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U Otto

Publications and source records attributed to U Otto.

At least 37 records · Page 2Linked to original sources

Antiproliferative and cytotoxic effects of single and combined treatment with tumor necrosis factor alpha and/or alpha interferon on a human renal cell carcinoma xenotransplanted into nu/nu mice: cell kinetic studies.

A human renal cell carcinoma serially transplanted into nude mice was treated with recombinant human tumor necrosis factor alpha (TNF-alpha), recombinant human alpha interferon (IFN-alpha), and a combination of both. All treatments resulted in a significantly reduced tumor growth. The greatest effect was obtained with the combination of TNF-alpha and IFN-alpha. This latter treatment completely eradicated tumors which were smaller than 50 mm3 at the beginning of treatment. Cell kinetic analysis using the bromodeoxyuridine technique and flow cytometry revealed a prolongation of the transition time through S-phase from 7.9 h in the case of control tumors to 10.5 h for tumors treated with IFN-alpha and TNF-alpha. Single treatment with either TNF-alpha or IFN-alpha had only minor effects. The bromodeoxyuridine labeling index was unaffected by IFN-alpha (16.6%; control, 15.2%) but was reduced to 12.1 and 11.7% when tumors were treated with TNF-alpha and IFN-alpha plus TNF-alpha, respectively. The calculated potential doubling times were 2.3 and 2.8 days, respectively, for tumors treated with TNF-alpha or IFN-alpha plus TNF-alpha. When treated with IFN-alpha, the potential doubling time (1.7 days) was similar to that of the control (1.6 days), indicating that the main effect of TNF-alpha was antiproliferative. Conversely, the calculated cell loss factors increased after IFN-alpha and combined treatment but not after TNF-alpha treatment. Combined treatment augmented cytotoxicity, but the cell kinetic characteristics of surviving cells remained similar to those of tumors treated with TNF-alpha alone. Histological analysis showed a distinctly reduced mitotic activity but no coagulative necroses after treatment with TNF-alpha. IFN-alpha and, in particular, IFN-alpha plus TNF-alpha induced cytoplasmic vacuolization, nuclear pyknosis, and cell death, which resulted in tumor regression. These data suggest that, in this particular tumor model, TNF-alpha produces mainly antiproliferative effects, whereas IFN-alpha acts via cytotoxic mechanisms.

Animals↗

Comparison of different schedules of cytostatic intravesical instillations in patients with superficial bladder carcinoma: final evaluation of a prospective multicenter study with 419 patients.

In a prospective multicenter study we compared the value of various protocols of mitomycin C and doxorubicin instillation for the prevention of recurrent tumors in patients whose superficial bladder tumors (stages TA and T1) had been removed by transurethral resection. The 3-year and short-term instillation protocols were compared to each other and to a combination of 2 protocols. Evaluation after a mean followup of 28 months confirmed the value of cytostatic bladder instillation in preventing recurrence and progression of tumor in patients with superficial bladder carcinoma. There was no significant difference between the results of long-term and short-term prophylaxis; their combination achieved the best results. Doxorubicin and mitomycin yielded similar results; mitomycin was better tolerated.

Administration, Intravesical↗

[Long-term results in the treatment of metastasizing kidney carcinoma using recombinant alpha-2 or gamma interferon].

To evaluate whether response to alpha-2- or gamma-interferon in metastatic renal cell carcinoma is associated with a prolonged survival, we studied a total of 65 patients being treated in two phase-II- or phase-III-trials between 1984 and 1986 with one of these interferons. After a median follow-up of 3 years for the alpha-interferon-treated patients and of more than 4 years for gamma-interferon-therapy, respectively, there is a significantly increased duration of survival for patients showing an objective response or stabilisation of the disease due to either therapy compared to those with continuing progression. Therapy with alpha-interferon leading to objective remissions in 26% or with gamma-interferon with an objective response rate of 36% therefore is beneficial for responding patients and can be performed with moderate side effects on an out-patient basis.

