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Rajeev Kumar

Publications and source records attributed to Rajeev Kumar.

At least 19 recordsLinked to original sources
PubMed2025

Moss BRCA2 lacking the canonical DNA-binding domain promotes homologous recombination and binds to DNA.

BRCA2 is crucial for mediating homology-directed DNA repair (HDR) through its binding to single-stranded DNA (ssDNA) and the recombinases RAD51 and DMC1. Most BRCA2 orthologs have a canonical DNA-binding domain (DBD) with the exception of Drosophila melanogaster. It remains unclear whether such a noncanonical BRCA2 variant without DBD possesses a DNA-binding activity. Here, we identify a new noncanonical BRCA2 in the model plant Physcomitrium patens (PpBRCA2). We establish that PpBRCA2 is essential for genome integrity maintenance, somatic DNA double-strand break (DSB) repair, HDR-mediated gene targeting, and RAD51 foci recruitment at DNA break sites. PpBRCA2 is also critical for DSB repair during meiosis. Interestingly, PpBRCA2 interacts strongly with RAD51 but weakly with DMC1, suggesting a distinct meiotic function compared to other BRCA2 homologs. Despite lacking the canonical DBD, PpBRCA2 binds ssDNA through its disordered N-terminal region and efficiently promotes HDR. Our work highlights that the ssDNA binding capacity of BRCA2 homologs is conserved regardless of the presence of a canonical DBD and provides a deeper understanding of BRCA2's functional diversity across species.

BRCA2 Protein↗
PubMed2007

Transrectal ultrasound-guided biopsy of prostate voxels identified as suspicious of malignancy on three-dimensional (1)H MR spectroscopic imaging in patients with abnormal digital rectal examination or raised prostate specific antigen level of 4-10 ng/ml.

Results of the evaluation of transrectal ultrasound (TRUS) guided needle biopsy of voxels identified as suspicious of malignancy on magnetic resonance spectroscopic imaging (MRSI) in a large cohort of men (n = 83) with abnormal digital rectal examination (DRE) [prostate specific antigen (PSA) 0-4 ng/ml] or PSA less than 10 ng/ml, are reported. Three-dimensional (1)H MRSI was carried out at 1.5 T using a pelvic-phased array coil in combination with an endorectal surface coil. Voxels were classified as suspicious of malignancy based on Cit/(Cho + Cr) metabolite ratio. TRUS-guided biopsy of suspicious voxels was performed using the z- and x-coordinates obtained from MR images and two to three cores were taken from the suspected site. A systematic sextant biopsy was also carried out. MRSI showed voxels suspicious of malignancy in 44 patients while biopsy revealed cancer in 11 patients (25%). Patients who were negative for malignancy on MRSI were also negative on biopsy. An overall sensitivity of 100%, specificity of 54%, negative predictive value of 100% and accuracy of 60% were obtained. The site of biopsy was confirmed (n = 20) as a hypo-intense area on repeat MRI while repeat MRSI revealed high choline and low citrate. The overall success rate of MRI-directed TRUS-guided biopsy of 25% was higher compared with a 9% success rate achieved without MR guidance in another group of 120 patients. Our results indicate that TRUS-guided biopsy of suspicious area identified as malignant from MRSI can be performed using the coordinates of the voxel derived from MR images. This increases the detection rate of prostate cancer in men with PSA level <10 ng/ml or abnormal DRE and also demonstrates the potential of MR in routine clinical practice.

Adenocarcinoma↗
PubMed2006

The 'scrubbed surgeon' in robotic surgery.

One of the principal reasons for the rapid progress of robotic surgery has been its advantage in allowing laparoscopy naïve surgeons to offer minimal access surgery to their patients. While this may continue to be an advantage of this modality, it has to be remembered that this has often been possible primarily due to the availability of an assistant who has at least basic laparoscopy skills that permit the performance of critical patient side tasks. We review the literature on the role of the assistant or the 'scrubbed surgeon' in robotic surgery and discuss the advantages of a properly trained assistant in a developing and established robotic surgery program.

Clinical Competence↗
PubMed2006

Correlation between metabolite ratios and ADC values of prostate in men with increased PSA level.

