Search PubMed⌕ Search

Biomedical subjects

Y Tomoda

Publications and source records attributed to Y Tomoda.

At least 109 records · Page 6Linked to original sources

Transforming growth factor-beta 1 induces morphological changes accompanied by extracellular matrix reconstitution in cultures of avian retinal pigmented epithelial cells.

The mechanisms of cell differentiation have been extensively studied with an avian retinal pigmented epithelial cell (PEC) culture system. Transforming growth factor-beta (TGF-beta) has been reported to have stimulatory or inhibitory effects on differentiation depending on tissue type. Although the mechanism by which TGF-beta exerts diverse effects is unknown, changes in the extracellular matrix (ECM) are believed to be related to the effects of TGF-beta. Therefore, the effects of TGF-beta 1 on the cellular morphology and the distribution of ECM components such as laminin, tenascin, fibronectin, and types I and IV collagens were investigated in confluent cultures of differentiated PECs during a period of 6 days. We found that differentiated PECs with polygonal morphology and pigmented granules changed to pleomorphic and less pigmented cells 4 days after the addition of TGF-beta 1. These changes were preceded by changes in the distribution of ECM components, particularly laminin and tenascin after 2 days. The effects of TGF-beta on the differentiation of PECs are discussed.

Animals↗

[The levels of aztreonam in the cord bloods and tissues after administration to pregnant women].

The monobactam antibiotic aztreonam (AZT) was administered by intravenous drip infusion to women with intrauterine infections at 6-hour intervals and its concentrations in the maternal blood, umbilical blood, and umbilical tissue were determined at parturition to evaluate its transport to the umbilicus and fetus, and this accumulation in the tissue. Further, umbilical tissue was cultured to detect bacteria and examined histologically to evaluate the efficacy of AZT its treatment of omphalitis. Neither maternal nor umbilical blood showed any signs of drug accumulation, and there was a correlation between maternal and umbilical blood levels of AZT and time lapsed after most recent administration. Umbilical tissue levels of AZT tended to increase with time for about 12 hours after the start of administration, but showed no tendency to further rise thereafter. The umbilical tissue cultures were negative for causative pathogens 12 hours or more after the initial dosing. Histological examination of umbilical tissue was negative for omphalitis 12 hours or more after the start of administration in all but one patient. After the administration of AZT to pregnant women with intrauterine infections, it was detected in the umbilicus and fetus in high concentrations at parturition without appreciable tissue accumulation, newborn infection or adverse reaction. The overall results suggest that AZT is clinical effective when used in the treatment of omphalitis.

Aztreonam↗

[Neonatal EEG findings soon after birth in the intrauterine growth retarded infant].

We performed electroencephalograms in 32 neonates of intrauterine growth retardation (IUGR) within seven days of birth. EEG findings were compared with those observed in neonatal brain damage. Seven EEGs had a dysmature pattern which is seen in the subacute and chronic stages of prolonged and mild neonatal brain depression, and five had a disorganized pattern which is seen in the subacute and chronic stages of severe neonatal brain depression. The other EEGs had a normal neonatal pattern. Seven neonates who had a dysmature pattern were severe IUGR (< or = 2.5 SD). Their head circumference was retarded at birth, and the S/D ratio of the umbilical artery increased, suggesting chronic brain damage in utero. On the other hand, five neonates displaying a disorganized pattern were preterm IUGR (< 37 weeks). They had NST abnormalities. The abnormal EEG pattern observed in IUGR was similar to that observed in postnatally injured neonates. The abnormalities in EEGs are correlated with the degree of later neurological sequelae. The present study suggested that the EEG of IUGR recorded immediately after birth was useful in evaluating their intrauterine environments and postnatal neurological outcome.

Brain Diseases↗

[A left-handed patient with disturbance of manipulating objects].

