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Biomedical subjects

C A Olsson

Publications and source records attributed to C A Olsson.

At least 127 records · Page 7Linked to original sources

Induction of the TRPM-2 gene in cells undergoing programmed death.

RNA and protein products encoded by the testosterone-repressed prostate message-2 gene (TRPM-2) are induced to high levels, coordinate with the onset of cell death, in numerous rodent models of inducible tissue damage. These models include cell death initiated by hormonal stimuli (prostate regression), pressure insult (renal atrophy after ureteral obstruction), developmental stimuli (necrosis of interdigital tissue), and cytotoxic injury (chemotherapeutic regression of a tumor). Sequence analysis of cDNA encoding TRPM-2 revealed its close homology with a product referred to as SGP-2 or clusterin expressed constitutively by Sertoli cells; however, the immunologically related polypeptides expressed in regressing tissues differ in molecular mass from the forms secreted by the testis. Although the function(s) of the products encoded by the TRPM-2 gene remains unclear, their presence provides a remarkable and early indicator of programmed cell death in many types of mammalian cells.

Animals↗

Calcium channel antagonists delay regression of androgen-dependent tissues and suppress gene activity associated with cell death.

Androgen deprivation subsequent to castration of an adult male rat results in the regression of sexual accessory tissues. Regression of these tissues involves the massive death of androgen-dependent cells. Using the rat ventral prostate gland as a model to study androgen-programed cell death, we have characterized a series of molecular events that accompany its regression. This analysis has shown that there was a sequential induction of specific gene transcripts in the ventral prostate gland following castration. The first event in this cascade was an abrupt induction of transcripts encoding c-fos. Since c-fos expression has been linked to perturbations in intracellular Ca2+ levels, we investigated whether membrane-mediated Ca2+ flux might be an early physiological step involved in the death of prostatic cells. To test this, rats were treated simultaneously upon castration with either verapamil or nifedipine, two different calcium channel antagonist drugs. Compared to the ventral prostate glands of untreated castrated rats, the glands of the calcium channel antagonist-treated rats showed a significant delay in all parameters associated with regression (loss of wet weight and DNA content and delay in histological changes associated with prostatic regression). The seminal vesicle glands of treated rats also showed signs of delayed regression. Furthermore, calcium channel antagonists suppressed the induction of transcripts encoding both c-fos and testosterone-repressed prostate message-2 (TRPM-2), a gene expressed exclusively by dying cells, during the first 62 hr following castration. These findings further support a role for calcium ion influx in the pathway leading to hormonally programed prostate cell death, and suggest the intriguing possibility that modulation of this activity can alter the process by which cells die.

Androgens↗

Gene expression in renal growth and regrowth.

To elucidate the molecular events associated with postnatal and compensatory renal growth, the expression of growth/differentiation genes (c-fos, c-myc, c-H-ras, c-K-ras), a stress-related gene (HSP70) and a structural gene (collagen type IV, alpha 1 and 2) were examined. Northern analysis of messenger ribonucleic acid from the newborn mouse reveals high levels of expression of HSP70, c-H-ras, and c-K-ras during the first week of life. By day 40 HSP70-related and c-H-ras expression decreases somewhat, c-K-ras remains unchanged and collagen type IV, which encodes for the renal glomerular basement membrane, expression decreases significantly. During compensatory renal growth increased expression of HSP70, c-H-ras and c-K-ras occurs. The results seem to indicate that growth/differentiation genes may be necessary for continued cell growth (hypertrophy) in postnatal and compensatory renal growth, and that collagen type IV formation continues up through week 2 of postnatal growth consistent with the interval of glomerular basement membrane formation.

Animals↗

Stress incontinence: classification and surgical approach.

We present a modified classification for stress urinary incontinence based on the nature of vesical neck descent and the integrity of the intrinsic sphinteric mechanism. Surgical treatment was undertaken in 72 patients with this classification. With a minimum followup of 18 months there was a 94 per cent cure rate with respect to stress incontinence. However, in 14 patients significant frequency and urgency developed, which persisted for at least 6 months postoperatively. Of these patients 13 had undergone a pubovaginal sling procedure, 3 of whom had refractory symptoms, including urge incontinence, which resulted in augmentation cystoplasty in 2 and supravesical urinary diversion in 1.

