine and dextrose solution combination sclerotherapy in chyluria.

OBJECTIVES: To evaluate the effectiveness of combination (povidone iodine and 50% dextrose) renal pelvic instillation sclerotherapy (RPIS) as a minimally invasive therapy for chyluria resistant to conservative treatment. METHODS: A total of 50 patients with chyluria and hematochyluria (28 men and 22 women) were included in the study. Initially, all were offered conservative antifilarial drug therapy and dietary fat restriction. Intravenous urography was done in all cases to document normal renal functional status. In the patients in whom chyluria persisted after 3 weeks of conservative therapy, cystoscopic lateralization was done and a 5F open-ended ureteral catheter was positioned under local anesthesia. The same was left attached to a 16F Foley catheter for 3 days of RPIS. A solution of 5 mL of 5% povidone iodine and 5 mL of 50% dextrose was instilled twice a day with the patient in the Trendelenburg position for 3 days. In cases of bilateral efflux, the dominant side was treated first. The opposite side was subjected to a similar instillation sclerotherapy schedule after 6 weeks if chyluria persisted. RESULTS: Of the 50 patients, only 4 responded to conservative therapy. The remaining 46 patients underwent combination RPIS. The mean follow-up was 24 months. Complete remission of chyluria or hematochyluria occurred in 40 (87%) and persisted in 6 patients (13%). Of the 6 patients in whom symptoms persisted, 2 developed chyluria on the side opposite the one treated with RPIS. Another 2 patients developed recurrence on the same side after remaining asymptomatic for 6 months after RPIS. All four of these patients subsequently underwent chylolymphatic disconnection and nephropexy (two open and two laparoscopic) with a successful outcome. The final 2 patients with persistent symptoms were lost to follow-up. CONCLUSIONS: Combination sclerotherapy using a 5% povidone iodine and 50% dextrose solution is a safe and cost-effective minimally invasive therapy for chyluria refractory to conservative treatment.

Adult↗

The efficacies of affected-limb care with penicillin diethylcarbamazine, the combination of both drugs or antibiotic ointment, in the prevention of acute adenolymphangitis during bancroftian filariasis.

Repeated attacks of adenolymphangitis (ADL) contribute significantly to the progression of chronic lymphoedema in lymphatic filariasis. They are a cause of stigma and, since they may prevent work and require treatment for which payment must be made, of economic loss. The aim of the present study was to improve the treatment of ADL attacks, which is currently mostly empirical. In a double-blind, placebo-controlled, clinical study, 150 subjects who had each suffered at least two ADL attacks in the preceding year were enrolled and randomly allocated to a programme of self-care of the affected limb (after an intensive training programme) and one of five treatments for 12 months. The subjects were supplied with tablets and ointment so that they could take oral penicillin (800 mg/day), oral diethylcarbamazine (DEC; 1 mg/kg.day) or both of these drugs (at the same doses), or apply framycetin ointment to the affected limb, or just take placebo tablets and apply placebo (zinc-oxide) ointment. Placebo tablets and placebo ointment were used so that neither the subjects nor those assessing the responses to treatment were aware of the treatment arm to which each subject had been assigned. The subjects were requested to continue with the affected-limb care after they had stopped taking the tablets and applying the cream, and were followed-up for 24 months from the first treatment.Overall, the mean incidence of ADL attacks decreased from 2.7 episodes/person-year in the pre-treatment year to just 0.38 episode/person-year during the treatment year (P< 0.01). The greatest reduction in incidence was seen in the 58 subjects who received penicillin (with or without DEC). Even in the placebo group, however, the incidence of ADL in the treatment year was significantly lower than that seen in the pre-treatment year, indicating that affected-limb care on its own helps to prevent some attacks. In all groups except the placebo, the incidence of ADL attacks in the year post-treatment exceeded that seen in the treatment year, indicating that chemoprophylaxis needs to be continued for more than a year if such attacks are to be prevented. In most (84%) of the attacks recorded, titres of anti-streptococcal antibodies were seen to be elevated (compared with those recorded during convalescence),indicating that streptococci have a role in the aetiology of ADL. It is recommended that a combination of penicillin prophylaxis and affected-limb care be incorporated into filariasis-control programmes, to decrease morbidity.

Acute Disease↗

QTL analysis for grain protein content using SSR markers and validation studies using NILs in bread wheat.

