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Biomedical subjects

K Tsutsui

Publications and source records attributed to K Tsutsui.

At least 163 records · Page 9Linked to original sources

Effects of PRL and FSH on LH binding and number of Leydig cells in hypophysectomized mice.

The effects of PRL and FSH on testicular LH receptors were studied in hypophysectomized (hypox) mice. From the eleventh day after hypophysectomy, they were given 100 micrograms ovine (o) PRL and/or 2 micrograms oFSH in two injections per day for 10 days. Hypophysectomy reduced the weight of testis, epididymides and seminal vesicles, and the LH binding to the testis. Treatment with oPRL and/or oFSH in hypox mice resulted in an increase in the weight of testis and epididymides, and the LH binding per testis. There was no difference between the testicular LH binding in oFSH- and oPRL-treated mice. Histological examination showed that oPRL and/or oFSH treatment in hypox mice restored normal spermatogenesis. Administration of oFSH to hypox mice led to an increase in the number of typical Leydig cells, whereas oPRL was not effective. These results suggest that either PRL or FSH stimulates the LH binding to the testis, but that the action of PRL and FSH on the increase in testicular LH binding is different.

Animals↗

Combined effect of radiation and YM-881 (SMANCS) on murine tumors and bone marrow.

The combined effect of radiation and YM-881 (SMANCS) was studied in vitro and in vivo. When 0.25 microgram/ml of YM-881 was simultaneously combined with radiation, during and after irradiation for 30 min in total, Dq decreased from 3.3 Gy to 1.4 Gy without changing D0 in the dose-survival curve of exponentially growing SCC VII tumor cells. Five or ten times administrations of 0.1 mg/kg YM-881 at an interval of 24 h did not inhibit tumor growth. However, administration of 0.1 mg/kg YM-881 just before every irradiation which was repeated five times at an interval of 24 h yielded dose modifying factors (DMFs) of 1.8-1.2 when the tumor response to treatment was evaluated by the time for the tumors to regrow to three times the original volume. Administration of YM-881 ten times just before every irradiation yielded DMFs of 1.3-1.2. Adverse effects of the combination on bone marrow were examined by spleen colony assay. After five injections of 0.1 mg/kg YM-881, the mean number of CFU-S per femur decreased to 77% of the pretreatment level, but this was not significant statistically (0.1 greater than p greater than 0.05). The slope of radiation response curve for CFU-S per femur was not affected by the combination.

Animals↗

[Cell kinetic effects of a single PUVA treatment on rapidly proliferating epidermis of the stripped skin of guinea pigs].

This study investigated the cell kinetic effects of a single treatment with PUVA on guinea pig epidermis after tape stripping. Flow cytometry was used to determine the proportion of cells in S phase and G2 + M phase. Bromodeoxyuridine incorporation was used to determine the labeling index. Conventional histological techniques were used to observe the mitotic index. An initial decrease followed by a subsequent significant increase compared to the non-PUVA-treated controls was observed in all parameters studied except the mitotic index, which was below or around the control level until 168 hours after the treatment with PUVA. The results obtained in this study suggest that PUVA induces a partial blocking at G1-S boundary for short duration, and that when the partial G1 block is released, then the cells of stimulated epidermis enter DNA synthesis and pass through the S phase to the G2 phase in partial synchrony. It is also suggested that PUVA blocks the passage of cells from the G2 phase to mitosis, resulting in an long-lasting accumulation of cells in the G2 phase.

Animals↗

[Radiographic staging procedures and radiotherapy of malignant lymphoma].

Radiographic studies play an important role in the clinical staging of malignant lymphoma (ML). Conventional procedures are plain chest X-ray, lymphangiography, gastrointestinal series, and 67Ga scintigraphy. Gastro-intestinal series is essential in non-Hodgkin's lymphoma (NHL) of Waldeyer's ring and thyroid. 67Ga scintigraphy is a non-invasive procedure useful in the screening of ML. Recently marked improvements have been made in the diagnostic modalities. CT scan and NMR have made it very easy to diagnose ML of the central nervous system and detect the extension of tumors at all sites. In some cases with Hodgkin's disease (HD), staging laparotomy is necessary, but not in cases with NHL. If tumors are localized, subtotal or total nodal irradiation is performed for patients with HD, and generous involved field is employed for NHL with or without combined chemotherapy at our department. Good local control is obtained except for NHL of the central nervous system at a total dose of 40-50 Gy. NHL is prone to relapse outside the radiation field. Therefore we consider that combined chemotherapy is indicated for NHL such as T-cell lymphomas, those with high grade histology classified according to the Working Formulation, and with involvement of lymph nodes larger than 6 cm in diameter.