Proton magnetic resonance spectroscopic imaging (MRSI) and diffusion-weighted imaging (DWI) were carried out in men with increased prostate-specific antigen (PSA) level. Forty subjects [controls (Group I) and patients (Groups II and III with PSA >20 and 4-20 ng/ml, respectively)] were investigated using endorectal coil at 1.5 T prior to transrectal ultrasound (TRUS)-guided biopsy. Metabolite ratio [citrate/(choline+creatine)] and apparent diffusion coefficient (ADC) were calculated for identical voxels. In patients, voxels that showed lower metabolite ratio showed reduced ADC in the peripheral zone (PZ) of the prostate, and voxels with increased metabolite ratio showed higher ADC. Metabolite ratios were used to predict areas of malignancy if the ratio was <1.4 and if ADC value was <1.17 x 10(-3) mm(2)/s. Patients in Group II had lower metabolite ratio and ADC in the PZ compared to controls and Group III. All 13 were positive for malignancy in MR, while 12 of 13 were positive on TRUS-guided sextant biopsy. In Group III, certain voxels of PZ that showed reduced metabolite ratio also showed lower ADC. A positive correlation was observed between metabolite ratio and ADC. MR predicted areas of malignancy in PZ in 15 of 20 patients; however, only six were positive on TRUS-guided biopsy perhaps due to high false-negative rate of TRUS-guided biopsy. Results show positive correlation between MRSI and DWI and their potential in detection of malignancy, thereby improving the diagnosis especially in patients with PSA level of 4-20 ng/ml.

Aged↗
PubMed2006

Comparison of NMP22 BladderChek test and urine cytology for the detection of recurrent bladder cancer.

OBJECTIVE: To assess the clinical performance of the NMP22 BladderChek test, which is a qualitative test, and to compare it with voided urine cytology for the detection of recurrent bladder cancer. We also evaluated whether cystoscopy can be omitted from the surveillance protocol by combining the two tests. METHODS: A total of 131 patients with a history of superficial transitional cell carcinoma of the bladder provided urine samples before a cystoscopic examination. Urine samples were assayed for the presence of NMP22 using the NMP22 BladderChek test and cytology was performed by a cytopathologist. Selected patients underwent a biopsy, with appropriate additional therapy. Results of the two tests were compared with that the results of cystoscopy, which was retained as the gold standard. For positive biopsies, the results of the NMP22 test and cytology were also correlated with the tumor stage and grade. RESULTS: Of the 46 recurrences detected by cystoscopy, the NMP22 test was positive in 39 cases and cytology in 19 cases. The sensitivity of the NMP22 test was 85%, which was significantly greater than that of cytology (41%). In particular, for low-risk tumors it was eight times more sensitive than cytology. The specificities of the NMP22 test and cytology were 77 and 96%, respectively. Combining the two tests increased overall sensitivity to 91%. However, 9% of the tumors were still not detected. CONCLUSION: The NMP22 BladderChek test is an in vitro qualitative test that is easily available and cheap; it can be performed by a urologist in the office and results can be interpreted within 30 min. The NMP22 test is superior to cytology for all grades and stages in the detection of recurrence in patients with a history of superficial bladder cancer. Our study indicates that the NMP22 test can be used as a substitute for urine cytology. The NMP22 test cannot replace cystoscopy, but it can be used as an adjunct to cystoscopy in the surveillance protocol for patients with superficial bladder cancer.

Adult↗
PubMed2006

Depression in mild cognitive impairment in a community sample of individuals 60-64 years old.

OBJECTIVE: This cross-sectional study examined the prevalence and characteristics of depression in subjects with mild cognitive impairment (MCI). The data presented here are from the first wave of the longitudinal Personality and Total Health Through Life 60+ (PATH 60+) Project. METHOD: A total of 2551 community-dwelling individuals in the age range 60-64 years were recruited randomly through the electoral roll. They were screened using a short cognitive battery and those who screened positive underwent detailed medical and neuropsychological assessments. There were 29 subjects who fulfilled the Mayo Clinic criteria for MCI and these were compared to 520 controls. Subjects were evaluated for depression symptoms and DSM-IV major and minor depression syndromes. RESULTS: Subjects with MCI had more minor depression and higher scores on a symptom scale. However, a multivariate examination of specific symptoms showed that the differences were confined to only two motivation-related symptoms ("felt slowed up" and "little interest or pleasure"). CONCLUSION: Motivation-related depressive symptoms are more relevant in subjects with MCI than mood-related symptoms.

Australia↗
PubMed2006

Hormone replacement therapy, brain volumes and white matter in postmenopausal women aged 60-64 years.

