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D Yamada

Publications and source records attributed to D Yamada.

At least 19 recordsLinked to original sources
PubMed2001

Phase I trial of concomitant vinorelbine, paclitaxel, and pelvic irradiation in cervical carcinoma and other advanced pelvic malignancies.

OBJECTIVE: The aim of this study was to determine the feasibility and toxicity of concomitant vinorelbine, paclitaxel, and pelvic radiation therapy (RT) in patients with advanced cervical cancer and other pelvic malignancies. METHODS: Eligible patients included those with large or locally advanced cervical cancer. In addition, patients with other advanced gynecologic malignancies were eligible. In part I, vinorelbine was administered as a single agent during pelvic RT at a starting dose of 10 mg/m(2)/week with subsequent cohorts being escalated in 5 mg/m(2)/week increments. In part II, paclitaxel was added to vinorelbine (20 mg/m(2)/week) and pelvic RT at a starting dose of 20 mg/m(2)/week. RESULTS: Thirty-three women with pelvic malignancies (22 cervix, 6 vagina, 3 endometrium, 2 vulva) were enrolled. Twenty-seven received vinorelbine and 6 received both paclitaxel and vinorelbine in combination with pelvic RT. Escalating vinorelbine doses to 25 mg/m(2)/week were well tolerated, with the primary toxicity being hematologic. RT was delayed in only 1 patient due to acute hematologic toxicity. In contrast, the combination of paclitaxel, vinorelbine, and pelvic RT was not well tolerated. Five of 6 patients (83%) experienced grade > or = 2 leukopenia, with 2 patients missing > 1 cycle of chemotherapy. Moreover, RT was delayed for 1 week in 2 of 6 patients (33%). CONCLUSIONS: Concomitant pelvic RT and vinorelbine with doses to 25 mg/m(2)/week is well tolerated. The addition of paclitaxel to this combination is associated with significant hematologic toxicity and is thus not a feasible approach.

Adult↗
PubMed2001

Outcome of endometrial carcinoma patients with involvement of the uterine serosa.

OBJECTIVE: The goal of this work was to evaluate the outcome of endometrial carcinoma patients undergoing primary surgery who have serosal involvement (SI). METHODS: Between 1980 and 1998, 562 women underwent primary surgery for endometrial cancer at the University of Chicago. Thirty-nine were noted to have SI. FIGO stages were IIIA (19), IIIB (1), IIIC (7), and IV (12). Of the 19 IIIA patients, 15 had solitary SI. Twenty-six patients received pelvic radiation therapy (RT) with or without vaginal brachytherapy (VB). One patient received whole-abdomen radiation therapy, and 13, adjuvant chemotherapy. Solitary SI patients received pelvic RT with or without VB as their sole adjuvant therapy. Disease-free survivals (DFSs) were estimated using the method of Kaplan and Meier and prognostic factors were analyzed by the log-rank test. RESULTS: With a median follow-up of 30.3 months, the 5-year actuarial DFS of the entire group was 28.9%. Factors correlated with disease recurrence included tumor stage (P = 0.003) and lymph node involvement (P = 0.04). In addition, patients with solitary SI had a better 5-year DFS (41.5% vs 20%, P = 0.04) than patients with SI plus other extrauterine sites. Relapse occurred in 23 women overall and in 7 of 15 solitary SI patients. The most common site of disease recurrence was distant both in the entire group and in the solitary SI patients. While abdominal recurrences were common in the entire group, they were infrequent in solitary SI patients. CONCLUSION: Endometrial carcinoma patients with SI have a high rate of relapse and a poor outcome. Even when patients have extrauterine disease limited to SI, the outcome is relatively unfavorable. Nonetheless, our results demonstrate the need to distinguish patients with solitary SI and those with SI plus other extrauterine disease sites.

Adult↗
PubMed2001

Determination of plasma prothrombin level by Ca2+-dependent prothrombin activator (CA-1) during warfarin anticoagulation.

