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Biomedical subjects

K Hasumi

Publications and source records attributed to K Hasumi.

At least 145 records · Page 8Linked to original sources

Changes in bone mineral density and fracture prevalence in Japanese women after oophorectomy.

The bone changes after gynecological surgery during the early phase of recovery were examined. The subjects were randomly selected from women who had undergone bilateral oopho-hysterectomies (OOX, n = 98, 46.0 +/- 5.0 year-old) or hysterectomies (HX, n = 75, 43.6 +/- 4.6 year-old) within 4 years prior to entering the study. The ovarian functions in the HX group were presumed to be intact following the hysterectomies, judging from the cytological evaluation of the vaginal pap smears. The bone morphological changes in both groups were examined to measure the cortical thickness of the metacarpal bone (MCI) on hands X-ray film using microdensitometry, and the posterior/anterior height ratios (P/A ratio) of the entire vertebral bodies, on vertebral X-ray films using a digitizer. The changes in bone mineral densities in both groups were measured by dual energy X-ray absorptiometry at lumbar vertebrae (L2-4 BMD) and by microdensitometry at the metacarpal cortical bone; the bone densities of metacarpal bone were referenced by the density of aluminum step wedge on the same X-ray films. The prevalence of vertebral body fractures (P/A ratio greater than 1.4) in the OOX group (5.1%) was 3.9 times higher than that in the HX group (1.3%). There was a significant decrease in MCI in the OOX group compared with the HX group (p less than 0.01). L2-4 BMD in the OOX and HX group were 1.07 +/- 0.15 and 1.16 +/- 0.13 g/cm2, respectively (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The immunohistochemical localization of new membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) in human and cynomolgus monkey placentae.

New membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) were investigated by avidin-biotin immunoperoxidase technique in the human and cynomolgus monkey placentae, decidua and umbilical cords. In human early placentae, MP2 A, B, C, and E were localized mainly in the membrane of villous syncytiotrophoblasts and cytotrophoblasts. Histiocytes in the villous stroma were positive for MP2 A, B, D, and E. In human term placentae, obvious positive staining for MP2 A, B, C, and E was observed in the membrane of villous syncytiotrophoblasts, in the amniotic epithelium, and in the umbilical cord sheath. Histiocytes in the villous stroma were positive for MP2 A, B, C, E, and especially for MP2 D. Importantly, MP2 A, C, and E were positive in polymorphonuclear neutrophils, since most of these common antigens are also carcinoma-associated, suggesting clinical usage of MP2 proteins as a new tumor marker. In the cynomolgus monkey placentae, similar immuno-staining results were obtained. The monkey can thus serve as a experimental model for the investigation of the placental proteins.

Amnion↗

Isolation, characterization and biological activities of concanamycins as inhibitors of lysosomal acidification.

Four new analogues of concanamycin family, designated concanamycins D, E, F G, were isolated from the mycelium of Streptomyces sp. A1509 by solvent extraction, silica gel column chromatography and HPLC. Structures of these compounds were identified by the combination of spectroscopic analyses. All of these compounds were structurally related to concanamycins A, B and C, which had been isolated previously, and inhibited the acidification of rat liver lysosomes at 10(-11)-10(-9) M concentration. The structure-activity study showed that the 18-membered macrolide ring and the 6-membered hemiketal ring portions of the molecules of concanamycin family are responsible for potent inhibitory activity.

Animals↗

Acaterin, a novel inhibitor of acyl-CoA: cholesterol acyltransferase produced by Pseudomonas sp. A92.

Acaterin, a novel inhibitor of acyl-CoA: cholesterol acyltransferase (ACAT), was isolated from a culture broth of Pseudomonas sp. A92 by Diaion HP-20 column chromatography, solvent extraction and reverse phase HPLC. Spectroscopic analyses of the compound yielded 3-(1-hydroxyoctyl)-5-methyl-2(5H)-furanone as the proposed structure. In the presence of oxidized low density lipoprotein, acaterin inhibited the synthesis of cholesteryl ester in macrophage J774 by 50% at a concentration of 45 microM. Acaterin also inhibited ACAT activity in the rat liver microsomes by 50% at a concentration of 120 microM. Kinetic studies suggested that inhibition of ACAT by acaterin was noncompetitive with respect to oleoyl-CoA.