Research on the structural and functional effects of hormone replacement therapy on the brain has produced inconsistent results. This paper reports on cross-sectional associations between hormone replacement therapy use and volumes of brain structures measured using magnetic resonance imaging in 213 postmenopausal women aged 60-64 years recruited from a large population study. Of these, 64 were current hormone replacement therapy users, 69 previous users and 80 had never used hormone replacement therapy. No differences were observed between groups in total grey matter, white matter, hippocampal or amygdalar volumes, severity or volume of white matter hyperintensities, or in different measures of brain atrophy. While acknowledging the limitations of a cross-sectional study, the results argue against hormone replacement therapy being protective against brain changes associated with ageing in women in their early 60s.

Brain↗
PubMed2006

Reconstructive surgery for the management of genitourinary tuberculosis: a single center experience.

PURPOSE: We evaluated the role of surgery for genitourinary tuberculosis with special emphasis on reconstructive procedures. MATERIALS AND METHODS: Case records of 241 patients with genitourinary tuberculosis who underwent surgery at our center during a period of 17 years were reviewed. Clinical features, organ involvement, investigations, treatment and outcome of therapy were studied. RESULTS: There were 129 males and 112 females with a mean age of 34.6 years. The most common presentation was irritative voiding symptoms. Azotemia was seen in 54 (22.4%) cases. The most commonly involved organ was the kidney in 130 (53.94%) cases. Preoperative bacteriologic diagnosis was confirmed in 70 (29%) cases. All patients received antitubercular drug therapy for 9 months. A total of 248 procedures, including 33 endoscopic, 87 ablative and 128 reconstructive, were performed with some patients requiring more than 1 procedure. Early complications, which mainly involved the bowel, were seen in 19 (7.88%) cases. Bacteriologic cure was achieved in all culture positive cases. Renal functional parameters stabilized or improved in 44 of 54 patients (81.5%) in whom they were deranged at presentation. CONCLUSIONS: Genitourinary tuberculosis is common in developing countries. Diagnosis is often delayed because of late presentation and many patients present with cicatrization sequelae. A combination of antitubercular drug therapy and judicious surgery achieves satisfactory results in the majority of cases. With improved antitubercular drug therapy and experience with the use of bowel segments in the urinary tract, more reconstructive procedures are being performed with satisfactory outcomes. In patients who undergo reconstructive procedures, a rigorous and prolonged followup is necessary.

Adolescent↗
PubMed2006

Beware! Fungal urosepsis may follow endoscopic intervention for prolonged indwelling ureteral stent.

We present a 38-year-old lady with a prolonged indwelling ureteral stent that had been placed for pain relief after development of Steinstrasse following extracorporeal lithotripsy for a 2.5-cm left renal calculus. The patient developed candidal urosepsis within 6 hours after ureteroscopy and percutaneous nephrolithotomy (PCNL) for the removal of residual fragments. She subsequently recovered on systemic antifungal therapy in the form of intravenous amphotericin B and achieved complete stone clearance after repeat ureteroscopy and PCNL. Fungal urosepsis is known to complicate the postoperative course in chronically debilitated patients with poor nutritional status or those with diabetes or other significant comorbities. To our knowledge, this is the first reported case of a patient with no significant comorbities developing fungal urosepsis after endoscopic intervention for a long-term indwelling ureteral stent.

Adult↗
PubMed2006

Comparison of standard transurethral resection, transurethral vapour resection and holmium laser enucleation of the prostate for managing benign prostatic hyperplasia of >40 g.

OBJECTIVES: To compare the safety and efficacy of two alternatives for surgically treating symptomatic benign prostatic hyperplasia (BPH), i.e. transurethral vapour resection of the prostate (TUVRP) and holmium laser enucleation of the prostate (HOLEP), with transurethral resection of the prostate (TURP), the standard surgical therapy, as treating large prostates is associated with greater morbidity, and to date there is no simultaneous comparison of these three methods. PATIENTS AND METHODS: We prospectively randomized 150 patients (50 in each group) with BPH and glands of >40 g to undergo either TURP, TUVRP or HOLEP. The evaluation before treatment included urine culture, serum prostate specific antigen (PSA) level estimation, the International Prostate Symptom Score (IPSS), peak urinary flow rate (Q(max)), and transabdominal ultrasonography to estimate prostate size and postvoid urine residue (PVR). The operative duration, blood loss, resected tissue weight, change in levels of haemoglobin and serum sodium, nursing contact time, duration of catheterization, and complications were noted. After surgery patients were reassessed for the IPSS, Q(max) and PVR at 6 months and 1 year. RESULTS: The patients in all three groups had comparable characteristics before surgery. The mean operating duration and intraoperative irrigant used for TUVRP was less than for HOLEP or TURP, and blood loss with HOLEP and TUVRP was less than with TURP (all P < 0.001). Postoperative irrigation, nursing contact time, and catheter duration were significantly less for HOLEP than TURP or TUVRP, and for TUVRP than TURP. At follow-up, patients in all groups had a significant improvement from baseline in IPSS, Q(max,) and PVR, but the differences between the groups were not significant at 6 months or 1 year. CONCLUSIONS: HOLEP and TUVRP are both acceptable alternatives to TURP for treating large prostate glands, with less perioperative morbidity and comparable efficacy at 6 months and 1 year.