BACKGROUND AND AIM OF THE STUDY: The carinactivase-1 (CA-1) test is a new method for monitoring plasma prothrombin levels during warfarin anticoagulation therapy. METHODS: A total of 192 patients were allocated to two groups. Group A patients (n = 42) were controls (no warfarin); group B patients (n = 150) received warfarin. A Ca2+-ion and Boc-Val-Pro-Arg-pNA (a chromogenic substrate for thrombin) were added to 10-fold diluted plasma, after which prothrombin was activated with CA-1. Prothrombin levels were determined by measuring the extent of p-nitoroaniline liberation. RESULTS: The mean prothrombin level was 112.8 +/- 20.0 microg/ml in group A (Gaussian distribution), and 53.3 +/- 19.6 microg/ml in group B. In group B, correlations were found between the CA-1 test and prothrombin levels measured by prothrombin time (PT; r = 0.61, p <0. 01), PT-INR (r = 0.61, p <0.01), Thrombotest (TT; r = 0.57, p <0.01) and Hepaplastin test (HPT; r = 0.69, p <0.01). CONCLUSION: The CA-1 test represents a viable method of monitoring the coagulation system. CA-1 recognized the Gla-domain of prothrombin, and activated prothrombin. The CA-1 test required only 10 microl of diluted blood plasma, and took approximately 30 min to complete. The CA-1 test also measures prothrombin levels, correlates excellently with other tests for coagulation, and compares well with currently available methods for determining the efficacy of warfarin.

Aged↗
PubMed2000

Intensity-modulated whole pelvic radiation therapy in patients with gynecologic malignancies.

PURPOSE: To evaluate the ability of intensity-modulated radiation therapy (IMRT) to reduce the volume of small bowel irradiated in women with gynecologic malignancies receiving whole pelvic radiotherapy (WPRT). METHODS AND MATERIALS: Ten women with cervical (5) or endometrial (5) cancer undergoing WPRT were selected for this analysis. A planning CT scan of each patient was obtained following administration of oral, i.v., and rectal contrast. The clinical target volume (CTV) was defined as the proximal vagina, parametrial tissues, uterus (if present), and regional lymph nodes. The CTV was expanded uniformly by 1 cm in all directions to produce a planning target volume (PTV). The bladder, rectum, and small bowel were also delineated in each patient. Two plans were created: a standard "4-field box" with apertures shaped to the PTV in each beam's eye view and an IM-WPRT plan designed to conform to the PTV while minimizing the volume of normal tissues irradiated. Both plans were normalized to deliver 45 Gy to the PTV. Isodose distributions and dose-volume histograms (DVH) were compared. RESULTS: The IM-WPRT plan reduced the volume of small bowel irradiated in all 10 patients at doses above 30 Gy. At the prescription dose, the average volume of small bowel irradiated was reduced by a factor of two (17.4 vs. 33.8%, p = 0.0005). In addition, the average volume of rectum and bladder irradiated at the prescription dose was reduced by 23% in both cases (p = 0.0002 and p = 0.0005, respectively). The average PTV doses delivered by the conventional and IM-WPRT plans were 47.8 Gy and 47.4 Gy, respectively. Corresponding maximum doses were 50.0 Gy and 54.8 Gy, respectively. However, on average, only 3.2% of the PTV received greater than 50.0 Gy in the IM-WPRT plans. CONCLUSION: Our results suggest that IM-WPRT is an effective means of reducing the volume of small bowel irradiated in women with gynecologic malignancies receiving WPRT. This approach potentially offers a method for reducing small bowel complications in patients with gynecologic malignancies.

Endometrial Neoplasms↗
PubMed2000

One versus two intracavitary brachytherapy applications in early-stage cervical cancer patients undergoing definitive radiation therapy.

PURPOSE: The purpose of this study was to compare the outcomes of early stage cervical cancer patients undergoing definitive radiation therapy (RT) with one versus two low-dose-rate intracavitary brachytherapy (ICB) applications. METHODS AND MATERIALS: Between 1983 and 1993, 140 stage IB-IIA patients underwent whole-pelvis RT (WPRT) and ICB. Prior to 1988, 56 patients (40%) received two ICB applications. After 1988, our policy was modified and subsequently 84 (60%) patients underwent one application. Patient, tumor, and treatment characteristics, outcome, and complications of the two groups were compared. RESULTS: The groups were balanced in terms of race, hemoglobin level, histology, grade, treatment duration, chemotherapy, and follow-up. The single-application group, however, had more stage IB disease, had small (< or =4 cm) tumors, and received higher WPRT and lower point A doses. Overall, the two groups had similar 5-year local control (P = 0.83) and disease-free (P = 0.23) and cause-specific (P = 0.29) survival rates. Moreover, no differences were seen when analyzed by tumor size or stage. On multivariate analysis, the number of applications was not correlated with recurrence (P = 0.59, hazard rate = 1.1, 95% confidence interval = 0.6-2.2). Chronic complications were similar in the two groups. CONCLUSION: Our nonselected comparison of one versus two ICB applications in early-stage cervical cancer patients reveals comparable outcomes and complication rates for the two approaches. These results support the use of a single application in early-stage patients undergoing definitive RT.

