Biomedical subjects

Anil Kapoor

Publications and source records attributed to Anil Kapoor.

18 recordsLinked to original sources

PubMed2006

Laparoscopic management of advanced renal cell carcinoma with level I renal vein thrombus.

OBJECTIVES: To present our series of laparoscopic radical nephrectomy in patients with level I tumor thrombus. The existence of renal vein tumor thrombus presents a technical challenge in securing hilar control during the resection of a renal mass. To our knowledge, this experience represents one of the largest series of laparoscopic nephrectomy for renal cell carcinoma associated with a macroscopic renal vein thrombus. METHODS: From April 2002 to June 2004, 12 patients (8 men and 4 women) were diagnosed with renal masses. In addition to computed tomography, cavography and magnetic resonance imaging were used to determine the levels of tumor thrombi preoperatively in those who had suspicious involvement of the renal vein on computed tomography. RESULTS: Laparoscopic nephrectomy was performed in a standard fashion. Hand-assisted laparoscopic nephrectomy was used in 6 cases involving large tumors with bulky hilar adenopathy. All renal veins were stapled using an endoscopic vascular stapler. Intraoperative laparoscopic ultrasonography was used to delineate the extent of the vein thrombus in 4 cases to enable proper stapler positioning. No intraoperative complications occurred, and 2 cases were electively converted to open nephrectomy. The postoperative narcotic requirements and hospitalization times were low. Pathologic examination of the tumor specimens demonstrated negative resection margins in all patients. CONCLUSIONS: In carefully selected patients, laparoscopic resection of renal masses with level I renal vein thrombi is feasible. Because of technical considerations that may be identified intraoperatively, early conversion to open nephrectomy should be anticipated. Long-term results regarding oncologic control continue to be assessed.

Carcinoma, Renal Cell↗

PubMed2006

ATM activation is accompanied with earlier stages of prostate tumorigenesis.

The ATM (ataxia telangiectasia mutated) kinase plays an essential role in maintaining genome integrity by coordinating cell cycle arrest, apoptosis, and DNA damage repair. Phosphorylation of ATM at serine 1981 (ATMpSer1981) by DNA damage activates ATM, which subsequently phosphorylates H2AX Ser139 (gammaH2AX), Chk2 Thr68 (Chk2pThr68), and p53 Ser15 (p53pSer15). To determine the role of the ATM pathway in prostate cancer tumorigenesis, we have analyzed 35 primary prostate cancer specimens for ATMpSer1981 (ATM activation), Chk2pThr68, gammaH2AX, and p53pSer15 by immunohistochemistry (IHC) in normal glands, prostatic intraepithelial neoplasias (PINs), and carcinomas. Increases in the intensities of ATMpSer1981, Chk2pThr68, and gammaH2AX and in the percentage of cells that are positive for ATMpSer1981, Chk2pThr68, or gammaH2AX were observed in PINs (p<0.001) compared to normal prostatic glands and carcinoma. However, this pattern of immunostaining was not seen for p53pSer15. Thus, ATM and Chk2 are specifically activated in PINs. As PINs are generally regarded as precursors of prostatic carcinoma, our results suggest that ATM and Chk2 activation at earlier stages of prostate tumorigenesis suppresses tumor progression, with attenuation of ATM activation leading to cancer progression.

Aged↗

PubMed2006

Robot-assisted laparoscopic renal artery aneurysm reconstruction.

We report the surgical management of an expanding 2.5-cm left-sided renal artery aneurysm using a robotic-assisted laparoscopic approach. Using the da Vinci surgical robotic system, we resected the aneurysm, and the anterior-inferior branch of the renal artery was reconstructed with an end-to-end anastomosis. The operative time was 360 minutes, hospitalization length of stay was 3 days, and postoperative analgesic requirements were minimal. Follow-up imaging and functional analysis demonstrated resolution of the aneurysm and preservation of renal function. This technique highlights the ability of surgical robotics to expand indications for minimally invasive surgery in complex cases.