Adult↗
PubMed2006

Early patency rates after the two-suture invagination technique of vaso-epididymal anastomosis for idiopathic obstruction.

OBJECTIVES: To prospectively evaluate the results of vaso-epididymostomy, using a two-suture microsurgical invagination technique, when used for men with azoospermia due to an obstruction at the vaso-epididymal junction. PATIENTS AND METHODS: Between December 2002 and November 2004, 29 men with idiopathic obstructive azoospermia underwent vaso-epididymostomy with the two-suture invagination technique. The patency rate was assessed by return of sperm in the semen after surgery. RESULTS: In all, 23 men provided at least one postoperative semen sample. The mean (range) follow-up was 7.6 (1.5-30) months. In 11 of these men (48%), patency was shown at a mean of 3.2 (1.5-7) months after surgery. The median sperm density was 17 (10-65) million/mL. Four men had normal sperm density and motility (>20 million/mL; >50% total motility). CONCLUSIONS: Men with idiopathic vaso-epididymal junction obstruction can have significant sperm positivity after vaso-epididymostomy. With a patency rate of nearly half within a year of surgery, vaso-epididymostomy should be the first line of therapy for these men.

Adult↗
PubMed2006

Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome.

AIM: To study the occurrence of Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome (KFS). METHODS: Blood and semen samples were collected from azoospermic patients with KFS (n = 14) and a control group of men of proven fertility (n = 13). Semen analysis was done according to World Health Organization (WHO) guidelines. Blood samples were processed for karyotyping, fluorescent in situ hybridization (FISH) and measurement of plasma follicle stimulating hormone (FSH) by radioimmunoassay. To determine Y chromosome microdeletions, polymerase chain reaction (PCR) of 16 sequence tagged sites (STS) and three genes (DFFRY, XKRY and RBM1Y) was performed on isolated genomic DNA. Testicular fine needle aspiration cytology (FNAC) was done in selected cases. RESULTS: Y chromosome microdeletions spanning the azoospermia factor (AZF)a and AZFb loci were found in four of the 14 azoospermic patients with KFS. Karyotype and FISH analysis revealed that, of the four cases showing Y chromosome microdeletion, three cases had a 47,XXY/46,XY chromosomal pattern and one case had a 46,XY/47,XXY/48,XXXY/48,XXYY chromosomal pattern. The testicular FNAC of one sample with Y chromosome microdeletion revealed Sertoli cell-only type of morphology. However, no Y chromosome microdeletions were observed in any of the 13 fertile men. All patients with KFS had elevated plasma FSH levels. CONCLUSION: Patients with KFS may harbor Y chromosome microdeletions and screening for these should be a part of their diagnostic work-up, particularly in those considering assisted reproductive techniques.

Adolescent↗
PubMed2005

Clinical and neuroimaging correlates of mild cognitive impairment in a middle-aged community sample: the personality and total health through life 60+ study.

This cross-sectional study aimed at determining the clinical and structural brain magnetic resonance imaging correlates of mild cognitive impairment (MCI). The data presented here are from the first wave of the longitudinal Personality and Total Health through Life 60+ project. 2,551 community-dwelling individuals in the age range of 60-64 years were recruited randomly through the electoral roll. They were screened using Mini-Mental State Examination and a short cognitive battery. Those who screened positive underwent detailed medical and neuropsychological assessments. Of the 224 subjects who screened positive, 117 underwent a detailed assessment. Twenty-nine subjects fulfilled the Mayo Clinic criteria for MCI. Magnetic resonance imaging scans were analyzed for 26 subjects with MCI as well as normal controls. Subjects were clinically evaluated for depressive symptoms and major and minor depression syndromes. Logistic regression analysis was performed predicting MCI from anterior and mid-ventricular brain ratios, cortical atrophy measures, hippocampal volumes, volumes of amygdala and white matter hyperintensities after adjusting for age, gender, years of education, depression and physical disability. None of the neuroanatomical substrates appeared as predictors of MCI. The only predictors were higher depression scores and fewer years of education. Structural neuroimaging may not have an added advantage in the detection of MCI in middle-aged community-dwelling subjects. It may be that this age group is too young for such brain changes to be identified.