Adult↗
PubMed2000

Age as a prognostic factor for recurrence in patients with endometrial carcinoma.

PURPOSE: The aim of this study was to evaluate age as a prognostic factor for recurrence in endometrial cancer patients treated with primary surgery. METHODS: Between 1983 and 1998, 455 endometrial cancer patients underwent primary surgery at our institution. Patients were divided into three age groups based on age at diagnosis: Group A (age <60, n = 156), B (age 60-69, n = 147), and C (age >/=70, n = 152). Clinicopathologic, treatment factors, and outcome were compared among the three groups. Prognostic factors were evaluated by univariate and multivariate analysis. RESULTS: The three age groups had a similar distribution of most pathologic features including stage, histology, cervical involvement, positive cytology, adnexal involvement, nodal metastases, serosal involvement, and lymphovascular invasion (LVI). Older women had a higher rate, however, of deep (>1/2) myometrial invasion (P < 0.0001) and grade 3 tumors (P < 0.0001). The extent of surgical staging and use of adjuvant radiation therapy were similar. Five-year disease-free survivals (DFS) of Groups A, B, and C were 74.3, 70.2, and 60.3%, respectively (P = 0.08). A significant difference in DFS was seen when Groups A and B were combined and compared with Group C (72.0 vs 60.3%, P = 0.03). Multivariate analysis confirmed the significance of race, stage, grade, and LVI. Age was not found to be associated with recurrence (HR 1.1, 95% C.I. 0.91-1.5, P = 0.21). CONCLUSION: Our results reveal that, in a large cohort of comparably staged and treated endometrial carcinoma patients, age is not a prognostic factor for recurrence.

Age Factors↗
PubMed2000

Improvement by the insulin-sensitizing agent, troglitazone, of abnormal fibrinolysis in type 2 diabetes mellitus.

This study evaluated abnormal fibrinolysis in diabetic patients in terms of the pathophysiological significance and reversibility by oral hypoglycemic agents. Forty-seven patients with type 2 diabetes mellitus were randomly treated for 4 weeks with glibenclamide (n = 23) or troglitazone (n = 24). Before and after treatment, glycemic control, steady-state plasma glucose and insulin (SSPG and SSPI, respectively), and markers of fibrinolysis (tissue plasminogen activator [tPA] and plasminogen activator inhibitor-1 [PAI-1]) were analyzed in each patient. Pretreatment plasma PAI-1 in diabetic patients, but not tPA, was well correlated with the severity of retinopathy assessed by the fluorescence technique. Four weeks of treatment with troglitazone significantly decreased hemoglobin A1c (HbA1c), SSPG, and PAI-1 without an alteration of tPA. The troglitazone-induced decrease in plasma PAI-1 (50.3 v28.8 micromol/L; P < .05) was correlated with HbA1c (8.80% v7.21%, r = .539, P < .01) and SSPG (16.2 v 8.97 mmol/L, r = .562, P < .01) but not with SSPI. In contrast, treatment with glibenclamide for 4 weeks also reduced the HbA1c titer to almost the same extent as troglitazone (1.38% v 1.59%), but did not change the plasma PAI-1 or SSPG titer. These results suggest that an abnormal fibrinolytic state, especially overproduction of PAI-1, may be a pathogenic factor in the development of diabetic complications such as retinopathy, which may be improved by correction of the insulin resistance with troglitazone.

Aged↗
PubMed1999

Nucleotide sequence of a cDNA encoding a common precursor of disintegrin flavostatin and hemorrhagic factor HR2a from the venom of Trimeresurus flavoviridis.

