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T Morita

Publications and source records attributed to T Morita.

At least 73 records · Page 4Linked to original sources
PubMed2001

Preparation of gelatin microparticles by co-lyophilization with poly(ethylene glycol): characterization and application to entrapment into biodegradable microspheres.

Gelatin microparticles were prepared by co-lyophilization with poly(ethylene glycol) (PEG) as a protein micronization adjuvant. Aqueous solutions containing gelatin and PEG at various mixing ratios were freeze-dried. The lyophilizates were dispersed in methylene chloride and subjected to particle size analysis. The particle size decreased as the PEG/gelatin ratio increased. The microparticles isolated from the suspension had spherical microdomains with sizes ranging from 1 to 10 microm, which indicated that phase separation between PEG and gelatin during freezing was involved in the formation mechanism of gelatin microparticles. By using this technology, gelatin microparticles with an average size of less than 10 microm, with high purity of more than 90% and with good dispersibility could be obtained with high yield. The gelatin microparticles with average sizes from 5 to 20 microm were applied to encapsulation into biodegradable PLGA/PLA microspheres via a solid-in-oil-in-water emulsion process. The entrapment efficiency was highly dependent on the particle size and the size distribution, signifying that solid microparticles with an average diameter of less than 5 m and an maximal diameter of less than 10 microm would be required for effective encapsulation. These gelatin microparticles would be useful for studying and developing various drug delivery systems.

Biodegradation, Environmental↗
PubMed2001

Enhancement of sensitivity to capecitabine in human renal carcinoma cells transfected with thymidine phosphorylase cDNA.

The purpose of the present study was to examine directly the role of thymidine phosphorylase (TP) in the sensitivity of renal cell carcinoma (RCC) to a novel fluoropyrimidine carbamate, capecitabine. TP cDNA-transfected RCC are used in these experiments to provide a basis for improved therapeutic benefit in chemoimmunotherapy. Human RCC line KU2 cells were transfected with pcDNA3.1/zeo(+) with or without human TP cDNA by the lipofectin method. We established a clone transfected with pcDNA3.1/zeo(+)/TP (KU2-TP15) and a clone transfected with pcDNA3.1/zeo(+) as a control (KU2-C1). TP expression levels (mean +/- SD) examined by enzyme-linked immunosorbent assay (ELISA) were 1.3 +/- 0.14 U/mg protein in KU2, 1.6 +/- 0.57 U/mg protein in KU2-C1 and 216 +/- 25.6 U/mg protein in KU2-TP15. Immunohistochemical staining of subcutaneous tumors established in Balb/c nu/nu mice showed that KU2-TP15 was strongly positive for TP expression, whereas KU2 and KU2-C1 were negative. Sensitivities in vitro to 5-fluorouracil (5FU), 5'-deoxy-5-fluorouridine (5'DFUR) and capecitabine in KU2-TP15 were significantly enhanced compared with those in KU2 or KU2-C1. A moderate but statistically significant bystander effect was observed in vitro. KU2-TP15 tumors showed significant increase in the in vivo sensitivities to 5'DFUR and capecitabine as compared with the vehicle alone while KU2-C1 tumors did not. The difference in tumor-free rate in mice bearing KU2-TP15 at 2 months after the cessation of treatment was statistically significant between the capecitabine treatment group and the controls, the 5FU treatment group and the 5'DFUR treatment group. The present study clearly provides direct evidence for the role of TP in mediating the sensitivity of RCC to capecitabine.

Animals↗
PubMed2001

Rhodocytin induces platelet aggregation by interacting with glycoprotein Ia/IIa (GPIa/IIa, Integrin alpha 2beta 1). Involvement of GPIa/IIa-associated src and protein tyrosine phosphorylation.

