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Biomedical subjects

Y Terashima

Publications and source records attributed to Y Terashima.

At least 91 records · Page 5Linked to original sources

Maximal cytoreductive surgery and high dose cisplatin chemotherapy for advanced ovarian cancer.

Fifty-eight stage III patients treated at The Jikei University Hospital were analysed retrospectively, in order to clarify the combination effect of maximal cytoreductive surgery and high dose cisplatin based chemotherapy in advanced ovarian cancer. They were divided into 4 groups by treatment they received which was as follows: Group A (n = 25); total abdominal hysterectomy (TAH), bilateral salpingooophorectomy (BSO) and omentectomy (OMTX) done at primary surgery and followed by 5 courses of "low dose" CAP therapy (cyclophosphamide 200 mg/sq m, adriamycin 20 mg/sq m, cisplatin 35 mg/sq m every 4 weeks for 5 courses). Group B (n = 4); TAH, BSO and OMTX carried out at primary surgery and followed by "high dose" CAP therapy (cyclophosphamide 200 mg/sq m, adriamycin 20 mg/sq m, cisplatin 70 mg/sq m, every 4 weeks for 5 courses and every 8-12 weeks for 5 courses thereafter). Group C (n = 13) received TAH, BSO and OMTX at the primary operation and paraaortic and pelvic lymphadenectomy (LNX) at the second look operation (SLO) with "high dose" CAP therapy as did Group B. Group D (n = 16), TAH, BSO, OMTX, LNX with maximal efforts made to reduce the size of the residual tumor to less than 2 cm at the primary surgery followed by "high dose" CAP therapy. The 3 year and 5 year survival rate of each group were as follows: Group A 15.6%, 15.6%, Group B 25.0%, 0%, Group C 81.8%, 0% and Group D 50.8%, 38.1%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Macrophages in the urine in acute bacterial cystitis.

In the previous study in this series of studies concerning the role of macrophages in urinary tract infection, we attempted to detect macrophages in the urine of acute bacterial cystitis patients by nonspecific esterase staining of urinary sediment, however none of the leukocytes stained, probably because of cell damage caused by the urine and by centrifugation. In the present study, detection of macrophages in urine was again attempted, this time by prompt transfer of urinary leukocytes to culture medium after minimum centrifugation, 1 hr culture in a glass bottom chamber and non-specific staining of leukocytes adhering to glass. Macrophages in urine were detected by this method, and they comprised 5.9% of the adherent leukocytes, although macrophage spreading, which implies macrophage activation and is often seen in the early stage of nonbacterial prostatitis, was hardly ever observed. The percentages of adherent leukocytes were not correlated with urine osmolarity, probably because the effect of urine was minimized by prompt transfer of urinary leukocytes to culture medium after the urine samples had been collected. There have been quite few studies involving culture of urinary leukocytes in the past. Our simple techniques, such as prompt transfer of urinary leukocytes to culture medium after centrifuging with minimum gravity and for a minimum period of time, appear to be useful in the study of urinary leukocytes using other cells which appear in urinary tract infection, as well as cytokines and antibiotics, to clarify cellular mechanisms of defenses in urinary tract infection.

Acute Disease↗

Ca2+ sensitivity of skinned uterine muscle fibers in unilaterally pregnant rats.

We prepared chemically skinned uterine muscle fibers from both horns of unilaterally pregnant rats and investigated the effect of gestation on the Ca2+ sensitivity of the Ca(2)-induced contraction. The Ca2+ sensitivity was defined as the pCa (minus logarithm of free calcium concentration) required for half maximum activation of force production. Gravid horns did not show any statistical difference in the Ca2+ sensitivity between normal pregnant and unilaterally pregnant rats. Non-gravid horns of unilaterally pregnant rats before Day 14 of gestation showed the same behavior in the Ca2+ sensitivity as horns of normal pregnant rats. After Day 15 of gestation the Ca2+ sensitivity of non-gravid horn also increased but significantly less than that of gravid horn. Taking into account the hormonal situation, the present results suggest that some local factors, such as an increased size of conceptus (fetus and placenta) and/or intercellular binding conditions of myometrium modulated by the gap junction formation and the appearance of connexin molecules, may also be requisite for the regulation of the contractile activity associated with parturition and delivery of the fetus and placenta.

