Biomedical subjects
Publications and source records attributed to O Ishiko.
We report a case of a perforated sigmoid diverticulum abscess that was difficult to differentiate from an ovarian tumor. A 53-year-old woman was diagnosed with an ovarian tumor, but laparotomy revealed a perforated sigmoid diverticulum abscess and appendicitis, with normal ovaries.
Haptoglobin (Hp) possesses many functions in the immune system and angiogenesis as well as scavenging released hemoglobin, and thus it is speculated that Hp may also play a critical role in the reproductive process. To investigate the possible involvement of Hp in the outcome of in vitro fertilization and embryo transfer (IVF-ET), the serum Hp of 50 patients who underwent IVF-ET was analyzed by the Western blot method. The results showed a higher pregnancy rate in the patients with the Hp2-2 phenotype (38%) than in those with the Hp2-1 phenotype (16%) (p = 0.08), and the serum alpha 2 subunit levels in the patients who achieved pregnancy within four attempts at IVF-ET were higher than in the others (p < 0.05). The results of this study suggest that Hp is involved in the outcome of IVF-ET.
Cyclooxygenase-2 (COX-2) expression was investigated immunohistochemically in 57 epithelial ovarian neoplasms and in histologically normal ovaries. Positive immunostaining for COX-2 was observed in 78.6% (22/28) of the ovarian cancers and in 66.7% (14/21) of the borderline-malignant tumors. The rate of expression was significantly higher among the ovarian cancers than the benign cystadenomas (4/8; 50%) (p<0.05). There was a significant correlation between vascular endothelial growth factor (VEGF) expression and microvessel count (MVC), but no correlation between COX-2 expression and MVC. There was a significant correlation between VEGF expression and COX-2 expression in all of the ovarian neoplasms as a whole (p<0.05). These findings suggest that an increase in COX-2 expression may be associated with malignant transformation and tumorigenesis of epithelial ovarian neoplasms.
Transferrin has been shown to have cytoprotective functions. The aim of this study was to evaluate the effect of antibody against CD71 (transferrin receptor) on survival potential of erythroid progenitor cells. After anti-CD71 IgG or control IgG was reacted with cells for 20 min on ice, the uptake of transferrin-bound 59Fe by the MEL cells or the mouse bone marrow cells during 2-day incubation without erythropoietin was measured. Erythropoiesis was evaluated by addition of erythropoietin after 4-5 weeks' culture without erythropoietin or beta-mercaptoethanol, and production of cells containing hemoglobin was compared by immunocytological methods. MEL cells reacted with anti-CD71 IgG incorporated more transferrin-bound 59Fe than MEL cells reacted with control IgG. Uptake of transferrin-bound 59Fe by mouse bone marrow cells reacted with anti-CD71 IgG was also greater than by cells reacted with control IgG. Erythrocytes developed from cells reacted with anti-CD71 IgG and cultured for 4-5 weeks, but few erythrocytes developed from cells reacted with control IgG. Bone marrow cells depleted of TER119+ cells, CD34+ cells, or CD45+ cells and reacted with CD71 antibody did not differentiate into erythrocytes. Survival potential of erythroid progenitor cells were enhanced by reaction with anti-CD71 antibody.
An anemia-inducing substance (AIS) was found as a protein, with a molecular weight of 50,000 on SDS electrophoresis gel, that decreased the osmotic resistance of erythrocytes. In this study, the plasma fraction containing AIS is shown to inhibit mouse erythroblast formation in vitro. The addition of the plasma fraction from a patient with an advanced malignant neoplasm to a liquid culture of mouse bone marrow cells with erythropoietin results in low numbers of erythroblast formation and low cellular yields of alpha- and beta-globin mRNAs. These inhibitions were not observed after immunoadsorption of the plasma fraction with an antiserum against AIS.