Although glycoprotein Ia/IIa (GPIa/IIa, integrin alpha(2)beta(1)) has established its role as a collagen receptor, it remains unclear whether GPIa/IIa mediates activation signals. In this study, we show that rhodocytin, purified from the Calloselasma rhodostoma venom, induces platelet aggregation, which can be blocked by anti-GPIa monoclonal antibodies. Studies with rhodocytin-coupled beads and liposomes loaded with recombinant GPIa/IIa demonstrated that rhodocytin directly binds to GPIa/IIa independently of divalent cations. In vitro kinase assays and Western blotting of GPIa immunoprecipitates revealed that Src and Lyn constitutively associate with GPIa/IIa and that Src activity increases transiently after rhodocytin stimulation. Src specifically associates with p130 Crk-associated substrate (Cas) in a manner dependent upon Cas phosphorylation, suggesting that Src is responsible for Cas tyrosine phosphorylation. While all these phenomena occur early after rhodocytin stimulation in a cAMP-resistant manner, tyrosine phosphorylation of Syk and phospholipase Cgamma2, intracellular Ca(2+) mobilization, and platelet aggregation occur later in a cAMP-sensitive manner. Cytochalasin D, which interferes with actin polymerization and blocks receptor clustering, inhibits all the rhodocytin-mediated signals we examined in this study. We suggest that rhodocytin, by clustering GPIa/IIa, activates GPIa/IIa-associated Src, which then mediates downstream activation signals.

Animals↗
PubMed2001

Clinical and pathologic findings in 52 consecutively autopsied cases with multiple myeloma.

We studied clinical features and pathologic findings in 52 consecutively autopsied patients with multiple myeloma in our center between 1979 and 1998. Distant extraosseous involvement was found in 33 patients (63.5%). Thirty-one patients (59.6%) were proven to have infection at autopsy, among which pneumonia was most common site of infection. Amyloidosis was shown in 8 patients. Second malignancies were observed in 4 cases. The three major causes of death were hemorrhage, infection, and renal failure, which accounted for death in approximately 70% of the patients. Advances in the anticancer and antimicrobial chemotherapies might have decreased deaths due to myeloma itself or infection.

Aged↗
PubMed2001

Evaluation of the rodent micronucleus assay by a 28-day treatment protocol: Summary of the 13th Collaborative Study by the Collaborative Study Group for the Micronucleus Test (CSGMT)/Environmental Mutagen Society of Japan (JEMS)-Mammalian Mutagenicity Study Group (MMS).

To examine whether micronucleus tests can be incorporated into general toxicology assays, we performed micronucleus tests applying the treatment protocols typically used in such assays. In this 13th Collaborative Study of the CSGMT, both rats and mice were tested, although rats were used in the majority of the studies. Fifteen mutagens were tested in rats, mainly by oral (p.o.) administration. Micronucleus induction was evaluated 2, 3, and 4 days, and 1, 2, 3, and 28 days after the beginning of the treatment in the peripheral blood, and at 28 days in the bone marrow. Of the 15 chemicals that induced micronuclei in rats in short-term assays, two chemicals (1,2-dimethylhydrazine.2HCl and mitomycin C) were negative in all our experiments, possibly because of insufficient dose levels. The remaining 13 were positive within the estimated dose range of a general toxicology assay, suggesting the possibility of integrating the micronucleus assay into general toxicology assays. Three patterns were observed in micronucleus induction during the period of repeated treatment: (1) gradual increases in micronucleus frequency with sequential doses, (2) a peak at 3-5 days followed by gradual decreases in micronucleus frequency with sequential doses, and (3) a rapid increase in micronucleus frequency followed by a plateau. We evaluated factors that might have been involved in those patterns, such as the spleen function, target organ exposure, extramedullary hematopoiesis, hypothermia, and hypoxia. Another factor we considered was dosage. Because the dosages employed in a general toxicity assay are usually lower than those used in short-term micronucleus assays, this discrepancy was considered the greatest potential problem for integrating the micronucleus assay into general toxicology assays. Our results indicate that the integration of the micronucleus assay into a 28-day toxicological assay is feasible. To serve this purpose, blood samples collected 4 days after the beginning of treatment and blood and bone marrow samples collected at autopsy should be examined. Furthermore, although it is recognized that mice may be suitable for performing independent micronucleus assays, we propose that rats can provide biologically important and relevant information regarding potential chemical mutagens that can be evaluated under conditions used in the conduct of general toxicology studies.