The venom of Trimeresurus flavoviridis has three disintegrins that act as platelet aggregation inhibitors by binding to integrin alphaIIb beta3 on platelets through its Arg-Gly-Asp sequence. We isolated the cDNA encoding the flavostatin precursor that is one of the disintegrins in T. flavoviridis venom. The open reading frame consisted of four regions, a pre-peptide region, a metalloprotease region, a spacer region and a disintegrin region, indicating that the flavostatin precursor belongs to the metalloprotease/disintegrin family. Surprisingly, the deduced amino acid sequence of the metalloprotease region was completely consistent with that of hemorrhagic metalloprotease HR2a, which indicated that this metalloprotease released from the flavostatin precursor functions as a hemorrhagic factor. These observations indicated that a disintegrin and a hemorrhagic metalloprotease were synthesized as a common precursor. Thus, our results support the hypothesis that a disintegrin is synthesized as a metalloprotease/disintegrin precursor and matures by cleavage from the precursor molecule.

Amino Acid Sequence↗
PubMed1999

CA-1 method, a novel assay for quantification of normal prothrombin using a Ca2+ -dependent prothrombin activator, carinactivase-1.

We established a novel prothrombin assay, designated CA-1 method, for quantification of normal prothrombin in application of a Ca2+ -dependent prothrombin activator, carinactivase-1 (CA-1), found in the venom of Echis carinatus leucogaster. On microplate, thrombin converted from normal prothrombin in plasma sample by CA-1 cleaves a thrombin specific chromogenic substrate, t-butoxy-Val-Pro-Arg-p-nitroanilide and liberates p-nitroaniline. Then, the normal prothrombin level is decided by measuring the velocity of p-nitroaniline liberation. Normal prothrombin levels in plasma from warfarin-treated individuals were highly correlated with coagulant activities assayed by both prothrombin time and thrombotest. CA-1 method is not only a rapid and highly sensitive chromogenic microplate assay for quantification of normal prothrombin in the range of 10-200 ng/100 microl in plasma samples but also suitable for analyses of many samples in a short time. In addition, normal prothrombin levels obtained by CA-1 method are not inhibited by EDTA and heparin, which reduce prothrombin time and thrombotest activities. CA-1 method is a novel assay for monitoring coagulant activity in warfarin-treated individuals.

Aniline Compounds↗
PubMed1999

Thiazolidinediones down-regulate plasminogen activator inhibitor type 1 expression in human vascular endothelial cells: A possible role for PPARgamma in endothelial function.

The effect of peroxisome proliferator-activated receptor (PPAR) gamma activators, thiazolidinediones, on plasminogen activator type 1 (PAI-1) was examined in cultured human umbilical vein endothelial cells (HUVEC). Tumor necrosis factor alpha (TNF-alpha) enhanced PAI-1 secretion and mRNA expression by approximately 2-fold. The thiazolidinediones, troglitazone and pioglitazone, decreased basal and TNF-alpha-stimulated PAI-1 secretion and mRNA expression in HUVEC in a dose-dependent fashion. PPARgamma mRNA in HUVEC could be detected by reverse transcriptase-polymerase chain reaction using specific primers. These results suggest that PPARgamma may regulate PAI-1 expression in HUVEC and that thiazolidinediones have a therapeutic potential for improving endothelial dysfunction observed in insulin resistance.

Base Sequence↗
PubMed1999

Magnetic Effect on Ion-Exchange Kinetics.

Effects of magnetic exposure on an ion-exchange process are investigated, employing ion-exchange resins. The electrolyte solution, resin suspension, and water are mixed in a container, and the mass transfer coefficient is determined by measuring the change of the ionic concentration in the bulk. Two methods of magnetic exposure are performed: case (1) in which only the electrolyte solution is exposed to the magnetic field and case (2) in which only the resin suspension is exposed to the magnetic field. The following features are found in both cases: (i) the film mass transfer rate reduces by about 5% when the exposure time is greater than 25 min, (ii) the magnetic effect is reduced by adding the alcohol, (iii) the magnetic effect remains for about 3 days but disappears after 6 days, and (iv) the magnetic effect is observable in the solutions of structure-disordering ions, but not in the solutions of structure-ordering ions. As for the temperature dependence, the magnetic effect decreases with temperature in case (1) but it stays constant in case (2). It is postulated that the magnetic effects are attributable to the stabilization of water molecules around the structure-ordering ion and those on the resin surface. Copyright 1999 Academic Press.

Journal Article↗
PubMed1997

Prothrombin and factor X activator activities in the venoms of Viperidae snakes.

