Biomedical subjects

K Ohama

Publications and source records attributed to K Ohama.

At least 37 records · Page 2Linked to original sources

PubMed2000

Meiotic segregation analysis of a 14;21 Robertsonian translocation carrier by fluorescence in situ hybridization.

Meiotic segregation of chromosomes 14 and 21 in sperm from a 14;21 Robertsonian translocation carrier was analyzed with dual-color FISH using two locus-specific DNA probes (Tel 14q and LSI 21). The frequency of normal or chromosomally balanced sperm, resulting from alternate segregation, was 88.42%. The frequency of unbalanced sperm, resulting from adjacent segregation, was 11.25%. These observed frequencies deviated significantly from the theoretical frequencies (33.33% and 66.67%, respectively) based on random chromosome segregation, with sperm resulting from alternate segregation being preferentially produced in the translocation carrier. With respect to the chromosomally unbalanced sperm, the frequency of 21q disomic sperm was 2.45%, which is in agreement with the frequencies of unbalanced fetuses or offspring at the time of amniocentesis or at term (0-4.3%) reported by others. Although the frequency of 14 or 21 nullisomic sperm should be theoretically equal to that of 14q or 21q disomic sperm in both the carrier and controls, the frequency of nullisomic sperm was significantly higher than that of disomic sperm in the carrier (P=0.0009 for chromosome 14, P<0.0001 for chromosome 21) but not in the controls (P=0.091 for chromosome 14, P=0.74 for chromosome 21). This evidence suggests the occurrence of maturation arrest during spermatogenesis of the carrier.

Adult↗

PubMed2000

Macrophage-colony stimulating factor inhibits the growth of human ovarian cancer cells in vitro.

The effect of macrophage-colony stimulating factor (M-CSF), which regulates the growth and differentiation of haematopoietic progenitor cells on the growth of ovarian cancer cells was investigated in three ovarian cancer cell lines in vitro. The spontaneous growth of these cells was significantly inhibited by the addition of M-CSF in a concentration-dependent manner over 96 h of culturing. The maximum response was obtained with 10 ng/ml (3857 U/ml) of M-CSF by counting the viable cell number using the trypan blue exclusion assay. [(3)H]-thymidine incorporation by these cells was also suppressed following a 96-h incubation with M-CSF. The inhibitory effect of M-CSF was reversed by the addition of anti-M-CSF monoclonal antibody. Flow cytometric analysis revealed that the treated ovarian cancer cells arrested at the G0/G1 phase of the cell cycle. These cells expressed M-CSF receptors on their surface as detected by Scatchard plot analysis using (125)I-labelled M-CSF. These results indicate that M-CSF has an antitumour activity for ovarian cancer cells and suggest that it can be applied for the treatment of this disease.

Antineoplastic Agents↗

PubMed2000

Three-year study of estrogen alone versus combined with progestin in postmenopausal women with or without hypercholesterolemia.

This study compares the effects of long-term hormone replacement therapy on the lipid profile of postmenopausal women with or without hypercholesterolemia, with a comparison of 2 different regimens over a 3-year period. A total of 209 women were enrolled in this prospective, nonrandomized trial. They were classified into 2 groups according to baseline serum levels of total cholesterol and low-density lipoprotein (LDL) cholesterol. The hypercholesterolemic group consisted of 83 subjects with a total cholesterol level of 220 mg/dL or higher and LDL cholesterol 140 mg/dL or higher. The normocholesterolemic group consisted of 126 subjects with normal total and LDL cholesterol levels. Therapy was assigned as follows: 44 subjects in the hypercholesterolemic group and 67 in the normal cholesterol group with a total hysterectomy received conjugated equine estrogen (CEE) 0.625 mg/d, while 39 subjects in the hypercholesterolemic group and 59 in the normal cholesterol group with a physiological menopause received CEE 0.625 mg/d plus medroxyprogesterone acetate 2.5 mg/d. Fasting blood samples were monitored periodically for 3 years. Nine women withdrew from the study. Hormone replacement therapy had a more favorable effect in the hypercholesterolemic group versus the normal cholesterol group by decreasing total and LDL cholesterol, 7.0% and 16.6%, versus the normal cholesterol group, 0.8% and 3.9%. Serum levels of high-density lipoprotein (HDL) cholesterol were increased in both groups (hypercholesterolemic, 14.4%; normal cholesterol group, 26.5%), with the increase being larger in the normal cholesterol group. These changes were similar with both treatments and were maintained over 3 years. Serum levels of triglyceride were also increased in both groups, with the increase being statistically significant only in the group with normal cholesterol levels at baseline. There were no consistently reported side effects of therapy. The effects of postmenopausal hormone replacement therapy, estrogen with or without progestin, on the lipid profile appear to be related to the subject's baseline lipid values. Thus, such therapy may have a more favorable effect on LDL cholesterol in postmenopausal women with hypercholesterolemia, with the beneficial effect being maintained over 3 years.