We reported a left-handed patient with the disturbance of manipulating objects and the object pantomime. The patient was a 72-year-old man, admitted to Osaka Medical College Hospital complaint of the difficulty of object manipulation. The patient was alert, well oriented and attentive. On neurological examination the patient revealed grasp reflex in his left hand. On neuropsychological examination the patient spoke fluently, but his verbal comprehension was slightly disturbed. He could name popular objects only 9 out of 20 objects. On praxis examination he could pantomime the socially accustomed movements by command visually pantomime. He did not reveal buccofacial apraxia and constructional apraxia. However, the patient could not manipulate both single and pleural objects actually and pantomime without objects. On MRI the lesion was found in both frontal lobe, right medial frontal lobe and right temporal lobe. SPECT findings demonstrated that the bilateral parietal lobes were preserved and we speculated that the right supplementary motor area was assumed to be a crucial lesion for manipulating objects in the patient.

Aged↗

Successful in vitro fertilization and pregnancy by micromanipulation with epididymal sperm.

PURPOSE: To examine the effectiveness of micromanipulation on the treatment of the patients with obstructive azoospermia, subzonal insemination or partial zona dissection was performed using epididymal sperm of the 23 patients, and the in vitro fertilization and embryo transfer (IVF-ET) outcomes were analyzed. RESULTS: Fertilized oocytes were obtained in 11 cycles of the 25 treated cycles, and six pregnancies were established by the subsequent ET. Through the analysis of 13 cycles in which both the micromanipulation and usual IVF insemination were performed, the fertilization rate per oocyte with the micromanipulation [25% (28/113)] was significantly higher than that with the usual insemination method [4% (4/102)]. The micromanipulation was most useful for the treatment of the patients with congenital absence of the vas deferens. Moreover, there was no need to aspirate a large volume of the epididymal fluid, but it was essential to prepare more than 10 mature oocytes retrieved. CONCLUSIONS: These results indicate that micromanipulation with epididymal sperm is an effective treatment for obstructive azoospermia, and careful preparations of sperm and well-controlled ovarian hyperstimulation are necessary for successful IVF-ET.

Adult↗

The value of Doppler ultrasound in the diagnosis and management of twin-to-twin transfusion syndrome.

To evaluate the efficiency of the Doppler examination of umbilical arterial blood flow for the antenatal diagnosis and the monitoring of fetal condition during intrauterine treatment of twin-to-twin transfusion syndrome (TTTS), we studied 33 pairs of twins including 5 TTTS cases. In all cases umbilical arterial blood flow was examined by Doppler ultrasound and pulsatility index (PI) was calculated as umbilical arterial impedance. In twins with TTTS, PI of the recipient was outside the normal range and the difference of PI was greater than +0.5. In discordant twins without TTTS and concordant twins, the PI was within the normal range and the difference of PI ranged from -0.5 to +0.5. In 2 cases these findings were found before the appearance of fetal hydrops. In 2 TTTS cases transmaternal digitalization prevented the development of hydrops in the recipient. The difference of PI decreased with improvement in the fetal condition, and vice versa. Our data suggested that, in cases with TTTS, Doppler examination of umbilical arterial blood flow was effective in predicting fetal hydrops. Doppler was also very useful for monitoring the fetal condition during intrauterine treatment.

Adult↗

Different pattern of zymography between human gynecologic normal and malignant tissues.

OBJECTIVE: Our purpose was to evaluate type IV collagenase in ovarian and endometrial cancer tissues. STUDY DESIGN: Tissue specimens were obtained from patients with ovarian and endometrial cancer and uterine myoma. Gelatinase activity was detected by zymography and quantitated by densitometer. RESULTS: Four dominant gelatinases were detected in ovarian and endometrial cancer tissues: 200, 130, 92, and 72 kd gelatinase. Other forms observed were 83 kd gelatinase, which is an active form of 92 kd gelatinase, and 66 kd gelatinase, which is an active form of 72 kd gelatinase. Densitometric analysis showed that the 92 kd/72 kd ratio in ovarian cancer tissues was significantly higher than in normal ovarian tissues (p < 0.05) and that the 66 kd/72 kd ratio was higher in ovarian cancer tissues (p = 0.07). Both ratios in endometrial cancer tissues were significantly higher than in normal endometrial tissues (p < 0.05). CONCLUSION: Gelatinase activity was remarkably higher in ovarian and endometrial cancer tissues. Especially, 92, 83, and 66 kd gelatinases were clearly detected in cancer tissues, suggesting that these gelatinases were related to the malignant phenotype, because degradation of the components of the basement membrane such as type IV collagen is necessary for cancer cells to metastasize.