Anastomosis, Surgical↗

PubMed2006

A platform of high-efficiency nonviral gene transfer in mouse osteoblast cells in vitro.

We have previously established mouse genetic models and identified the genetic components of quantitative trait loci (QTL) on mouse chromosomes that contribute to phenotypes such as bone size, bone density, and bone's anabolic response to mechanical loading. However, these regions contain dozens of unknown genes that are needed for functional testing. In this study, we provided a protocol of nucleoporation with high efficiency by using a commercial nucleofection buffer and Gene Pulser to deliver a test gene into bone cells for functional studies. We cloned an osteoblast differentiation-specific gene osterix (Osx) from a mouse bone cDNA library into a pHGCX expression vector and used nucleoporation to deliver pHGCX/ Flag-Osx into the nuclei of MC3T3-E1 cells. We then examined the transfection efficiency, transgene expression, and function. Our results have demonstrated that nucleoporation can deliver a transgene into MC3T3-E1 osteoblast cells with approx 94% transfection efficiency, and express a functional Flag-Osx fusion protein capable of inducing cell differentiation as measured by an increase in alkaline phosphatase (ALP) activity. Therefore, this experimental system provides a rapid, safe, and efficient cell-based model of high-throughput phenotypic screening to identify candidate genes from physically mapped regions that are important for osteoblast differentiation.

3T3 Cells↗

PubMed2005

Spontaneous fractures in the mouse mutant sfx are caused by deletion of the gulonolactone oxidase gene, causing vitamin C deficiency.

UNLABELLED: Using a mouse mutant that fractures spontaneously and dies at a very young age, we identified that a deletion of the GULO gene, which is involved in the synthesis of vitamin C, is the cause of impaired osteoblast differentiation, reduced bone formation, and development of spontaneous fractures. INTRODUCTION: A major public health problem worldwide, osteoporosis is a disease characterized by inadequate bone mass necessary for mechanical support, resulting in bone fracture. To identify the genetic basis for osteoporotic fractures, we used a mouse model that develops spontaneous fractures (sfx) at a very early age. MATERIALS AND METHODS: Skeletal phenotype of the sfx phenotype was evaluated by DXA using PIXImus instrumentation and by dynamic histomorphometry. The sfx gene was identified using various molecular genetic approaches, including fine mapping and sequencing of candidate genes, whole genome microarray, and PCR amplification of candidate genes using cDNA and genomic DNA as templates. Gene expression of selected candidate genes was performed using real-time PCR analysis. Osteoblast differentiation was measured by bone marrow stromal cell nodule assay. RESULTS: Femur and tibial BMD were reduced by 27% and 36%, respectively, in sfx mice at 5 weeks of age. Histomorphometric analyses of bones from sfx mice revealed that bone formation rate is reduced by >90% and is caused by impairment of differentiated functions of osteoblasts. The sfx gene was fine mapped to a 2 MB region containing approximately 30 genes in chromosome 14. By using various molecular genetic approaches, we identified that deletion of the gulonolactone oxidase (GULO) gene, which is involved in the synthesis of ascorbic acid, is responsible for the sfx phenotype. We established that ascorbic acid deficiency caused by deletion of the GULO gene (38,146-bp region) contributes to fractures and premature death because the sfx phenotype can be corrected in vivo by treating sfx mice with ascorbic acid and because osteoblasts derived from sfx mice are only able to form mineralized nodules when treated with ascorbic acid. Treatment of bone marrow stromal cells derived from sfx/sfx mice in vitro with ascorbic acid increased expression levels of type I collagen, alkaline phosphatase, and osteocalcin several-fold. CONCLUSION: The sfx is a mutation of the GULO gene, which leads to ascorbic acid deficiency, impaired osteoblast cell function, and fractures in affected mice. Based on these and other findings, we propose that ascorbic acid is essential for the maintenance of differentiated functions of osteoblasts and other cell types.