Female↗

Contemporary cystectomy versus preoperative radiation plus cystectomy for bladder cancer.

The role of preoperative radiation therapy (RT) as an adjunct to radical cystectomy (C) was studied by reviewing 58 consecutive patients requiring bladder removal during 1980-1982 for transitional cell carcinoma (TCC). Thirty-six patients underwent RT + C; 22 had C alone. The sole reason for choosing between RT + C versus C was physician prejudice favoring one form of therapy over another. Pretreatment clinical staging was similar in both groups, slightly favoring the RT + C group with only 25 percent versus 36 percent of C patients with clinical stage exceeding B1. Pathologic stage distribution similarly favored the RT + C group slightly with only 56 percent versus 68 percent of C patients having lesions with P-stage greater than B1. Thirty-three percent of patients in the RT + C group had papillary lesions in contrast to only 27 percent in the C alone group. There was only one postoperative death in each group. Three-year minimal follow-up was available in all surviving patients. One-, two-, and three-year survival free of disease was 94 percent, 80 percent, and 70 percent, respectively, in the group treated by C alone. Similar figures for the RT + C group were 86 percent, 76 percent, and 60 percent, respectively. Projected five-year survival rates for both groups regardless of preoperative RT was over 60 percent. All but one failure in the RT + C group had 4,000 rad or more preoperative radiation. This contemporary study shows no advantage of preoperative radiation in patients requiring cystectomy for transitional cell carcinoma of the bladder.

Carcinoma, Transitional Cell↗

The limited usefulness of external beam radiotherapy in the control of superficial bladder cancer.

Thirty-seven patients with superficial bladder cancer (Ta, T1) who failed local control were treated with external beam radiotherapy: 22 received full dose radiotherapy without interval cystoscopic monitoring and 15 followed a protocol in an attempt to select a subgroup of radiosensitive tumours. Both the unselected and protocol treated patients demonstrated the limited usefulness of external beam radiotherapy in the treatment of superficial bladder cancer.

Dose-Response Relationship, Radiation↗

Continent urinary diversions: review of current surgical procedures and radiologic imaging.

Continent urinary diversions are currently gaining wide acceptance as alternatives to the ileal conduit following cystectomy for neoplasm or bladder dysfunction. Clean, intermittent catheterization of the reservoir (pouch) at regular intervals obviates the inconvenience of wearing an external stomal appliance. A variety of surgical techniques have been described for continent pouches. These techniques make use of the small bowel alone (Camey and Kock techniques) or a combination of cecum and terminal ileum (Indiana, Mainz, Penn, and King techniques). The optimum pouch protects the upper tracts by prevention of reflux, provides urinary continence, and has sufficient capacity to require catheterization no more frequently than every 3-6 hours. Simplified construction techniques for the commonly encountered pouches are graphically presented, and a method is suggested for the study of continent diversions.

Cecum↗

Multiple primary neoplasms in association with prostate cancer in black and white patients.

The current study follows up the 983 patients who were diagnosed as having prostate cancer at the Columbia-Presbyterian Medical Center in New York City between 1970 and 1979 and of whom 106 (11.5%) developed a multiple primary malignant neoplasm (MPMN) in addition to their prostate cancer by January 1, 1986. Of the 283 black patients, 32 (11.3%) developed an MPMN involving 35 sites excluding prostate. Of the 636 white patients, 74 (11.6%) developed an MPMN in association with their prostate cancer. Comparing observed incidence rates to expected on the basis of SEER incidence data, two malignant tumors, urinary bladder cancer and malignant lymphoma, appeared to occur in excess in the present series of patients. The excess of urinary bladder cancer in our series could be explained by detection bias due to the routine use of cystoscopy. The excess incidence of lymphoma in our series appears significant but its etiology is unexplained.

Adult↗

Enhanced expression of the c-myc protooncogene in high-grade human prostate cancers.