Adult↗

[Experimental microbiological research on instrument and denture disinfection with a disinfectant spray for dental practice and the use of patients. 2. Virological studies; the evaluation summary].

Carrier experiments using Echo- and Influenza-viruses on denture basis resins and fragments of orthodontic appliances resulted in good and even very good virucidal effects of disinfectant sprays Desident and Fesia-sept. The application of the disinfectant as spray seem to be advantageous, but is not recommendable. The diverse causes of this conclusion are discussed and an alternative way is proposed.

Aerosols↗

[Experimental microbiological research on instrument and denture disinfection with a disinfectant spray for dental practice and the use of patients. 1. The formulation of the problem and bacteriological studies].

Three disinfectant sprays (Arugeen, Desident and Fesia-sept) proved to be very efficient against pure cultures of aero bacteria species, Cand. albicans, saliva flora and entero- and influenza viruses. The methods included carrier experiments using denture basis resins, fragments of orthodontic appliances and screws (instead of instruments).

Aerosols↗

[Use of electronic data processing at a urologic polyclinic--a program packet for recording and evaluating data of specialized consultations].

A software package was developed for computerized recording and processing of clinical data in a urological out-patient clinic. In a pilot study this program proved to be useful for the rapid evaluation of all important clinical and laboratory results of patients with renal cell carcinoma, and its use also accelerated the preparation of medical reports. The experience gained in this initial project shows that the application of this newly developed concept of data processing can easily be extended to routine out-patient followup in other special areas within the field of oncology.

Aftercare↗

[Initial experiences in diagnosis of graft rejection following clinical heart transplantation. Detection of graft-directed activated T-cells].

The binding of antigen-loaded carrier to mononuclear cells of heart transplant recipients has been investigated by means of an antigen-specific rosette technique. The increase of rosette forming cells and the inhibition of this reaction with monoclonal antibodies against activated T-cells is a sign of a beginning rejection. 3-6 days later infiltrating immunological competent cells are seen in biopsy.

Adult↗

The panorama of psychiatric emergencies in three different parts of Sweden.

A total of 1226 psychiatric emergencies from three socially different catchment areas in Sweden were analyzed. Data were obtained over 28 consecutive days at the beginning of 1985. Very small differences were found between urban and rural catchment areas, which is probably due to a high degree of equality for both social and medical services throughout Sweden. The largest diagnostic subgroup was patients with an alcohol problem (33%). A measure of the patients network of close relatives, yielded small differences between the diagnostic subgroups.

Adult↗

[Treatment of metastatic kidney cancer with recombinant alpha-2 or gamma interferon. Results of 2 clinical phase II and III studies].

In a phase-II and a phase-III study patients with histopathologically documented metastatic renal cell carcinoma were treated either with gamma-interferon in two different doses (100 micrograms/m2 3x/week for 4 h i.v. every other week or 500 micrograms/m2 5x/week for 24 h i.v. every other week) or with alpha-2-interferon alone (18 x 10(6) U 3x/week weekly i.m.) or in combination with vinblastine (0.1 mg/kg every third week i.v.). The purpose of these studies was to evaluate the response rate, the duration of response, the survival, the efficacy and the toxicity of the different forms of treatment. The overall response rate to gamma-interferon was 30% in both regimens. The response rate of treatment with alpha-2-interferon was found to be 31%. The duration of response ranged between 2 and 34+ months in patients treated with gamma-interferon and between 2 and 24+ months in those receiving alpha-2-interferon. Patients with objective tumor response showed a significantly longer survival than those not responding (p = 0.0056). Low-dose-gamma-interferon and alpha-2-interferon treatment could be easily done on an outpatient basis. In conclusion, interferon treatment seems to be of value in the therapy of patients with well documented progressive disease in metastatic renal cell cancer.