Animals↗

Immunohistochemical and ultrastructural investigation of new membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) in gynecologic neoplasms.

New membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) were investigated immunohistochemically by avidin-biotin immunoperoxidase technique and immunoelectron microscopy in various gynecologic neoplasms and normal gynecologic tissues. MP2 A and MP2 B were not specific for malignant tumors. MP2 C was present in 67-100% of ovarian carcinomas, 100% of benign dermoid cysts, and 77% of endometrial carcinomas. Except for endocervical adenocarcinomas, MP2 D was hardly detectable in gynecologic malignancies. Although MP2 E was hardly detectable in benign gynecologic tumors, this protein was present in ovarian carcinomas, uterine squamous carcinomas, endocervical adenocarcinomas, and endometrial adenocarcinomas. These results suggest a possible clinical application of these MP2 proteins as a new tumor marker for gynecologic malignancies.

Biomarkers, Tumor↗

[Multimodal treatment for advanced, ovarian cancer patients with poor performance status--its effectiveness and limitations].

We assessed the feasibility of the sequential multimodal treatment including neoadjuvant chemotherapy for far advanced ovarian cancer patients not amenable to a standard modality because of poor medical status. Seven consecutive advanced ovarian cancer patients presented with massive ascites (5 with pleural effusion). Based on the priming theory, immunotherapy with OK432 (s.c. priming with 0.2 KE of OK432 followed by a local injection with 10KE of OK432) was successfully applied to a carcinomatous effusion. Thereafter, patients were treated with 4-6 courses (13-20 wks) of "low-dose consecutive CP (CPM 500 mg/m2, day 1; CDDP 10 mg/m2, day 1-7), which delivered 1CR, 5PR and 1NC (tumor regression rate: 30-100%). Subsequently, the patients underwent radical surgery including small/large bowel resection, splenectomy and diaphragma resection in addition to hysterectomy, bilateral adenectomy and omentectomy, with tumor resectability being 100% in 4 cases and 90% < (residual 2 cm) in 3. Postoperatively, patients received intraperitoneal (IP) chemo-immunotherapy and were followed up with IP washing cytology through an implanted reservoir. Mean survival time was 17.1 months (10-32) with the follow up interval being 10-32 months. Four patients with complete tumor resection are alive with no evidence of disease for 14-32 months. Among 3 incomplete patients, 2 with persistent/recurrent disease received further IP chemotherapy and the remaining one died of the disease at 15 months from the start of therapy. Thus, the present multimodality indicates the possibility of a "cure" for far advanced ovarian cancer patients with poor performance status.

Adenocarcinoma↗

[Time course changes in bone mineral density and calcium metabolism after oophorectomy].

Time course changes in bone mineral density and calcium metabolism after oophorectomy were investigated in comparison with those in hysterectomized and pre-operated women, retrospectively. A total of 191 women who had a regular menstrual period for 1 year prior to entering the study or to the operation, were divided into 3 groups; group 1 consisted of 33 women who were admitted to receive a gynecological operation (pre-OP group), group 2 consisted of 57 women who received hysterectomy within 5 years prior to entering the study (HX group) and group 3 consisted of 101 women who received hysto-oophorectomy (bilateral) at the same timing as the HX group (OOX group). All the subjects had their bone mineral density measured at the lumbar vertebrae (L2-4BMD) by means of dual energy X-ray absorptiometry (DXA) and at the metacarpal bone by the microdensitometrical (MD) method. Serum and urinary parameters related to bone and calcium metabolism were also evaluated. After dividing the subjects in accordance with the length of time after the operation, the time course changes in each parameter were calculated. In the 2 years after OOX, the L2-4BMD decreased significantly and rapidly, and the change in L2-4BMD in the subsequent period was quiescent. In the HX group, there was no significant change in L2-4BMD. When the period after the OOX was divided into 2 subcategories in accordance with the speed of decline in lumbar BMD as the rapid and the slow phases, the time course changes in blood and urine parameters showed different trends.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Cytomorphologic, cytometric and histomorphologic observations after laser therapy for cervical lesions.

