Biomedical subjects

K Tsutsui

Publications and source records attributed to K Tsutsui.

At least 145 records · Page 8Linked to original sources

PubMed1992

Bronchopulmonary disease in ulcerative colitis.

Two cases of ulcerative colitis are described: a 33-year-old woman who developed widespread bronchiectasis 7 months after undergoing colectomy, and a 72-year-old man whose colonic disease began coincidentally with the appearance of diffuse interstitial pulmonary infiltrates. In both cases, clinical correlation and common patterns of response of lung and bowel diseases suggested that the co-existence of these two pathologies might not be merely a casual relation.

Adult↗

PubMed1992

[Pharmacokinetic study and side effects of chronic daily administration of oral etoposide].

Eleven inoperable patients with non-small cell lung cancer were treated as a maintenance therapy with oral etoposide 25 mg daily. The toxicity appeared during the chemotherapy were assessed in all cases, but the blood concentration of the drug were measured in 5 cases on the first and the seventh day of treatment. While the peak plasma level (Cmax) was 0.92 +/- 0.43 microgram/ml on the first day and 1.02 +/- 0.30 micrograms/ml on the seventh day of chemotherapy, AUC was 12.3 +/- 5.41 micrograms.hr/ml and 11.9 +/- 4.52 micrograms.hr/ml on the first and the seventh day, respectively. Cumulative effect of the drug did not exist, since in any of these two measurements there was no significant statistical difference between values obtained on the first and on the seventh day. Regarding the toxicity of the drug, bone marrow suppression with abnormal reduction of peripheral white blood cells was observed. Though grade 2 adverse reaction was found in 6 cases, stopping drug administration for 2 weeks, enabled to re-administer the drug. Alopecia and liver or renal injury were not observed, and in spite of the presence of nausea and anorexia in one case, maintenance therapy could continue in all cases. Based on these results we concluded that etoposide can be safely administered as a maintenance therapy on out-patient basis.

Administration, Oral↗

PubMed1992

[Obstructive pneumonitis in lung cancer patients--a retrospective study].

We evaluated the frequency and the backgrounds of lung cancer patients with obstructive pneumonitis. Among 84 cases of lung cancer, 35 presented with bronchial obstruction at bronchoscopy or on radiological studies. Of these 35 cases, 8 had infectious obstructive pneumonitis. This complication was observed more commonly in patients with squamous cell carcinoma. A comparative analysis of the immunological and nutritional states before the occurrence of bacterial complication was performed on patients with infectious obstructive pneumonitis and those with non-infectious obstructive pneumonitis. The serum concentration of total protein, albumin and total cholesterol was significantly lower in patients who subsequently developed bronchial obstruction and bacterial infection, compared to concentrations in patients with non-infectious obstructive pneumonitis. Similarly, there was significant decrease in the number of peripheral lymphocytes, and neutrophils as well as a significant reduction of the serum concentration of IgM in the group of patients with infectious complications. These results suggest that nutritional and immunological deficiencies, in association with local airway obstruction, may be determining factors in the occurrence of infectious obstructive pneumonitis in patients with lung cancer.

Aged↗

PubMed1991

cDNA and deduced amino acid sequence of a mouse DNA repair enzyme (APEX nuclease) with significant homology to Escherichia coli exonuclease III.