QTL interval mapping for grain protein content (GPC) in bread wheat was conducted for the first time, using a framework map based on a mapping population, which was available in the form of 100 recombinant inbred lines (RILs). The data on GPC for QTL mapping was recorded by growing the RILs in five different environments representing three wheat growing locations from Northern India; one of these locations was repeated for 3 years. Distribution of GPC values followed normal distributions in all the environments, which could be explained by significant g x e interactions observed through analyses of variances, which also gave significant effects due to genotypes and environments. Thirteen (13) QTLs were identified in individual environments following three methods (single-marker analysis or SMA, simple interval mapping or SIM and composite interval mapping or CIM) and using LOD scores that ranged from 2.5 to 6.5. Threshold LOD scores (ranging from 3.05 to 3.57), worked out and used in each case, however, detected only seven of the above 13 QTLs. Only four (QGpc.ccsu-2B.1; QGpc.ccsu-2D.1; QGpc.ccsu-3D.1 and QGpc.ccsu-7A.1) of these QTLs were identified either in more than one location or following one more method other than CIM; another QTL (QGpc.ccsu-3D.2), which was identified using means for all the environments, was also considered to be important. These five QTLs have been recommended for marker-assisted selection (MAS). The QTLs identified as above were also validated using ten NILs derived from three crosses. Five of the ten NILs possessed 38 introgressed segments from 16 chromosomes and carried 42 of the 173 markers that were mapped. All the seven QTLs were associated with one or more of the markers carried by the above introgressed segments, thus validating the corresponding markers. More markers associated with many more QTLs to be identified should become available in the future by effective MAS for GPC improvement.

Analysis of Variance↗

Maternal height and labour outcome.

The aim of this study was to assess if maternal height has an effect on duration of labour, mode of delivery and birth weight. This was a retrospective analysis of casenotes of 1000 white primigravidae in a district general hospital. Spearman's rank correlation coefficient, logistic regression analysis, and Pearson's correlation coefficient was used to determine the relation between height and duration of labour, height and mode of delivery and birth weight, respectively. Odds ratio was used to quantify the association. There was no significant association between height and duration of labour. There was a statistically significant positive correlation between height and birth weight and a negative association between height and incidence of caesarean sections. A cut-off height of 160 cm is proposed as a screening tool to predict a need for caesarean section.

Adult↗

The effect of hysterectomy on urinary symptoms and residual bladder volume.

This was a prospective, clinical study to evaluate the effect of abdominal and vaginal hysterectomy for benign indications on urinary symptoms and residual bladder volume. One hundred and seven women undergoing hysterectomy for benign conditions were included in the study that took place in a district general hospital between April 1998 and January 2000. Urinary symptoms such as stress incontinence of urine, urgency, frequency, nocturia, sensation of incomplete voiding and voiding difficulties were considered. A questionnaire was filled out and the residual bladder volume measured with a 'Bard' bladder scanner on three occasions-before the operation, postoperative days 3 or 4 and at the 6-week postoperative visit. Statistical analysis involved using a generalised estimating equation and significance assessed at the 5% level. Each woman acted as her own control. There was no evidence of changes in nocturia and voiding difficulties after surgery. All other symptoms and residual bladder volumes decreased significantly postoperatively. The type of hysterectomy did not have an effect.

Adult↗

Molecular approaches for the evaluation of immune responses to zona pellucida (ZP) and development of second-generation ZP vaccines.

It has long been established that there are major variations in both the immunogenicity and antigenicity of native zona pellucida (ZP) proteins. These differences appear to be more pronounced with respect to genetically engineered ZP proteins, which do not have native post-translational modifications (for example glycosylation and sulphation). As the number of animal species that are now included in population management programmes using native porcine zona pellucida (PZP) proteins expands, it is increasingly important to carry out studies to evaluate the immune response variations among different species as well as the individual variation within a species. In an attempt to compare these complex immune responses, we have evaluated antibodies from numerous species immunized with native, genetically engineered ZP and synthetic ZP peptides. Such an immunocontraceptive method could have great potential. These studies are critical not only for the development of predictable immune responses that result in permanent sterilization versus reversible contraceptive effects, but also for predicting which vaccinogens (native ZP protein versus genetically engineered ZP proteins) might have detrimental effects on animal and human populations.

Animals↗

Gene expression in papillary thyroid carcinoma reveals highly consistent profiles.

Papillary thyroid carcinoma (PTC) is clinically heterogeneous. Apart from an association with ionizing radiation, the etiology and molecular biology of PTC is poorly understood. We used oligo-based DNA arrays to study the expression profiles of eight matched pairs of normal thyroid and PTC tissues. Additional PTC tumors and other tissues were studied by reverse transcriptase-PCR and immunohistochemistry. The PTCs showed concordant expression of many genes and distinct clustered profiles. Genes with increased expression in PTC included many encoding adhesion and extracellular matrix proteins. Expression was increased in 8/8 tumors for 24 genes and in 7/8 tumors for 22 genes. Among these genes were several previously known to be overexpressed in PTC, such as MET, LGALS3, KRT19, DPP4, MDK, TIMP1, and FN1. The numerous additional genes include CITED1, CHI3L1, ODZ1, N33, SFTPB, and SCEL. Reverse transcriptase-PCR showed high expression of CITED1, CHI3L1, ODZ1, and SCEL in 6/6 additional PTCs. Immunohistochemical analysis detected CITED1 and SFTPB in 49/52 and 39/52 PTCs, respectively, but not in follicular thyroid carcinoma and normal thyroid tissue. Genes underexpressed in PTC included tumor suppressors, thyroid function-related proteins, and fatty acid binding proteins. Expression was decreased in 7/8 tumors for eight genes and decreased in 6/8 tumors for 19 genes. We conclude that, despite its clinical heterogeneity, PTC is characterized by consistent and specific molecular changes. These findings reveal clues to the molecular pathways involved in PTC and may provide biomarkers for clinical use.