Animals↗
PubMed2001

Intracellular calcium level required for calpain activation in a single myocardial cell.

We have hypothesized that calpain mediates myocardial injury induced by Ca(2+)overload. However, in vitro study demonstrated that the calcium requirement for calpain activation is around 10 microm, which is difficult to reach without the cell collapsing. Furthermore, because calpastatin is abundant in the myocardial cell, calpain may not be activated in physiological conditions. To elucidate whether calpain is activated by the calcium concentration reachable in myocardial living cells, we measured the calpain activity and the calcium concentration simultaneously in isolated guinea-pig cardiomyocytes. t-Butoxycarbonyl-Leu-Met-7-amino-4chlorimethylcoumarin (Boc-Leu-Met-CMAC), a fluorescent substrate of calpain, and/or fura red, a calcium indicator, were loaded into isolated cardiomyocytes together, and their fluorescence were measured separately. Intracellular Ca overload was induced by changing the superfusate from normal Tyrode solution to a sodium-free one. After changing the solution, fluorescence intensity of fura red and Boc-Leu-Met-CMAC did not change for a while, then fluorescence intensity of fura red began to rise. This was followed by the fluorescence intensity of Boc-Leu-Met-CMAC starting to rise 160+/-45 s after [Ca(2+)](i)increase. The relative fluorescence intensity of fura red increased to 1.37+/-0.32 folds of the control at the point that calpain became active. The calcium concentration at this point was estimated as 451 n m. These results indicate that calpain is activated by the slight rise of Ca concentration in intact cardiomyocytes.

Animals↗
PubMed2001

Antitumor immunity induced by irradiated tumor cells producing macrophage colony-stimulating factor.

We previously reported that administration into mice of mouse lymphoid leukemia L1210 cells engineered to secrete macrophage colony-stimulating factor (M-CSF) could lead to tumor rejection. Here, we demonstrate that inoculation with irradiated M-CSF-producing cells protects mice against a subsequent challenge with unmodified parental tumor cells. We used 2 experimental protocols: the inoculation with irradiated M-CSF-producing L1210 cells (EM5) before the challenge with parental cells and after the challenge with parental cells. Both protocols effectively improved the survival rate of mice compared with protocols in which irradiated non-M-CSF-producing L1210 cells (EM-mock) were inoculated. Inoculation with 1 x 10(2) irradiated EM5 cells was sufficient to prolong the survival time of mice subsequently challenged with 1 x 10(4) parental cells. In vivo depletion experiments with administration of antibodies suggested the involvement of CD4+ T cells, CD8+ T cells, and natural killer (NK) cells in the antitumor effect. Consistent with these findings, the cytotoxic T lymphocyte activity of splenocytes from EM5-inoculated mice was higher than that from EM-mock-inoculated mice, and L1210 tumors were heavily infiltrated by CD4+ T cells and NK cells as well as macrophages in EM5-inoculated mice.

Animals↗
PubMed2001

Electroconvulsive therapy impairs systolic performance of the left ventricle.

PURPOSE: In this observational study, we examined left ventricular systolic performance during electroconvulsive therapy (ECT), using an echocardiographic automated border detection system. METHODS: Nine ASA I or II patients scheduled for ECT were studied. Bilateral ECT was performed after the administration of propofol 1 mg x kg(-1), succinylcholine 1 mg x kg(-1), and assisted mask ventilation with 100% oxygen. Cardiac function was monitored by transthoracic echocardiography, prior to anesthesia induction and throughout the ECT procedure until ten minutes after the seizure. RESULTS: Increased end-systolic area and decreased fractional area change were observed at one minute after the seizure compared to the awake condition. No regional wall motion abnormalities were observed in all patients both at baseline condition and during the ECT CONCLUSION: Systolic performance of the left ventricle estimated by echocardiography decreased transiently in the immediate period after the electric shock.