We purified a mouse DNA repair enzyme having apurinic/apyrimidinic endonuclease, DNA 3'-phosphatase, 3'-5'-exonuclease and DNA 3' repair diesterase activities, and designated the enzyme as APEX nuclease. A cDNA clone for the enzyme was isolated from a mouse spleen cDNA library using probes of degenerate oligonucleotides deduced from the N-terminal amino acid sequence of the enzyme. The complete nucleotide sequence of the cDNA (1.3 kilobases) was determined. Northern hybridization using this cDNA showed that the size of its mRNA is about 1.5 kilobases. The complete amino acid sequence for the enzyme predicted from the nucleotide sequence of the cDNA (APEX nuclease cDNA) indicates that the enzyme consists of 316 amino acids with a calculated molecular weight of 35,400. The predicted sequence contains the partial amino acid sequences determined by a protein sequencer from the purified enzyme. The coding sequence of APEX nuclease was cloned into pUC18 SmaI and HindIII sites in the control frame of the lacZ promoter. The construct was introduced into BW2001 (xth-11, nfo-2) strain cells of Escherichia coli. The transformed cells expressed a 36.4-kDa polypeptide (the 316 amino acid sequence of APEX nuclease headed by the N-terminal decapeptide of beta-galactosidase) and were less sensitive to methyl methanesulfonate than the parent cells. The fusion product showed priming activity for DNA polymerase on bleomycin-damaged DNA and acid-depurinated DNA. The deduced amino acid sequence of mouse APEX nuclease exhibits a significant homology to those of exonuclease III of E. coli and ExoA protein of Streptococcus pneumoniae and an intensive homology with that of bovine AP endonuclease 1.

Amino Acid Sequence↗

PubMed1991

A mouse DNA repair enzyme (APEX nuclease) having exonuclease and apurinic/apyrimidinic endonuclease activities: purification and characterization.

A mouse repair enzyme having priming activity on bleomycin-damaged DNA for DNA polymerase was purified to apparent homogeneity and characterized. The enzyme extracted from permeabilized mouse ascites sarcoma (SR-C3H/He) cells with 0.2 M potassium phosphate buffer (pH 7.5) was purified by successive chromatographies on phosphocellulose, DEAE-cellulose, phosphocellulose (a second time), Sephadex G-100, single-stranded DNA cellulose and hydroxyapatite. The purified enzyme has an Mr of 34,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Enzymatical studies indicated that it is a multifunctional enzyme having exonuclease, apurinic/apyrimidinic endonuclease and phosphatase activities, similar to Escherichia coli exonuclease III. This enzyme is tentatively designated as APEX nuclease for apurinic/apyrimidinic endonuclease and exonuclease activities. The amino acid composition, amino-terminal amino acid sequence and an internal amino acid sequence of APEX nuclease are determined.

Amino Acid Sequence↗

PubMed1991

Detection of possible DNA repair enzymes on sodium dodecyl sulfate-polyacrylamide gels by protein blotting to damaged DNA-fixed membranes.

A novel method for detecting possible DNA repair enzymes on sodium dodecyl sulfate-polyacrylamide gels by blotting them onto a damaged DNA-fixed membrane is presented. To prepare the membrane, highly polymerized calf thymus DNA immobilized on a nylon membrane is damaged chemically. Enzymes, either homogeneous or crude, that are possibly involved in the priming step of DNA repair are fractionated by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and are renatured to active form by incubating the gel in an appropriate buffer. The renatured enzyme is then blotted onto the damaged DNA-fixed membrane, a process during which incision and/or excision are introduced to the damaged DNA by the enzymes. The incision and/or excision provide priming sites for repair DNA synthesis in the subsequent step in which the membrane is incubated with DNA polymerase in the presence of alpha-32P-labeled substrate. The site of substrate incorporation on the membrane reflecting the molecular weight of the repair enzyme is finally visualized by autoradiography. The present technique is established using Escherichia coli exonuclease III and a DNA-fixed membrane treated with bleomycin or acid-depurinated. By application of this method, a priming factor (an exonuclease) involved in the initiation of bleomycin-induced DNA repair is detected in the extract of mouse ascites sarcoma cells, and thus the molecular weight of the enzyme is estimated. Some apurinic/apyrimidinic endonucleases of mammals are also detected by the present procedure.

Animals↗

PubMed1991

Adenohypophysectomy in the zebra finch.

Castration and replacement of gonadal steroids have been used extensively in order to examine the hormonal regulation of song and sexual behaviors in passerine birds. However, recent studies have reported that levels of gonadal hormones may remain high following castration. In order to circumvent this problem, adenohypophysectomy might be advantageous. In this study we describe a technique for removing the anterior pituitary gland in a small passerine species (the zebra finch, Poephila guttata) using a parapharyngeal approach. The completeness of the adenohypophysectomy in individual male and female birds was examined by measuring gonadal weights as well as plasma levels of luteinizing hormone. The results indicate that this technique can be successfully applied to zebra finches. Removal of the anterior pituitary gland may represent a more effective means than gonadectomy for lowering circulating levels of gonadal hormones.

