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Biomedical subjects

P Narayan

Publications and source records attributed to P Narayan.

At least 163 records · Page 9Linked to original sources

Biochemical, cytogenetic, and morphological characteristics of human primary and metastatic prostate cancer cell lines.

Metastatic properties of human prostatic cancer cell lines (ND-1 and DU-145) were examined using various biochemical techniques. DU-145 cells had a higher metastatic potential than ND-1 cells. Cytogenetic analysis by G-banding demonstrated an aneuploid karyotype with considerable structural rearrangement. ND-1 cells had a modal chromosome number range lower than DU-145 cells (45-66, compared to 54-62). Ploidy analysis revealed that DU-145 cells showed hyperdiploidy with a greater amount of proliferation than the majority of ND-1 cells. Electron microscopic studies revealed little change in the cell morphology of either line. DU-145 cells had lower phosphatidyl choline levels and higher sphingomyelin levels than ND-1. DU-145 cells had much lower arachidonic acid levels than ND-1 cells. SDS-polyacrylamide gel electrophoresis revealed protein differences between the two cell lines. This study demonstrates for the first time that lipids, proteins and cytogenetic parameters differ in human primary and secondary prostate cancer cell lines.

Adenocarcinoma↗

Surgical treatment of female urethral carcinoma.

Urethral cancer is the only genitourinary neoplasm with a predilection for women, the ratio being 4:1. The histologic type depends on the cells of origin. Squamous-cell carcinoma predominates, with adenocarcinoma and transitional-cell carcinoma being less common and undifferentiated carcinoma, malignant melanoma, mixed tumors, clear-cell carcinoma, and cloacogenic carcinoma accounting for the remaining lesions. The authors describe the various options for the management of low-stage and high-stage cancers and of cancers arising in urethral diverticula.

Adenocarcinoma↗

31P spectroscopy of the human prostate gland in vivo using a transrectal probe.

Using a transrectal probe, good quality 31P magnetic resonance spectroscopy of the human prostate was performed safely, consistently, and in a reasonable amount of time (average of 60 min). Initial results indicate that transrectal 31P MRS has the ability to characterize the phosphorylated metabolites of normal, hyperplastic, and malignant prostates. This study demonstrated that malignant prostates are characterized by significantly decreased levels of phosphocreatine (PCr) and increased levels of phosphomonoesters (PME) as compared to healthy prostates.

Adult↗

Characterization of prostate cancer, benign prostatic hyperplasia and normal prostates using transrectal 31phosphorus magnetic resonance spectroscopy: a preliminary report.

We assessed the ability of 31phosphorus (31P) transrectal magnetic resonance spectroscopy to characterize normal human prostates as well as prostates with benign and malignant neoplasms. With a transrectal probe that we devised for surface coil spectroscopy we studied 15 individuals with normal (5), benign hyperplastic (4) and malignant (6) prostates. Digital rectal examination, transrectal ultrasonography and magnetic resonance imaging were used to aid in accurate positioning of the transrectal probe against the region of interest within the prostate. The major findings of the in vivo studies were that normal prostates had phosphocreatine-to-adenosine triphosphate (ATP) ratios of 1.2 +/- 0.2, phosphomonoester-to-beta-ATP ratios of 1.1 +/- 0.1 and phosphomonoester-to-phosphocreatine ratios of 0.9 +/- 0.1. Malignant prostates had phosphocreatine-to-beta-ATP ratios that were lower (0.7 +/- 0.1) than those of normal prostates (p less than 0.02) or prostates with benign hyperplasia (1.1 +/- 0.2, p less than 0.01). Malignant prostates had phosphomonoester-to-beta-ATP ratios (1.8 +/- 0.2) that were higher than that of normal prostates (p less than 0.02). Using the phosphomonoester-to-phosphocreatine ratio, it was possible to differentiate metabolically malignant (2.7 +/- 0.3) from normal prostates (p less than 0.001), with no overlap of individual ratios. The mean phosphomonoester-to-phosphocreatine ratio (1.5 +/- 0.5) of prostates with benign hyperplasia was midway between the normal and malignant ratios, and there was overlap between individual phosphomonoester-to-phosphocreatine ratios of benign prostatic hyperplasia glands with that of normal and malignant glands. To verify the in vivo results, we performed high resolution magnetic resonance spectroscopy on perchloric acid extracts of benign prostatic hyperplasia tissue obtained at operation and on a human prostatic cancer cell line DU145. The extract results confirmed the differences in metabolite ratios observed in vivo. We conclude that transrectal 31P magnetic resonance spectroscopy can characterize metabolic differences between the normal and malignant prostate.