Animals↗

PubMed2005

Identification of a novel Wee1 isoform.

We have identified a novel isoform of Wee1 kinase (Wee1i), which uses Met215 of Wee1 as its initiation codon. RT-PCR, Western blot, and in situ hybridization verified wee1i expression in mammalian cells, rat brain, and rat thymus. Recombinant and partially purified Wee1i from rat thymus displayed kinase activity comparable to or higher than Wee1. The N-terminal 214 residues of Wee1 facilitate its ubiquitin-dependent degradation to trigger mitotic entry. Since Wee1i, lack of these 214 residues, it may evade this degradation and thus provide constitutive Wee1-like kinase activity to inhibit mitotic cell proliferation. Thus, Wee1i may play an important role in differentiation and in tumor suppression.

Animals↗

PubMed2005

Terminal loop cutaneous ureterostomy in renal transplantation: an under utilized urinary diversion technique.

PURPOSE: We evaluated the effectiveness of terminal loop cutaneous ureterostomy as a means of urinary drainage in kidney transplant recipients during a 20-year period. MATERIALS AND METHODS: Five cadaveric and 2 living related patients underwent kidney transplantation with terminal loop cutaneous ureterostomy between 1984 and 2004. These patients had no usable bladder or they were not suitable candidates for intermittent catheterization. RESULTS: Followup was 20 months to 17 years. One patient underwent stomal revision 5 months after renal transplantation. Current serum creatinine 4 years later was 166 mumol/l. The remaining 6 patients had no evidence of ureteral obstruction and rarely had bacteriuria or urinary tract infections. Four patients had a functioning allograft with normal serum creatinine. One patient died with a normally functioning allograft and the remaining patient lost his graft due to chronic rejection. No patient in this series lost the graft due to a urological cause. Overall outcomes included excellent allograft function with minimal infection or stomal stenotic complications. CONCLUSIONS: Terminal loop cutaneous ureterostomy is a simple, safe and alternative means of urinary diversion in patients with renal transplant and a defunctionalized lower urinary tract.

Adult↗

PubMed2005

Primary small cell carcinoma of the ureter.

Primary small cell carcinoma of the ureter is a rare clinico-pathological entity. We present a report of primary ureteric small cell carcinoma and pathological correlates.

Aged↗

PubMed2005

Laparoscopic nephrectomy for emphysematous pyelonephritis.

Emphysematous pyelonephritis is a serious suppurative infection of the renal and extrarenal tissues. Controversies exist surrounding the appropriate management of this life-threatening condition with advocates for both medical management alone and percutaneous drainage combined with nephrectomy. The laparoscopic approach for nephrectomy is quickly becoming the standard of care for benign disease of the kidney and low-stage renal cancers. We report a case of a 60-year-old diabetic male undergoing successful laparoscopic nephrectomy for right emphysematous pyelonephritis, and our procedural technique. To our knowledge, this is the first report of laparoscopic nephrectomy in the setting of emphysematous pyelonephritis. Carefully selected patients with emphysematous pyelonephritis may benefit from the advantages of laparoscopic nephrectomy in centers with sufficient laparoscopic experience.

Diabetic Nephropathies↗

PubMed2005

Urological manifestations of BK polyomavirus in renal transplant recipients.