To analyze the healing process after laser therapy for cervical lesions, the clinical, cytologic, histologic and colposcopic features in 109 cases were studied chronologically. The healing process of the cervical epithelium usually began from both the squamous and columnar epithelial borders, starting around the 10th day after laser therapy; the process covered the whole tissue defect with multilayered epithelium within seven weeks. Inflammatory changes also usually abated within that time. Cytomorphologically, laser therapy resulted in the occurrence of (mostly degenerated) "fiber-type" and orangeophilic cells in smears taken during the first two weeks after treatment. Tissue repair cells were seen in smears collected from the first posttherapy day through the fourth week after laser therapy. Using computer-assisted image cytometry, the reparative cells in samples taken shortly after treatment (roughly, the first to fifth days) exhibited more hyperchromatic (3-4N) nuclei than did those in later samples; however, the mean DNA content of the early reparative cells was generally concentrated around that of the 2N reference cells. These findings suggest that follow-up, including cytologic and colposcopic examination, for the early detection of residual or recurrent lesions should start in the eighth week and continue periodically for at least one year.

Biopsy↗

[An overview of new prognostic factors for ovarian cancer].

One of the most characteristic features of epithelial ovarian cancer is its inherent heterogeneity with respect to biological behavior ranging from the relatively indolent nature of borderline tumors to highly aggressive malignant diseases. This can be reflected in a wide variety of prognostic factors, among which the stage of disease is by far the most important, followed by histologic subtype, histologic grade, volume of residual disease, age at diagnosis, and performance status (PS). Within a given stage, histologic grade is the most powerful prognostic factor in stage I disease, followed by dense adherence and large volume of ascites. On the other hand, the main prognostic factor in more advanced stage disease (II-IV) includes an effect of chemotherapy and a volume of residuum, and PS. However, these factors alone cannot always predict patients' survival correctly. A number of new and potentially valuable prognostic factors have emerged as a result of the recent technical advances in molecular genetics, flow cytometric analysis, development of monoclonal antibody, immunohistochemical study, and steroid hormone receptor analysis. This article reviews some of these newly developed "investigational" prognostic variables, as well as the "widely accepted" clinicopathological prognostic factors.

Cell Division↗

Unstable amplification of the chromosomal gene for 3-hydroxy-3-methylglutaryl coenzyme A reductase in compactin-resistant CR200 cells.

CR200 cells, a compactin-resistant clone of mouse FM3A cells, overaccumulate 3-hydroxy-3-methylglutaryl coenzyme A reductase. The elevated reductase activity is not regulated normally by low-density lipoprotein, mevalonate and 25-hydroxycholesterol. The amounts of reductase protein and mRNA were elevated in CR200 cells by 40- to 60-fold, as compared to those in parental FM3A cells and the rate of reductase transcription and the number of copies of reductase gene were increased in CR200 cells by 20- to 50-fold. In the parental cells, mevalonate and 25-hydroxycholesterol suppressed reductase transcription by greater than 90%, while that in the mutant cells was suppressed by only 20-50%, suggesting a regulatory alteration in the gene transcription in CR200 cells. When CR200 cells were grown for 10-20 weeks in the absence of compactin, levels of the gene amplification were reduced from approx. 50-fold to approx. 2-fold, along with a marked decrease in reductase activity and compactin-resistance of the cells. While the gene amplification was unstable, minute chromosomes were not seen in the cells and centrifugal fractionation and in situ analysis demonstrated that the amplified reductase gene was present on 2-3 chromosomes in the pseudotetraploidal CR200 cells having approx. 78 chromosomes. From these results it was concluded that the amplified reductase gene, which is responsible for overaccumulation of reductase, is located on chromosomes but is unstable in CR200 cells.

Animals↗

Identification of koningic acid (heptelidic acid)-modified site in rabbit muscle glyceraldehyde-3-phosphate dehydrogenase.

