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T Otto

Publications and source records attributed to T Otto.

At least 73 records · Page 4Linked to original sources
PubMed1997

Protein kinase C isoenzymes in rat and human cardiovascular tissues.

1. We have compared the expression of protein kinase C (PKC) activity and immuno-detectable isoenzymes in cytosolic and membrane extracts of rat and human cardiovascular tissues (heart, kidney, aorta, saphenous vein). Experiments were performed in raw extracts and upon combined diethylaminoethylcellulose (DEAE) and phenylsepharose column chromatography. 2. PKC activity that bound to DEAE mostly eluted with 200 mM NaCl. DEAE-purified PKC from all tissues except rat kidney bound almost quantitatively to phenylsepharose and eluted with 0.5-0 M NaCl. 3. Immunoblots with an antibody against classical PKCs and the activator profile for phosphatidylserine, diolein and Ca2+ revealed that the PKC from rat kidney, which did not bind to phenylsepharose, was most probably due to a proteolytically-generated, constitutively active PKC which is not under the control of a regulatory subunit. 4. Studies in the reference tissue, rat brain, demonstrated that all PKC isoenzymes investigated (classical PKCs alpha, beta, gamma, new PKCs delta, epsilon, eta, theta, and atypical PKCs zeta, lambda, iota) have similar DEAE and phenylsepharose chromatography elution profiles. In the functional assay an inhibitor of all known PKC isoenzymes, bisindolylmaleimide, and a specific inhibitor of classical PKCs, Gö 6976, both inhibited PKC from rat brain completely and with high potency indicating that the functional assay preferentially detects classical PKC isoenzymes. 5. Each PKC isoenzyme had a tissue-specific expression profile which was similar in rat and man. The classical PKC alpha, the new PKCs delta and epsilon and all atypical PKCs were detectable in most tissues, whereas the PKC beta and PKC gamma were not detected in any pheripheral tissue; PKC eta and PKC theta were found in some tissues. 6. We conclude that combined DEAE and phenylsepharose chromatography is useful to enrich and detect PKC isoenzymes; no major species differences in tissues-specific expression patterns appear to exist between rat and man.

Animals↗
PubMed1997

Phase II study: adjuvant single-agent carboplatin therapy for clinical stage I seminoma.

OBJECTIVE: Though para-aortal and ipsilateral iliacal radiation is the established adjuvant treatment for clinical stage I seminoma, promising results have been reported on adjuvant single-agent carboplatin therapy. PATIENTS AND METHODS: We treated 43 patients with clinical stage I seminoma according to this option. They received 2 courses of single-agent carboplatin (400 mg/m2) at an intervall of 3 weeks. Therapy could be performed on an outpatient basis within 2 h. RESULTS: Therapy was well tolerated. Apart from minor gastrointestinal disorders and mild myelosuppression, no adverse reactions were observed. The median follow-up is 28 months. Up to now no recurrences have been noted. CONCLUSIONS: If the recurrence rate remains as low as after adjuvant radiotherapy, which should be proved in a phase III study, single-agent carboplatin therapy will be an alternative adjuvant approach for clinical stage I seminoma.

Adult↗
PubMed1997

Improved prognosis assessment for patients with bladder carcinoma.

Urothelial carcinomas are heterogeneous diseases with an aggressive clinical potential. To date, the most used prognostic factors for bladder carcinomas are grade and stage, which are based on histopathological parameters that are often not reliable in predicting a clinical outcome. Here, we evaluated the clinical outcome of 100 patients with urothelial carcinomas with follow-up information for more than 2 years after surgery in relation to the expression of two cell surface antigens, ie, E-cadherin and autocrine motility factor receptor (AMF-R, gp78). Frozen bladder tissues were serially cut, stained either with hematoxylin and eosin for grading, with the anti-gp78 antibodies, or with anti-E-cadherin antibodies to determine level of expression. Of 63 patients presented at the time of diagnosis with pathological loss of E-cadherin associated with increased gp78 expression, 39 (62%) succumbed to tumor progression or death. Of 37 patients with normal E-cadherin and gp78 expression positive and negative, respectively, 36 (97%) had favorable disease outcomes (P < 0.0001). The results suggest that in bladder carcinomas abnormal expression of both E-cadherin and gp78 results in a poor disease outcome, independent of tumor stage and grade.