OBJECTIVES: BK polyomavirus (BKV) disease in renal transplant recipients has become an increasingly problematic clinical entity. Complications of BKV disease lead to chronic allograft nephropathy and ultimately loss in greater than 50% of cases. We reviewed our experience with BKV disease over a 5-year period. PATIENTS AND METHODS: We performed 155 cadaveric and 168 live-related transplants between January 2000 and June 2005. During this period, seven patients had biopsy-confirmed BKV disease, which compromised the renal function of six cadaveric and one live-related renal transplant recipients. BKV was suspected as a potential cause of renal function deterioration after eliminating other possibilities. BKV was then confirmed by detecting viral DNA in urine samples by polymerase chain reaction (PCR) and visualizing viral particles in allograft biopsies by electron microscopy. RESULTS: The deterioration of allograft function in five renal transplant recipients was due to polyomavirus-associated nephropathy and two due to ureteric stenosis. Upon confirmation of BKV, overall immunosuppression was reduced or modified with follow-up of 5 to 44 months. However, additional rescue therapies were used to stabilize allograft function including ciprofloxacin, intravenous immunoglobulin, and leflunomide. One patient died and another lost his allograft due to non-compliance and reverted to hemodialysis, but renal function in the remaining five allografts has remained stable at higher serum creatinine levels. CONCLUSIONS: The management of BKV disease in renal transplant recipients is not yet clearly defined. However, early recognition of urological sequelae and modification of immunosuppressive therapy are essential to ensure adequate long-term function of these allografts.

Adult↗

PubMed2004

ATM activity contributes to the tumor-suppressing functions of p14ARF.

P14/p19ARF (ARF) plays a major role in the activation of p53 by oncogenic signals. The biochemical basis of this has not been fully elucidated. We report here that forced expression of p14ARF enhances phosphorylation of p53 serine 15 (p53S15) in NIH3T3, IMR90 and MCF7 cells. Ectopic expression of the oncogenes c-myc, E2F1 and E1A, all of which activate p53 at least partially via ARF, lead to p53S15 phosphorylation in IMR90 cells. In addition, ectopic expression of p53 also results in p53S15 phosphorylation, suggesting that this is a common event in the ARF-p53 tumor suppression system. Furthermore, p53-, p14ARF-, c-myc- and E2F1-, but not E1A-, induced p53S15 phosphorylation was substantially reduced in AT fibroblasts (GM05823). Downregulation of ATM in MCF7 cells using RNA interference (RNAi) technology significantly attenuated p14ARF- and p53-induced phosphorylation of p53S15. Ectopically expressed ARF in NIH3T3 cells induced ATM nuclear foci and activated ATM kinase. Functionally, ectopic expression of p14ARF and c-myc inhibited the proliferation of IMR90 but not ATM null GM05823 cells, and p14ARF-induced inhibition of MCF7 cell proliferation was significantly attenuated by downregulation of ATM by RNAi. Taken together, these data show a functional role for ATM in ARF-mediated tumor suppression.

3T3 Cells↗

PubMed2004

Prevention of mother to child transmission of HIV.

Perinatal transmission is the most common cause of HIV infection in pediatric population below the age of 15 years. Much progress has been made to decrease the risk of transmission than just offering the option of medical termination of pregnancy to the mother. Future research is needed not only to develop the simple preventive program, but also to make it more cost effective, acceptable and accessible to the general population. Following review article focuses on the factors affecting the transmission of HIV, strategies for prevention of MTCT with special reference to use of nevirapine and breast-feeding practices in HIV positive mother. The role of counseling and voluntary testing is also stressed upon.

Anti-HIV Agents↗

PubMed2004

Laparoscopic versus open partial nephrectomy.