Combined Modality Therapy↗

[Results of radiation therapy for medulloblastoma].

Results of radiation therapy for cerebellar medulloblastoma at Kyoto University Hospital were reviewed. Between 1962 and 1988, 30 patients with histologically-proven medulloblastoma completed radiotherapy. Before 1971, the treatment volume was either the posterior fossa only or posterior fossa plus spinal axis, but after 1972, it was extended to include the entire neuraxis. The mean dose was 48 Gy to the posterior fossa, 36 Gy to the whole brain, and 25 Gy to the spinal axis. The 5-year survival rate and 5-year relapse-free survival rate estimated by the Kaplan-Meier's method were 36% and 37%, respectively, for total cases, but were as high as 79% and 80%, respectively, for the recent 10 patients. This improvement in the treatment results appeared to be due to extensive tumor resection and improved radiotherapy technique, and not to the use of chemotherapy. The prognosis was significantly better in patients treated with craniospinal irradiation than in those otherwise treated. There was a trend towards better survival in patients who received 50 Gy or more to the posterior fossa or 24 Gy or more to the spinal axis, compared to the patients who received lower doses to each site. No significant morbidity of radiotherapy was seen. Four of the six surviving patients who were treated below age 12 have a mental retardation and/or a short stature, but one patient treated at age 5 has a normal growth and a good intelligence. From these analysis, it is recommended to irradiate craniospinal axis and posterior fossa up to 25-35 Gy and 50-55 Gy, respectively.

Adolescent↗

Incorporation of exogenous circular DNA into large catenated networks in isolated nuclei. Evidence for involvement of the nuclear scaffold.

Circular plasmid DNA was efficiently converted into huge catenated intranuclear networks by incubation with isolated nuclei in the presence of ATP. The network production is abolished by omission of ATP, strongly inhibited by etoposide (VP-16), but only slightly inhibited by antibody to topoisomerase I, indicating that the major enzyme responsible for catenation is DNA topoisomerase II. Under optimal conditions, a single nucleus incorporates about 4.2 x 10(4) DNA rings into its networks. Under the light microscope, networks retrieved from nuclei appear like spheres of various sizes. Sedimentation analysis showed that most of the networks are composed of thousands of catenated rings, which was confirmed by electron microscopy. Data from experiments that caused partial disruption of the networks were submitted to analysis based on probable models of catenane structure. The results suggest that the predominant pattern is a linear alignment of catenated rings. Similar networks are formed when the nuclear scaffold is incubated with circular DNA in the presence of nuclear extract containing topoisomerase II. Titration experiments showed that the scaffold binds a stoichiometric amount of the substrate and that a critical level of DNA is required for network formation. The results are consistent with the idea that DNA-binding sites are fixed on the scaffold and mediate catenation of bound DNA circles by holding them in close proximity to each other. We propose that catenation by the nuclear scaffold also occurs in intact nuclei, suggesting additional roles for the scaffold in vivo.

Adenosine Triphosphate↗

Changes in the testicular binding of luteinizing hormone and plasma testosterone concentrations in the Djungarian hamster subjected to different photoperiods and temperatures and effects of long-term testosterone treatment on the binding.

The effects of artificial photoperiod, temperature, and long-term testosterone treatment on testicular luteinizing hormone (LH) binding were studied in adult male Djungarian hamsters. In hamsters transferred to long-day (LD; 16 hr light, 8 hr dark) photoperiod 8 weeks after adaptation in short-day (SD; 8 hr light, 16 hr dark) photoperiod of 25 degrees C, testicular growth was associated with an increase in the total LH binding per two testes and a decrease in LH binding per unit testicular weight. Plasma testosterone levels reached a peak 47 days after transfer to LD and tended to decrease thereafter, while the testes continued growing. In contrast, when hamsters reared under LD conditions at 25 degrees C for 12 weeks were transferred to SD, testicular regression was associated with a decrease in plasma testosterone and the total LH binding per two testes and an increase in LH binding per unit testicular weight. A significant decrease in LH binding per unit weight compared to SD controls was observed in those hamsters exposed to SD with continuous testosterone treatment. The testosterone treatment tended to induce decrease in the total LH binding. Scatchard plot analyses of the binding suggested that changes in LH binding were due to changes in the number of binding sites. When sexually mature male hamsters were subjected for 8 weeks to two different ambient temperatures (7 degrees C and 25 degrees C) and photoperiods (LD and SD), the difference between the two temperature groups was statistically not significant regarding the weights of testes, epididymides, and prostates; plasma testosterone levels; and LH binding in either LD or SD group. These results suggest that photoperiod is a more important environmental factor than temperature for the regulation of testicular activity and LH receptors and that testosterone reduces the number of LH receptors per unit testicular weight in adult male Djungarian hamsters.

