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Biomedical subjects

K Hasumi

Publications and source records attributed to K Hasumi.

At least 199 records · Page 11Linked to original sources
PubMed1988

Inactivation of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase by koningic acid.

Koningic acid, a sesquiterpene antibiotic, is a specific inhibitor of the enzyme glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12). In the presence of 3 mM of NAD+, koningic acid irreversibly inactivated the enzyme in a time-dependent manner. The pseudo-first-order rate constant for inactivation (kapp) was dependent on koningic acid concentration in saturate manner, indicating koningic acid and enzyme formed a reversible complex prior to the formation of an inactive, irreversible complex; the inactivation rate (k 3) was 5.5.10(-2) s-1, with a dissociation constant for inactivation (Kinact) of 1.6 microM. The inhibition was competitive against glyceraldehyde 3-phosphate with a Ki of 1.1 microM, where the Km for glyceraldehyde 3-phosphate was 90 microM. Koningic acid inhibition was uncompetitive with respect to NAD+. The presence of NAD+ accelerated the inactivation. In its absence, the charcoal-treated NAD+-free enzyme showed a 220-fold decrease in apparent rate constant for inactivation, indicating that koningic acid sequentially binds to the enzyme next to NAD+. The enzyme, a tetramer, was inactivated when maximum two sulfhydryl groups, possibly cysteine residues at the active sites of the enzyme, were modified by the binding of koningic acid. These observations demonstrate that koningic acid is an active-site-directed inhibitor which reacts predominantly with the NAD+-enzyme complex.

Animals↗
PubMed1988

Establishment of tumor-specific immunotherapy model utilizing vaccinia virus-reactive helper T cell activity.

It was previously demonstrated that preimmunization of mice with live vaccinia virus (VV) and subsequent immunization with VV-infected (modified), syngeneic tumor cells resulted in enhanced induction of tumor-specific immunity through a cellular collaboration between VV-reactive helper T (VV-Th) cells and tumor-specific effector cell precursors. On the basis of this augmenting system, a tumor-specific immunotherapy model was established in which a growing tumor regressed. C3H/HeN mice were pretreated with cyclophosphamide to eliminate nonspecific suppressor T cell activity and subsequently inoculated (primed) s.c. with live VV, leading to augmented induction of VV-Th cell activities. Four weeks later, the mice were inoculated i.d. with syngeneic X5563 myeloma cells. Six days after the tumor cell inoculation, live VV was injected into the tumor mass three times at 2-day intervals. Seven of ten mice which had received VV priming and subsequent VV injection into the tumor mass exhibited complete tumor regression. On the contrary, mice which had received mere intratumoral VV injection in the absence of VV priming failed to exhibit appreciable tumor regression. Mice whose tumor had completely regressed (regressor mice) by the above VV immunotherapy were shown to have acquired systemic anti-tumor immunity, which was confirmed by a challenge with syngeneic tumor cells after the tumor regression. In vitro analysis of these immune mice revealed that potent tumor-specific cytotoxic T lymphocyte responses were preferentially induced, but with no detectable anti-tumor antibody responses. Such a potent tumor-specific immunity was not observed in mice which had received an intratumoral VV injection in the absence of VV priming. Thus the results clearly indicate that the tumor regression was accompanied by concurrent generation of a potent tumor-specific immunity, suggesting that the cellular collaboration between VV-Th cells and tumor-specific effector cell precursors is also functioning in this VV-immunotherapy protocol, likewise the immunoprophylactic model. Therefore, the present model provides an effective maneuver for tumor-specific immunotherapy and this system will be theoretically applicable to human cancer treatment.

Animals↗
PubMed1988

Immunotherapy of tumor-bearing mice utilizing virus help.