Adult↗

Long-term follow-up of patients with epithelial carcinoma of the ovary.

OBJECTIVES: To determine the long-term outcomes of patients with epithelial ovarian cancer. METHODS: A group of 298 patients with epithelial ovarian cancer were treated with combination chemotherapy between July 1979 and January 1986 at the Tokai Ovarian Tumor Study Group. Long-term results of these patients were analyzed. RESULTS: Five-year survival and 10-year survival rates of all the patients were 53% and 47%, respectively. Five-year survival and 10-year survival rates for stage I were 89% and 79%, 59% and 56% for stage II, 27% and 22% for stage III, and 9% and 9% for stage IV, respectively. Survival of mucinous and endometrioid cell types were decreased after 5 or more years. In stages II-IV, cisplatin-based chemotherapy produced better results than mitomycin-C, 5-Fu, cytarabine (MFC) therapy. CONCLUSIONS: Long-term results of epithelial ovarian cancer were not favorable even in mucinous and endometrioid cell types. For long-term results, cisplatin-based chemotherapy was effective in advanced ovarian cancer. Long-term follow-up of ovarian cancer is important and necessary.

Antineoplastic Combined Chemotherapy Protocols↗

Sensitisation of human ovarian carcinoma cells to cis-diamminedichloroplatinum (II) by amphotericin B in vitro and in vivo.

Human ovarian carcinoma cells (HRA) were sensitised to cis-diamminedichloroplatinum (II) (CDDP) 2.7-, 5.5- and 12.1-fold by treatment with amphotericin B (AMB) at concentrations of 2.1, 5.4 and 10.8 microM, respectively. Moreover, intracellular accumulation of platinum after a 2-h exposure to CDDP was increased significantly with AMB treatment. We prepared HRA cell-inoculated nude mice as an experimental therapeutic model for human advanced ovarian carcinoma. Ascites was evident after 7 to 9 days of intra-peritoneal (i.p.) inoculation of HRA cells, and mice died due to intra-abdominal carcinomatosis after 11 to 14 days [mean survival time (MST): 12.4 +/- 1.1 days]. Treatment with AMB (2.0 mg/kg) alone 4 days after inoculation increased MST by only 1.4 days. Simultaneous treatment with CDDP (1.0 to 2.0 mg/kg) and AMB (0.5 to 2.0 mg/kg) produced a significant increase in MST compared to treatment with CDDP alone. Maximal MST (30.1 days) was observed by treatment with 2.0 mg/kg CDDP plus 2.0 mg/kg AMB, whereas MST with 2.0 mg/kg CDDP alone was 16.4 days. A further drug accumulation study demonstrated that platinum accumulation in tumour tissues in nude mice treated with CDDP and AMB increased significantly compared to treatment with CDDP alone. These results indicate that intraperitoneal combination chemotherapy with CDDP and AMB is effective in an experimental animal model of advanced ovarian carcinoma.

Amphotericin B↗

Human monoclonal antibody [1-1-2D] against cancer of the uterine cervix.

To obtain a human monoclonal antibody (h-MAb) against cancer of the uterine cervix, lymphocytes from the regional lymph nodes of 14 patients with cervical cancer were fused with a mouse-human heterohybridoma [II]. Of 6,419 hybridomas, 1,295 produced human immunoglobulins (IgG 670, IgM 737). We isolated clone [1-1-2D], which has produced human IgM with stability for more than a year. This antibody reacted with three of five cell lines of cervical cancer but not with normal fibroblasts. Histoimmunostaining showed positive responses to 9/15 specimens of cervical cancer and in 2/7 specimens from cases of cervical dysplasia. Most of the normal human and fetal tissues showed no positive immune response. The positive immune response of [1-1-2D] to the cell membrane observed by the fluorescence antibody method disappeared after periodate treatment and was weakened by trypsin. Neuraminidase did not affect immune reactivity. This antibody showed a positive response by the thin-layer chromatography immunostaining method and precipitated a glycoprotein having a molecular weight of 38 kD. These results suggested that the epitope of the [1-1-2D] antibody is present on a carbohydrate moiety not containing sialic acid that is carried on protein and lipid moieties.