Animals↗

Properties of follicle-stimulating hormone receptors and changes during annual breeding cycle in the testis of short-tailed bandicoot rat, Nesokia indica.

Some properties and seasonal changes of follicle-stimulating hormone (FSH) receptors in the testis of short-tailed bandicoot rat, Nesokia indica, were studied. The binding of FSH was highly specific for mammalian FSHs and located primarily in the testis. The Scatchard plot analyses of the binding of FSH to the testicular preparations of N. indica showed straight lines similar to those of albino Wistar rats, suggesting the presence of a single class of FSH-binding sites. The mean dissociation constants (Kds) for FSH receptors of N. indica were 1.416 (0.964-2.667, 95% confidence interval) nM in December, 1986; 1.348 (0.885-2.849) nM in April, 1987; and 3.039 (1.678-16.127) nM in August to October, 1987. No significant differences were found among the three groups, but they were all significantly greater than those in Wistar rats. The FSH binding per unit weight of tissue during non-breeding phase (June, 1987) was lower than those during other phases (December, 1986; April and August-October, 1987). Calculated numbers of FSH-binding sites showed no statistically significant differences among the latter three phases. In June preparations the number of binding sites was not determined due to their extremely low binding capacity.

Animals↗

Variation in tumor response to fluosol-DA (20%).

The effects of Fluosol-DA 20% (FDA) and carbogen (95% O2/5% CO2) on radiosensitivity of the three experimental tumors, SCC VII tumor, RIF-I tumor, and transplanted mammary tumor of C3H/He mouse, subcutaneously inoculated in the leg were examined. The effect of FDA plus carbogen, and carbogen alone on radiosensitivity of SCC VII and RIF-I tumors was tested using the in vivo-in vitro assay. The growth curves were obtained for both SCC VII tumor and transplanted mammary tumor. The effect of the combination of FDA and carbogen was only observed in the transplanted mammary tumor. In the other two tumors, only the effect of inspiring carbogen was observed. We concluded that the effect of FDA on the radiosensitivity of experimental tumors varies with the kind of tumor systems.

Animals↗

The effect of arterial oxygen content on the results of radiation therapy for epidermoid bronchogenic carcinoma.

Anemia is believed to be an important prognostic factor in treating cancer patients by radiation therapy. One possible explanation for this is tumor oxygenation. With respect to tumor oxygenation, the arterial oxygen content (CaO2) may be of more importance than the hemoglobin (Hb) level. This study shows the relationship between the CaO2 and tumor response to radiation therapy. Forty-two patients with epidermoid bronchogenic carcinoma, treated by irradiation alone between April 1982 and March 1986, were reviewed. Regression of the tumor after radiation therapy was calculated as a percent change in the tumor area. Arterial oxygen partial pressure (PaO2), Hb level, and percent oxygen saturation of Hb in arterial blood (SaO2) were measured within 2 weeks of commencement of radiation therapy and the CaO2 was calculated. The rank correlation coefficients between the maximum percent regression of the tumor and the PaO2, the Hb level and the CaO2 were 0.36, 0.34, and 0.46, respectively. Statistical analyses of the data indicate that the group of patients with CaO2 over 14.5 ml/dl exhibited greater tumor regression and longer survival periods than the group of patients with CaO2 below 14.5 ml/dl. Similarly patients with PaO2 over 90 mmHg or Hb level over 11 g/dl, exhibited significantly greater tumor regression and longer survival periods than those with PaO2 below 90 mmHg and Hb level below 11 g/dl. There were no significant differences in the length of survival periods with respect solely to the Hb level or the PaO2. It was concluded that the CaO2 is more important than the Hb level in determining tumor response to radiation therapy. This is considered as important indirect evidence of the existence of hypoxic fractions of cells in human tumors.

Adult↗

Rapid purification of squirrel monkey retrovirus-H major gag protein by high performance liquid chromatography.

The major gag protein (p34) of squirrel monkey retrovirus-H was purified in one chromatographic step by anion-exchange high performance liquid chromatography. The virus in a crude fraction was disrupted with Brij 35 in the presence of three kinds of protease inhibitors. The soluble virus lysate was injected into a Polyanion SI column, and p34 was eluted with a linear salt gradient. The recovery of the protein was about 60%. The purified p34 was nearly homogenous as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining.

Animals↗

Unique features of monoclonal IgG2b in the cleavage reaction with pepsin.