Aged↗

PubMed2000

Expression of telomerase reverse transcriptase mRNA and its quantitative analysis in human endometrial cancer.

Three major components of telomerase, i.e., human telomerase RNA (hTERC), telomerase-associated protein (TEP1), and the human telomerase reverse transcriptase (hTERT), have been identified. Among them, TERT expression is very closely related to telomerase activity. The purpose of this study was to evaluate the implications of TERT expression and telomerase activity in endometrial cancer. Fresh surgical specimens of 36 endometrial carcinomas (CA group) and 9 samples of postmenopausal endometrial tissue without malignancy (NP group) were obtained at operation in our hospital. These specimens were analyzed for telomerase activity and TERT expression by TRAP assay and RT-PCR, respectively, and the detection and quantitative analysis were made. The results for endometrial cancer were compared with those for normal endometrium and with the clinical data. In the CA group, TERT expression was detected in 35/36 subjects (97.2%), whereas in 1/9 subject (11.1%) from the NP group. Relative TERT mRNA expression was 0.50 in the CA group, and this was significantly higher compared with the level of 0.10 in the NP group (p<0.05). Telomerase activity was detected in 34/36 subjects (94.4%) from the CA group and in 3/9 subjects (33.3%) from the NP group (p<0.05), while the RTA was 30.9 and 0.2, respectively (p<0.05). There was a significant correlation between the relative TERT expression and RTA (n=45, R=0.413, p<0.05). RTA was significantly higher at an advanced surgical stage (FIGO II, III or IV) than at an early stage (FIGO 0 or I) (52.4 vs. 20.4, p<0.05), but other clinical factors showed no relationship with TERT and RTA values. The detection and quantitative analysis of telomerase activity and TERT expression is helpful for distinguishing malignant from normal endometrium when the patient is postmenopausal, even if the tumor is very small or of low malignancy.

Adenocarcinoma↗

PubMed2000

Expression of matrix metalloproteinases (MMP-2, MMP-9, MT1-MMP) and their inhibitors (TIMP-1, TIMP-2) in common epithelial tumors of the ovary.