Animals↗

Amniotic fluid enhances allogeneic cytotoxic T cell responses, whereas it suppresses mitogen-stimulated lymphocyte proliferation.

Mouse amniotic fluid has been shown to suppress T lymphocyte proliferation and suggested to be important in regulating immunity during pregnancy. In allogeneic pregnancy, cytotoxic T cells in pregnant lymphocytes against paternal transplantation antigen are impaired. We examined the effect of amniotic fluid to the alloreactive CTL responses. Although the amniotic fluid suppressed Con A or LPS stimulated lymphocyte proliferation as previously reported, the amniotic fluid taken from syngeneic C57BL/6 pregnant mice or allogeneic C57BL/6 x BALB/c pregnant mice enhanced the anti-H-2d or anti-H-2k CTL responses dose-dependently. We speculate that amniotic fluid contains not only immunosuppressive factors but also immunoenhancing factors which upregulate the allogeneic CTL responses.

Amniotic Fluid↗

Potentiation of cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) by amphotericin B in BALB/c nude mice bearing human ovarian carcinoma cells.

Human ovarian carcinoma cells (HRA) were sensitized to cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) 1.2-, 2.1- and 3.4-fold by treatment with amphotericin B (AMB) at concentrations of 2.1, 5.4, and 10.8 microM, respectively. Moreover, the intracellular accumulation of platinum after 2-h exposure to CBDCA was increased significantly by AMB treatment. For estimating the enhancing effect of AMB on CBDCA cytotoxicity in vivo, we prepared HRA cell-inoculated nude mice. Ascites was evident 7 to 9 days after intraperitoneal (i.p.) inoculation of HRA cells, and the mice died of intraabdominal carcinomatosis 11 to 14 days (mean survival time (MST): 12.0 +/- 1.0 days) after inoculation. Treatment with AMB (2.0 mg/kg) alone increased the MST by only 1.2 days. Simultaneous treatment with CBDCA (12 or 15 mg/kg) and AMB (0.5 to 2.0 mg/kg) produced a significant increase in MST compared to treatment with CBDCA alone. Maximal MST (38.5 days) was obtained by treatment with 15 mg/kg CBDCA plus 2.0 mg/kg AMB, whereas the MST with 15 mg/kg CBDCA alone was 15.8 days. A drug accumulation study demonstrated that platinum accumulation in tumor tissues after i.p. treatment with CBDCA and AMB in tumor-bearing nude mice was increased significantly compared to treatment with CBDCA alone. These findings indicate that intraperitoneal combination chemotherapy with CBDCA and AMB is useful in nude mice with advanced ovarian carcinoma.

Amphotericin B↗

Expression of aminopeptidase N on human choriocarcinoma cells and cell growth suppression by the inhibition of aminopeptidase N activity.

We previously found that an aminopeptidase inhibitor, ubenimex (bestatin), had a growth-suppressive effect on choriocarcinoma cell lines in vitro. To clarify the mechanism of this action, we investigated the expression of aminopeptidase N (AP-N/CD13) on choriocarcinoma cells and other human tumor cells. Two choriocarcinoma cell lines, NaUCC-4 and BeWo, had higher AP-N activity than other cell lines (358.8 and 340.2 nmol/h/10(6) cells, respectively), as did human myeloid leukemia cell line, HL-60 (373.8 nmol/h/10(6) cells). These choriocarcinoma and leukemia cell lines with abundant AP-N activity showed much higher sensitivity to bestatin (IC50 = 0.5, 2.1 and 1.0 micrograms/ml, respectively) than the other cell lines. By immunoblotting and immunocytochemical staining, AP-N was detected as an approximately 165-kDa protein and localized on the cell membrane in choriocarcinoma cells. We also examined the effects of two other aminopeptidase inhibitors and three anti-CD13 monoclonal antibodies (MAbs) (WM15, MCS2 and MY7) on the growth of NaUCC-4 cells. Cell growth was markedly suppressed by the AP-N inhibitor actinonin as well as bestatin, but not by the AP-B inhibitor arphamenine. Of the three MAbs, only WM15, which is able to inhibit AP-N activity, suppressed cell growth in a dose-dependent manner. These results indicate that AP-N inhibitors show a growth-suppressive effect, presumably through inhibition of the enzymatic activity of AP-N on tumor cells, and suggest that AP-N may play important roles in the growth of certain tumors, such as choriocarcinoma and leukemia.