Biomarkers, Tumor↗

Expression of P2X2 and P2X3 receptor subunits in rat carotid body afferent neurones: role in chemosensory signalling.

1. Hypoxic chemotransmission in the rat carotid body (CB) is mediated in part by ATP acting on suramin-sensitive P2X purinoceptors. Here, we use RT-PCR, cloning and sequencing techniques to show P2X2 and P2X3 receptor expression in petrosal neurones, some of which develop functional chemosensory units with CB receptor clusters in co-culture. 2. Single-cell RT-PCR revealed that hypoxia-responsive neurones, identified electrophysiologically in co-culture, expressed both P2X2 and P2X3 mRNA. 3. Isohydric hypercapnia (10 % CO(2); pH 7.4) caused excitation of chemosensory units in co-culture. This excitation depended on chemical transmission, with ATP acting as a co-transmitter, since it was inhibited by reduction of the extracellular Ca(2+):Mg(2+) ratio and by the purinoceptor blocker suramin (50-100 microM). 4. Hypoxia and isohydric hypercapnia could separately excite the same chemosensory unit, and together the two stimuli interacted synergistically. 5. Using confocal immunofluorescence, co-localization of P2X2 and P2X3 protein was demonstrated in many petrosal somas and CB afferent terminals in situ. Taken together, these data indicate that ATP and P2X2-P2X3 purinoceptors play important roles in the peripheral control of respiration by carotid body chemoreceptors.

Adenosine Triphosphate↗

The role of laparoscopy in second-look evaluations for ovarian cancer.

BACKGROUND: The aim of this study was to evaluate the accuracy and safety of laparoscopic second-look operations in patients with ovarian cancer. METHODS: We retrospectively reviewed the medical records of all patients who have undergone laparoscopic second-look procedures for ovarian cancer at our institution. RESULTS: From July 1993 to December 1998, 150 patients underwent laparoscopic second-look operations. The mean age of patients was 53 years (range, 25-78 years). The majority of patients (87%) had Stage III or IV disease at initial surgery; the remainder were Stage II or unstaged. Eighty-two patients (54%) had had optimal cytoreduction at the time of their initial surgery. All patients had completed primary chemotherapy and were clinically disease-free based on imaging studies and CA-125 levels at the time of second look. Sixty-nine patients (46%) were found to have pathologically negative second looks; thus, the rate of positive second-look evaluations was 54%. The rate of conversion to laparotomy was 18/150 (12%). In 3 cases this was secondary to bowel injury; one patient sustained a bladder injury; the remainder of conversions to laparotomy were for secondary cytoreduction. There was only 1 case where the patient was found to have extensive adhesions and laparoscopy was abandoned. The overall rate of major complications was 2.7%. CONCLUSIONS: In our experience, laparoscopy is a safe and accurate method of second-look assessment in patients with ovarian cancer. The incidence of complications is low, particularly in this group of patients, all of whom have undergone prior abdominal surgery. The rate of negative evaluations and the rate of recurrences in patients with negative second looks are equivalent to those described in studies of second-look assessment by laparotomy.

Adult↗

Predictors of positive axillary lymph nodes after sentinel lymph node biopsy in breast cancer.

OBJECTIVE: The purpose of this study was to determine the factors that predict the presence of metastasis in nonsentinel lymph nodes (SLN) when the SLN is positive. METHODS: A prospective database was analyzed and included patients who underwent SLN biopsy for invasive breast cancer from July 1997 to August 2000 (n = 442). One hundred (22.6%) patients had one or more positive SLNs, and were analyzed to determine factors that predicted additional positive axillary nodes. RESULTS: Of the 100 patients with a positive SLN, 40 patients (40%) had additional metastasis in non-SLNs. The only significant variables that predicted non-SLN metastasis were tumor lymphovascular invasion (P = 0.004), extranodal extension (P < 0.001), and increasing size of the metastasis within the SLN (P = 0.011). In analyzing just those patients who had lymphovascular invasion, extranodal extension, and a SLN metastasis > 2mm, 92% were found to have additional positive nodes. CONCLUSIONS: In patients with invasive breast cancer and a positive sentinel lymph node, lymphovascular invasion, extranodal extension, and increasing size of the metastasis all significantly increase the frequency of additional positive nodes.

Adult↗

Detoxification of aqueous zinc using fluorapatite--bearing lean grade rock phosphate.

Detoxification of aqueous zinc was studied using the adsorption technique by application of fluorapatite bearing low grade phosphate as a sorbent. The effects of particle size of adsorbent, contact time, initial concentration of zinc and temperature on the adsorption process were studied. Initial rate of adsorption of zinc increases with time up to 30 min and thereafter it reaches equilibrium. Percent adsorption is adversely affected by increase in initial concentration of zinc and increase in particle size of sorbent. Adsorption processes follow first order kinetics and are found to be exothermic.

Absorption↗