Adult↗
PubMed2001

Hepatosplanchnic oxygenation is better preserved during mild hypothermic than during normothermic cardiopulmonary bypass.

PURPOSE: To assess and compare the effects of normothermic and mild hypothermic cardiopulmonary bypass (CPB) on hepatosplanchnic oxygenation. METHODS: We studied 14 patients scheduled for elective coronary artery bypass graft surgery who underwent normothermic (>35 degrees C; group I, n=7) or mild hypothermic (32 degrees C; group II, n=7) CPB. After induction of anesthesia, a hepatic venous catheter was inserted into the right hepatic vein to monitor hepatic venous oxygen saturation (ShvO(2)) and hepatosplanchnic blood flow by a constant infusion technique that uses indocyanine green. RESULTS: The ShvO(2) decreased from a baseline value in both groups during CPB and was significantly lower at ten minutes and 60 min after the onset of CPB in group I (39.5 +/- 16.2% and 40.1 +/- 9.8%, respectively) than in group II (61.1 +/- 16.2% and 61.0 +/- 17.9%, respectively; P <0.05). During CPB, the hepatosplanchnic oxygen extraction ratio was significantly higher in group I than in group II (44.0 +/- 7.2% vs 28.7 +/- 13.1%; P <0.05). CONCLUSION: Hepatosplanchnic oxygenation was better preserved during mild hypothermic CPB than during normothermic CPB.

Cardiopulmonary Bypass↗
PubMed2001

Perioperative management of biventricular failure after closure of a long-standing massive arteriovenous fistula.

PURPOSE: To report the perioperative management of arteriovenous fistula (AVF) closure in a patient with high-output heart failure and pulmonary hypertension. CLINICAL FEATURES: In a 71-yr-old man, closure of a long-standing massive AVF between the right femoral artery and vein was performed. After closure of the AVF, his pulmonary artery pressure (PAP) increased from 52/21 mmHg to 68/26 mmHg, his cardiac index decreased from 5.27 L.min(-1).m(-2) to 3.18 L.min(-1).m(-2), and his pulmonary wedge pressure increased from 15 mmHg to 32 mmHg due to an acute increase in afterload. Co-administration of prostaglandin E and a phosphodiesterase III inhibitor improved the cardiac index and the PAP. CONCLUSIONS: Surgical closure of the fistula may not always lead to resolution of the high output cardiac failure. In this case, afterload management using arterial dilators (prostaglandin E1, phosphodiesterase III inhibitor), use of inotropic drugs (phosphodiesterase III inhibitor), and close attention to volume status was crucial for a successful outcome after surgical AVF closure.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

Comparison of the kinetic disposition of and serum gastrin change by lansoprazole versus rabeprazole during an 8-day dosing scheme in relation to CYP2C19 polymorphism.

BACKGROUND: Little is known about differences in the disposition kinetics and pharmacological effects on gastrin levels between lansoprazole and rabeprazole given in a repeated dosing scheme with respect to the polymorphic CYP2C19. AIM: To provide preliminary information that should be considered when prescribing proton-pump inhibitors (PPIs) for the treatment of acid-related diseases with reference to the CYP2C/9 genotypic status. METHODS: Helicobacter pylori-negative healthy volunteers were divided into the following three groups (n = 5 each) on the basis of genotyping for CYP2C19: homozygous (hmEMs) and heterozygous extensive metabolizers (htEMs), and poor metabolizers (PMs). All received once-daily 30-mg doses of lansoprazole or 10-mg doses of rabeprazole during an 8-day course in a crossover manner. RESULTS: The relative values for the area under the serum concentration-time curve (AUC) of lansoprazole and rabeprazole in the hmEMs, htEMs, and PMs after the final doses were 1:1.7:3.9 and 1:1.7:3.8, respectively. The relative AUCs of gastrin in the hmEMs, htEMs, and PMs were 1.6:2.6:3.1 for lansoprazole and 1.6:2.6:2.9 for rabeprazole, respectively. CONCLUSION: The disposition kinetic behavior of the two PPIs is co-segregated with CYP2C19. The magnitude of CYP2C19-dependent drug availability in the systemic circulation and resulting gastrin response appears to be fairly similar between the two drugs within the same CYP2C19 genotypic groups after a multiple-dosing regimen.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Thymidine phosphorylase/platelet-derived endothelial cell growth factor (PD-ECGF) associated with prognosis in renal cell carcinoma.