Utilizing vaccinia virus (VV), a tumor-specific immunotherapy model was established in which a growing tumor regressed. C3H/HeN mice were primed with VV after low dose irradiation to generate amplified VV-reactive T cell activities. Then 4 weeks later, the mice were inoculated i.d. with syngeneic MH134 hepatoma cells, and 6 days after the tumor cell inoculation, live VV was injected into the tumor mass 3 times at 2-day intervals. Of 10 mice which had received VV priming and subsequent VV injection into the tumor mass, 8 exhibited complete tumor regression. On the contrary, mice which had received only intratumoral VV injection without VV priming failed to exhibit appreciable tumor regression. Mice whose tumor had completely regressed following the VV immunotherapy were shown to have acquired systemic antitumor immunity, which was confirmed by a challenge with syngeneic tumor cells after immunotherapy. In vitro analysis of these immune mice revealed that potent tumor-specific antibody responses were preferentially induced, but with no detectable antitumor cytotoxic T lymphocyte (CTL) responses. Such a potent tumor-specific immunity was not observed in mice which had received intratumoral VV injection in the absence of VV priming. Thus, the results clearly indicate that tumor regression was accompanied by the concurrent generation of a potent tumor-specific immunity, suggesting that cellular cooperation between VV-reactive T cells and tumor-specific effector cells might be functioning in this VV immunotherapy protocol. Therefore, the present model provides an effective maneuver for tumor-specific immunotherapy. This system is, in principle, applicable to the human situation.

Animals↗
PubMed1988

[Cytological study on uterine sarcoma].

Between 1958 and 1985 (28 years), 53 cases of uterine sarcoma were seen at the Cancer Institute Hospital. Their cytological examination produced the following findings: 1) The positive rate in preoperative cytologic diagnostic tests was a low 21.7 percent for pure sarcoma and 70.0 percent for mixed mesodermal tumor. 2) The preoperative cytologic diagnosis and the final histologic diagnosis agreed in only 13.0 percent of pure sarcoma and 16.7 percent of mixed mesodermal tumor cases. 3) About one-half of the cases of mixed mesodermal tumor were diagnosed preoperatively as adenocarcinoma. 4) The positive rate in the cytologic diagnosis and the clinical stage were not correlated. 5) The positive rate in the cytologic diagnosis was high in cases of intracavity growth type sarcoma, but all cases of intramuscular localized type sarcoma were negative.

Adenocarcinoma↗
PubMed1988

Immunotherapy of advanced gynecologic cancer patients utilizing mumps virus.

Immunotherapy utilizing mumps virus (MV) was applied to 22 patients with advanced gynecologic cancer. Therapy schedule was based on the established concept of augmenting antitumor immunity utilizing virus-reactive helper T cell (Th) activity in a mouse system. Briefly, presensitization of cancer patients was performed subcutaneously (s.c.) with 10(8) PFU of mumps virus (MV). After increasing the anti-MV antibody activity of patients, 10(9) PFU of MV was administered locally or systemically. Marked clinical response was obtained by local (intraperitoneal or intrathoracic) injection of MV in patients with ascites or pleural fluid who had received preimmunization with MV. However, unprimed patients or patients with large tumor mass did not respond well to MV therapy. None of the patients showed untoward response to MV therapy except for controllable transient fever.

Adult↗
PubMed1988

[The clinical significance of murine monoclonal antibody (1H1) prepared against human pancreatic cancer cell line BxPC-3].

A new murine monoclonal antibody (1H1) was prepared by immunizing mice i.p. with human pancreatic cancer cell line (BxPC-3). The antibody reacted with 8 of 48 cultured cell lines that were all adenocarcinoma. Thin sections of normal and cancerous tissues were examined by immunoperoxidase staining. Thirty-nine of 48 (81%) pancreatic cancers, 11 of 23 (48%) gastric cancers, 12 of 18 (67%) colorectal cancers, 9 of 19 (48%) breast cancers, 2 of 5 (40%) lung cancers and 2 of 2 (100%) duodenal cancers were stained positively, but 5 islet cell tumors, 3 esophageal cancers and 2 hepatomas were not stained positively. Normal gastro-intestinal tract of adult or fetus was stained weakly or hardly stained. SDS-PAGE showed that 1H1 antigen recognized by 1H1 Mab had a relative molecular weight of over 400 K. Da. Immunoelectron microscopical study has shown that the antigen recognized by 1H1 antibody was localized in the cell membranes of the BxPC-3 cells. 1H1 antigen was found to be present in culture-spent medium of BxPC-3 cells by ELISA. Thus, 1H1 antibody may be useful for early detection of pancreatic cancers.