Animals↗

PubMed1991

A radiotherapeutic experience for localized extranodal non-Hodgkin's lymphoma: prognostic factors and re-evaluation of treatment modality.

Between 1966 and 1988, 149 patients were treated with radiotherapy for localized extranodal lymphoma. The average total dose given was 39.8 Gy for low grade disease and 48.7 Gy for all other disease. Of the 149 patients, 60 also received adjuvant chemotherapy. Twenty-four had low grade lymphoma, 109 had intermediate grade disease, and 16 had high grade disease, histologically. The distribution of histological grade and T/B phenotype varied with the primary site. Low grade lymphomas were found mainly in the orbit, and T-cell lymphomas were found in the nasal cavity and nasopharynx. The 5-year survival rates according to tumor location were 89% for oral cavity, 86% for paranasal sinus, 83% for thyroid, 69% for orbit, 47% for Waldeyer's ring (WAR), 44% for testis, 23% for CNS, 21% for nasal cavity and 60% for other sites. Histological grade and T/B phenotype both had prognostic importance. Combined chemotherapy significantly improved the survival rate only for disease with intermediate or high grade histology. Other prognostic factors according to the primary site were the bulk of lymph node for WAR disease, the radiation dose for CNS disease, bone erosion for orbital disease, stridor for disease of the thyroid, and the tumor stage for disease of both the testis and the thyroid.

Adolescent↗

PubMed1991

Effects of tumor necrosis factor and hyperthermia on Meth-A tumors.

The combined effects of purified human natural tumor necrosis factor (TNF) and hyperthermia were investigated in a transplanted TNF-sensitive Meth-A tumor model. We assessed the sequence and interval for the two treatments, the temperature that caused maximal heat sensitization, and the effects of pH modification on this combination therapy. Tumor response was evaluated by means of a tumor growth delay assay. TNF at a dose of 50 JRU/g caused significant tumor growth delay. A synergistic effect of TNF and hyperthermia was observed when TNF was administered 10 min before heating. This thermal enhancement of the action of TNF became more prominent with an increase in the heating temperature. Tumor growth delay was maximal when TNF was given immediately before or after hyperthermia. However, after an increase in the time interval to more than 2 h, there was no enhancement of growth delay. Injection of glucose (5 g/kg) caused a significant fall in pH at 10 and 30 min after administration. Further enhancement in tumor growth delay was seen with the trimodality of glucose, TNF, and heat compared to combined treatment with heat and either TNF or glucose at a hyperthermia of 42 degrees C. This effect was not obtained with heating to 40 degrees C. TNF appears to be a potent heat sensitizer when an appropriate temperature and time interval between hyperthermia and TNF administration are used. Trimodality treatment with hyperthermia, TNF, and glucose may be a new method of anticancer therapy.

Animals↗

PubMed1991

Pituitary and gonadal hormone-dependent and -independent induction of follicle-stimulating hormone receptors in the developing testis.

The number of FSH receptors increases during testicular development in several species of mammals. Hypophysectomy and hormonal replacement were performed to identify the factors that induce developmental changes in testicular FSH receptors. Male rats of the Wistar/Tw strain were hypophysectomized at 9, 16, 23, or 30 days or 3 months of age. These rats were killed 10 days after surgery along with intact control rats, and the testes were removed for receptor assay. A group of intact rats was killed on the day of surgery as initial controls. All of the hypophysectomized immature rats showed a higher density of FSH binding (FSH binding per unit weight) and a lower total FSH binding (FSH binding per two testes) compared with each of the matched intact control rats. In contrast to FSH binding, not only the total LH binding but also the density of LH binding were invariably lower in the hypophysectomized rats than in the intact control rats. Unlike hypophysectomy at other immature ages, surgery at 9 days of age was followed by significant increases in testicular weight, density of FSH binding, and total FSH binding compared with those values in the initial control rats. There was no significant effect of hypophysectomy on total FSH binding in adult animals, in contrast to the marked decrease in total LH binding. When male rats hypophysectomized at 25 days of age were injected with FSH for 5 days beginning on the 11th day after surgery, dose-dependent increases in total FSH binding and testicular weight were observed. Testosterone treatment induced an increase only in the total FSH binding, but its effect was less potent. Scatchard plot analyses of the binding suggested that changes in FSH binding with age, after hypophysectomy, and after hormonal administration were due to changes in the number of binding sites. Plasma FSH concentrations in all postoperative rats were below or at the level of detectability, indicating that hypophysectomy was successful. In normal immature rats, a significant increase in the plasma FSH level was detected only from 9-19 days of age, in contrast to the continuous increase in total FSH binding during testicular development. These results suggest that FSH and testosterone act as hormonal factors to induce an increase in the number of FSH receptors in the developing testis. Other factors that are independent of pituitary and sex hormones may also contribute to FSH receptor induction.