We investigated the correlation between thymidine phosphorylase (TP)/platelet-derived endothelial cell growth factor (PD-ECGF) expression, angiogenesis, and prognosis in renal cell carcinoma (RCC) patients. We prepared paraffin block specimens from 56 postradical nephrectomy RCC patients. The preparations were immunohistochemically stained using anti-CD34 antibody and anti-TP antibody. Angiogenic findings were evaluated based on both microvessel density (MVD) and renal arteriography findings as classified by Roosen et al. TP expression showed heterogeneity in 56 patients: 11 (19.6%) were negative, 28 (50.0%) weak, and 17 (30.4%) positive. There was no correlation between TP expression, MVD, and renal arteriography. There was no TP expression in chromophobe types. Univariate analysis showed a significant correlation between survival and TP expression, patient age, tumor infiltration type, pathologic T- and N-stages, venous involvement, distant metastasis, and tumor grade. There was no correlation between survival and MVD or renal arteriography. Multivariate analysis showed a significant correlation between survival and pathologic T-stage, distant metastasis, tumor infiltration type, and TP expression. TP expression in RCC may be an independent prognostic factor rather than just an index for angiogenesis.

Adult↗
PubMed2001

Determinants of the sensation of thirst in terminally ill cancer patients.

While a sensation of thirst causes severe distress for a certain proportion of cancer patients in the terminal stage, the factors contributing to this symptom have not been established. To clarify the association between sensation of thirst and medical factors, especially dehydration, a cross-sectional observational study was performed on terminally ill cancer patients receiving inpatient hospice care. On admission to a palliative care unit, 88 consecutive patients underwent blood sampling and were requested to rate the intensity of thirst on a visual analogue scale (VAS). Physicians prospectively evaluated factors that might potentially be contributing to the symptom. The mean VAS score for thirst was 5.0+/-2.8, and 18% of the patients complained of severe thirst with a VAS score of > or = 8. No significant correlations were observed between the VAS score for thirst and the values of total protein, blood urea nitrogen (BUN), creatinine, sodium, osmolality, hematocrit, atrial natriuretic peptide (ANP), and biochemical dehydration defined by the levels of BUN, creatinine, sodium and osmolality. On the other hand, dehydration defined by ANP level (< or = 15 pg/ml), hyperosmolality (> or = 300 mosmol/kg), gastrointestinal cancer, survival, performance status, oral intake, vomiting, and stomatitis were significantly associated with the severity of thirst. In addition, mouth breathing and opioids were determined to be a potential clinical cause of severe thirst when a retrospective chart review was carried out. In conclusion, sensation of thirst is a frequent symptom in terminally ill cancer patients and is associated with dehydration, hyperosmolality, poor general conditions, stomatitis, oral breathing, and opioids. Careful assessments and treatment of underlying causes is important to alleviate patients' distress.

Aged↗
PubMed2001

Transgenic medaka overexpressing a melanin-concentrating hormone exhibit lightened body color but no remarkable abnormality.

Melanin-concentrating hormone (MCH) is a cyclic heptadecapeptide that concentrates melanin granules in the melanophores and lightens the body color of a fish. To investigate the utility of MCH as a reporter gene, a transgenic medaka strain overexpressing the MCH gene was established and its phenotypic features were examined. The salmon MCH gene driven by cytomegalovirus promoter was injected into 100 fertilized eggs of the HNI-1 medaka strain, which exhibits black body color. One F(0) female transmitted the transgene and a lightened body color phenotype to the F(1) generation. A homozygous transgenic strain was established by crossing F(2) fish homozygous for the transgene. Expression of the transgene was detected in several organs by Northern blotting. The melanin granules of transgenics were highly shrunk. Bioassay using scales confirmed the secretion of MCH into blood, and the MCH concentration was estimated between 0.5 and 5 microM. Development, growth, feeding behavior, and reproduction of transgenics did not differ significantly among transgenic and nontransgenic siblings. The result whereby enhanced MCH expression induced a change in body color, but no remarkable abnormality, suggests the usefulness of MCH as a novel reporter gene with unique features.

