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Biomedical subjects

Y Terashima

Publications and source records attributed to Y Terashima.

At least 73 records · Page 4Linked to original sources
PubMed1994

Comparative studies of genes encoding thermostable L-2-halo acid dehalogenase from Pseudomonas sp. strain YL, other dehalogenases, and two related hypothetical proteins from Escherichia coli.

We have determined the nucleotide sequence of the gene encoding thermostable L-2-halo acid dehalogenase (L-DEX) from the 2-chloroacrylate-utilizable bacterium Pseudomonas sp. strain YL. The open reading frame consists of 696 nucleotides corresponding to 232 amino acid residues. The protein molecular weight was estimated to be 26,179, which was in good agreement with the subunit molecular weight of the enzyme. The gene was efficiently expressed in the recombinant Escherichia coli cells: the amount of L-DEX corresponds to about 49% of the total soluble proteins. The predicted amino acid sequence showed a high level of similarity to those of L-DEXs from other bacterial strains and haloacetate dehalogenase H-2 from Moraxella sp. strain B (38 to 57% identity) but a very low level of similarity to those of haloacetate dehalogenase H-1 from Moraxella sp. strain B (10%) and haloalkane dehalogenase from Xanthobacter autotrophicus GJ10 (12%). By searching the protein amino acid sequence database, we found two E. coli hypothetical proteins similar to the Pseudomonas sp. strain YL L-DEX (21 to 22%).

Amino Acid Sequence↗
PubMed1994

[A phase II study of BMS-181339 in patients with ovarian cancer. BMS-181339 Ovarian Cancer Study Group].

We conducted a multicenter Phase II study of BMS-181339 in patients with ovarian cancer. The facilities participating were 23 in number. The total number of cases registered for the study were 62; 57 of them entered for evaluation in drug efficacy, and 58 cases were evaluable in drug safety. All the cases were previously treated with chemotherapy including platinum-based drugs. The clinical responses of BMS-181339 were as follows: CR, 1 case; PR, 13 cases; MR, 3 cases; NC, 13 cases and PD, 27 cases. The response rate was 24.6% (95% CI: 14.1-37.8%). Histologically, the drug showed its efficacy on serous adenocarcinoma 28.2% (11/39), mucinous adenocarcinoma 20.0% (1/5) and clear cell adenocarcinoma 20.0% (1/5). In regional evaluation, the drug demonstrated its efficacy not only on endopelvic lesions 19.0% (4/21) and abdominal lesions 14.3% (2/14), but also on remote metastatic lesions such as hepatic metastasis 30.8% (4/13) and lung/pleura 33.3% (2/6). The drug also showed its efficacy on the cases 22.9% (8/35) refractory to the platinum-based drugs. Major adverse reactions were fever 63.8% (37/58), alopecia 59.3% (32/54), peripheral nerve disorders 28.1% (16/57) such as numbness of the extremities, nausea/vomiting 24.1% (14/58), arthralgia 20.7% (12/58) and diarrhea 20.7% (12/58) etc.. Abnormal alterations in laboratory test values were an incidence rates of 100% for both leukopenia and neutropenia. However, these symptoms were clinically manageable by transient withdrawal of medication, dose reduction and administration of antibiotics and G-CSF. In addition, decrease in hemoglobin 93.1% (54/58), decrease in platelet counts 31.0% (18/58), elevation in GOT 27.6% (16/58), in GPT 31.0% (18/58) and in LDH 20.7% (12/58) were seen, but no serious organopathy was observed. Thus, we confirmed that BMS-181339 was a clinically useful chemotherapeutic agent in patients with ovarian cancer.

Adenocarcinoma, Clear Cell↗
PubMed1994

[Phase I clinical study of 21-consecutive-day oral administration of etoposide].