Age Factors↗
PubMed1997

Odor-guided fear conditioning in rats: 1. Acquisition, retention, and latent inhibition.

Three experiments examined the acquisition, retention, and latent inhibition of odor-guided fear conditioning in rats. The results of Experiment 1 indicate that forward conditioned stimulus (CS)-unconditioned stimulus (US) pairings resulted in robust freezing responses to subsequent presentation of the CS alone. In Experiment 2, rats in one group (PRE) received unreinforced preexposures to the odorant CS, and those in a second group (NON) were not preexposed to the odorant. All rats then received forward CS-US pairings. PRE rats exhibited a marked attenuation of freezing to subsequent exposure to the CS relative to NON rats. All rats were then retested at one of the following posttraining delays: 17, 24, or 31 days. Freezing behavior of the NON rats declined significantly across these delays, whereas rats in the PRE group froze no more at any delay than they had 24 hr after training. Experiment 3 examined the contextual specificity of latent inhibition. Only those rats that were preexposed and trained in the same context exhibited latent inhibition. These results indicate that odor-guided fear conditioning is a robust and useful paradigm suitable for future studies of the neural bases of associative learning.

Animals↗
PubMed1996

Detection of chromosomal DNA gains and losses in testicular germ cell tumors by comparative genomic hybridization.

To extend the results of conventional cytogenetic analysis of testicular germ cell tumors (TGCTs), we applied the new molecular cytogenetic method of comparative genomic hybridization (CGH), which enables the detection of chromosomal imbalances without the need for dividing cells. DNA from II TGCTs was studied by CGH. In all tumors examined, gain of 12p, mostly of the whole p arm, could be demonstrated. However, in three tumors, an amplification of 12p material restricted to the chromosomal bands 12p11.2-p12.1 was found. Further fluorescence in situ hybridization (FISH) analysis using a yeast artificial chromosome (YAC) that was previously mapped to that region revealed multiple copies of that chromosomal segment in interphase nuclei of these tumors. This finding is an important clue to the localization of candidate protooncogenes at 12p involved in TGCTs. Gains of small chromosomal regions at 2p, 4q, 6p, and 19p were also detected recurrently. Furthermore, gains of chromosomes 8, 14, 21, and X as well as loss of chromosome 13 were frequent findings. In conclusion, CGH provides new insights into genetic alterations of TGCTs. By using CGH, chromosomal subregions could be identified that may harbor genes involved in the pathogenesis of this malignancy.

Adolescent↗
PubMed1996

A randomized multicenter trial of adjuvant therapy in superficial bladder cancer: transurethral resection only versus transurethral resection plus mitomycin C versus transurethral resection plus bacillus Calmette-Guerin. Participating Clinics.

PURPOSE: A randomized multicenter trial was done to compare transurethral resection only to transurethral resection plus adjuvant mitomycin C and bacillus Calmette Guerin (BCG) instillation for treatment of superficial bladder cancer (stage pTa/1 grades 1 to 3 except primary stage pTa grade 1). MATERIALS AND METHODS: Included in the study were 337 patients with superficial stage pTa/1 grades 1 to 3 bladder cancer except primary stage pTa grade 1 tumors. One group underwent transurethral resection alone. Mitomycin C (20 mg./50 ml. sodium chloride) was given every 2 weeks during year 1 and once a month during year 2. BCG (120 mg/50 ml. sodium chloride was instilled once a week for 6 weeks and once a month for 4 months. RESULTS: At a median followup of 20.2 months, a decrease in recurrence rate was noted for both drug instillations compared to transurethral resection only. The relative risk of recurrence was 0.508 after mitomycin C and 0.618 after BCG instillation compared to transurethral resection alone. There was no significant difference between the mitomycin C and BCG instillations. The progression rate was comparable in all 3 therapy groups, with an estimated common progression rate of 4.22% per year. Side effects occurred most frequently during or after BCG instillation, most often consisting of cystitis. One patient required cystectomy because of ulcerating cystitis and a prostatic abscess subsequent to unsuccessful tuberculostatic therapy. There were no systemic complications. CONCLUSIONS: Our study showed a positive effect of adjuvant chemotherapy and immunotherapy on decreasing tumor recurrence rate. No influence was observed concerning progression rate, which was low overall.