Amygdala↗
PubMed2005

Modified expanded corrole-ferrocene conjugates: syntheses, structure and properties.

Syntheses, characterization and properties of expanded corrole-ferrocene conjugates are reported. Ferrocenyl group are covalently linked to the corrole macrocycle through three different spacers groups. The synthetic strategy involved prior insertion of ferrocene with spacers to the dipyrromethane unit followed by a "3+2" acid-catalyzed oxidative coupling methodology. The optical and emission data of the expanded corrole-ferrocene conjugates depend on the nature and length of the spacer groups and the maximum effects are seen where ferrocene is directly linked to the meso carbon of macrocycle. The single crystal X-ray structure of two expanded corrole-ferrocene conjugates; [22]pentaphyrin (1.1.0.1.0) with different meso substituents, clearly reveal shortening of the C-C bond length linking the meso carbon and the aryl substituent containing the ferrocene moiety relative to meso aryl substituents without ferrocene. The results suggest that an electronic interaction between the two pi systems. Electrochemical data reveal harder oxidation for the ferrocene unit in the conjugates relative to free ferrocene; this suggests the electron donating nature of the ferrocene. The first corrole ring oxidation shows easier oxidation relative to 1 and the magnitude of shifts in potential is inversely proportional to the length of spacer. The molecular first hyperpolarizabilities (beta) measured at 1064 nm by HRS method vary in the range 20-32x10(-30) esu and imply that the beta values can be increased by enhancing the number of mobile electrons in the conjugation. The conjugates form 1:1 metal complex with the Rh(I) where rhodium is coordinated to one amino and one imino nitrogen of the dipyrromethane unit.

Crystallography, X-Ray↗
PubMed2005

Characterisation of plant tocopherol cyclases and their overexpression in transgenic Brassica napus seeds.

Tocopherols, collectively known as vitamin E, are only synthesised in photosynthetic organisms. Tocopherol cyclase (TC) catalyses the formation of the chromanol headgroup of the various tocopherol isoforms. TCs from Arabidopsis and maize (Zea mays) were expressed in Escherichia coli and purified. Analysis of the enzymatic properties revealed similarities but also differences between the two enzymes. Overexpression of chimeric TC gene constructs in developing seeds of transgenic rapeseed plants enhanced and modified the relative abundance of individual tocochromanol species in the seed oil, indicating a regulatory function of the enzyme in prenyllipid metabolism.

Arabidopsis↗
PubMed2005

Long-term safety, efficacy, dosing, and development of resistance with botulinum toxin type B in cervical dystonia.

Short-term studies of cervical dystonia (CD) have demonstrated botulinum toxin type B (Bot B) to be safe and efficacious at doses of 5,000 to 10,000 units, but few long-term studies have been published and the safety and efficacy of higher doses has not been established. Additionally, there are few studies describing the development of resistance to Bot B in those with and without prior resistance to botulinum toxin type A (Bot A). We reviewed our experience with 24 patients treated with Bot B for up to 64 months. Patients were treated with Bot B for 26.2 +/- 20.4 months (range, 3-64 months) with a mean treatment dose of 14,828 +/- 6,824 units (range, 2,500-28,000 units). At last follow-up, 12 patients demonstrated ongoing benefit, 8 patients had become secondarily resistant, and 4 patients were primary nonresponders possibly due to the severity and nature of their CD. Nine of the 12 continued responders and 7 of the 8 secondary nonresponders to Bot B had prior probable or definite clinical resistance to Bot A. No severe adverse events related to Bot B were seen. Treatment of patients with severe CD who continue to show a beneficial response to Bot B injections commonly requires doses of 15,000 units and rarely greater than 20,000 units. Patients may continue to respond for up to 64 months. Prior Bot A resistance may be a risk factor for the development of resistance to Bot B; nevertheless, Bot B can be a useful long-term alternative in some Bot A-resistant CD patients.

Adult↗
PubMed2005

Separated quadrupolar field experiment.

We describe an NMR experiment that produces spectra correlating the first-order quadrupolar spectrum and the central transition spectrum of half-integer quadrupolar spins, allowing one to separate the quadrupolar parameters in overlapping spectra under both static and magic-angle-spinning conditions. Promising fields of applications include situations where the sample cannot easily be rotated, or where it cannot be rotated at the magic angle.

Magnetic Resonance Spectroscopy↗