Animals↗

Plasma insulin and glucagon responses to intravenous infusion of propionate and their autonomic control in sheep.

Propionate (0, 1, 2, 4, 8, 16, 32, and 64 mumol.kg BW-1 x min-1 for 30 min) was infused i.v. to investigate the physiological effects of propionate on insulin and glucagon responses in sheep. An i.v. propionate infusion (32 mumol.kg BW-1 x min-1 for 30 min) with adrenergic and cholinergic blockades was also conducted to clarify the role of autonomic innervation in the control of propionate-induced insulin and glucagon responses. In the experiment in which we studied responses to propionate infusion, the concentrations of plasma insulin and glucagon during propionate infusion increased (P < .05) from the preinfusion concentrations at infusion rates of > 4 and 8 mumol.kg BW-1 x min-1, respectively. The incremental response areas of plasma insulin and glucagon during propionate infusion increased (P < .05) at infusion rates of > 16 and 32 mumol.kg BW-1 x min-1, respectively. In the experiment studying the effects of adrenergic and cholinergic blockades on responses to propionate, the insulin incremental response area during propionate infusion was suppressed (P < .05) by atropine infusion but it was not influenced by phentolamine, propranolol, or hexamethonium infusions. The glucagon response area was suppressed (P < .05) by phentolamine infusion, but it was not influenced by propranolol, atropine, or hexamethonium infusions. It is concluded that in sheep 1) propionate may have a physiological role in stimulating insulin and glucagon responses, 2) the propionate-induced insulin response is partly due to the parasympathetic nervous system through activation of a muscarinic receptor, and 3) the propionate-induced glucagon response is stimulated by adrenergic alpha-receptors.

Animals↗

[Studies of prognostic factor and chemotherapeutic effect of epithelial ovarian cancer using Cox's proportional hazard model].

To make clear the prognostic factor and chemotherapeutic effect of epithelial ovarian cancer, a multiple-center study involving 22 hospitals in Japan was conducted using Cox's proportional hazard model. A total of 1,181 cases were reviewed. Clinical stage, histologic type, and residual tumor diameter were significant prognostic factors, but the degree of tissue differentiation was not. The effect of remission induction chemotherapy was assessed with or without CDDP, and a distinct prognostic difference was noted. Among the patients receiving CDDP + ADM + other chemotherapeutic agents (PA group), CDDP + other chemotherapeutic agents (PO group) and CDDP only (P group), the prognosis of the PO group was better than for the P group. The long-term prognosis improving effect of chemotherapy was assessed. Neither maintenance chemotherapy based on oral administration of pyrimidine fluoride nor immunotherapy had any long-term prognosis improving effect, while intermittent chemotherapy based on CDDP resulted in improved prognosis.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinical application of transrectal ultrasonic therapy to nonbacterial prostatitis and prostatodynia cases which were resistant to conventional drug therapy].

A total of 25 patients with nonbacterial prostatitis and prostatodynia which were resistant to conventional drug therapy underwent 5 minutes course of transrectal ultrasonic therapy in association with application of 1% hydrocortisone acetate cream to the anterior rectal wall for consecutive 8 days. The efficacy of the treatment was evaluated only by comparison of symptom scores for subjective symptoms obtained before and after treatment. Excellent results, which were defined as more than 70% reduction of symptom scores after treatment, were obtained in 5 (27.8%) among 18 evaluable cases in which symptom scores before treatment were more than 4, good (40-69% reduction of scores) in 4 (22.2%), fair (10-39% reduction of scores) in 4 (22.2%) and poor (less than 10% reduction of scores) in 5 (27.8%). Because of good clinical efficacy and the absence of complication, transrectal ultrasonic therapy combined with hydrocortisone acetate cream application was thought to be useful for the treatment of nonbacterial prostatitis and prostatodynia cases which responded poorly to the conventional therapy.