We conducted a multi-institutional phase I clinical study on a 21-consecutive-day oral administration of etoposide in 12 patients with malignant tumor. The initial dose was 25 mg/body/day and then raised to 50 mg/body/day and eventually to 75 mg/body/day. The dose limiting factor was leukopenia and the maximum tolerated dose (MTD) was 75 mg/body/day. Leukopenia was observed in all 4 patients registered at 75 mg/body/day. Two of 4 patients showed WBC count nadirs of less than 2,000/microliters. The two patients had less than 1.5 m2 body surface area. Thrombocytopenia and hemoglobin decrease were mild compared to leukopenia. Other adverse reactions were as follows; anorexia (75.0%), nausea/vomiting (58.3%) alopecia (46.1%). No sign of accumulation after 21-consecutive-day oral administration of etoposide was seen on pharmacokinetic parameters. As for anti-tumor efficacy, a partial response was noted in a patient with lung metastasis of cervical cancer at the 75 mg/body/day dose level. A recommended dose for phase II study was 75 mg/body/day for 21 consecutive days with a one-week interval. However, for a patient with a body surface area less than 1.5 m2 or with a severe prior chemotherapy, 50 mg/body/day would be considered appropriate.

Administration, Oral↗
PubMed1994

[Studies on clinical usefulness of new tumor markers of ovarian cancer, CA54/61 and CA602--III. Measurement of serum samples from patients with various benign or malignant diseases].

Serum samples from patients with benign or malignant diseases were measured for the newly developed tumor markers CA54/61 and CA602 with the respective EIA kits for assessment of their utility as tumor markers. A total of 5236 patients were entered into the study, consisting of ovarian cancer patients, those with other cancers, pregnant women, and healthy volunteers. The CA54/61-positive rate with a cut-off value of 12 U/ml was 61.2% for ovarian cancers (50.4% with a cut-off value of 20 U/ml). A positive rate of 75.0% (64.4%) was achieved for mucinous cystadenocarcinoma, which was high, compared with that for CA125. On the other hand, the false-positive rate was 12.2%(5.9%) for benign ovarian tumors, and as low as 18.5%(8.7%) for endometriosis. The CA602-positive rate with a cut-off value of 63 U/ml was as high as 76.0% for ovarian cancers (69.8% with a cut-off value of 90 U/ml). On the other hand, the false-positive rate was relatively high at 21.9% (12.6%) for benign ovarian tumors, and 56.7% (40.0%) for endometriosis. These positive rates were therefore similar to those for CA 125. The levels of both CA54/61 and CA602 antigens well reflected the postoperative prognosis. These results suggest the utility of CA54/61 and CA 602 as tumor markers of ovarian cancers.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1993

Mutation of the Ki-ras protooncogene in human endometrial hyperplasia and carcinoma.

Previous studies have demonstrated that some human endometrial carcinomas contain an activating point mutation in codon 12 of the Ki-ras protooncogene. To examine the hypothesis that this mutation may occur at an earlier stage of neoplastic progression in the endometrium, we analyzed 89 samples of premalignant endometrial hyperplasia and an additional 84 samples of endometrial carcinoma for point mutations of Ki-ras codon 12. Mutations were found in all three types of endometrial hyperplasia, simple, complex, and atypical, with no clear evidence of a differential distribution in any particular type. Furthermore, the overall incidence of Ki-ras mutations in the hyperplasia specimens (16%) was similar to the incidence detected in carcinomas (18%), indicating that ras mutation may represent an early event in a subset of endometrial carcinomas. When the tissue samples were segregated as to country of origin, the frequency of this mutation was approximately 2-fold higher in hyperplasia and carcinoma samples from Japan than from the United States, where the incidence, clinicopathological characteristics, and risk factors for endometrial carcinoma differ dramatically. There was no apparent correlation, however, between ras mutation and any pathological, histological, or clinical parameter examined, except survival. The presence of a ras mutation was inversely associated with death from disease, suggesting that this molecular feature may characterize a subset of endometrial carcinomas with a good prognosis.

Adult↗
PubMed1993

CD4+ T cell clones isolated from human renal cell carcinoma possess the functional characteristics of Th2 helper cells.

