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Biomedical subjects

U Otto

Publications and source records attributed to U Otto.

At least 55 records · Page 3Linked to original sources
PubMed1988

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

Xenogenic transplantation of human bladder- and renal-cell carcinoma into NMRI mice treated with cyclosporin A and into NMRI nu/nu mice. Introduction of a new experimental cancer model.

128 tumors from three different human renal-cell carcinomas and from one human transitional bladder cancer were transplanted into NMRI mice treated with cyclosporin A at various dosages. Their acceptance rate, proliferation rate, and morphologic and growth characteristics were studied and compared with those of the same human tumors after transplantation into NMRI nu/nu mice. The acceptance rate was 80% in mice treated with cyclosporin A at 100 mg/kg-1 and 150 mg/kg-1/day. The highest acceptance rate was observed after transplantation into nu/nu (thymus-aplastic) mice (100%). Morphologically, the transplanted tumor was similar in the two animal groups and identical with the primary tumors. Metastases were not seen in either animal model. The NMRI mice treated with cyclosporin A had leukocyte infiltration into the transplanted tumor. The growth rate of the human tumors in normal mice depended on the cyclosporin A dosage, and was highest in the nu/nu mice. The proliferation rates of the transplanted human tumors, as judged by flow cytometry, were rather similar in all groups.

Animals↗
PubMed1987

Long-term serial transplantation of different human bladder carcinomas into NMRI nu/nu mice. Histologic, flow cytometric and growth studies.

Sixteen human bladder carcinomas (BCs) were transplanted into NMRI nu/nu mice with an acceptance rate of 62.5%. Six of the 16 (37.5%) BCs were successfully retransplanted up to 14 passages. Histologic grading and traumatization during surgery influenced the acceptance rate. Grade-I tumors were rarely accepted, unless they were obtained during open surgery, rather than by transurethral resection (TUR). Specimens taken by TUR or by electric cut during open surgery were almost never accepted. Identity of the transplanted tumor tissue with the original human BCs could be demonstrated by flow cytometry and by light microscopy through several passages in all accepted tumors. However, although the tumors retained their major structural features, their proliferative activity increased, particularly that of grade-I tumors. The five tumors that were transitional-cell carcinomas and could be subpassed had three characteristics not seen before in transplanted renal cell carcinomas: tumor growth started after a delay which shortened with each further passage; growth rates of tumors only in their first passage correlated with the prognosis of the corresponding patients, and with each further passage, tumor growth accelerated until a doubling time of about 1 week was observed. From then on, tumor growth was almost identical in all five tumors. In contrast to our experience with transplanted renal cell carcinomas, flow cytometric evaluation of the transplanted and further passaged BCs revealed changes in DNA index and an increase in proliferative rate and it seems that BCs were strongly influenced by host factors.

Animals↗
PubMed1987

Determination of androgen, progestin and estrogen receptors with two different assays in renal cell carcinoma.

Twenty-one renal cell carcinomas were analyzed for the presence of androgen progestin and estrogen receptors by agar gel electrophoresis and a dextran-coated charcoal assay. An androgen receptor could be demonstrated in 3 tumors, a progestin or estrogen receptor was not detectable. It was therefore concluded that renal cell carcinoma is generally not a hormone-dependent tumor, and a hormonal treatment of metastatic renal cell carcinoma as first-line therapy does not seem to be justified.

Carcinoma, Renal Cell↗
PubMed1987

[Transplantation antigen specific rosette test and its inhibition with autologous serum--a new immunologic method for predicting rejection crisis following allogeneic organ transplantation].

A combination of transplantation-antigen-specific rosette test with inhibition of rosette formation, using autologous serum, was used in postoperative follow-up checks on patients who had undergone allogeneic kidney transplantation and proved successful in early diagnosis or prediction of rejection episodes even before clinical manifestation. The numbers of antigen-detecting and antigen-binding cells differed considerably from each other, depending on patients who had undergone kidney transplantation. Almost complete inhibition of antigen detection was generally achieved by addition of patient serum. If sensitization to alloantigen in excess of the limit value (30 RBZ/10(3) KHZ) is accompanied by rosette formation with autologous serum addition in excess of about 18 RBZ/10(3) KHZ, clinically relevant rejection can be expected to occur after another two or three days and will have to be treated by immunosuppressives. Such partial or even complete elimination of rosette inhibition is usually only of short length (one day) and has rarely been observed to last longer. No rejection calling for treatment will develop, on the other hand, as long as blocking serum factors provide for high-stability inhibition of any bond of transplantation antigen (rosette formation). Constantly low rosette formation with serum addition and without was exhibited by control persons (blood donors, patients with cerebrocranial trauma) in daily examinations. Limit values of 18 or 30 RBZ/10(3) KHZ were not surpassed.