Administration, Topical↗

Investigation of the clinical value of assessing renal size on computed tomography in autosomal dominant polycystic kidney disease.

We examined relationship between serum creatinine concentration (Scr) and renal size on CT scans on 32 occasions in 25 patients with autosomal dominant polycystic kidney disease (ADPKD). As a result, a significant correlation was observed when the Scr was less than 5 mg/dl, as shown by the correlation coefficient (r) and P values of 0.803 and 0.0001, respectively. However, these values changed to 0.482 and 0.0093, respectively when 2 cases with Scr 6.2 and 6.4 mg/dl were included, and further changed to 0.005 and 0.9775 when an additional 4 cases with Scr 7.8, 9.9, 11.1 and 20.1 mg/dl were included. Renal size is therefore thought to be a useful parameter of renal function when the Scr is less than 5 mg/dl in ADPKD, but not when the Scr exceeds 6 mg/dl, and is regarded as useless for predicting the time at which dialysis would be required.

Creatinine↗

[The influence of pulmonary "venous" compliance on the static pulmonary compliance: a study of patients with left-sided heart disease with normal respiratory function].

In heart diseases, such as mitral stenosis and angina pectoris, the static pulmonary compliance has been reported to be decreased. By definition, the pulmonary "venous" system consists of the pulmonary veins and the left atrium. It plays an important role as the reservoir for the left ventricle. In this laboratory, the pulmonary "venous" compliance (Cp"v") has been evaluated as delta V/delta P of a short segment of the P"V" volume-pressure curve. To evaluate the influence of Cp"v" on the static pulmonary compliance and to speculate about the mechanisms of the reduction in static pulmonary compliance in left-sided heart disease, hemodynamic data and static pulmonary compliance (Cst) were measured in 27 patients with left-sided heart disease. Cst was measured with esophageal balloon technique in a sitting position. The static volume-pressure curve was fitted by a sigmoid model: V = Vm/(1 + e(A-P)/kappa), where kappa is a shape constant and an index of the lung stiffness. The pulmonary blood volume (PBV) was estimated with our own method, using radionuclide (RN) angiocardiography. The mean pulmonary artery wedge pressures (PAW) were measured using a floating catheter. Cp"v" was calculated as the delta V/delta P from the increment of pulmonary "venous" volume (delta V) and that of PAW (delta P) that occurred during passive elevation of the legs. Pulmonary arterial compliance (Cpa) was obtained from an analysis of the diastolic decline in pulmonary arterial pressure wave forms.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

[Twenty one multicentral studies on prognosis of advanced ovarian cancer; focused on correlation between primary surgical procedure following adjuvant chemotherapies and 4 year survival rates].

The treatment outcome of 778 patients with stage III ovarian cancer treated by surgery and chemotherapy between 1976 and 1990 in 21 institutions was analyzed retrospectively. Survival of patients treated between 1985 and 1990 was significantly superior to that before 1985 (Kaplan-Meier, p < 0.01). Four year survival rates were found to be distributed from 5 to 52% among institutions (p < 0.001, log-rank test). When survival rates were compared according to the relative dose intensity (RDI) of CDDP administered, patients who were given CDDP RDI > or = 0.9 had a favorable prognosis. The twenty-one institutions were divided into two groups: Standard (total abdominal hysterectomy and bilateral salpingo-oophorectomy) vs. standard+debulking (of as much gross tumor as can safely be performed) according to the operative procedure which was performed in each hospital. It was found that the four-year survival rate for patients treated in hospitals where standard surgery was done was 22.9 +/- 12.2%, whereas that in hospitals adopting standard+debulking surgery was 34.4 +/- 10.1% (p = 0.03, t-test). When the hospitals were divided into 4 groups according to combination of the operative procedure and CDDP RDI, the four year survival rates were 17.5 +/- 8.3% for standard+debulking+CDDP RDI < 0.9, 39.0 +/- 1.4% for standard+CDDP RDI > or = 0.9, 28.8 +/- 11.5% for standard+debulking+CDDP RDI < 0.9 and 37.8 +/- 8.0% for standard+debulking+CDDP RDI > or = 0.9.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

Detection of topoisomerase I gene point mutation in CPT-11 resistant lung cancer cell line.