Journal Article↗
PubMed2001

Atlantoaxial subluxation in an adult secondary to retropharyngeal abscess.

Atlantoaxial subluxation secondary to a retropharyngeal abscess is well described in children, but very rare in adults. Only two adult cases have been reported in the literature. We present a case of severe atlantoaxial subluxation in an adult secondary to retropharyngeal abscess. His atlas-dens interval was very large, up to 10 mm in flexion. We tried external fixation with a neck collar initially, but for remaining instability, surgical fusion was performed. The mechanism of subluxation is attributed to softening of the ligament allowing greater mobility at the joint. The etiology of this process is speculative.

Atlanto-Axial Joint↗
PubMed2001

Effects of high dose opioids and sedatives on survival in terminally ill cancer patients.

Concerns that high dose opioids and sedatives might shorten patient survival could contribute to insufficient symptom alleviation for terminally ill cancer patients. To examine the effects of opioids and sedatives prescribed in the final 48 hours on patient survival, a re-analysis of the prospectively collected data was performed on 209 hospice inpatients. Patient characteristics and clinical symptoms were prospectively recorded, and information about the use of opioids and sedatives in the last two days was collected by a chart review. Opioids were prescribed in 82% of the patients, with a median dose of 80 mg oral morphine equivalent (OME)/48 hours. Sixty percent received some sedative medications, mainly haloperidol (43% of total sample, 7.5 mg/48 hours), midazolam (23%, 23mg/48 hours), and hydroxyzine (15%, 50 mg/48 hours). There were no significant differences in survival between the patients who received different doses of opioids (<240, 240--599, and > or =600 mg OME/48 hours) and of benzodiazepines (0, 1--59, and > or =60 mg parental midazolam equivalent/48 hours). Also, the survival of patients with haloperidol, hydroxyzine, and other sedative medications did not differ from those without. Furthermore, an addition of use of opioids and sedatives in the final 48 hours into the multiple regression model for survival prediction achieved no significant increase in predictability. In conclusion, opioids and sedatives used for symptom control in the last days are not associated with patient survival. They are safe and useful medications to palliate severe distress in the terminal stage of cancer when administered with a low initial dosage and adequate titration.

Aged↗
PubMed2001

Underlying pathologies and their associations with clinical features in terminal delirium of cancer patients.

Delirium is a common complication in terminally ill cancer patients. Identification of underlying pathologies and prediction of clinical features may improve effective symptom alleviation. This study aims to clarify precipitating factors and their associations with clinical features of terminal delirium. Consecutive hospice inpatients who developed delirium were prospectively evaluated following a structured protocol. Among 237 patients followed until death, 245 episodes of delirium were identified in 213 patients. Precipitating factors for delirium were disclosed in 93% of the 153 cases in which investigations were completed. Mean number of etiologies was 1.8 +/- 1.1 per patient, and two or more factors were recognized in 52%. The main pathologies identified were hepatic failure, medications, prerenal azotemia, hyperosmolality, hypoxia, disseminated intravascular coagulation, organic damage to the central nervous system, infection, and hypercalcemia. Occurrence of hyperactive delirium and the requirement for symptomatic sedation significantly correlated with hepatic failure, opioids, and steroids, while dehydration-related pathologies were significantly associated with hypoactive delirium. Complete recovery was frequently achieved in cases with medication- and hypercalcemia-induced delirium, whereas a low remission rate was related to hepatic failure, dehydration, hypoxia, and disseminated intravascular coagulation. In conclusion, standard examinations can confirm factors potentially contributing to delirium and thereby predict the severity of agitation and clinical outcomes.

Aged↗