The underlying cause for the observed poor antitumor activity of lymphocytes resident, in situ, in freshly resected human renal cell carcinoma (RCC) is unknown. To examine the basis for this observation we evaluated 217 T cell clones established from 20 consecutive patients with renal cell carcinoma. Of these, 75% were CD4+, 22% were CD8+, and 3% were NK+. Cytotoxic T cell function of CD4+ and CD8+ T cell clones was assessed by antibody-induced triggering of the TcR/CD3 complex. Nearly 93% of the CD4+ clones possessed poor cytolytic activity defined as < 50% killing (E:T, 50:1). Alternatively, nearly 80% of CD8+ clones possessed strong cytolytic activity defined as > or = 50% killing. In all T cell clones tested, MHC nonrestricted killing against Daudi or K562 was not observed. Overall, 77% of the T cell clones isolated from patients with RCC in this study were characterized by poor antitumor cytotoxic function; only 22% of the clones displayed strong cytolytic activity. Clones with strong cytotoxic function were tested for cytotoxic function against autologous tumor. However, all clones tested demonstrated little to no tumoricidal activity against autologous tumor. These results indicate that cytolytic T cells, while present in RCC, are not effectively activated by tumor to express CTL function. The immunobiology of CD4+ T cell clones was further evaluated. Thirty-two CD4+ clones from seven patients revealed distinct patterns of cytokine production following TcR/CD3 activation. CD4+ clones could be divided into IL-2 nonproducers and IL-2 producers. A total of 27/32 clones did not produce IL-2 following activation and IFN-gamma production by IL-2 nonproducers was more than threefold less than that by IL-2 producers. However, no differences were found in the levels of IL-4, IL-6, GM-CSF, or TNF-alpha between the two groups. Antitumor cytotoxicity mediated by CD4+ clones did not correlated with cytokine production. These results demonstrate that among T cells resident in human RCC, the predominant type of lymphocyte population consists of noncytolytic helper CD4+ T cells capable of secreting IL-4, but importantly not IL-2, and low levels of IFN-gamma following activation, thus resembling murine Th2 cells. Only a minor contribution by Th0-like cells was observed (i.e., CD4+ clones capable of secreting IL-2, IL-4, and IFN-gamma following activation).(ABSTRACT TRUNCATED AT 400 WORDS)

CD4-Positive T-Lymphocytes↗
PubMed1993

Dynamic changes in stress fiber expression in rat uterine vein endothelial cells associated with pregnancy.

En face endothelial preparations of rat uterine vein were stained with rhodamine-phalloidin to investigate the dynamics of stress fiber expression during pregnancy. In prepregnant animals, somewhat plump, spindle-like endothelial cells of the uterine vein had only a few short stress fibers. With the progress of pregnancy, however, many long stress fibers appeared within the elongated endothelial cells. Within 2 hr after delivery, these stress fibers became dramatically decreased in number as the cells reverted from an elongated to a plump shape and returned to the prepregnancy level by 14 days postpartum. The uterine vein showed a significant increase in length during pregnancy and quickly shortened after delivery. Thus, expression of stress fibers in endothelial cells of the uterine vein seems to be related to the tension loaded on this vessel during its elongation in parallel with the marked growth of the uterine body during pregnancy. This study shows that stress fibers are dynamic structures that may serve to maintain endothelial cell integrity during the exertion of tensile stress on the vessel wall.

Actins↗
PubMed1993

Usefulness of resting thallium-201 delayed imaging for detecting myocardial viability in patients with previous myocardial infarction.

To test the feasibility of resting thallium-201 (201Tl) initial and delayed scintigraphy for detecting the area of viable myocardium, we performed single photon emission computed tomography (SPECT) in 57 patients with previous myocardial infarction (MI). All had received coronary arteriography (CAG) and left ventriculography (LVG). Initial and delayed myocardial imagings were carried out 10 min and 2 hours, respectively, after the injection of 201Tl at rest. Redistribution was judged by visual interpretation and/or the circumferential profile curve, and found in the infarcted or its adjacent area in 40 of the 57 cases (70.2%). A negative washout (net increase of 201Tl uptake in delayed image) was detected in 17 of these 40 cases. In 10 of the 57 patients, both exercise and rest-injected 201Tl myocardial images were obtained at exercise and rest, and compared visually. The areas of abnormal perfusion were smaller in the resting delayed images than those seen after exercise in 9 of the 10 cases, and were equal in one case. Thus, resting 201Tl delayed myocardial scintigraphy appears to reduce the underestimation of the size of the viable myocardium by the usual 201Tl images obtained after exercise or by single initial images obtained at rest in patients with previous MI.

Adult↗
PubMed1993

Thallium-201 myocardial SPECT findings at rest in sarcoidosis.