The mechanism of body weight loss in the tumor-bearing state is still unclear. In this study, we investigated expressions of apoptosis regulatory proteins in the skeletal muscle of tumor-bearing and diet-restricted rabbits, and tried to evaluate the differences between the two groups. The apoptotic index (AI) in the tumor-bearing group was 28.1+/-2.84 on day 10. By day 20, many more apoptotic cells were found (AI: 40.5+/-3.20), but then after day 20 their numbers gradually decreased (AI: 9.67+/-2.22 on day 30 and 0.93+/-0.96 on day 40). By contrast, no apoptotic cells were detected in the diet-restricted group at any of the times examined. Bcl-2 immunoreactivity was either not detected at all or only weakly observed in both groups. By contrast, Bax expression increased gradually after implantation in the tumor-bearing group. Bax expression in skeletal muscle cell was graded (moderate) 10 days after tumor implantation, and (high) by day 20, in 2 of the 5 tumor-bearing rabbits. After day 20, however, Bax immunoreactivity decreased continuously in the tumor-bearing group. By contrast, hardly any Bax-immuno-positive cells were detected in the diet-restricted group. These results suggest that loss of body weight in the tumor-bearing group is different from that in the diet-restricted group, and is related to apoptosis of skeletal muscles.
Endocervical epithelium from women treated with gonadotropin releasing hormone agonist (GnRH agonist) were compared with those from untreated women, using metachromatic stain with toluidine blue and immunohistochemistry, for estrogen and progesterone receptors. Smaller endocervical epithelium with lower intraepithelial mucus and more prominent nuclear distribution of estrogen receptors were seen in a woman who was treated for twelve months with GnRH agonists, as compared with those from an untreated premenopausal woman.
Cyclooxygenase-2 (COX-2) has been reported to be associated with tumor progression and angiogenesis and we previously reported that an increase in COX-2 expression might be associated with malignant transformation and tumorigenesis of epithelial ovarian neoplasms. In this study, COX-2 expression of ovarian mature cystic teratomas with malignant transformation, a rare entity accounting for just 1.8% of all mature cystic teratomas, was investigated using immunohistochemical techniques. There were 89 cases of mature cystic teratomas treated with surgery as their initial therapy at Osaka City University Medical School Hospital between 1995 and 2001. Ten cases of these were selected for study; five cases of mature cystic teratoma with malignant transformation, and five cases of mature benign teratoma. Expressions of CD34, vascular endothelial growth factor (VEGF), and COX-2 were investigated. Expressions of VEGF and COX-2 were strong in tissues of mature cystic teratomas with squamous cell carcinoma; however, expressions of them were hardly apparent in mature benign teratomas and in mature cystic teratomas with adenocarcinomas. These results tend to suggest that COX-2 is associated with tumor growth and progression in mature cystic teratomas with squamous cell carcinoma, as opposed to mature benign teratomas and mature cystic teratomas with adenocarcinomas.
The mechanisms of excessive body weight gain after diet-restriction are still unclear. In this study, we investigated expression of angiogenic factors in adipose tissue and skeletal muscle of rabbits which had rebound weight gains; trying to make inquiries into the mechanisms of this rebound weight gain. Ten rabbits were divided into two groups. One group had free food intake (group C), and the other group had restricted food intake until day 40 of the experiments and then had free food intake (group DR). Specimens of adipose tissue and skeletal muscle were collected from each rabbit on days 20, 40, and 60 after the initial examination, and expressions of CD34, vascular endothelial growth factor (VEGF), and platelet-derived endothelial cell growth factor (PD-ECGF) were investigated. Expression of VEGF was significantly strong in the adipose tissue of group DR at the recovery period of body weight. In conclusion, rebound weight gain after a restricted-diet may be associated with angiogenesis in adipose tissue, and the angiogenesis may be induced by VEGF.
The body's weight loss mechanism while in a tumor-bearing state is still unclear. In this study, we investigated expressions of angiogenic factors in the adipose tissue of tumor-bearing and diet-restricted rabbits evaluating the differences between the two groups. We postulated that low nutrition induced vasculogenesis to transport nutrition in the adipose tissues of diet-restricted rabbits, unlike in tumor-bearing rabbits, and that vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) were related to angiogenesis of the adipose tissues. Although we investigated the expressions of VEGF and PD-ECGF immunohistochemically in tumor-bearing and diet-restricted rabbits, there was no significant difference between the two groups. Whether angiogenesis of the adipose tissue in the diet-restricted animals may be observed during the nutritional recovery period should be investigated.