CPT-11, a recently developed topoisomerase I (Topo I) inhibitor, attracts the attention not only of basic researchers but also of clinicians because of its high antitumor activity. The CPT-11 resistant human lung cancer cell line, PC-7/CPT, showed 10-fold resistance compared to parental cell line, PC-7. The total activity of Topo I in the resistant cell line was one fourth that of the parental sensitive cell line. The Topo I from the resistant cells was also 5-fold more resistant to the inhibitory effect of CPT-11 than that of the parental cells. We speculated that the alteration of the Topo I gene may be responsible for the change in topoisomerase activity of the CPT-11 resistant cell line. Therefore, we analyzed the mutation of Topo I gene using the method of single strand conformation polymorphism of polymerase chain reaction and the reverse transcriptase. We divided Topo I cDNA into ten fragments which overlapped each other and covered whole coding sequences of the Topo I cDNA. We observed mobility shift of two fragments in the PC-7/CPT, suggesting the presence of some mutations in these fragments. We performed the direct-sequencing of these portions by the dideoxy chain termination method and observed an altered sequence having a G to A base change in PC-7/CPT. This base substitution results in replacement of the conserved threonine at 729 position with alanine. These results suggest that the point mutation of Topo I gene is related to the decreases of Topo I activity and the sensitivity to Topo I inhibitor in PC-7/CPT cells.

Antineoplastic Agents, Phytogenic↗

CA54/61 as a marker for epithelial ovarian cancer.

Using a new one-step, double-determinant enzyme immunoassay, we performed quantitative measurements of a mucin-type glycoprotein antigen (CA54/61) that we recently detected in sera of ovarian carcinoma patients. When the cutoff value was set at 12 units/ml, at which a high diagnostic efficiency was demonstrated [or at 20 units/ml (mean + 3 SD of healthy females)], the positive rates of ovarian serous, mucinous, clear cell, and endometrioid carcinomas were 76% (or 63%), 63% (or 55%), 57% (or 52%), and 50% (or 38%), respectively. Even in mucinous cystadenocarcinoma, more than one-half of the cases were positive, indicating the potential utility of the assay in the diagnosis of mucinous tumors. In sera from patients with benign ovarian tumors, only 9% (or 4%) of the cases were positive, indicating the quite high specificity of this test for ovarian carcinomas. To make a comparison between CA54/61 and CA125, we set the cutoff level of CA125 at 110 units/ml, at which value a high diagnostic efficiency was demonstrated [or at 35 units/ml (mean + 3 SD of healthy females)]. When both CA54/61 and CA125 were assessed in sera from 36 patients with mucinous cystadenocarcinoma, the positive rates of CA54/61 and CA125 were 64% (or 56%) and 36% (or 56%), respectively, suggesting that CA54/61 is of clinical value as a new tumor marker for ovarian cancers, including mucinous tumors.

Adult↗

Mechanism of cross-resistance to a camptothecin analogue (CPT-11) in a human ovarian cancer cell line selected by cisplatin.