In 41 patients with sarcoidosis (diagnosed according to criteria recommended by the Committee on Diffuse Pulmonary Disease, Ministry of Health and Welfare, Japan 1988), thallium-201 (201Tl) myocardial SPECT was performed to investigate: (1) the ability of 201Tl SPECT to detect cardiac involvement of sarcoidosis with images recorded at rest and 2 hours later, and (2) the relationships between 201Tl myocardial SPECT findings and the activity of sarcoidosis or endomyocardial biopsy findings. As to the abnormal findings in 201Tl myocardial SPECT, (1) a low density area was seen in 13 of 41 cases (31.7%) and non-uniform uptake was found in 17 cases (41.5%), (2) the mean washout ratio (n = 39) was 16.5 +/- 7.4%, which is significantly (p < 0.05) lower than that found in normal subjects, 23.9 +/- 7.5% (n = 10). Of the 19 patients judged visually to be normal, 5 patients had a reduced mean washout ratio less than 12%. Thus, the incidence of abnormal findings including all types of abnormality, on 201Tl myocardial SPECT in sarcoidosis was 63.4% (26/41 cases). In studying the relationship between 201Tl myocardial SPECT findings and the activity of sarcoidosis (as measured by the serum ACE (angiotensin converting enzyme) or lysozyme level, or the presence of more than 30% symphocyte fraction in BALF (broncho-alveolar lavage fluid)), 20 (80%) of 25 cases with 201Tl abnormality were judged to be active sarcoidosis, while only 6 (37.5%) of 16 cases with normal findings on 201TI SPECT were judged to be active.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Survival characteristics of metastatic renal cell carcinoma patients treated with lymphokine-activated killer cells plus interleukin-2.

The immunologic manipulation of patients with metastatic renal cell carcinoma using lymphokine-activated killer (LAK) cells in conjunction with systemic interleukin-2 (IL-2) has been examined under conditions in which the life-threatening toxicities associated with IL-2 treatment have been virtually eliminated. We have examined tumor regression in vivo as well as the survival characteristics of 12 patients with metastatic renal cell carcinoma following immunotherapy. Five of 12 (42%) patients experienced tumor regression exceeding 50 percent following treatment. To determine if immunotherapy had influenced the length of survival, all patients were followed until the time of death. Previous studies have characterized the length of survival of metastatic renal cell cancer patients according to a combination of risk factors unique for each patient. In this model, patients were categorized into risk groups based on the number of risk factors. Survival was found to be dependent on risk factors such as performance status, time from initial diagnosis, number of metastatic sites, recent weight loss, and prior cytotoxic chemotherapy. On completion of the LAK cell immunotherapy protocol, patients were categorized as nonresponders or responders. In addition, they were assigned to risk groups based on their unique profile of risk factors at the time of entry into the protocol. Using this model, we found the median survival of nonresponders (23 months) to be no different from responders (24 months), p > 0.05. This was directly attributable to differences in risk factors which characterized members in these two response groups. However, the observed median survival of nonresponders following therapy was 1.9-fold longer than their projected survival based on the risk factors. Furthermore, the observed median survival of responders was 3.4-fold longer than projected from their risk factors. These results suggest that regardless of response status to therapy, cellular immunotherapy may play a role in mediating a significant palliative effect on the metabolic characteristics of these patients leading to extended survival.

Carcinoma, Renal Cell↗
PubMed1993

Insulin responsiveness to glucose and tissue responsiveness to insulin during lactation in dairy cows.

The hyperglycemic clamp and hyperinsulinemic euglycemic clamp techniques were conducted to assess insulin responsiveness to glucose and tissue responsiveness to insulin in lactating and nonlactating Holstein cows. In the hyperglycemic clamp experiment, blood glucose concentrations were clamped at 50 mg/dl above the pre-infusion values by variable rates of glucose infusion. The mean plasma insulin increments over the baseline (insulin responsiveness to glucose) during hyperglycemia were lower (P < .05) in lactating cows than in nonlactating cows (23 vs. 102 microU/ml). In the hyperinsulinemic euglycemic clamp experiment, insulin was infused at the constant rate of 6.0 mU.kgBW-1.min-1 for 2 hr, and glucose was concomitantly infused at a variable rate to maintain the pre-infusion concentrations of blood glucose. Glucose infusion rates (tissue responsiveness to insulin) were similar (3.2 mg.kgBW-1.min-1) for lactating and nonlactating cows. It is concluded that insulin responsiveness to glucose is reduced, and tissue responsiveness to insulin remains unchanged during lactation in Holstein cows.