Adenocarcinoma↗
PubMed1988

[Differential diagnosis of early carcinoma of the uterus].

Benign diseases which should be distinguished from early carcinoma of the uterus include dysplasia, condyloma, and papilloma of the cervix; and hyperplasia and polyp of the endometrium. Cervical smear, colposcopy, cone biopsy are useful for diagnosis of early cervical cancer. Endometrial smear, hysteroscopy, endometrial curettage and CT are essential for diagnosis of early endometrial cancer.

Adenocarcinoma↗
PubMed1988

[Increases in the modified surgery in early cancers].

Early cancers are small in size and localized; many of them have no infiltration or metastasis. It has been gradually clarified what procedure of reduced operation can be feasible without fail to its radicalness to what type of early cancer, as a result of detailed studies on the findings concerning the development of early cancers as well as evaluations of recurrent cases and distant results. Techniques of reduced operation for the treatment of cancers of the thyroid, mammary glands, female reproductive organs and stomach have been improved as early cancer patients increase in number and our understanding of the pathogenesis of early cancers is promoted.

Breast Neoplasms↗
PubMed1988

[Relationship between peritoneal cytology and prognosis in endometrial carcinomas].

From 1971 to 1985, peritoneal cytologic examination was performed at the time of operation in 235 previously untreated patients with endometrial carcinoma. The relationship between the cytologic findings and prognoses by stage was investigated. The results were as follows: 1. In the peritoneal cytologic examination, 44 (18.7%) out of 235 cases were positive for cancer cells in all stages, 25 (14.5%) out of 173 cases in stage I, 7 (21.2%) out of 33 cases in stage II, and 8 (32.0%) out of 25 cases in stage III. 2. Among the 20 cases of stage I endometrial carcinoma that had no macroscopic metastasis and had positive peritoneal cytologic findings for cancer cells, 5- and 10-year cumulative survival rates were 94.7 and 94.7%, against 92.7% and 90.9% in cases with negative peritoneal cytology respectively. The recurrence rate in the same stage was 12.0% for positive cases, against 9.5% for negative cases. No significant differences between positive and negative cases were found. 3. In stages II and III, the difference between the survival rates for 9 cases which have positive peritoneal cytology without macroscopic peritoneal metastasis and 47 cases with negative peritoneal cytology were not statistically significant. 4. In endometrial carcinoma without macroscopic peritoneal metastasis, the appearance of cancer cells in peritoneal cytologic examination is not correlated with the prognosis.

Ascitic Fluid↗
PubMed1988

[Significance of preoperative diagnosis of endometrial carcinoma by angio-CT].

Angio computed tomography (CT) was performed in 87 previously untreated patients with endometrial carcinoma to study its clinical usefulness. All the patients subsequently underwent surgery and the angio CT findings were correlated with the surgical and pathologic findings. The results were as follows: 1. The tumor appeared as areas of low density in comparison with the surrounding myometrium after intraarterial infusion of contrast medium. 2. Angio CT proved to be useful in determining the depth of myometrial invasion. The myometrial invasion measured from the serosal surface in millimeters was assessed on angio CT. The CT findings were correlated well with pathologic findings. 3. Patients with intact myometrium greater than 10mm from the serosal surface assessed by angio CT had no nodal metastases. Angio CT provides a better display of cross-sectional uterine pathology than CT after intravenous infusion of contrast medium. The depth of myometrial invasion measured from the serosa on angio CT seems to be a useful prognostic factor in patients with endometrial carcinoma.