The sesquiterpene antibiotic koningic acid (heptelidic acid) has been previously demonstrated to modify glyceraldehyde-3-phosphate dehydrogenase in specific manner, probably by binding to the sulfhydryl residue at the active site of the enzyme (Sakai, K., Hasumi, K. and Endo, A. (1988) Biochim. Biophys. Acta 952, 297-303). Rabbit muscle glyceraldehyde-3-phosphate dehydrogenase labeled with [3H]koningic acid was digested with trypsin. Reverse-phase HPLC revealed that the label is associated exclusively with a tryptic peptide having 17 amino acid residues. Microsequencing and fast atom bombardment mass spectrometry demonstrated that the peptide has the sequence Ile-Var-Ser-Asn-Ala-Ser-Cys-Thr-Thr-Asn-Cys-Leu-Ala-Pro-Leu-Ala-Lys. In comparison to the amino acid sequence of glyceraldehyde-3-phosphate dehydrogenase from other species, this peptide is in a highly conserved region and is part of the active site of the enzyme. The cysteine residue corresponding to the Cys-149 in the pig muscle enzyme, which has been shown to be an essential residue for the enzyme activity, was shown to be the site modified by koningic acid. Structural analyses of the reaction product of koningic acid and L-cysteine suggested that the epoxide of koningic acid reacts with the sulfhydryl group of cysteine residue, resulting in a thioether.

Amino Acids↗

Application of boronated anti-CEA immunoliposome to tumour cell growth inhibition in in vitro boron neutron capture therapy model.

An immunoliposome containing a 10B-compound has been examined as a selective drug delivery system in boron neutron-capture therapy. Liposomes, conjugated with monoclonal antibodies specific for carcinoembryonic antigen (CEA) were shown to bind selectively to cells bearing CEA on their surface. The immunoliposomes attached to tumour cells suppressed growth in vitro upon thermal neutron irradiation and suppression was dependent upon the concentration of the 10B-compound in the liposomes and on the density of antibody conjugated to the liposomes. The results suggest that immunoliposomes containing the 10B-compound could act as a selective and efficient carrier of 10B atoms to target tumour cells in boron neutron-capture therapy.

Antibodies, Monoclonal↗

Pannorin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor produced by Chrysosporium pannorum.

Pannorin, a naphthopyrone that inhibits 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis, was isolated from a culture broth of Chrysosporium pannorum M10539 by solvent extraction, Bio-Gel P-6 column chromatography and reverse phase HPLC (Silica ODS). Spectroscopic analyses of the compound yielded 4,8,10-trihydroxy-5-methyl-2H-naphtho[1,2-b]pyran-2-one as the proposed structure. Pannorin inhibited HMG-CoA reductase and in vitro sterol synthesis 50% at a concentration of 160 microM.

Animals↗

[Maintenance of the activation of peritoneal macrophage in patients with ovarian cancer by the repeated administration of sizofiran and interferon gamma].

Four patients with ovarian cancer were treated with a 20mg injection of sizofiran, a MW 450,000 beta-1,3-glucan, intramuscularly one day before and 4,7,11,14,18 and 21 days after second look laparotomy and with the administration of 2 million units of interferon gamma intraperitoneally at 0,4,7,11,14,18 and 21 days after second look laparotomy. Peritoneal macrophages were obtained from the patients by peritoneal washing with saline through an indwelled tube. The number of macrophages was increased to about 30 times after the treatment. The concentrations of interleukin 1, interferon gamma, tumor necrosis factor and prostaglandin E2 in the media of 24-hour cultured macrophage with 10 micrograms/ml of LPS were also increased throughout the treatment. These data suggest that the every 3 to 4 day treatment with sizofiran and interferon gamma maintained the activation of peritoneal macrophages which might lead to retention of the antitumor activity in patients with ovarian cancer.

Adult↗

[Maintenance of housewife activity and the quality of familiar interactions by home continuous infusion chemotherapy in patients with recurrent gynecological cancer].