We examined a series of 29 surgical specimens of benign and malignant human prostate tissue for the expression of both the cHa-ras and c-myc protooncogenes. Northern blots were prepared using polyadenylated mRNA extracted from nine prostatic adenocarcinomas, 19 benign hypertrophied prostates (BPH) and one normal prostate. When the Northern blots were hybridized to a probe for cHa-ras, only one specimen of BPH showed an appreciable amount of the 1.2-kb transcript homologous to cHa-ras. Upon reprobing these blots with c-myc, six cancers showed a considerable amount of a 2.4-kb transcript homologous to c-myc. Three other cancers and all the benign tissue showed little or no detectable 2.4-kb c-myc transcript. On retrospective analysis, the cancers with elevated c-myc transcripts were found to have a Gleason score of 5 and above (poorly differentiated tumors), while the cancers with little or no c-myc transcripts were all of Gleason score 4 and lower. Finally, we compared our ability to detect c-myc transcripts in mRNA extracted from a surgically derived prostate tumor with mRNA extracted from the same tumor subject to a sham electrocautery procedure, as would occur during transurethral resection. The electrocautery procedure decreased both the intensity and the integrity of the c-myc signal in mRNA from the tumor. Thus, our exclusive use of surgically derived prostate tumors may be the reason we are able to detect an elevation in the expression of c-myc mRNA in high-grade tumors.

Adenocarcinoma↗

Complications of artificial urinary sphincter around intestinal segments in reconstructed exstrophy patients.

Nine patients 15 to 28 years old underwent placement of the artificial urinary sphincter around an internal intestinal urinary reservoir. A total of 15 complications was experienced in 8 patients and 13 secondary procedures were necessary. Eight patients are completely continent and 1 has nighttime enuresis. The most common complication encountered was reduction in bowel luminal circumference underlying the sphincter cuff.

Adolescent↗

Prognostic variables in patients with transitional cell carcinoma of the renal pelvis and proximal ureter.

Recent technological advances in urological endoscopic surgery of the renal pelvis and proximal ureter via ureteroscopy or percutaneous nephroscopy have made it possible to consider parenchymal-sparing procedures in patients with transitional cell carcinoma. To define the role of these procedures in the management of renal pelvic or proximal ureteral transitional cell carcinoma we analyzed retrospectively 31 patients who underwent nephroureterectomy for transitional cell carcinoma of the renal pelvis and/or proximal ureter. High grade upper urinary tract transitional cell carcinoma and a history of metachronous or synchronous bladder transitional cell carcinoma were independent adverse prognostic factors. However, patients with low grade upper urinary tract transitional cell carcinoma and no evidence of a urothelial field change had a 100 per cent 5-year survival rate. It would appear that parenchymal-sparing endoscopic techniques should be regarded with caution in patients with either high grade transitional cell carcinoma of the renal pelvis and proximal ureter or a history of bladder cancer.

Adolescent↗

Prostate cancer in men less than 45 years old: influence of stage, grade and therapy.

We analyzed patients with histologically proved adenocarcinoma of the prostate to determine the natural history of prostatic cancer in men less than 45 years old. The mean age of the patients was 41 years (range 36 to 44 years). At presentation 5 patients were asymptomatic, 5 had voiding symptoms, 3 had bone pain, 3 had hematuria and 1 had testicular pain. Followup in these patients ranged from 19 to 270 months, with a mean of 111 months. Six patients with clinical stage B disease at diagnosis underwent radical retropubic prostatectomy. These patients enjoy projected 10 and 15-year survival rates of 100 and 82 per cent, respectively. Four patients with stage C disease died of prostatic cancer, although 1 survived for 204 months. Of 4 patients with stage D disease 3 died within 13 months, while 1 still is alive at 48 months. No patient with a Gleason tumor score of 8 to 10 survived more than 13 months. Patient age at presentation appears to be less important than clinical stage, histological grade or treatment modality in the prediction of the course of prostatic cancer. Young men with localized disease at presentation should be treated aggressively and they should have survival rates comparable to actuarial expectancy.