Matrix metalloproteinases (MMPs) are known to play an important role in cancer cell invasion by mediating the degradation of extracellular matrix proteins. The activity of such MMPs are regulated by tissue inhibitors of metalloproteinases (TIMPs). In this study, we investigated the immunohistochemical expression of MMP-2, MT1-MMP, TIMP-2, MMP-9, and TIMP-1 in 114 epithelial ovarian tumors (14 adenomas, 22 borderline tumors, and 78 adenocarcinomas). mRNA expression of MMP-2, MT1-MMP, and TIMP-2 was determined by RT-PCR in selected samples. The diffuse positive rates of MMP-2, MT1-MMP, TIMP-2, and MMP-9 in ovarian carcinomas were significantly higher than those in the borderline and in benign tumors. Conversely, the diffuse positive rate of TIMP-1 was higher in the benign and borderline ovarian tumors than that in ovarian carcinomas. The percentages of the cases with triple diffuse positive expression for MMP-2, MT1-MMP, and TIMP-2 within the same tumor was significantly higher in malignant tumors than those in borderline and in benign tumors. With respect to clinical stage, the triple diffuse positive rate in advanced-stage (stage II/III/IV) carcinomas was significantly higher than that in early-stage (stage I) carcinomas. A significantly higher triple diffuse positive rate was also observed in high-grade (grade 2/3) disease than in low-grade (grade 1) disease. Considerable levels of mRNA expression of MMP-2, MT1-MMP and TIMP-2 were detected in all selected samples that showed triple diffuse positive immunostaining, confirming the co-expression of MMP-2, MT1-MMP, and TIMP-2 at the transcriptional level within the same tumor. All cases with diffuse positive expression for MMP-9 showed regional or negative TIMP-1 expression. The diffuse positive rate of MMP-9 was significantly higher in ovarian carcinomas with lymph node metastasis than in those without lymph node metastasis. Our results suggest that the overexpression of MMP-2, MT1-MMP, TIMP-2, and MMP-9 and down-regulation of TIMP-1 may contribute to the development or enhanced growth capacity of ovarian tumors. Co-expression of MMP-2, MT1-MMP, and TIMP-2 within the same tumor seems to play an important role in the progression of ovarian cancer. Elevated MMP-9 expression together with low expression of TIMP-1 may also contribute to the lymph node metastasis of ovarian carcinoma cells.

Female↗

PubMed2000

Clinicocytopathological and immunohistochemical study of adenoma malignum of the uterine cervix.

Adenoma malignum is a rare type of very highly differentiated adenocarcinoma of the uterine cervix, and is quite difficult to diagnose because there are few findings definitely suggesting malignancy on cytologic or histologic examination. We recently encountered four patients with adenoma malignum and reviewed their clinicocytopathological and immunohistochemical findings. The most characteristic symptom was a watery discharge and an enlarged cervix was palpable, while multiple cystic lesions (MCL) were observed by transvaginal and abdominal ultrasonography, CT or MRI. On cytodiagnosis, the cervical gland cells formed large sheets or showed a palisading arrangement. Slightly enlarged nuclei and yellowish-orange staining of the cytoplasmic mucus were the characteristic findings. On histological examination, many cervical glands of different sizes were present and extended deep into the muscle layer, while branching or papillary growth into the lumen was also observed. On immunohistochemical study, HIK1083, a monoclonal antibody for gastric gland mucous cell mucin, was found to be positive in 3 of 4 cases, and this was fairly useful in the diagnosis of adenoma malignum.

Adenocarcinoma↗

PubMed1999

Analysis of segregation and aneuploidy in two reciprocal translocation carriers, t(3;9)(q26.2;q32) and t(3;9)(p25;q32), by triple-color fluorescence in situ hybridization.

Meiotic segregation patterns of chromosomes 3 and 9 were analyzed in sperm of two translocation carriers (t(3;9)(q26.2;q32) and t(3;9)(p25;q32)) by triple-color fluorescent in situ hybridization (FISH) with a telomeric DNA probe in addition to two centromeric probes. The frequencies of each sperm product resulting from alternate or adjacent I, adjacent II and 3:1 segregation in a t(3;9)(q26.2;q32) translocation carrier were 88.35%, 5.44% and 5.94%, respectively. On the other hand, the frequencies of each sperm product in a t(3;9)(p25;q32) translocation carrier were 89.23%, 6.02% and 4.48%, respectively. Of all the sperm products, the frequency of normal or chromosomally balanced sperm in a t(3;9)(q26.2;q32) and a t(3;9)(p25;q32) were 52.49% and 47.25%, respectively. The frequencies of each sperm product resulting from various segregations were different between both carriers and significantly deviated from the expected frequencies. Additional dual-color and triple-color FISH were performed to analyze aneuploidy rates for chromosomes 12, 17, 18, X and Y in order to detect any interchromosomal effect; no evidence of an interchromosomal effect was found.

Abortion, Habitual↗

PubMed1999

Inhibition of telomerase activity and cell proliferation by a reverse transcriptase inhibitor in gynaecological cancer cell lines.