We established a cisplatin-resistant human ovarian cancer cell line (HAC2/0.1) from the parent cell line (HAC2/P) by continuous exposure of HAC2/P to 0.1 microgram of cisplatin/ml. Drug sensitivity determined by colony assay revealed that HAC2/0.1 was 2.4 times as resistant to cisplatin as the parental cell line. HAC2/0.1 was 12.1 and 2.0 times as resistant to (4s)-4,11-diethyl-4-hydroxy-9-[(4-piperidinopiperidino)-carbony loxy]dione hydrochloride trithydrate (CPT-11) and 7-ethyl-10-hydroxy-CPT (SN-38; an active metabolite of CPT-11), respectively, than HAC2/P. We studied the mechanism of cross-resistance to CPT-11 in HAC2/0.1. The glutathione (GSH) content was higher in HAC2/0.1 than in HAC2/P. The activity of DNA topoisomerase I and the accumulation of CPT-11 and SN-38 were also the same. On the other hand, the conversion of CPT-11 to SN-38 in HAC2/0.1 was about 3-fold less than in HAC2/P. Treatment of the parent and resistant cell lines with buthionine sulfoxamine (BSO) decreased the GSH content of both cell lines and decreased the 50% inhibitory concentrations of all the tested drugs for HAC2/0.1. The accumulation of CPT-11 in HAC2/0.1 but not in HAC2/P was increased by BSO treatment. On the other hand, in HAC2/P the 50% inhibitory concentrations of SN-38 and CPT-11 were not influenced by BSO treatment. The 50% inhibitory concentration of CPT-11 for HAC2/0.1 was not reduced by BSO treatment to the level for HAC2/P, even though the GSH content had been reduced more than in HAC2/P. These results show that there is no clear relationship between GSH and resistance to CPT-11. The decreased conversion of CPT-11 to SN-38 is considered to be the main cause of resistance to CPT-11 in this cell line.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Estimation of right ventricular volume by modified echocardiographic subtraction method.

To evaluate the accuracy and clinical utility of right ventricular volume estimated by a modified echocardiographic subtraction method versus Krebs' original subtraction method, an experiment was performed on hearts excised from 25 animals (dogs, pigs, and cows) followed by a clinical study of 41 patients with heart disease. Right ventricular volume was measured by subtracting the left ventricular volume from that of the whole heart based on echocardiographic apical two- and four-chamber views by means of the area-length method. In the animal heart study, the coefficient of variation between the right ventricular volume estimated by the modified method and the true volume was +/- 13%. The regression equation was y = 0.94x + 4.15 (r = 0.987, p less than 0.001) and showed good correlation, whereas the right ventricular volume obtained by the original method underestimated the true volume (coefficient of variation = +/- 25%, y = 0.59x + 1.11; r = 0.976, p less than 0.001). In the clinical study, the coefficient of variation between right ventricular volume estimated by the modified echocardiographic method and RV volume estimated by radionuclide ventriculography was +/- 15%. The regression equation was y = 0.80x + 13.3 (r = 0.935, p less than 0.001). This correlation was better than that obtained by the original method (coefficient of variation = +/- 16%), where the regression equation was y = 0.60x + 2.43 (r = 0.888, p less than 0.001). Thus the accuracy of the modified subtraction method was validated, and this method showed a better correlation than the original method both experimentally and clinically.

Adolescent↗

Secondary cytokine production by lymphoid cells used in cellular immunotherapy.