Animals↗

PubMed1991

Peplomycin-induced DNA repair synthesis in permeable mouse ascites sarcoma cells.

DNA repair synthesis induced in permeable mouse ascites sarcoma cells by peplomycin, an antitumor antibiotic, was studied. Mouse ascites sarcoma (SR-C3H/He) cells were permeabilized with a low concentration of Triton X-100 in an isotonic condition. Permeable cells were treated with an appropriate concentration of peplomycin to introduce single-strand breaks in permeable cell DNA. DNA repair synthesis in peplomycin-treated permeable cells was measured by incubating the cells with four deoxynucleoside triphosphates in an appropriate buffer system. The DNA repair synthesis was enhanced by ATP and NaCl at near physiological concentrations. More than 90% of DNA synthesis in the present system depended on the peplomycin-treatment. The repair nature of the DNA synthesis was confirmed by a BrdUMP density shift technique. The repair patches were largely completed and ligated in the presence of ATP. Analyses using selective inhibitors for DNA polymerases showed that both DNA polymerase Beta and aphidicolin-sensitive DNA polymerases (DNA polymerase alpha and/or delta) were involved in the repair DNA synthesis.

Animals↗

PubMed1991

[A case of symmetrical and bilateral tuberculoma of both lung apices].

A 28-year-old man with solitary nodular shadows in both lungs was admitted. The erythrocyte sedimentation rate was accelerated, with elevation of the serum IAP values, and the tuberculin reaction was strongly positive. The X-Ray film of the chest revealed symmetrical and bilateral nodular shadow in both lung apices. Both nodular lesions revealed a tendency to grow, pleural indentation and spiculated margins. Moreover, the tomogram film showed convergence of the pulmonary vein branch in the central part of the left apex nodule. Since it was extremely difficult to distinguish these lesions from malignant nodules based on just radiographic findings, an exploratory thoracotomy was carried out. The histologic diagnosis of both nodules was tuberculoma. Currently, the radiologic criteria used to distinguish between benign and malignant lesions are assessment of size, contour, absence or presence of tumor growing tendency by serial radiographs, calcification as well as the relation between the lesion with the pulmonary vasculature. It was concluded that, as was shown by this case, the radiographic criteria appear to be insufficient to categorize the nature of a lesion into benign or malignant. Consequently, more reliable non-invasive techniques would be desirable for the accurate diagnosis of tuberculosis.

Adult↗

PubMed1990

Extranodal non-Hodgkin's lymphoma of the head and neck. A clinicopathologic study in the Kyoto-Nara area of Japan.