Telomerase is a ribonucleoprotein which has a RNA template to bind and extend telomere ends, so prolonging the life of tumour cells. The aim of this study was to determine whether transcriptase function of telomerase could be inhibited by the reverse transcriptase inhibitors (RTI); azydothymidine (AZT), dideoxyinosine (ddI) and AZT-5' triphosphate (AZT-TP). We examined their effects on the proliferation of cancer cells and the antitumour effects of cisplatin in vitro. The three agents did not cause major changes in telomerase activity or telomere length in MCAS cells. However, in HEC-1 cells changes in telomerase activity and telomere length were observed that were dependent on the RTI concentration and duration of exposure. ddI and AZT-TP reduced telomerase activity and shortened the length of the telomere. In the presence of RTI, the antitumour effects of cisplatin were enhanced. This was particularly evident in HEC-1 cells where there was a marked reduction in cell proliferation, appearance of morphological changes and senescent-like cells in the presence of ddI or AZT-TP. In MCAS cells, TP53 expression was increased by ddI and AZT-TP, while p21 expression was unchanged. In HEC-1 cells the expression of both TP53 and P21 was increased by ddI. Continuous administration of RTI enhanced the cell growth inhibition of cisplatin. RTI also inhibited the proliferation of some cells.

Blotting, Southern↗

PubMed1999

Embryonal renal remnant in the gubernaculum testis.

We present a rare case of embryonal renal remnant found by chance as a mass in the gubernaculum testis during an operation on a right undescended testis. We discuss the relationship between this tissue and paradidymis or supernumerary kidney.

Choristoma↗

PubMed1999

Microsatellite instability and hMSH2 gene mutation in a triple cancer (colon cancer, endometrial cancer, ovarian cancer) patient in hereditary non-polyposis colorectal cancer (HNPCC) kindred.

A patient who had triple cancer (colon cancer, endometrial cancer, and ovarian cancer) in HNPCC kindred is reported. Her family history revealed the occurrence of colon cancer in her paternal aunt and in two cousins, fulfilling the minimum HNPCC criteria. Microsatellite instability analysis revealed replication error (RER)+ in all cancer lesions at 2 microsatellite loci (D1S191, BAT 40). SSCP analysis suggested germline mutation in exon 2 of the hMSH2 gene. This case showed the importance of complete family-history investigations to identify HNPCC patients. In the near future, definitive diagnosis of HNPCC will be possible on the basis of DNA studies.

Adenocarcinoma↗

PubMed1999

Frequent expression of mucin core protein MUC1 in non-neoplastic gallbladder mucosa from patients with pancreaticobiliary maljunction.

BACKGROUND: Gallbladder carcinoma is known to develop frequently in patients with pancreaticobiliary maljunction, though the causal relationship remains speculative. METHODS: Histopathologic changes, expression of mucin core protein MUC1 and MUC2, and cell proliferative activities in the gallbladder mucosa from 27 patients with panceaticobiliary maljunction and 21 control gallbladders were examined. Three cases of pancreaticobiliary maljunction were associated with gallbladder carcinoma. RESULTS: The lining epithelia of the non-neoplastic gallbladder mucosa of pancreaticobiliary maljunction showed frequently papillary hyperplasia and higher proliferative activities, when compared to the control. In 3 cases with carcinoma, MUC1 was expressed on the luminal border and in the cytoplasm of carcinoma cells, particularly in de-differentiated and invasive areas. MUC1 was variably expressed on the luminal surface of the lining epithelia of non-neoplastic gallbladder mucosa in babies, children, youths and adults with pancreaticobiliary maljunction. However, such expression was focally seen in 2 of the 21 control cases (p<0.01). MUC2 was scattered in the hyperplastic and carcinomatous epithelial cells appearing as goblet cells in pancreaticobiliary maljunction and control groups. CONCLUSIONS: This study suggests that persistent MUC1 expression and increased cell proliferative activities of non-neoplastic gallbladder epithelium of the patients with pancreaticobiliary maljunction after birth reflect an altered phenotype of epithelial cells and these abnormalities may be related to carcinogenesis in such patients.

Adult↗

PubMed1999

[A case of uterine cervical cancer in which UFT was an effective preoperative treatment].