Adult↗

Core biopsy instrument in the diagnosis of prostate cancer: superior accuracy to fine needle aspiration.

The recent availability of an automated core biopsy gun has made the performance of core biopsies of the prostate easier and better tolerated. A prospective study was conducted to compare the efficacy of fine needle aspiration to core biopsy with the gun. Among 94 patients subjected to both biopsy techniques at the same visit 30 (32%) had a positive diagnosis of prostate cancer. Core biopsy was positive in these 30 patients (100%), while fine needle aspiration was positive in 21 (70%). This study suggests that core biopsy with the gun is superior to fine needle aspiration in the diagnosis of prostate cancer.

Biopsy, Needle↗

Bladder substitution with ileocaecal (Mainz) pouch. Clinical performance over 2 years.

A series of 11 patients underwent ileocaecal bladder substitution (Mainz pouch) with urethral anastomosis after radical cystectomy and pelvic lymphadenectomy for moderate to high grade transitional cell carcinoma of the bladder. With 12 to 27 months of follow-up (mean 18), 6 patients are voiding and are dry day and night with timed voidings; 4 patients continue intermittent catheterisation because of inability to perform the Valsalva manoeuvre adequately, and 1 has a suprapubic tube because of stricture of the enterourethral anastomosis. Upper tract studies revealed dilation of 4 of 22 renal units and 1 patient required endourological intervention. Serum electrolyte studies revealed slightly elevated chloride levels in 6, mild hypocarbia in 3, and reduced vitamin B12 levels in all patients, but no megaloblastic anaemia. The Mainz pouch appears to have very satisfactory short- and intermediate-term results.

Anastomosis, Surgical↗

Nerve sparing and continence preservation during radical prostatectomy.

Prostate cancer is one of the most common malignancies occurring in men. During the last decade, several advances have been made in decreasing the morbidity of surgical therapy. Two major advances have included an improved understanding of the physiology of erection and anatomy of pelvic parasympathetic nerves mediating erectile function. Surgical techniques of 'nerve preservation' during surgery can preserve postoperative potency in 50-70% of patients with localized prostate cancer. In others the use of intracorporal vasoactive agents, vacuum suction devices and surgical techniques can additionally improve potency. Knowledge of the various mechanisms contributing to continence have additionally enabled modifications in surgical techniques to enhance continence rates postoperatively. Currently postoperative continence after radical prostatectomy occurs in over 95% of patients.

Humans↗

Alterations in sphingomyelin and fatty acids in human benign prostatic hyperplasia and prostatic cancer.

The present experiments were conducted to examine and characterize the lipid composition of benign prostatic hyperplasia (BPH) and prostatic cancer tissues (CAP). Lipids were extracted from these tissues and analyzed by thin layer chromatography (TLC) and gas liquid chromatography (GLC). The protein profiles of these tissues were analyzed by SDS-polyacrylamide gel electrophoresis. The results of these studies demonstrate that the principal lipids of BPH and CAP tissues are phosphatidyl choline, phosphatidyl ethanolamine, sphingomyelin, fatty acids and cholesterol. The sphingomyelin level is significantly higher in CAP tissues compared to BPH tissues. The differences in the enzymatic activities responsible for the biosynthesis and degradation of sphingomyelin appear to explain at least partially the alteration in sphingomyelin level between BPH and CAP tissues. The major fatty acids of phosphatidyl choline and phosphatidyl ethanolamine were palmitic (16:0), stearic (18:0), oleic (18:1) and arachidonic (20:4) acid. The arachidonic acid level was significantly decreased in CAP tissues compared to BPH tissues. SDS polyacrylamide gel electrophoresis revealed several protein differences between BPH and CAP tissues. The most significant difference was the decrease in 12 kDa protein in CAP tissues compared to BPH. The present data, therefore, suggests that there are significant alterations in sphingomyelin, fatty acids and protein profiles between BPH and CAP tissues.

Electrophoresis, Polyacrylamide Gel↗

N6-methyladenosine residues in an intron-specific region of prolactin pre-mRNA.