OBJECTIVES: To compare, retrospectively, the results of laparoscopic partial nephrectomy (LPN) to open partial nephrectomy (OPN) using a tumor size-matched cohort of patients. Limited data are available comparing LPN to OPN in the treatment of small renal tumors. METHODS: Between September 2000 and September 2003, 27 LPNs and 22 OPNs were performed to treat renal masses less than 4 cm. Patient demographics and tumor location and size (2.4 +/- 1.0 cm versus 2.9 +/- 0.9 cm, respectively; P = not statistically significant) were similar between the LPN and OPN groups. RESULTS: Although the mean operative time was longer in the LPN than in the OPN group (210 +/- 76 minutes versus 144 +/- 24 minutes; P <0.001), the blood loss was comparable between the two groups (250 +/- 250 mL versus 334 +/- 343 mL; P = not statistically significant). No blood transfusions were performed in either group. The hospital stay was significantly reduced after LPN compared with after OPN (2.9 +/- 1.5 days versus 6.4 +/- 1.8 days; P <0.0002), and the postoperative parenteral narcotic requirements were lower in the LPN group (mean morphine equivalent 43 +/- 62 mg versus 187 +/- 71 mg; P <0.02). Three complications occurred in each group. With LPN, no patient had positive margins or tumor recurrence. Also, direct financial analysis demonstrated lower total hospital costs after LPN (4839 dollars+/- 1551 dollars versus 6297 dollars+/- 2972 dollars; P <0.05). CONCLUSIONS: LPN confers several benefits over OPN concerning patient convalescence and costs, despite prolonged resection times at our current phase of the learning curve. Long-term results on cancer control in patients treated with LPN continue to be assessed.

Adult↗

PubMed2004

Comparison of laparoscopic radical renal surgery in morbidly obese and non-obese patients.

BACKGROUND AND PURPOSE: Laparoscopic radical nephrectomy is rapidly becoming accepted as the preferred management of low-stage renal masses not amenable to partial nephrectomy. Minimally invasive surgery is advantageous to decrease perioperative and postoperative morbidity and allows patients to return to normal activities faster. Obesity has been a relative contraindication to this technique, and these patients have traditionally undergone open surgery. We present a review of 23 morbidly obese patients in comparison with patients who were not morbidly obese who underwent radical laparoscopic nephrectomy and nephroureterectomy at our institution. PATIENTS AND METHODS: Hospital charts between April 2001 and October 2003 were reviewed for morbidly obese patients undergoing transperitoneal laparoscopic renal surgery who were compared with age- and sex-matched control patients who underwent laparoscopic renal surgery in the same institution for similar indications. The data were collected at the time of the surgery. RESULTS: Twenty-three patients with a mean BMI of 42.2 kg/m2 underwent successful transperitoneal laparoscopic surgery. The mean specimen mass was 865 g, which was significantly larger than in the control group. The mean operative time was 200 minutes, which was around half an hour longer than in the matched group. The mean estimated blood loss was 243 mL, which was comparable to that of the controls. There were two perioperative complications, and the mean hospital stay was 4.5 days, 1 day longer than in the control group. CONCLUSIONS: Laparoscopic transperitoneal renal surgery is technically more difficult in morbidly obese patients but is a feasible, effective, minimally invasive method of removing renal malignancies. It offers decreased respiratory and cardiac morbidity in this higher-risk population. This study showed a complication profile similar to that in non-obese patients.

Aged↗

PubMed2004

McMaster experience with laparoscopic pyeloplasty.

PURPOSE: Laparoscopic pyeloplasty has been developed as a minimally invasive alternative to open pyeloplasty for the treatment of ureteropelvic junction obstruction (UPJO). Several series have been published with similar success rates for the two procedures. We present our initial experience with laparoscopic pyeloplasty. MATERIAL AND METHODS: A retrospective review of 29 consecutive patients (mean age 37 years) who underwent Laparoscopic dismembered Hynes-Anderson pyeloplasty in our institution between January 2001 to April 2003 was performed. All patients had flank pain with radiologic findings consistent with ureteropelvic junction obstruction and impaired drainage on diuretic renal scan. Patients were assessed at 6 weeks with an ultrasound and assessment of pain, then an intravenous pyelogram (i.v.p.) and diuretic renogram were completed at 6 months along with a repeat clinical assessment. RESULTS: Twenty-nine patients underwent the procedure with one patient converted to an open procedure due to difficulties with the anastomosis. Mean operating time was 225 minutes, which decreased with experience. Mean blood loss was 50 cc and no patient required transfusion. Mean hospital stay was 2.5 days. Mean follow-up was 12 months. Twenty-six patients had complete resolution of their pain and an improvement on ultrasound was demonstrated, but only six patients showed improvement in function on i.v.p. or renogram at 6 months. In five patients with 25% or less differential renal function preoperatively, the function was worse or negligible despite complete resolution of symptoms. One patient developed stent migration requiring repositioning and another developed calcification on the distal end of the stent requiring cystolithalopaxy prior to stent removal. CONCLUSIONS: In our experience, laparoscopic pyeloplasty offers excellent symptomatic relief in a minimally invasive fashion with low morbidity for adult patients with ureteropelvic junction obstruction. In patients with borderline function (25% or less) preoperatively and with a normal functioning contralateral kidney, nephrectomy should be a consideration.