A Ca(2+)-dependent prothrombin activator, carinactivase-1 (CA-1), was previously found in the venom of Echis carinatus leucogaster. In the present study, the activities of CA-1-like enzymes were screened in the venoms of various Viperidae snakes. The addition of 1 mM Ca2+ ions to the venoms of only Echis snakes in Viperidae produced considerably high prothrombin activator activity, indicating that only the Echis snake venoms contain not only the Ca(2+)-independent prothrombin activator, ecarin, but also Ca(2+)-dependent activator(s). CA-1-like activators and ecarin in the venom of each Echis snake were efficiently separated by Blue Sepharose column chromatography. The venoms of the various Viperidae snakes were also examined for factor X activator activity. The venoms of genera Daboia, Vipera, Cerastes, Echis, Calloselasma and Bothrops contained factor X activator activity in the presence of Ca2+ ions. Cerastes cerastes and Calloselasma rhodostoma venoms also had Ca(2+)-independent factor X activator activity.

Animals↗
PubMed1997

Purification and characterization of a Ca2+ -dependent prothrombin activator, multactivase, from the venom of Echis multisquamatus.

We previously found a novel Ca2+-dependent prothrombin activator, designated as carinactivase-1, in Echis carinatus leucogaster venom [D. Yamada, F. Sekiya, and T. Morita (1996) J. Biol. Chem. 271, 5200-5207]. Of the Viperidae snake venoms examined, the Echis multisquamatus venom had the strongest carinactivase-like activity. We isolated and characterized the carinactivase-like prothrombin activator in E. multisquamatus venom. From 50 mg of E. multisquamatus venom, we isolated 2.3 mg of a Ca2+-dependent prothrombin activator designated as multactivase. Unlike other Echis snake venoms, the E. multisquamatus venom contained no ecarin-like Ca2+-independent prothrombin activator. The structure and function of multactivase are similar to those of carinactivase. Multactivase is composed of a catalytic subunit with metalloprotease activity and a regulatory subunit comprising two homologous polypeptides bound by S-S bridge(s), and it activates prothrombin via recognition of the Ca2+-bound conformation of its Gla domain. We developed a chromogenic assay involving multactivase for normal prothrombin activity in plasma from individuals orally administered anticoagulants. The normal prothrombin activity, as a percentage, measured with multactivase was highly correlated with the prothrombin time. Multactivase is useful for the simple quantification of normal prothrombin in plasma from warfarin-treated individuals.

Amino Acid Sequence↗
PubMed1996

Isolation and characterization of carinactivase, a novel prothrombin activator in Echis carinatus venom with a unique catalytic mechanism.

The venom of the viper Echis carinatus contains a metalloprotease, ecarin, that is a potent prothrombin activator. We here show that the venom is also rich in another prothrombin activator, which does not belong to any known category of prothrombin activators. The novel enzyme, designated carinactivase-1 (CA-1), consists of two subunits held together non-covalently but very tightly. One subunit is a 62-kDa polypeptide that has metalloprotease activity and is homologous to the single-chain enzyme ecarin; the other subunit of 25 kDa consists of two disulfide-linked polypeptides of 17 and 14 kDa, and this subunit resembles the anticoagulant in the habu snake venom, IX/X-bp, that specifically binds the Gla domains of coagulation factors IX and X in a Ca2+-dependent fashion. The activation of prothrombin by CA-1 requires Ca2+ ions at millimolar concentrations and in the absence of Ca2+ ions this enzyme is virtually inactive. By contrast, activation by ecarin is completely independent of Ca2+ ions. CA-1, unlike ecarin, does not activate prothrombin derivatives, in which binding of Ca2+ ions has been perturbed, namely prethrombin-1 and acarboxyprothrombin. Furthermore, the isolated catalytic subunit, although its activity is greatly reduced as compared to that of the holoenzyme, no longer requires Ca2+ ions for the activation of prothrombin. Reconstitution with the non-catalytic 25-kDa subunit restores high level activity and the dependence on Ca2+ ions. Finally, prothrombin activation by CA-1 is inhibited by prothrombin fragment 1, and the isolated non-catalytic subunit is capable of binding fragment 1 in the presence of Ca2+ ions. From these observations, we postulate the following unique mechanism for the activation of prothrombin by CA-1. The enzyme primarily recognizes the Ca2+-bound conformation of the Gla domain in prothrombin via the 25-kDa regulatory subunit, and the subsequent conversion of prothrombin to active thrombin is catalyzed by the 62-kDa catalytic subunit.

Amino Acid Sequence↗