Adult↗

Cytostatic intravesical instillation in patients with superficial bladder carcinoma for the prevention of recurrent tumors.

The value of various protocols of mitomycin C and adriamycin instillation for the prevention of recurrent tumors in patients whose superficial bladder tumors (TA, T1) had been removed by transurethral resection was compared in a prospective multicenter study. Three-year and short-term instillation protocols were compared with each other and with the combination of the two. Evaluation after a mean follow-up of 20 months confirmed our previous conclusion of the great value of cytostatic bladder instillation to prevent recurrent tumors and tumor progression in patients with superficial bladder carcinoma. There is no significant difference between long-term and short-term prophylaxis, but combination has achieved the best results. Similar results were obtained with adriamycin and mitomycin but adriamycin was less well tolerated.

Administration, Intravesical↗

Recombinant interferon gamma in the treatment of metastatic renal cell carcinoma. Results of a phase II trial.

A clinical Phase II study was performed to evaluate the efficacy and safety of treatment with interferon gamma in patients with metastatic renal cell carcinoma. Patients received interferon gamma by two different regimens: 1. 100 micrograms/m2 3x/week i.v. over 4 h every other week--low dose. 2. 500 micrograms/m2 5x/week i.v. over 24 h every other week--high dose--for non-responders to regimen 1. The response rate, duration of response, survival and toxicity in the two regimens were evaluated. Treatment with interferon gamma resulted in an overall response rate of 31%, with a duration of response ranging between 2 and 44+ months. Patients responding objectively to interferon gamma or showing stable disease survived significantly longer than non-responders (p = 0.0056).

Adult↗

Stability of human renal cell carcinomas during long term serial transplantation into nude mice: histopathology, nuclear grade, mitotic rate, and DNA content in thirty tumors.

Thirty human renal cell carcinomas, subpassaged into NMRI-nu/nu mice, were analyzed during long term serial transplantation (range, 10-50 passages) with regard to their histological differentiation, mitotic activity, and DNA content. A quantitative methodology was applied to determine the mitotic rate. The DNA content was measured by flow cytometry. Only five tumors (four primaries and one metastasis) changed their mitotic rate significantly (P less than 0.01). In each case this change was paralleled by a simultaneous alteration of the DNA content. Histological pattern and nuclear grade remained stable in all but one tumor where the change in histological pattern occurred simultaneously with changes in DNA index and mitotic rate. These results indicate that the majority of renal cell carcinomas remain stable during long term serial transplantation, at least with regard to the parameters examined. This is a basic prerequisite for making the grafting of renal cell carcinomas into nude mice a reliable in vivo model for drug sensitivity testing. However, since a few of the transplanted tumors showed instability, continuous monitoring of phenotypic and genotypic tumor features is necessary during long term xenotransplantation.

Animals↗

Testis-specific beta 2 tubulins are identical in Drosophila melanogaster and D. hydei but differ from the ubiquitous beta 1 tubulin.

In Drosophila as in many organisms beta tubulins are encoded by a gene family. We have determined the complete nucleotide sequences coding for the beta 1 and beta 2 tubulins of Drosophila melanogaster and the beta 2 tubulin of D. hydei, and found these insect beta tubulins to be highly conserved and like beta tubulins of other organisms. This is discussed with reference to the possible functional domains of these proteins. The beta 1 tubulin gene of Drosophila is constitutively expressed, whereas the beta 2 tubulin is expressed specifically in the testes. In D. melanogaster the amino acid sequences of these proteins are 95% homologous, differing at only 25 positions. In the testes the beta 2 tubulin participates in different microtubules as shown by genetic analysis (Kemphues et al. 1982). Interestingly, all of the amino acids characteristic of the testis-specific beta 2 tubulin are also present in the corresponding gene of D. hydei. Of special interest is the high degree of conservation of the carboxy-terminal domain in these functionally equivalent beta tubulins.

Amino Acid Sequence↗