We report a case in which UFT was effective as a preoperative treatment for stage II b cervical cancer. The patient was a 66-year-old female whose chief complaint was brown vaginal discharge. Following cytological, histological and CT examinations, a diagnosis was made of papillary squamous cell carcinoma invading the vagina and left parametrium. We administered UFT (600 mg/day, for 5 days) as one course, and conducted two courses with an interval of 2 days. The tumor had shrunk 2 weeks later and a radical hysterectomy was performed after additional treatment with intraarterial cisplatin (120 mg/body) infusion. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD), which are enzymes in 5-FU metabolism, and the labeling index (ID) of DNA fragmentation in the tumor were estimated before and after UFT. The results showed that TS was 0.69 pmol/g tissue and DPD 39.98 pmol/mg/min before UFT, and that LI of DNA fragmentation was 21.8 +/- 5.0% before UFT and 37.9 +/- 16.2% after UFT. We suggest that preoperative UFT administration is an effective treatment for cervical cancer, and that TS, DPD and LI of DNA fragmentation might be useful biomarkers to estimate the sensitivity of UFT.

Aged↗

PubMed1998

Protective protein/cathepsin A loss in cultured cells derived from an early-infantile form of galactosialidosis patients homozygous for the A1184-G transition (Y395C mutation).

Galactosialidosis is a human autosomal recessive lysosomal storage disease caused by a genetic defect of protective protein/cathepsin A (PPCA). The patients in a Japanese family with the severe early-infantile form of galactosialidosis were revealed to be homozygous for the A1184-G transition in the PPCA gene in both alleles, which leads to the Y395C substitution. The acid carboxypeptidase (cathepsin A) and lysosomal neuraminidase activities were markedly decreased in cultured fibroblasts and chorionic villus cells derived from the patients, although the decrease in beta-galactosidase activity was less. Immunoblot and immunocytochemical analyses showed that neither the precursor nor the mature form of the PPCA gene product was present in the cultured cells. The Y395C mutation was revealed to cause the loss of the translated product, that determines the severity of the clinical phenotype.

Amino Acid Substitution↗

PubMed1998

Lifespan of human memory T-cells in the absence of T-cell receptor expression.

To evaluate the intrinsic lifespan of human memory T-cells in the absence of T-cell receptor signaling, we used radiation-induced mutant CD4+ T-cells lacking surface expression of TCR/CD3 complex as an in vivo cell marker. We analyzed the long-term kinetics of TCR/CD3 - mutant T-cells among CD4+ CD45RA+ naive and CD4+ CD45RA- memory T-cell fractions in peripheral blood of gynecological cancer patients receiving radiotherapy. Both the proportion and number of these mutant T-cells decayed exponentially with time following radiotherapy. The estimated half-life of mutant memory T-cells was 2 to 3 years and did not differ from that of mutant naive T-cells. These results indicate that the lifespan of mature CD4+ T-cells is limited regardless of their memory or naive phenotype in the absence of TCR/CD3 expression. This finding may suggest that continued T-cell receptor signaling is required for lifetime maintenance of human memory T-cells.

Adult↗

PubMed1998

Chromosome analysis in human oocytes remaining unfertilized after in-vitro insemination: effect of maternal age and fertilization rate.

The incidence of chromosomal abnormalities was studied in 719 unfertilized human oocytes obtained from our in-vitro fertilization (IVF) programme. To make chromosome preparations, a gradual fixation/air-drying method was utilized. Of 388 oocytes successfully karyotyped, 70 (18.0%) were abnormal. The abnormalities included 33 aneuploidies (8.5%) (14 hyperhaploidies and 19 hypohaploidies), 25 diploidies (6.4%) and 15 structural abnormalities (3.9%), three of them being accompanied by aneuploidy. Of the 33 aneuploidies, 16 (48.5%) showed the loss or gain of dyads (so-called non-disjunction), while 17 (51.5%) showed the loss or gain of monads (so-called predivision). There was no maternal age-dependent increase in the incidence of aneuploidy. Unfertilized oocytes from patients with a high fertilization rate (>25%) had a significantly higher (11.4%, P < 0.05) incidence of diploidy compared with the oocytes from the remaining patients (4.3 and 4.0%), suggesting that diploid oocytes might have a lower fertilizing ability.