Adjuvants, Immunologic↗
PubMed1996

An intra-operative seminal and prostate emission test as a control for nerve-sparing procedures in primary and secondary retroperitoneal lymphadenectomy.

OBJECTIVE: To determine the value of an intra-operative electrostimulatory test of post-ganglionic nerves for the preservation of ejaculation in primary and secondary retroperitoneal lymph-node dissection (RLND). PATIENTS AND METHODS: Between 1991 and 1994, 21 patients with non-seminomatous testicular cancer of clinical stage A and 15 patients with bulky or clinical stage C disease underwent primary or secondary RLND, respectively. During surgery, post-ganglionic nerves were electrostimulated at 30 Hz and up to 20 V, for 3-10 s. Emissions were recorded simultaneously by suprapubic ultrasonography of the seminal vesicals and bladder neck (in 36 patients) and by endoscopy of the posterior urethra (in 11 patients). RESULTS: A positive intra-operative emission test in 15 pathological stage A (with bilateral nerve-sparing) and six pathological stage B (with contralateral nerve-sparing) patients predicted the post-operative preservation of antegrade ejaculation. In the group undergoing secondary RLND, the test allowed the identification and sparing of the emission-related nerves in four of 15 patients with a residual mass consisting of necrosis/fibrosis, and preserved antegrade ejaculation after surgery. CONCLUSIONS: A positive result in the seminal emission test predicted the preservation of antegrade ejaculation after surgery. The test is not necessary in patients with clinical stage A disease, but improves the chances of reducing morbidity. If the residual mass consists of necrosis or fibrosis, then electrostimulation during secondary RLND can help to identify important nerve structures when their origin is unknown initially. However, attempts to retain nerve function must not jeopardize the patient's survival. The test can be an option for clinical stage B disease with initial bilateral RLND, to identify and preserve emission-relevant nerves while the retroperitoneal space is removed radically. The test may also give additional information about the physiology of emission.

Ejaculation↗
PubMed1996

Drugs for treatment of benign prostatic hyperplasia: affinity comparison at cloned alpha 1-adrenoceptor subtypes and in human prostate.

1. We have previously shown that among alpha 1-adrenoceptor antagonists used or investigated for the treatment of benign prostatic hyperplasia, tamsulosin discriminates alpha 1-adrenoceptor subtypes in rat tissues whereas alfuzosin and naftopidil do not. We now expand these studies to additional drugs (doxazosin, terazosin) being used and/or investigated for this purpose, and have evaluated all of these drugs at cloned subtypes and in human prostate. 2. Competition binding studies were performed with [3H]-prazosin in membrane samples from rat spleen, kidney and cerebral cortex and human prostate and with cloned alpha 1-adrenoceptors expressed in COS cells. Doxazosin and terazosin did not discriminate alpha 1-adrenoceptor subtypes in rat kidney and cerebral cortex. In contrast, the subtypes present in the tissues were well discriminated by the alpha 1A-adrenoceptor-selective reference drug WB 4101. 3. Alfuzosin, doxazosin, naftopidil and terazosin did not discriminate cloned alpha 1-adrenoceptor subtypes transiently expressed in COS cells whereas tamsulosin and WB 4101 did. 4. In human prostate, alfuzosin, doxazosin, naftopidil and terazosin did not discriminate the alpha 1-adrenoceptor subtypes present in this tissue whereas tamsulosin and the alpha 1A-adrenoceptor-selective reference drugs WB 4101, phentolamine and 5-methylurapidil did. Based on data with the alpha 1A-adrenoceptor-selective drugs, human prostate contains alpha 1A- and alpha 1B-adrenoceptors in an approximate 70:30% ratio. 5. We conclude that tamsulosin, in common with WB 4101, but in contrast to alfuzosin, doxazosin, naftopidil, and terazosin is selective for alpha 1A-adrenoceptors which appear to dominate in the human prostate; the therapeutic relevance of this selectivity remains to be assessed in clinical studies.

Adrenergic alpha-Antagonists↗
PubMed1996

Results of postchemotherapy adjunctive retroperitoneal lymph node dissection in non-seminomatous germ cell cancer patients.