N6-methyladenosine (m6A) residues occur at internal positions in most cellular and viral RNAs; both heterogeneous nuclear RNA and mRNA are involved. This modification arises by enzymatic transfer of a methyl group from S-adenosylmethionine to the central adenosine residue in the canonical sequence G/AAC. Thus far, m6A has been mapped to specific locations in eucaryotic mRNA and viral genomic RNA. We have now examined an intron-specific sequence of a modified bovine prolactin precursor RNA for the presence of this methylated nucleotide by using both transfected-cell systems and a cell-free system capable of methylating mRNA transcripts in vitro. The results indicate the final intron-specific sequence (intron D) of a prolactin RNA molecule does indeed possess m6A residues. When mapped to specific T1 oligonucleotides, the predominant site of methylation was found to be within the consensus sequence AGm6ACU. The level of m6A at this site is nonstoichiometric; approximately 24% of the molecules are modified in vivo. Methylation was detected at markedly reduced levels at other consensus sites within the intron but not in T1 oligonucleotides which do not contain either AAC or GAC consensus sequences. In an attempt to correlate mRNA methylation with processing, stably transfected CHO cells expressing augmented levels of bovine prolactin were treated with neplanocin A, an inhibitor of methylation. Under these conditions, the relative steady-state levels of the intron-containing nuclear precursor increased four to six times that found in control cells.

Adenosine↗

Effect of testosterone on the glycosphingolipid composition of the rat kidney.

A series of experiments was conducted to examine the effect of subcutaneous administration of synthetic testosterone (500 micrograms/100 g body weight) on the acidic and neutral glycolipids. The kidney glycosphingolipids were separated by using Sep-Pak cartridge column. Florisil column, and high performance thin layer chromatography, and analyzed by gas liquid chromatography. Testosterone administration increased the total content of ceramide, acidic and neutral glycolipids. The increase in total neutral glycolipids was mainly due to an increase in glucosyl- and globotetraosylceramide. The increase in total gangliosides was due to the increase in GM3 (hematoside) and "others". The relative percentage of N-glycolylneuraminic acid in GM3 was increased whereas the relative percentage of sphingoside and phytosphingosine were increased and decreased, respectively, in GM3, glucosyl- and globotetraosylceramide. The relative percentage and chain length of hydroxy and nonhydroxy fatty acids of major glycosphingolipids were altered in this organ.

Animals↗

Prostatic oncology.

Prostate cancer is the most common cancer in men in the United States. Management of prostatic cancer has evolved over the last two decades based on a clearer understanding of the natural history and on improvements in the techniques of radiation therapy, surgery, and hormonal manipulation. Additionally, better methods of prevention and treatment of complications have helped to provide curative therapies for more patients of all ages. Discussion on these topics is followed by a section on special problems in management of elderly patients with prostate cancer.

Aged↗

Androgen sensitivity of rat prostate carcinoma studied by 31P NMR spectroscopy, 1H MR imaging, and 23Na MR imaging.

31P NMR spectroscopy, 1H magnetic resonance (MR) imaging, and 23Na MR imaging were used to study the biochemical difference between nine hormone-sensitive and six hormone-resistant rat prostate cancers and to follow bioenergetic and morphologic changes subsequent to androgen deprivation in the hormone-sensitive model. Neither 1H nor 23Na MR image characteristics were useful in distinguishing androgen-sensitive from androgen-resistant prostate cancer nor in identifying androgen deprivation. 31P NMR spectroscopy did detect bioenergetic differences between the hormone-sensitive and hormone-resistant tumors. Baseline spectra showed a significantly higher PCr/ATP ratio (mean 0.86 +/- 0.09 SEM) for hormone-sensitive tumors than for hormone-resistant tumors (mean 0.26 +/- 0.07 SEM). By 3 days after androgen deprivation (orchiectomy (castration], PCr/ATP ratios had decreased noticeably; by 1 week, the decrease was statistically significant and remained so for the rest of the study (3 weeks). It appears that 31P NMR spectroscopy is useful in detecting androgen sensitivity of prostatic carcinoma.

Androgens↗

Transrectal probe for 1H MRI and 31P MR spectroscopy of the prostate gland.

A transrectal probe for 1H imaging and 31P MR spectroscopy of the prostate gland is described. The probe is covered with plastic and consists of an insectional portion containing an rf coil and a handle containing a tuning and matching circuit. Using this transrectal probe, 1H MR images and the first 31P MR spectra of the in situ canine prostate were obtained. Serial alterations in prostate size and changes in the ratio of phosphomonoesters to ATP ratio following orchiectomy were observed. Transrectal images of the prostate appear to be superior to conventional whole body coil images in the canine. For the first time a device to obtain high signal-to-noise 1H images and 31P spectra of the in situ prostate has been constructed. This will allow the assessment of transrectal imaging and spectroscopy as tools for medical studies of prostate pathophysiology.