The clinicopathologic features of 114 Japanese patients with extranodal non-Hodgkin's lymphoma of the head and neck region were analyzed. The median age was 60.5 years and the male:female ratio was 1.5:1. The most common site of involvement was Waldeyer's ring, followed by the oral cavity, thyroid gland, paranasal sinuses, nasal cavity, and larynx. Seventy-five percent of the patients were in Stage I or Stage II at admission. Histologically, diffuse lymphoma accounted for 94% and follicular lymphoma for 6% of cases. The histologic grade according to the Working Formulation System of the National Cancer Institute was low in 11%, intermediate in 75%, and high in 14% of cases. Immunohistochemical study showed that the majority of the cases were of B-cell type and only 13 cases (11%) were of the T-cell type. Peripheral T-cell lymphomas (eight cases) mainly occurred in the nasopharynx and nasal cavity, whereas four of five thymic T-cell lymphomas were found in the palatine tonsil. The over-all 5-year survival rate was 54%, and the factors affecting survival were sex, histologic grade, T/B phenotype, clinical stage, and the site of initial presentation. Five-year survival with nasal cavity and Waldeyer's ring lymphoma was 24% and 46%, respectively. The poor prognosis of lymphomas at these sites might result from the predominance of T-cell lymphoma, the paucity of low grade lymphoma, and the relatively high incidence of cases that were in an advanced stage at presentation. In Stage II, patients treated with combined therapy tended to have a better 5-year survival rate than those treated with radiotherapy alone.

Adolescent↗

PubMed1990

Improved survival rate in primary intracranial lymphoma treated by high-dose radiation and systemic vincristine-doxorubicin-cyclophosphamide-prednisolone chemotherapy.

Thirty patients with histologically proven primary intracranial non-Hodgkin's lymphoma were treated at Kyoto University. Ten of them were treated prospectively with a radiation-chemotherapy protocol. All but four specimens were recently reexamined and classified according to the Working Formulation system. The predominant histologic types were diffuse large cell type, large cell immunoblastic type, and diffuse mixed small and large cell type, seen in 38%, 21%, and 21% of cases, respectively. Before 1980, 16 patients were treated with postoperative radiation without definite chemotherapy, and only one has survived more than 5 years. Local recurrence was the most common cause of failure. In 1981, the authors started a protocol in which four to six courses of systemic chemotherapy with vincristine, doxorubicin, cyclophosphamide, and prednisolone (VEPA) was given after whole brain radiation (30-40 Gy) with a local boost up to 50 to 60 Gy. Eight patients completed this protocol, and all of them are alive at 16 to 100 months after diagnosis, with three patients surviving more than 5 years. Only one patient developed recurrence. On the other hand, six patients who did not complete or receive chemotherapy after 1981 are dead or alive with recurrence. Correlation between the Working Formulation subtype and prognosis was not clear because of the variety of treatment. Two patients receiving chemotherapy developed brain necrosis, which was fatal in one case, and the other two patients treated with the protocol are in a poor state without signs of recurrence. Chemotherapy may enhance the radiation effect on normal brain tissue as well as tumor. Combination of radiotherapy and chemotherapy can improve the survival rate, but the optimal dosage needs to be investigated further.

Adolescent↗

PubMed1990

[Clinical results of conventional fractionation radiotherapy for glottic and supraglottic laryngeal cancers--the usefulness of hyperfractionation for these cancers].

Ninety patients with glottic and eighteen patients with supraglottic laryngeal cancer (anyN, M0) were treated by conventional fractionation radiotherapy between July, 1963 and August, 1988. Tumor control and cause specific survival were evaluated according to tumor location (glottic or supraglottic) and tumor size (T1, T2, T3, or T4). As a result, the steepness of dose-response curve for the tumor control in T1-2 glottic and T2 supraglottic tumors was more slanting upwards than that in other laryngeal tumors, and the patients whose tumors were irradiated at larger doses had a tendency to survive longer. These results suggested that T1-2 glottic and T2 supraglottic laryngeal tumors can have a good application for hyperfractionation radiotherapy which is a radiation therapy with multiple fractions per day with a small fraction size and with which tumors can receive larger radiation doses than with conventional fractionation radiotherapy. Five patients with glottic or supraglottic tumors treated by hyperfractionation radiotherapy obtained CR, and now show no recurrence. We are going to investigate the usefulness of hyperfractionation radiotherapy after treating more patients with Twice-A-Day fractionation radiotherapy.

Adult↗

PubMed1990

Effects of prolactin and bromocryptine on the regulation of testicular luteinizing hormone receptors in mice.