Graft Rejection↗
PubMed1986

Malignancy index based on flow cytometry and histology for renal cell carcinomas and its correlation to prognosis.

Fifty-five human renal cell carcinomas, removed by nephrectomy, were classified using flow cytometry and histology. The parameters obtained by flow cytometry were DNA index, fractions of cells in the phases, and fractions of tumor cells versus normal cells. From histology, the routine classification of tumor structure and morphology were obtained, and a nuclear grading according to Arner et al. (Acta Chir Scand [Suppl] 346:1-12, 1965) was determined. All parameters including tumor stage according to Robson et al. (J Urol 101:297-301, 1969) were subjected to discriminant analysis in order to define a malignancy index. The patients were divided into two groups with good and poor prognosis (low and high risk). Those patients who were free of multiple metastases in 2 years and more after nephrectomy were assigned to the group "good prognosis"; those who developed multiple metastases for 2 years represented the "poor prognosis" group. The malignancy index determined by discriminant analysis yielded 91% correct predictions of prognosis.

Carcinoma, Renal Cell↗
PubMed1986

Prognosis of renal cell carcinoma related to nuclear grade, DNA content and Robson stage.

In 135 renal cell carcinomas (RCCs), nuclear grade, Robson stage and DNA content, determined by flow cytometry, were related to the 3-year survival rates of the respective patients. All three parameters showed prognostic value, nuclear grading being most effective. Combined evaluation of the parameters showed that staging and also DNA determination add supplementary prognostic information. As the four nuclear grades clearly uncover the biological potential of RCC, they are regarded as the most significant criteria for the prognostic assessment of RCC.

Adult↗
PubMed1986

Long-term serial transplantation of 30 different human renal cell carcinomas into NMRI (nu/nu) mice: flow cytometric, histologic, and growth studies.

Thirty human renal cell carcinomas were transplanted into NMRI (nu/nu) mice. The take rate from surgical specimens was 100%, and all tumors were established as permanent transplantable tumor lines. The xenotransplants were followed up to around passages 10-50. In addition to histology and volume growth the DNA indices (DI), proportion of tumor cells, and fractions of cells in the phases of the cycle were measured by flow cytometry. All 30 tumors retained their primary histologic structure and cellular morphology throughout all passages. The DI, as ascertained by the DNA content per cell of G1-phase tumor cells divided by the DNA content per cell of normal diploid G1-phase cells, remained the same as those in the original tumors in 21 of 27 xenotransplants. Three original lymph nodes or metastases were not available for flow cytometry. During passage, 4 of 30 tumors changed their DI. In 2 of these cases the tumor doubling time (td), the proportion of tumor cells versus the proportion of host cells, and the fractions of cells in the cell cycle phases changed simultaneously. All other tumor lines were stable in td, DI, proportion of tumor cells, and fractions of cells in the phases during serial transplantation. However, the measure of parameters varied considerably between individual tumors of every passage. Tumor growth rate was generally related to the prognosis of the patients from whom the tumor was derived.

Animals↗
PubMed1986

[Immunologic characterization of the rejection of the allogenic transplanted kidney in pigs with and without immunosuppression].