Adult↗

PubMed1998

Characteristic changes of large granular lymphocytes that strongly express CD56 in endometrium during the menstrual cycle and early pregnancy.

Large granular lymphocytes that strongly express CD56 (CD56++ LGL) constitute a major population of leukocytes in the secretory endometrium and pregnancy decidua and are considered to be involved in reproductive immunity and in maintaining the pregnancy. The present study aimed to reveal the relationship between the characteristic changes of CD56++ LGL and altered hormonal environment and/or trophoblast invasion in the endometrium. Cell surface markers of CD56++ LGL obtained from the endometrium during the menstrual cycle and early pregnancy were analysed using flow cytometry. The percentages of both CD56++ LGL that express activation antigens (CD69, HLA-DR) and those that express lymphocyte function associated antigen-1 (LFA-1) (CD11a/CD18) were highest in the proliferative phase and decreased gradually throughout the menstrual cycle. Expression of these antigens was further suppressed in the late secretory phase, as well as in the early stage of pregnancy. However, the percentage of CD56++ LGL that express these antigens was significantly higher in spontaneous abortions than in normal pregnancies. On the other hand, the percentage of CD56++ LGL that express CD45RA was lower during normal pregnancy than during the menstrual cycle. The present results suggest that characteristics alterations of CD56++ LGL are regulated by altered hormonal environment and by trophoblast invasion.

Abortion, Spontaneous↗

PubMed1998

Yolk sac tumor with a unique uniform hepatoid pattern histology.

BACKGROUND: Yolk sac tumors (YST) exhibit several different histological subtypes and the mechanisms of cellular differentiation and prognosis of each subtype remain unknown. RESULTS: We report two infants with sacrococcygeal YST; one represented a typical histological subtype and the other showed a hepatoid subtype with uniform histology. The isoform of alpha-fetoprotein (AFP) in the patient with the hepatoid pattern was examined by lectin-affinity immunoelectrophoresis and represented as a YST, but not hepatocellular, subtype. The patient with typical YST responded well to VAB-6 combination chemotherapy. However, this regimen was only partially effective to the patient with the pure hepatoid histological subtype, and an etoposide with ifosfamide and cisplatin (VIP) regimen as a salvage chemotherapy combined with complete tumor resection was useful to achieve complete remission (CR). Both of the patients have been in CR for more than four years.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Apolipoprotein E phenotype associations with plasma lipoproteins and bone mass in postmenopausal women.

OBJECTIVE: The aim of the study was to investigate the effects of apolipoprotein E (apo E) phenotype on plasma lipids and bone mass in postmenopausal Japanese women. METHODS: In 320 subjects aged 40-65 years (mean +/- SE, 54.0 +/- 0.6), apo E phenotype was determined by isometric electrophoresis. Phenotypic frequencies were 0.3% for E2/2 (n = 1), 8.1% for E3/2 (n = 26), 70.3% for E3/3 (n = 225), 0.6% for E4/2 (n = 2), 19.4% for E4/3 (n = 62) and 1.3% for E4/4 (n = 4). Apo E2/2 and apo E3/2 were classified as E2+ (n = 27); apo E3 homozygotes were placed in another group (E3/3; n = 225), as were apo E4/3 together with apo E4/4 subjects (group E4+; n = 66). Bone density and bone quality were assessed with a newly developed ultrasonic bone densitometer, and plasma lipids were also measured. RESULTS: Age, body mass index and years since menopause did not differ significantly between the three groups. The E4+ group had the highest levels of total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B, significantly higher than in the E2+ group. Plasma lipoprotein(a) concentrations were significantly higher in the E4+ group than in the other two groups. Ultrasonic parameters of bone density and quality tended to be lower in the E4+ group than in the E2+ group. CONCLUSIONS: The apo E4 allele was associated with high plasma cholesterol levels and an unfavorable change of bone structure in postmenopausal women.

Adult↗