Cisplatin-based chemotherapy is highly effective in non-seminomatous testicular cancer. Patients with advanced disease receive two to four cycles of polychemotherapy. Residual retroperitoneal masses after chemotherapy are suspected to contain active tumour tissue as well as mature teratoma. Therefore, a delayed retroperitoneal lymph node dissection remains necessary. A total of 123 patients with advanced non-seminomatous germ cell cancer underwent retroperitoneal surgery after two different regimes of cisplatin-based chemotherapy. The first group (n = 55) received a sequential alternating chemotherapy with Adriamycin/cisplatin and bleomycin/vinblastine (8.5 +/- 5 cycles, 1979-1985), the second group (n = 60) got a standard PEB scheme (cisplatinum /etoposide/bleomycin; 5.7 +/- 2.1 cycles, 1985-1991). Eight patients got other cisplatin-based combinations. All patients received adjunctive retroperitoneal surgery. After a mean follow-up period of 72 months, the patients treated with the sequential alternating scheme showed a survival rate of 50% (27/54, 1 patient lost to follow-up). After the PEB scheme a survival rate of 79% (46/58, 2 patients lost to follow-up) was found. 86% of the patients with retroperitoneal necrosis after retroperitoneal lymph node dissection (RPLND; n = 58) survived with no evidence of disease, as well as 82% of the patients with adult teratoma (n = 18). Only 47% of the patients with residual active carcinoma after RPLND (n = 47) survived within a follow-up period of (median) 72 months, despite further chemotherapy after RPLND. Residual tumor burden and type of histology after RPLND can partially predict the clinical outcome. A necrotic specimen in RPLND could not be predicted by any means, so that surgical removal of a residual retroperitoneal mass after chemotherapy remains necessary. Standard PEB chemotherapy is superior to sequential alternating chemotherapy.

Adult↗
PubMed1996

Recent considerations for hypospadias repair: results of 252 operations from 1985 to 1990.

OBJECTIVES AND METHODS: 252 hypospadias operations were performed at our department from 1985 to 1990. We conducted 173 primary repairs and 79 reoperations. In distal hypospadias (n = 98), we used the meatoplasty and granuloplasty procedure as well as the Mathieu technique. In penile hypospadias (n = 40), a tubularized dorsal preputial flap (Duckett procedure) was performed. Proximal and scrotal hypospadias (n = 23) were operated using a combination of Duckett's tube and the Thiersch-Duplay procedure. RESULTS: We saw a 15% complication rate in distal hypospadias, 36% in penile hypospadias, and 27% in proximal hypospadias. CONCLUSION: The Mathieu technique gave a complication rate of 35.5% in our hands, and so it was replaced by the island onlay flap technique as described by Duckett.

Adolescent↗
PubMed1996

Phase II study of interferon-gamma versus interleukin-2 and interferon-alpha 2b in metastatic renal cell carcinoma.

PURPOSE: In a randomized phase II study we evaluated response, survival and side effects of low dose recombinant interferon-gamma in 30 patients (group 1) versus recombinant interleukin-2 and interferon-alpha 2b in 30 (group 2) with metastatic renal cell carcinoma. MATERIALS AND METHODS: Group 1 received 200 micrograms interferon-gamma subcutaneously once a week. Group 2 received 4 x 4.8 x 10(6) IU/m.2 interleukin-2 subcutaneously on days 1 and 22, 2 x 4.8 x 10(6) IU/m.2 on days 2 and 23, and 2 x 2.4 x 10(6) IU/m.2 combined with interferon-alpha 2b subcutaneously at 3 x 10(6) IU/m.2 on days 3, 5, 24 and 26, and 6 x 10(6) IU/m.2 3 times weekly for 6 weeks. RESULTS: Toxicity grades 2 and 3 (World Health Organization) were observed in group 2 only. After followup of 13 months there was no remission in group 1 compared to 7 remissions in group 2, with 23 cases of progressive disease detected. CONCLUSIONS: Combination therapy showed an objective response rate of 23% (p = 0.01). Although survival was not a primary aim of the study, there was a tendency toward no significant difference in survival when evaluating these relatively small groups (p = 0.49).

Adult↗
PubMed1996

[Therapy of hormone refractory prostate carcinoma with mitoxantrone. A clinical phase II study].