Interleukin-2 (IL-2) has been used extensively in cellular immunotherapy trials as a systemic activator of the immune system as well as an ex vivo stimulant for lymphoid cell function. Despite the measurement of several in vitro and in vivo immunologic parameters related to cellular immunotherapy, determinants of successful cellular immunotherapy remain unknown. To further delineate the consequences of exposing peripheral blood lymphocytes to high concentrations of IL-2, we assessed the supernatants of IL-2-activated peripheral blood lymphocytes for production of tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma). Exposure of normal monocyte-depleted peripheral blood mononuclear cells (PBMC) to IL-2 caused a dose-dependent increase in secretion of TNF and IFN-gamma which increased linearly after 48 h in culture. Analysis of positively selected, highly purified PBMC subpopulations exposed to IL-2 revealed that TNF-alpha and TNF-beta were produced by both CD3+ and CD16+ subpopulations but not by CD22+ cells. These studies were extended to supernatants obtained from PBMC cultures used in the adoptive cellular immunotherapy of patients with advanced cancer. Patients treated with lymphokine-activated killer (LAK) cell immunotherapy were classified as responders (N = 14) or non-responders (N = 17) to therapy. We found no significant difference in the production of TNF between responders and nonresponders (22 +/- 9 U ml-1 vs. 20 +/- 6 U ml-1), P > 0.05. However, LAK cell supernatants harvested from non-responders contained a significantly higher level of IFN-gamma (232 +/- 94 U ml-1) compared with responders (42 +/- 14), P < 0.05. Furthermore, the linear association between IFN-gamma and TNF-alpha production was different between these two response groups (rs = -0.19 for non-responders and rs = 0.48 for responders). These results suggest that secondary cytokine production by adoptively transferred lymphocytesmay play an important role in the host response to cellular immunotherapy.

Cells, Cultured↗

A computerized tomographic study in patients with delusional and non-delusional depression.

This is a description of a computerized tomographic study of 45 non-delusional depressed, 29 delusional depressed patients and 77 neurotic control subjects. The cerebral atrophy ratio (CAR) on the three different slices and the ventricular ratio (VBR) of the anterior horn and the body of the lateral ventricles were calculated, analyzed and compared using Student's t test. Compared to the control subjects, the non-delusional depressive patients had greater CAR values than the controls but there were no significant differences of VBR values between the two groups. The patients with delusional depression had significantly larger CAR and VBR values than the non-delusional depressives and control subjects. The delusional depressives had greater brain atrophy than the non-delusionals and it was suggested that organic cerebral factors may have etiological significance in the depressions, especially the delusional depressives.

Adult↗

Ovarian mucinous cystadenocarcinoma producing alpha-fetoprotein. A case report.

A 62-year-old woman with a complaint of abdominal distention underwent surgery to remove a tumor in her left ovary. The serum alpha-fetoprotein (AFP) level was 4,130 ng/ml. Histologically, the tumor was diagnosed as a mucinous cystadenocarcinoma with a small area of solid proliferation of tumor cells. The cells of the latter part were shown immunohistochemically to possess AFP. We suppose that a part of the mucinous cystadenocarcinoma dedifferentiates and produces AFP.

Autopsy↗

Combined effects of diet and cold exposure on insulin responsiveness to glucose and tissue responsiveness to insulin in sheep.

Hyperglycemic clamp and hyperinsulinemic euglycemic clamp techniques were used to investigate effects of diet and cold exposure on insulin responsiveness to glucose and tissue responsiveness and sensitivity to insulin in adult rams. The sheep were fed a high-concentrate diet (80% concentrate and 20% roughage) and a high-roughage diet (20% concentrate and 80% roughage), both 70% above the ME requirement for maintenance, and were exposed to a thermoneutral environment (20 degrees C) and a cold environment (0 degrees C) for 2 wk. The estimated ME intake was greater (P < .01) for the high-concentrate diet than for the high-roughage diet. In the hyperglycemic clamp experiment, the ratio of the plasma insulin increment to the glucose infusion rate (insulin responsiveness to glucose) was lower during cold exposure than in the thermoneutral environment in sheep fed the high-concentrate diet but was unchanged in sheep fed the high-roughage diet. In the hyperinsulinemic euglycemic clamp experiment, the glucose infusion rate (tissue responsiveness to insulin) was higher (P < .01) for the high-concentrate diet than for the high-roughage diet, and it was also higher (P < .01) during cold exposure than in the thermoneutral environment, indicating that tissue responsiveness to insulin was intensified in sheep fed the high-concentrate diet during cold exposure associated with the higher energy intake. These results suggest that both reduced insulin responsiveness and enhanced tissue responsiveness to insulin in sheep exposed to cold were dependent on the type of diet.

Animal Feed↗