Animals↗
PubMed1993

Pancreatic insulin secretory response and insulin action in heat-exposed sheep given a concentrate or roughage diet.

The effects of heat exposure and type of diet on the insulin secretory response to glucose and glucose disposal in response to insulin action in female sheep were investigated employing hyperglycemic and euglycemic clamp techniques. Animals were divided into concentrate and roughage diet groups, and were maintained at the same intake levels of metabolizable energy and crude protein in both diets. Each diet group was subjected to either thermoneutral (20 degrees C, 70% RH) or hot (30 degrees C, 70% RH) environment, followed by glucose clamp experiments. Heat-exposed sheep showed significant increases in respiration rates (P < .001) and rectal temperature (P < .05). Plasma glucose concentrations in the basal conditions were lower (P < .01) in the hot environment than in the thermoneutral environment, but there was no significant difference in basal levels of plasma insulin between the environmental treatments. In the hyperglycemic clamp experiment, mean plasma insulin increments increased (P < .05) during the heat exposure period across diet treatments. The ratio of mean plasma insulin increment to glucose infusion rate tended to be higher (P < .07) in the hot environment than in the thermoneutral environment, but diet treatment did not affect the ratio of mean plasma insulin increment to glucose infusion rate. The euglycemic clamp technique showed that glucose infusion rates remained unchanged among treatments. Insulin secretion response to glucose could be stimulated in the hot environment.

Analysis of Variance↗
PubMed1993

Estrogen productivity of endometrium and endometrial cancer tissue; influence of aromatase on proliferation of endometrial cancer cells.

Aromatase, estrone (E1) sulfatase and E1 sulfotransferase activities were examined in endometrium and endometrial cancer tissue preparations. Aromatase and E1 sulfatase activities in endometrial cancer tissues were found to be significantly higher than in normal endometrial tissues. However, E1 sulfotransferase activity did not differ between benign and malignant tissue. We also examined the effect of testosterone (T) on aromatase activity and tritiated thymidine uptake (DNA synthesis) in various cultured cervical or corpus endometrial cancer cell lines (OMC-4, HHUA, Ishikawa, HEC-59). The results demonstrated that only the HEC-59 cell line had high aromatase activity and increased its DNA synthesis in response to T. This increase of DNA synthesis by T was not suppressed by simultaneous addition of cyproterone acetate, but was by tamoxifen. These data suggest that in situ estrogen production in endometrial cancer tissue is biologically important and that aromatase in cancer cells may contribute partially to cell proliferation if androgen substrate is provided.

Aromatase↗
PubMed1993

Aromatase activity and the effect of estradiol and testosterone on DNA synthesis in endometrial carcinoma cell lines.

Human endometrial and breast carcinoma cell lines were examined for aromatase activity and the effects of sex steroids (estradiol and testosterone) on DNA synthesis. Aromatase activity was high (greater than 500 fmol/10(7) cells/24 h) in the cell lines MCF-7 and OMC-2, moderate (100-499 fmol/10(7) cells/24 h) in the cell lines HEC-59 and Ishikawa, and low (less than 100 fmol/10(7) cells/24 h) in the HHUA cell line. A substantial stimulation of DNA synthesis by estradiol (10(-9)M) was observed in cell lines HEC-59, OMC-2, and MCF-7, with an increase in [3H]thymidine uptake of over 250%. The Ishikawa cell line was stimulated moderately (115-249%). No estradiol-induced increase in DNA synthesis was observed in HHUA. Responsiveness of DNA synthesis to testosterone was observed in cell lines that showed the greatest response to estradiol, namely HEC-59, OMC-2, and MCF-7. Otherwise, estrogen-responsiveness did not always correlated with a significant aromatase activity. These data suggest that some but not all endometrial carcinomas may possess an aromatase-dependent growth stimulating system.

Aromatase↗
PubMed1993

Long-term indwelling bilateral ureteral stents for bilateral hydronephrosis of unknown etiology.

We describe a rare case of long-term indwelling bilateral ureteral stents that were replaced yearly for 7 years because of azotemia associated with bilateral hydronephrosis of undetermined etiology on radiological examinations. During year 5 the patient had an uneventful gestation with delivery of a normal neonate by cesarean section. Hydronephrosis remained improved for 2 years after withdrawal of the stents.

Adult↗