Female↗
PubMed1988

[Significance of total hysterectomy in uterine cervical cancer persistent in the uterine cervix after radiotherapy].

Radiation therapy is an important means for treating advanced cases of cervical cancer. There are cases, however, in which cancer cells persist even after treatment has been completed. We in the Department of Gynecology at the Cancer Institute Hospital actively performed total hysterectomies in such patients with no distant metastases and no extension of the parametrial induration to the pelvic wall, and obtained favorable results. In the present study, the clinical stage, histological type, degree of removal of involved tissue, and relationship between the prognosis and the maximum diameter of the tumor in the extirpated uterus were examined in 28 patients with advanced cervical cancer treated during the thirty-year period from 1957 to 1986. The following results were obtained: 1. The clinical stage and histological type of the cancer prior to radiation therapy did not significantly affect the prognosis after total hysterectomy. 2. The 3-year survival rate for the patients in whom all involved tissue could be removed was 81.0 percent. In contrast, all those in whom complete removal was impossible survived less than 3 years, despite additional therapy. 3. Prognosis was better in the patients who had tumors with a maximum diameter of less than 2 cm than in those who had tumors with a maximum diameter of 2 cm or more (p less than 0.05). 4. Patients in whom all involved tissue could be removed and in whom the maximum diameter of the tumor was less than 2 cm had a good prognoses, with 88.9 percent surviving at least 3 years after surgery.

Adenocarcinoma↗
PubMed1987

Overaccumulation of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase in a compactin(ML-236B)-resistant mouse cell line with defects in the regulation of its activity.

Using a stepwise selection procedure, we have developed a line of mouse FM3A cells which is resistant to compactin (ML-236B), a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme-A (HMG-CoA) reductase. This line, designated CR200, expressed a stable phenotype of a greater than 100-fold higher resistance to the inhibitor and a 160-fold higher HMG-CoA reductase activity than did the parental FM3A cell line when grown in the presence of low-density lipoprotein (LDL). In contrast to its action in the parental cells, HMG-CoA reductase in CR200 cells was not suppressed by human LDL. The activity of both cell-surface binding and degradation of 125I-LDL was approximately 10% in CR200 cells as compared with that in parental cells. Affinity of the 125I-LDL binding in CR200 cells was similar to that in the parental cells. In addition, HMG-CoA reductase was not suppressed normally by mevalonate and 25-hydroxycholesterol in CR200 cells; suppression was 50-60% by both compounds under conditions where suppression was about 99% in the parental cells. Sterol synthesis from [3H]mevalonate was normal in the variant cells. These observations demonstrate two defects in CR200 cells: decreased levels of LDL receptor and a defective regulation of HMG-CoA reductase by one or more products derived from mevalonate. When grown without compactin for 21 weeks, the variant cells became slightly sensitive to compactin and concomitantly recovered partly from both defects. However, these phenotypes of CR200 cells were stable up to 15 months when exposed to compactin. These two defects may account for the overaccumulation of HMG-CoA reductase in CR200 cells and thereby for the resistance to compactin.

Animals↗
PubMed1987

A trial of topical idoxuridine for vulvar condyloma acuminatum.

The effect of 0.25% idoxuridine ointment on condyloma acuminatum of the vulva was investigated in a randomized, double-blind, placebo-controlled trial in 24 women. Idoxuridine inhibits DNA synthesis in mammalian cells and is a specific inhibitor of DNA viruses. Of the 24 women with vulvar condyloma acuminatum, 14 applied idoxuridine ointment and 10 a placebo ointment to the lesions twice daily for 2 weeks. In 11 out of 14 patients treated with idoxuridine the condylomata regressed completely. The treatment did not cause any side-effects. None of the women in the placebo group showed regression of the condylomata. Topical idoxuridine therapy is effective and non-toxic; it appears to be most effective for new condylomata.

Administration, Topical↗