Administration, Rectal↗

A comparison of fine needle aspiration and core biopsy in diagnosis and preoperative grading of prostate cancer.

Fine needle aspiration biopsy has been documented to be safe and accurate for the diagnosis of prostate cancer. A study was done based on 3 objectives to determine 1) whether performing core biopsies and fine needle aspiration in each patient with a prostate nodule increases the detection rate of prostate cancer, 2) the accuracy of preoperative grading by fine needle aspiration in predicting the final pathological grade in radical prostatectomy specimens and 3) the usefulness of fine needle aspiration in screening for unsuspected stage A prostate cancer. Of 203 consecutive patients undergoing prostate biopsies core and fine needle aspiration biopsies were performed in 121. An additional 58 patients underwent prostate biopsies just before transurethral resection of the prostate and 24 underwent radical prostatectomy. The diagnostic accuracy of fine needle aspiration was superior to that of core biopsy (82 versus 74 per cent). Performance of both biopsies yielded a higher percentage of positive diagnoses than either biopsy alone (32.2 per cent versus 24 and 28 per cent). Except in poorly differentiated cancers, fine needle aspiration is a poor predictor of final pathological grade. Fine needle aspiration is not useful in detecting stage A1 prostate cancer. Although fine needle aspiration has several distinct advantages over core biopsies, there is a definite learning curve before its use can be fully exploited. It is important to have an experienced pathologist and to perform both biopsies at each center until sufficient experience is accumulated.

Biopsy↗

An in vitro system for accurate methylation of internal adenosine residues in messenger RNA.

Some internal adenosine residues in messenger RNA are methylated posttranscriptionally in the nucleus. Most of the methylated adenosine residues in prolactin mRNA are in the 3' untranslated region. The site of methylation in the 3' end of prolactin mRNA was determined. This methylation reaction is highly specific; of the three adenosine residues in consensus sequences located in the 3' end, only one is methylated. An in vitro methylation system was developed in which bovine prolactin mRNA, synthesized in vitro with T7 RNA polymerase, was accurately methylated in a HeLa cell nuclear extract. The adenosine residue that was methylated in vitro was the same as the one methylated in vivo. This cell-free system, which accurately methylates the N6-position of adenosine residues in mRNA, will allow further study of the mechanism of adenosine methylation.

Adenosine↗

Lumbar herniation of the kidney.

We report a case of lumbar herniation of a kidney, resulting in intermittent ureteropelvic junction obstruction. Surgical repair of the lumbodorsal fascial defect resulted in resolution of the uretero-pelvic junction obstruction.

Adult↗

The benefits of combining early radionuclide renal scintigraphy with routine bone scans in patients with prostate cancer.

Based upon the rapid early renal excretion of bone imaging radiopharmaceuticals, we performed a prospective study to determine the use of combining renal evaluation with routine bone scans in 79 consecutive patients with prostate cancer. The radionuclide renal scintigraphy consisted of a 1-minute sequence of 2.5-second frames with a bolus injection of 99mtechnetium-methylene diphosphonate followed by a series of 2-minute images for 24 minutes. Whole body bone scans were performed after a 3-hour delay. All patients had at least 1 confirmatory study with excretory urography (62), ultrasonography (49) or computerized tomography (30). Results were interpreted independently and compared. Ten studies were normal. Radionuclide renal scintigraphy was able to identify 45 of 49 cortical abnormalities (90 per cent) with a false positive rate of 4 per cent. Accuracy of renal cyst detection was only 47 per cent (15 of 32 cases). All acutely obstructed kidneys were identified correctly by radionuclide renal scintigraphy (5 of 5 cases). Of 12 chronically obstructed kidneys 8 (67 per cent) were identified correctly. The 4 missed kidneys were small and nonfunctioning, and they were diagnosed correctly as such but obstruction as the etiology of nonfunction was unidentifiable by radionuclide renal scintigraphy. The false positive rate of obstructive diagnosis by radionuclide renal scintigraphy was 24 per cent (4 of 17 cases). These findings demonstrate that renal evaluation combined with routine bone scanning is an effective screening procedure for renal complications of prostate cancer; no significant abnormalities were missed. The procedure is entirely free of morbidity and does not add to the radiation dose from the bone scan. Furthermore, it is cost-effective, since it avoids the routine need for 2 separate procedures at followup of patients with prostate cancer.

Bone and Bones↗