The binding of luteinizing hormone (LH) to testicular homogenates increased gradually in mice from 15 to 60 days of age, while the level at 90 days was almost the same as that at 60 days. The plasma concentration of prolactin (PRL) increased significantly from 15 to 40 days and thereafter remained constant. In order to ascertain the influence of PRL on testicular receptors for LH, bromocryptine was injected subcutaneously for 10 days into immature (20-day-old) and adult (90-day-old) mice. In 20-day-old mice, treatment with bromocryptine significantly reduced the plasma levels of PRL but had no significant effects on the binding of LH to receptors in 30-day-old mice. However, in 90-day-old mice, treatment with bromocryptine led to a significant reduction in numbers of receptors for LH 10 days later. There was no difference in dissociation constants (Kd) between groups of oil-injected (Kd = 6.5 x 10(-10) M) and bromocryptine-injected (Kd = 4.6 x 10(-10) M) mice. The reduction in binding of LH per testis of 100-day-old mice after treatment with bromocryptine was eliminated by the simultaneous administration of ovine (o) PRL. The plasma level of follicle-stimulating hormone (FSH) in 100-day-old mice, which tended to be decreased as a result of treatment with bromocryptine, was markedly increased by treatment with oPRL. There were no distinct changes in binding of FSH in any of the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Two-step transformation of rat 3Y1 cells by the adenovirus E1A and E1B genes.

The transformation of rodent cells by the adenovirus E1A and E1B genes was very efficient when these genes were physically linked. When they were cleaved, the transformation became very inefficient. To clarify this difference, the chimeric E1B genes in which either the adenovirus enhancer or the human beta-actin promoter was linked to the 5' side of the E1B gene were introduced into rat 3Y1 cells. The saturation density of these cell lines (eB or APrB) was similar to that of parental 3Y1 cells. When eB or APrB cell lines were supertransfected with the E1A gene, discrete dense foci were developed after 5-6 weeks, while the supertransfection of 3Y1 derivative cell lines, in which the enhancer-unlinked E1B gene was introduced, did not develop any dense foci. Analysis of the E1A and E1B transcripts in these cell lines indicated that the E1B gene is efficiently expressed in the presence of the E1A gene products if the enhancer is linked to the E1B gene and that an increased level of E1B proteins is required for an efficient expression of the E1A gene. These results indicated that E1A and E1B genes in separate pieces of DNA are capable of cooperatively transforming 3Y1 cells if appropriate cis-acting elements are attached and high-level expressions are achieved.

Actins↗

PubMed1990

Effect of recombinant human granulocyte colony-stimulating factor on granulocytopenia in mice induced by irradiation.

We report the effect of human granulocyte colony-stimulating factor (hG-CSF) on the recovery from granulocytopenia induced by irradiation. Female 9-week old C3H/He mice were used. The irradiation schedule was as follows: Group 1 and 2 received whole-body irradiation of 1 Gy and 5 Gy, respectively, on day 0; Group 3 and 4 received whole-body irradiation of 0.5 and 1.0 Gy, respectively, for 5 consecutive days; Group 5 received upper hemibody irradiation of 3 Gy for 5 consecutive days. Daily subcutaneous injections of G-CSF (3 x 10(5) Unit/mouse) or 0.3 ml of saline to each group were started from the day after the first irradiation and continued for 18 days. Mice were sampled randomly from each group, and the total number of leukocytes, erythrocytes of peripheral blood, nucleated cells in femur, and spleen weight were counted and measured, respectively, on day 0, 3, 5, 7, 9, 12, and 18. The leukocyte counts decreased with an increase in radiation doses. In Group 1 and 2 mice, G-CSF enhanced the leukocyte count more than saline. In Group 3 mice, the recovery of leukocytopenia was facilitated by G-CSF, but in Group 4 mice, G-CSF had no effect on the leukocyte count decrease or on leukocytopenia recovery. In Group 5 mice, G-CSF greatly affected leukocytopenia recovery. Increase in spleen weight paralleled the peripheral leukocyte count. Daily administration of recombinant hG-CSF accelerated the granulocytopenia recovery which was induced by irradiation, and it may be a useful therapeutic agent for treating myelosuppressive cases.

Agranulocytosis↗