We investigated the expression of apoptosis regulatory proteins in the adipose tissue of tumor-bearing and diet-restricted rabbits, and analyzed the differences between the two groups. The apoptotic index in the tumor-bearing group was 25.1+/-12.4 on day 10 and increased to 27.2+/-14.4 by day 20. Thereafter, however, it gradually decreased, falling to 11.2+/-7.8 on day 30 and 0.67+/-0.88 on day 40. By contrast, no apoptotic cells were detected in the diet-restricted group at any of the times examined. Bcl-2 immunoreactivity was either not detected at all, or was only weakly observed in both groups. Bax expression, on the other hand, gradually increased after implantation in the tumor-bearing group. In 2 of the 5 tumor-bearing rabbits, Bax expression in adipocytes was moderate 10 days after tumor implantation, and strong by day 20, but steadily decreased thereafter. By contrast, hardly any Bax-immunopositive cells were detected in the diet-restricted group. These results suggested that loss of body weight in the tumor-bearing group was different from that in the diet-restricted group, and that it was related to adipocyte apoptosis.
Cyclooxygenase, which converts arachidonic acid into prostaglandins, has two types of isoforms, cyclooxygenase-1 and cyclooxygenase-2 (COX-2). The latter is thought to be essential for the ovulatory mechanism. However, expression or distribution of COX-2 in periovulatory human ovary has not been reported. The aim of our study was to examine COX-2 expression and distribution in pre- and postovulatory human ovary. COX-2 was detected by Western blot analysis of pre-ovulatory human ovarian follicular fluid. The levels of COX-2 in preovulatory fluid obtained from 20 subjects underwent in vitro fertilization and embryo transfer, and were assayed using enzyme immunoassay for human COX-2. The results showed 7.3+/-4.1 ng/ml (mean +/- SD) with a COX-2 level range of 2.7 to 19.5 ng/ml of follicular fluid. Detection of COX-2 is considered to reflect its production in the preovulatory follicle. Immunofluorescence microscopic examination of an ovary obtained from a woman at the postovulatory period showed distribution of COX-2 in interstitial but not in granulosa cells in a ruptured follicle. These findings collectively suggest the possibility that COX-2 is mainly produced in follicles in a preovulatory phase, while after ovulation, COX-2 is produced in interstitial cells in human ovary.
Resealed ghost of red blood cells (RBCs) from advanced cancer patients includes proteins with antigenicities common to an anemia-inducing substance that we separated from plasma of patients with advanced malignant neoplasms. Although cation influx in vitro in RBCs from a cancer patient is larger than that from a normal healthy volunteer, an antibody against anemia-inducing substance inhibited the in vitro cation influx in RBCs from the cancer patient. Activation of the cation influx with N-ethylmaleimide after reaction with the antibody reversed the effect to create a greater cation influx in RBCs from the patient, as compared with that from the healthy volunteer.
We have already reported satisfactory therapeutic results of cisplatin-based cyclic balloon-occluded arterial infusion chemotherapy (BOAI) because it enabled advanced cervical cancer of the uterus (cervical cancer) to be treated by simple total hysterectomy (STH). In the present study, we investigated the expression of apoptosis regulatory proteins in advanced cervical cancer treated by cyclic BOAI. The results showed that the proportion of Bax-positive cells was 75.2 +/- 5.6% after the first BOAI in the cases in which STH became possible (group C), and significantly lower, 11.6 +/- 11.7% (p=0.0001), in the cases in which STH remained impossible (group I). The proportion of Bax-positive cells was significantly higher in group C than in group I throughout the treatment period, but there was no significant difference in Bcl-2 expression between the two groups. The survival rate by the Kaplan-Meier method was significantly higher in group C than in group I. These results suggest that the antitumor effect of cyclic BOAI is closely associated with apoptotic cell death, which may in part be influenced by the expression of Bax.