Antibodies, Monoclonal↗

Development of an effective and simple insemination method for the in vitro fertilization of patients with male-factor infertility.

An insemination method involving mechanical removal of the cumulus and multiple oocytes per dish (MRC-MOPD) was applied to achieve in vitro fertilization (IVF) of patients with male-factor infertility, and the prognosis of IVF and embryo transfer was evaluated. Although the fertilization rate of patients with male-factor infertility was only 41.4% (12/29) using standard insemination methods, a 73.0% (27/37) fertilization rate was achieved with the MRC-MOPD method. Moreover, 10 patients with male-factor infertility who were treated with the MRC-COPD method achieved clinical pregnancy. A comparison of the results in the 10 patients who were treated with both methods in common reveals that the MRC-MOPD method also increased the fertilization rate per oocyte. The rate of occurrence of polyploid fertilization did not increase, although large numbers of sperm were inseminated via the MRC-MOPD method. These results indicate that the MRC-MOPD method is an effective and simple insemination technique to achieve successful IVF of patients with male-factor infertility.

Embryo Transfer↗

Recurrence of epithelial ovarian carcinoma after clinical remission.

One hundred and eighty-eight patients with epithelial ovarian carcinoma were treated with primary cytoreductive surgery and subsequent combination chemotherapy. The first recurrent findings such as sites and disease-free interval were analyzed in 141 patients who were clinically remitted 6 months after operation or chemotherapy. Fifty-seven cases had a recurrence. Five-year disease-free survival rates were 75, 72, 29, and 0% in stage I, II, III, and IV, respectively. Twenty-one of 22 patients with > 2 cm maximum residual tumor died, although they once achieved clinical remission. Significant differences were observed between histologic types, and the disease-free survival rate was lowest for serous cystadenocarcinoma. Nine of 15 stage IV patients with serous histology experienced remission, but none of the 8 in stage IV with other histologies did so, suggesting that serous adenocarcinoma is sensitive to chemotherapy and conducive to clinical remission. However, all stage IV patients in remission encountered a recurrence. Intra-abdominal cavity and lymph node were frequently the initial recurrent sites (38 and 27%, respectively). On the other hand, the incidence of distant recurrence was as high as 27%, and 8 of 16 cases with distant recurrence were stage I. Survival time after recurrence was not different among initial sites of recurrence and mean survival time was 15 months.

Female↗

Identification of two point mutations in the gene coding luteinizing hormone (LH) beta-subunit, associated with immunologically anomalous LH variants.

To analyze the structure of LH in three patients with immunologically anomalous LH, the whole coding region of the LH beta-subunit gene was examined. These patients were infertile, and their serum LH levels could not be measured with an immunoassay kit. Immunoblotting of the LH beta-subunit showed no marked changes in the molecular size of LH beta. Genomic DNA was extracted from peripheral lymphocytes of the patients and normal controls, and LH beta genes were amplified by the polymerase chain reaction technique, using primer pairs that are capable of specifically amplifying only the LH beta gene without interference by the CG beta genes. No deletions were observed in the coding regions of the LH beta gene of the patients. Nucleotide sequencing revealed two nucleotide substitutions in the LH beta gene of the patients, which cause amino acid replacements from Trp8 (TGG) to Arg8 (CGG) and Ile15 (ATC) to Thr15 (ACC). Restriction fragment length polymorphism analysis in three families indicated that the affected probands were homozygous, and their family members were heterozygous, except for their husbands. The heterozygotes showed reduced detectability with the LH immunoassay kit. These results suggest that these amino acid replacements are responsible for this immunologically anomalous variant.

Adult↗