So far, no curative treatment is available for hormone-refractory prostate carcinoma. Therapy is thus focused on alleviating symptomatic tumor progression with the aim of improving quality of life. Therefore, anthracyclin-derived mitoxantrone was administered to 25 patients with hormone-refractory prostate carcinoma and symptomatic progressive disease. After a median treatment of 13 weeks, a median of 4 cycles and a follow-up of 14 months, 48% of the patients (12/25) reported improvement in tumor-related pain; in 60% (15/25) there was improvement of the self-assessment symptom score and 32% of the patients (8/25) gained weight. Additionally, partial tumor response with regression of lymph-node metastases occurred in 3/25 patients (12%). In 10/25 patients the serum level of prostate-specific antigen (PSA) decreased as well as the alkaline phosphatase (AP) in 7/25 patients. Side effects subsequent to chemotherapy were leucopenia WHO grade III in 25% of the patients and thrombocytopenia WHO grade III in 3/25 and grade V (treatment-related death) in 1/25 patients. Non-hematological toxicity occurred in 2 patients (cardiotoxicity n = 1, nephrotoxicity n = 1, WHO grade II each).

Aged↗
PubMed1996

[Pediatric ureteral ureteral outlet obstruction and obstructive megaureter: observation or operation?].

Stenosis of the ureteropelvic junction and obstructive megaureter are still a diagnostic and therapeutic problems. So far, there is no reliable prognostic factor to predict the outcome of a primary dilated upper urinary tract under the "wait and see" strategy and to decide which child must be operated upon and which should not. In practice, basic diagnostic evaluation with sonography, possibly i.v.-pyelography and voiding cystography is accompanied by quantifying isotope-based procedures such as DMSA-uptake or diuretic renography. The Whitaker test has become less important. Based on the investigation by Koff et al., it seems to be possible to follow the "wait and see" procedure in more than 85% of the children without any loss of renal function of the dilated kidney.

Child↗
PubMed1996

[Are their individual decisions for urinary diversion? Indications and results of 200 consecutive patients].

During the past 20 years many continent urinary diversions have been established. The indications includes pelvic tumors, especially bladder cancer, and structural and functional disorders of the lower urinary tract with irreversible damage of storage or continence function. Given the variety of surgical diversion techniques, it seems feasible to consider the patient's individual pathoanatomical situation as well as his/her personal wishes. We report on 200 consecutive patients with supravesical urinary diversion. The analysis includes indications surgical technique, intra-and postoperative complications and patients' quality of life. The peri- and postoperative morbidity rate was 18.5%. Complications mainly comprised infections and obstruction of the urinary tract. The mortality rate was 4.5% and causes of death included bleeding, infection, urinary extravasation and bowel atonia. Patients with malignant disease and only palliative treatment showed disappointing results after on operation including continent urinary diversion: 30% of them had early complications. Several female patients with a catherizable continent urinary diversion could not handle the catheterization of the pouch, although the function of the urinary diversion was excellent. Therefore an indwelling catheter was placed in all these patients. Our analysis shows that the choice of urinary diversion has to consider the patient's pathoanatomical situation, as well as his/her age, general condition, mental and manual skills. In addition, renal function, the metabolic situation and previous therapies may influence the decision regarding supravesical urinary diversion in an individual case.

Adult↗
PubMed1995

Prognostic factors for bladder cancer.

Cancer of the urinary bladder is the fifth most common cancer in men and the second most urological malignancy in Western society [17], with an incidence rate per year of 29.8/100,000 males. Bladder tumors are distinguished as either invasive or superficial: invasive tumors are generally associated with poor prognosis, while 20-30% of superficial carcinomas recur and progress to become invasive and metastic [26, 27]. The most common prognostic factors for classification of urothelial cancer are staging and grading, which are based on morphological criteria. In the past decade, however, other criteria have been developed as a possible prognostic aid to better disease management, such as expression of specific cell surface antigens, DNA content, chromosomal aberrations, gene rearrangements and point mutations [26, 7]. Since most tumors of the bladder are carcinomas and are associated with dedifferentiation and high metastatic capability, we investigated whether reduced expression of so-called differentiation factors in combination with increased cell motility might be correlated with tumor progression.

Cell Adhesion↗