Specific chromosomal abnormalities, such as del(7q), t(12;14), 12 trisomy, or the rearrangement of 6p, are seen in approximately 30% of uterine leiomyomas despite their benign status. We investigated the association between the shrinkage of uterine leiomyomas treated with a GnRH agonist and the interstitial deletion of chromosome 7q, which is one of the most common chromosomal abnormalities in uterine leiomyomas. This study covered 29 women with uterine leiomyomas who were treated with a GnRH agonist before surgery. The volume of the largest myoma nodule was measured by means of MRI before and at 12 weeks after the beginning of GnRH agonist treatment, and the percentage of the reduction in volume was calculated. Genomic DNA was extracted from leiomyoma tissue and peripheral blood, and amplified by PCR using fluorescently-tagged oligonucleotide primers of twelve microsatellite loci on chromosome 7. The PCR products were analyzed for loss of heterozygosity (LOH) using an automated fluorescent DNA sequencer. Of the 29 informative tumors, five (17%) showed LOH with deletion of the common region, D7S491. The mean percentages of the reduction in volume of the largest myomas with LOH or without LOH were 32+/-13 and 18+/-58%, respectively (not significant). One tumor showing interstitial deletion of both alleles (homo-deletion) reduced in volume by 19%. Another tumor showing an extraband increased in volume by 13%. Although tumor specific chromosomal deletion suggested the existence of tumor suppressor genes in this region, there was no significant association between the shrinkage of uterine leiomyomas treated with a GnRH agonist and the interstitial deletion of chromosome 7q.
Clear cell adenocarcinomas (CA), unlike serous adenocarcinomas (SA) of the ovary, are often at stage I, are resistant to platinum-based drugs and have a poor prognosis. The causes of these differences are unclear. In this study, the differences in progression between CA and SA were examined in terms of apoptosis-related and tumor invasion-related factors. The 16 cases of CA and the 16 cases of SA were reviewed. Excised tissues were classified into primary or metastatic loci, and the expressions of survivin, Bcl-2 and matrix metalloproteinase-2 (MMP-2) in each locus immunohistochemically assayed. Whether the expression of each protein was correlated to prognosis was investigated and additionally the invasion ability of cell strains established from CA and SA were examined using in vitro invasion assay. CA at stage I showed significantly higher survivin expression than SA (p<0.05). In CA, survivin tended to be expressed higher in primary locus than in metastatic locus (p=0.068), however, Bcl-2 was expressed relatively higher in the latter (p=0.087). SA did not have these tendencies. While MMP-2 was expressed significantly higher in SA than in CA (p<0.05), and more so in metastatic locus than in primary locus of SA (p<0.05). Invasion assay showed that the invasion of cells derived from SA was significantly inhibited by tissue inhibitors of metalloproteinase-2, an MMP inhibitor. The disease-free interval was significantly shorter when survivin expression was observed in the nucleus. These results suggest that the expression of apoptosis inhibiting factors and enhanced invasion ability affect progression of CA and SA, respectively.
The mechanisms of cancer cachexia have not been elucidated. We previously reported that cyclic plasma perfusion using non-coated charcoal was effective in cancer cachexia. In the present study we investigated the angiogenic effect of cyclic plasma perfusion on adipose tissue. Twenty rabbits were divided into two groups, i.e., tumor-bearing rabbits subjected to cyclic plasma perfusion (n=10, PP group), and tumor-bearing rabbits subjected to sham-perfusion (n=10, SP group). The changes in body weight, total body fat, and expression of angiogenic factors were investigated. Loss of body weight and total body fat was significantly suppressed in the PP group. Apoptosis of adipocytes was seen in both groups only in the early stage of tumor bearing. Lipolytic activity in the PP group showed a lower ratio than that in the SP group. In the PP group, increased microvessel density and expression of vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) were seen at 40 days after transplantation. Similar findings were not seen in the SP group. These results suggest that cyclic plasma perfusion not only decreased lipolytic activity but induced angiogenesis in the adipose tissue.
OBJECTIVE: To study the metachromatic stainability of the endocervical epithelium. STUDY DESIGN: Surgical specimens that included endocervical epithelium were deparaffinized and stained with toluidine blue at various pH levels and after enzyme digestion. Glycosaminoglycans were separated from endocervical tissue and analyzed by electrophoresis. RESULTS: The endocervical epithelium stained metachromatically purple with toluidine blue in pH 4.1 buffer, but the staining disappeared after chondroitinase digestion. The electrophoretic mobility of the glycosaminoglycan fraction separated from the endocervical epithelium was compatible with nonsulfated chondroitin. CONCLUSION: Endocervical epithelium was identifiable from metachromatic staining below the internal os, and the electrophoretic results of the tissue extract suggested that nonsulfated chondroitin is the main component of glycosaminoglycans in endocervical epithelium.