Sixteen patients with recurrent gynecologic cancer were studied to evaluate maintenance of housewife activity and the quality of familiar interactions by the home continuous infusion of CDDP at a daily dose of 5 mg/body. A total dose of CDDP in one course was 100 mg/body, and more than one course was performed in every patient. Eight patients underwent intra-arterial infusion of CDDP by the 20-day continuous infusion and another 8 patients intra-venous infusion by 5-day continuous infusion every other week. The average caloric intake was 2201 kcal measured by the record of a three-day food intake during the treatment. 88% of the patients arouse between 6 and 7 in the morning, and all the patients cooked breakfast and supper, went shopping for food materials, cleaned a house and did the washing with the help of her family. All the patients accepted the treatment and were satisfied with it but appeared anxious about recurrence. Information or advice by the doctor was important to relieve their anxiety. Their husbands also accepted the treatment and tolerated well their wives, continuation of home therapy.

Activities of Daily Living↗

[A late phase II study of CPT-11 on uterine cervical cancer and ovarian cancer. Research Groups of CPT-11 in Gynecologic Cancers].

A late phase II study of CPT-11, a new derivative of camptothecin, in uterine cervical cancer and ovarian cancer was carried out by a cooperative study group at 26 institutions. Out of 144 patients enrolled, total cases were 110, involving 55 uterine cervical cancers and 55 ovarian cancers. In uterine cervical cancer, 5 cases of complete response (CR) and 8 cases of partial response (PR) were observed, with a response rate of 23.6% and a CR rate of 9.1%. In ovarian cancer, 13 cases of PR were observed, response rate was 23.6%. Both in uterine cervical cancer and ovarian cancer, the 95% confidence interval of response rate was 12.4-34.8%. In cases having undergone previous chemotherapy including platinum, derivatives, the response rate in ovarian cancer was 23.1% (12/52). In cases of uterine cervical cancer having previous radiotherapy, the response rate was 26.8% (11/41). In ovarian cancer of various histological types, a response was observed for not only serous cystadenocarcinoma but also mucinous cystadenocarcinoma, etc. A response was observed in distant metastatic lesions such as lung metastasis as well as primary lesion in uterine cervical cancer and ovarian cancer. Major adverse reactions were leukopenia, nausea and vomiting, diarrhea and anorexia, and these incidences (grade 2 or more) were 87.3, 60.3, 44.0 and 67.2%, respectively. Since some patients experienced severe adverse reactions, caution should be taken in treatment with CPT-11. Besides these reactions, alopecia was observed (33.1%), but severe adverse reactions such as nephropathy were not found. No significant difference in the efficacy and adverse reactions were observed between administration methods; A, 100 mg/m2 once weekly and B, 150 mg/m2 once every 2 weeks. Both were thought to be clinically useful. These results suggest that CPT-11 is clinically effective against uterine cervical cancer and ovarian cancer.

Adult↗

[Augmentative effect of sizofiran on the immune functions of regional lymph nodes in patients with cervical cancer].

Twenty mg of sizofiran (Schizophyllum glucan: SPG) was i.m. administered one day prior to surgery, or the same dose was injected 8 days and one day before surgery to 40 patients with cervical cancer and 15 with a benign tumor. Frozen sections of fresh pelvic lymph nodes from these patients obtained during surgery were stained by the ABC (Avidin-biotin-peroxidase complex) method with several monoclonal antibodies to define the surface phenotype of mononuclear cells. SPG led to a great increase in the number of cells stained with interleukin-2 receptor (IL-2R) and Leu 3a antibodies, mainly in PC, but with only a slight increase in the number of cells stained with Leu 2a, 7, 11, and M3 antibodies. This augmenting effect was more prominent in patients receiving two SPG injects that in those with a benign tumor. These results suggest that stimulus with some antigen (cancer antigen in the present study) may be required to induce immuno-augmentation by SPG which has no antigenicity. Interestingly, the above augmenting effects could be seen even in metastatic lymph nodes from advanced cervical cancer patients. SPG was thus revealed to be a potent biological response modifier leading to augmented helper T (Th) cell functions of pelvic lymph nodes in cervical cancer patients, among which an enhanced IL-2/IL-2R system was noted.

Adjuvants, Immunologic↗