After allogenic renal transplantation in pigs kinetics of the immunological reactivity have been investigated in order to diagnose rejection crisis. In a first series of 26 transplants without any immunosuppression we secured the diagnosis of rejection in 95% of cases of acute or chronic rejection by a combination of antigen-specific rosette test, inhibition of this parameter by autologous serum, complement dependent cytotoxicity and antibody dependent cell-mediated cytotoxicity. The antigen-specific rosette test reacts very early, 2-3 days before a bad clinical feeling in the course of acute rejection or 5-14 days by chronic rejection. Under the therapy with prednisolone and azathioprine we could not reach any prolongation of survival by arbitrary donor-recipient-selection. Under immunosuppression antibodies have never been observed by acute rejection in CDC and ADCC. In every case of acute rejection an increasing rosette formation of specific antigen binding cells appeared 2-3 days before an increasing of serum creatinine. In the case of other complications like infection or thrombosis this test is not reacting. However, by thrombosis of arteria or vena renalis there can be an increased specific rosette formation either independent of this process by beginning of immune reaction or by causal connection of both processes (necrotizing thrombotic rejection). So we have given the evidence, that the antigen-specific rosette test on a high level meets all requirements of a specific diagnosis of rejection under immunosuppression in pig.

Animals↗
PubMed1985

Behavioural and endocrine reactions in boys scoring high on Sennton neurotic scale viewing an exciting and partly violent movie and the importance of social support.

Psychoendocrine and behavioural effects elicited by viewing an exciting and partly violent movie were studied in 12-year-old boys (n = 42). The boys were divided into three groups. Group A (n = 13) consisted of boys scoring below the median value on the Sennton neurotic scale for vegetative and anxiety symptoms. Group B (n = 13) consisted of boys scoring above the median value on the Sennton neurotic scale. None of these boys had ever visited a psychiatric treatment centre, and they all came from the same school. A third group, Group C (n = 16), consisted of boys who, at least once, had visited an out-patient clinic at a child psychiatric treatment centre for neurotic problems. These boys attended different schools in the hospital catchment area. Group C had the same mean score on the Sennton neurotic scale as did Group B. By having two groups of boys scoring both high on the Sennton neurotic scale, one of which knew the other boys and one that did not, we were able to study possible effects of social support on psychobiologic reactions in neurotic boys. The boys' reactions to the movie were assessed by: self-ratings; direct observations of the boys by a team of trained child psychologists; and by analysis of urinary output of adrenaline, noradrenaline and cortisol. Group B rated their experience the strongest, viewing the movie, while Groups A and C rated themselves as rather unaffected by it. Group C was rated less verbally active, both during the control and the film periods, than were the other two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗
PubMed1985

Transplantation of human renal cell carcinoma into NMRI nu/nu mice. III. Effect of irradiation on tumor acceptance and tumor growth.

Irradiation of human renal cell carcinoma before radical tumor nephrectomy resulted in a significantly lower acceptance rate (1 of 7) in nude mice than for nonirradiated tumors (all of 13). The tumor tissue was transplanted into NMRI nu/nu mice immediately after nephrectomy. In this experimental system we demonstrated the reduced vitality of human tumor cells after irradiation. In a second series of experiments, 3 morphologically different human renal cell carcinomas were irradiated at various doses after establishment in nude mice. The irradiated tumor tissue was transplanted to the next passage. The morphology, proliferation rate and growth of these tumors were compared with those of nonirradiated controls. Radiation effect was dose dependent in the responding tumor types. The characteristics correlated with radiosensitivity were high proliferation rate (measured by flow cytometry), low cytologic grading and fast growth rate in the nude mice.

Animals↗
PubMed1985

Chemotherapy and human bladder carcinoma transplanted into NMRI nu/nu mice.

Transitional and squamous-cell carcinomas of the bladder that were transplanted and successfully retransplanted in further passages to NMRI nu/nu mice were used to test the efficacy of chemotherapy. Mitomycin and bleomycin consistently retarded tumor growth; results with platinex and methotrexate were variable. Combination therapy was not much better than single-drug therapy. Substances that proved effective in the mouse model produced some response in the corresponding patients in a series of patients on specific chemotherapy. In a previous study we have shown that tumor growth of transplanted human bladder carcinoma accelerates, unlike transplanted renal cell carcinoma when successfully subpassaged, resulting in a uniformly fast growing rate similar in all transplanted tumors including those which initially started with slow growing rates. Most importantly, however, tests in a given tumor conducted on a slow-growing early passage and on a fast-growing late passage produced different results. We concluded that this finding might explain the clinical observation that tumor remission due to chemotherapy in patients with metastatic bladder carcinoma does not last very long and seldom prolongs survival. It is assumed--it is not proved--that substances that proved effective in fast growing passages are probably likely to yield greater prolongation of life than those effective in slow-growing passages.

Aged↗