Adenocarcinoma↗

Enhanced expression of Harvey-ras oncogene in FANFT-induced transitional cell carcinoma.

The level of mRNA expression and DNA structure of c-H-ras were examined in a transitional cell carcinoma (TCC) induced in C3H/He mice and Fisher rats by N-(4,5-nitro-2-furylthiazolyl)formamide (FANFT) and carried as serially transplanted tumors. Neither amplification nor gross rearrangements were detected by Southern analysis in the FANFT tumor. Increased expression of c-H-ras was detected by Northern and in situ hybridization in both the FANFT-induced mouse and rat TCC, as compared to normal urothelium. No expression of six other cellular oncogenes was detected in the tumor. It appears that the increase in H-ras expression in the FANFT tumor is specific to this oncogene and that increased expression of the H-ras gene may play a role in bladder carcinogenesis.

Animals↗

Prediction of transcriptional activity based on gene association with the nuclear matrix.

In this report, we show that androgen-dependent genes expressed in rat ventral prostate, C1, C2 and C3, are enriched in residual DNA extracted from the nuclear matrix of ventral prostate. The enrichment is androgen-dependent and is likely to be related to their transcriptional activity. While this finding corroborates other data demonstrating that transcriptionally active genes can be protected from nuclease digestion by their association with the nuclear matrix, we have extended this analysis to show that nuclear matrix protection experiments can be used both to analyze tissue-specific expression among members of a highly related gene family and also to predict transcriptional activity of genes in particular tissues.

Androgen-Binding Protein↗

Flow cytometry: role in monitoring transitional cell carcinoma of bladder.

The ability to detect and monitor the course of transitional cell carcinoma (TCC) of the bladder using DNA histograms obtained from flow cytometry was studied. Voided urine and barbotage specimens were collected from patients with active TCC or a past history of TCC. These specimens were submitted to routine cytologic and flow cytometric analyses. Samples were considered to be positive if they met one or more of three criteria: if they had aneuploid or tetraploid peaks, if the DNA index of the major G1 peak was shifted more than 10 per cent from that of diploid cells, or if 15 per cent or more of the cells fell to the right of the major diploid G1 cell population thereby constituting a significant hyperdiploid cell population. Using these methods for patients with active disease, the detection rate was 91 per cent. In patients with a past history of TCC, positive histograms preceded the appearance of visible tumor in one third of the cases. Flow cytometry proved to be an excellent way of following patients with a past history of TCC or of screening patients suspected of having active disease. Following this protocol, few biologically active tumors go undetected. However, in 112 patients without a history of bladder cancer, the false positive or suspicious rate was 38 per cent. Before flow cytometry can be recommended as a widespread screening method for patients thought to be at risk of TCC of the bladder developing, this suspicious group will have to be eliminated.

Carcinoma, Transitional Cell↗

Combined Boari bladder flap-psoas bladder hitch procedure in ureteral replacement.

Uncomplicated injuries to the ureter are commonly treated with end-to-end ureteroureterostomy or reimplantation into the bladder. The Boari bladder flap and the psoas bladder hitch have been used separately when distal ureteral replacement is required. In cases of more extensive ureteral damage extending above the pelvic rim, more complex procedures have been performed. These procedures (transureteroureterostomy, intestinal replacement or renal autotransplantation) often represent a considerable surgical challenge and may be associated with numerous complications. Combining the principles of the psoas bladder hitch and Boari flap affords the clinician a means of traversing extensive ureteral defects with standard surgical techniques. We report herein patients with ureteral damage who have undergone replacement of various lengths of ureter with combined psoas hitch/Boari flap procedures. The technique is suitable for traversing ureteral defects at least to the lower pole of the kidney. An obvious advantage is that the replacement utilizes only normal urinary tract, it does not endanger ipsilateral kidney nor contralateral ureter or kidney and can be employed in patients with decreased renal function. In our experience ureteral replacement with the combination of the psoas bladder hitch and Boari bladder flap is an excellent method which is surgically simpler and safer than the other methods described for more extensive ureteral injuries.

Adult↗