Preparations of IgG2b purified from several mouse hybridoma clones were highly susceptible, compared to other subclasses, to peptic digestion under conditions usually used to prepare F (ab')2 fragments. Analyses of the digestion products revealed that no F (ab')2 was produced and that the main product was a Fab-like fragment. Demonstration of the hinge disulfides in the Fc portion clearly indicated that in IgG2b the primary peptic cleavage occurs on the NH2-terminal side of the inter-heavy chain disulfide bridge. The resulting Fab failed to bind with antigen, suggesting the importance of the CH1-hinge region in maintaining the native conformation of the antigen-binding site.

Animals↗

The correlation between cell survival curve and dose response curve of micronucleus (MN) frequency.

The correlation between cell survival curve and dose response curve of MN frequency following irradiations was studied using cytokinesis-block method. Both dose response curves were analyzed by linear quadratic model, i.e. SF = exp (-alpha D-beta D2) and MN frequency = aD + bD2 + C. A good correlation between alpha/beta and a/b ratios was observed in repeated paired experiments (= 0.97). When the cells were treated with BUdR, alpha-type radiosensitizer, a value in dose response curve of MN frequency increased but b value did not. These data present that MN frequency assay using cytokinesis-block method is available as a tool of rapid assay of radiosensitivity of cells.

Animals↗

Interleukin-1 inducing activity of a streptococcal preparation OK-432 and its fractions by human monocytes.

Interleukin-1 (IL-1) inducing activity of a streptococcal preparation OK-432 and its fractions by monocytes were investigated in patients with lung cancer and healthy subjects. The results showed that cell free extracts and cell wall fractions of OK-432 were the strong IL-1 inducing fractions. IL-1 activity released by OK-432-stimulated monocytes of patients with lung cancer fell within normal range. OK-432 stimulated intracellular IL-1 synthesis as well as extracellular release by monocytes. These results, therefore, suggested that OK-432 immunotherapy in patients with malignant diseases might be effective by increasing IL-1 production of monocytes.

Aged↗

Blastogenic responses of human lymphocytes to a streptococcal preparation OK-432 and its fractions.

This study was undertaken to examine the blastogenic responses of PBL to Streptococcal preparation OK-432 and its fractions. The results showed that OK-432 and its fractions, Su-PR and PM, have the mitogenic activity against human lymphocytes. The demonstration that PBL which had been cultured with OK-432 expressed IL-2 receptors and the blastogenic responses of PBL to OK-432 were inhibited by anti-IL-2 antibody suggested that IL-2 and IL-2 receptors might play a central role in OK-432-induced proliferation of human lymphocytes.

Adolescent↗

Combined effects of radiation and IUdR on experimental liver tumors and hepatocytes.

IUdR, a thymidine analogue, increased the radiosensitivity of SCC VII tumor cells. A decrease in Dq value of cell survival curve was more prominent compared with that in D0 value. However, in experimental liver tumors made by transplanting SCC VII tumors, the decrease in D0 value was apparent. Proportion of IUdR incorporated tumor cells in the liver increased with an increase in number of IUdR injections, and reached 52% after five administrations of the drug at an interval of twelve hours. However, few hepatocytes incorporated IUdR. The response of hepatocytes to radiation was evaluated by micronucleus appearance frequency. To accelerate the appearance of micronucleus in hepatocytes, partial hepatectomy was performed immediately after irradiations. No differences in micronucleus frequency were observed between the treated and untreated with IUdR.

Animals↗

Single-strand DNA cleavages by eukaryotic topoisomerase II.

A new purification method for eukaryotic type II DNA topoisomerase (EC 5.99.1.3) is described, and the avian enzyme has been purified and characterized. An analysis of the cleavage reaction has revealed that topoisomerase II can be trapped as a DNA-enzyme covalent complex containing DNA with double-stranded and single-stranded breaks. The data indicate that DNA cleavage by topoisomerase II proceeds by two asymmetric single-stranded cleavage and resealing steps on opposite strands (separated by 4 bp) with independent probabilities of being trapped upon addition of a protein denaturant. Single-strand cleavages were directly demonstrated at both strong and weak topoisomerase II sites. Thus, a match to the vertebrate topoisomerase II consensus sequence (sequence; see text) (N is any base, and cleavage occurs between -1 and +1) [Spitzner, J.R., & Muller, M.T. (1988) Nucleic Acids Res. 16, 5533-5556)] does not predict whether a cleavage site will be single stranded or double stranded; however, sites cleaved by topoisomerase II that contain two conserved consensus bases (G residue at +2 and T at +4) generally yield double-strand cleavage whereas recognition sites lacking these two consensus elements yield single-strand cleavages. Finally, single-strand cleavages with topoisomerase II do not appear to be an artifact caused by damaged enzyme molecules since topoisomerase II in freshly prepared, crude extracts also shows the property of single-strand cleavages.

Animals↗