Adolescent↗

PubMed2003

Herpes zoster infection: a rare cause of acute urinary retention.

Herpes zoster (HZ) infection has been reported as a rare cause of acute urinary retention. HZ infection involving sacral, thoracolumbar, and rarely high thoracic dermatomes is believed to occasionally cause motor and sensory neuropathy of the bladder. This is specifically achieved by the interruption of the detrusor reflex causing subsequent bladder atonia. As the course and management of this entity is quite benign, HZ should remain a diagnostic consideration in the management of urinary retention. We report a case of acute urinary retention of approximately 2.5 liters associated with HZ infection and review the proposed pathogenesis and therapeutic considerations in the management of this entity.

Acute Disease↗

PubMed2003

Technique of laparoscopic nephrectomy in a patient with previous urinary diversion.

Laparoscopic nephrectomy is quickly becoming accepted as the standard treatment for small renal neoplasms and benign renal disease. The presence of an ileal conduit has been termed a relative contraindication to laparoscopic surgery. A 58-year old female presented with recurrent pyelonephritis and hydronephrosis of her left kidney. Surgical removal was necessary and we considered a transperitoneal laparoscopic nephrectomy for her. The patient had an ileal conduit and it was because of this reason that only after careful consideration was it decided to attempt the surgery using the laparoscopic approach. We present our technique of transperitoneal laparoscopic nephrectomy in this patient with an ileal conduit and include technical suggestions that will help predict a successful outcome. The success of this case demonstrates that in certain circumstances, patients with urinary diversions can be offered laparoscopic nephrectomy and its benefits.

Female↗

PubMed2002

Apoptotic release of histones from nucleosomes.

Chromatin structure is influenced by histone modification, and this may help direct chromatin behavior to facilitate transcription, DNA replication, and DNA repair. Chromatin condensation and DNA fragmentation are the classic nuclear features but remain poorly characterized. It is highly probable that nucleosomal structure must be altered to allow these features to become apparent, but data to support this construct are lacking. We report here that in response to apoptotic signals from a death receptor (CD95 and tumor necrosis factor-alpha) or mitochondrial (staurosporine) apoptotic stimulus, the core nucleosomal histones H2A, H2B, H3, and H4 become separated from DNA during apoptosis in Jurkat and HeLa cells and are consequently detectable in the cell lysate prepared using a non-ionic detergent. The timing of this histone release from DNA correlates well with the progression of apoptosis. We also show expression of a caspase cleavage-resistant form of ICAD (ICAD-DM) in Jurkat and HeLa cells abolished DNA fragmentation and also dramatically reduced histone release in apoptotic cells. However, we demonstrate that apoptotic histone release is not an inevitable consequence of CAD/DFF-40-mediated DNA destruction as DNA fragmentation but not histone release occurs efficiently in tumor necrosis factor-alpha- and etoposide-treated NIH3T3 cells. Furthermore, in an in vitro apoptotic assay, incubation of apoptotic Jurkat cellular extract with non-apoptotic Jurkat nuclei led to nuclear DNA fragmentation without obvious histone release. Taken together, these data demonstrate that CAD/DFF-40 functions indirectly in mediating nucleosomal destruction during apoptosis.

3T3 Cells↗