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T Tamura

Publications and source records attributed to T Tamura.

At least 577 records · Page 32Linked to original sources
PubMed1995

Synthesis and structure-activity studies of a series of 1-oxa-8-azaspiro[4.5]decanes as M1 muscarinic agonists.

2,8-Dimethyl-1-oxa-8-azaspiro[4,5]decan-3-one (17), designed by incorporating the tetrahydrofuran ring moiety of muscarone into an 8-azaspiro[4,5]decane skeleton, and related 1-oxa-8-azaspiro[4.5]decanes were synthesized and assessed as M1 muscarinic agonists for the symptomatic treatment of dementia of Alzheimer's type. The compounds were tested for central muscarinic M1 and M2 receptor affinity and in vivo muscarinic activities: namely, amelioration of scopolamine-induced impairment in rat passive avoidance tasks, and induction of hypothermia, tremor, and salivary secretion. Compound 17 exhibited potent muscarinic activities in vitro and in vivo with no selectivity. Systematic modifications of 17 were conducted, and a number of compounds, including the 2-ethyl analogue (18), 3-methylene analogue (29), 3-dithioketal analogues (26, 28), and 3-oxime analogue (37) were found to display preferential affinity for M1 receptors over M2 receptors and, in addition, to exhibit potent antiamnesic activity sufficiently separated from hypothermia-inducing activity, taken as an index of cholinergic side effects, compared with the reference compound RS86 (1). Structure-activity relationships are discussed in comparison with those for muscarone analogues. Of these compounds only two, 2-ethyl-8-methyl-1-oxa-8-azaspiro[4.5]decan-3-one (18) and 2,8-dimethyl-3-methylene-1-oxa-8-azaspiro[4.5]decane (29), stimulated phosphoinositide hydrolysis in rat hippocampal slices, indicating partial agonistic activity for M1 muscarinic receptors. The optical resolution of 18 and 29 was performed. Eudismic ratios of both compounds in binding affinity were low, but M1 agonist activity resided preferentially in the (-)-isomers. The absolute configuration of (-)-29 was determined by X-ray crystal structure analysis to be S, being the same as that of muscarone. Based on the in vivo selectivity, (-)-29 was selected for clinical studies.

Alkanes↗
PubMed1995

Short-term outcome and long-term follow-up of percutaneous coronary intervention in patients aged 40 years or younger.

Forty five patients aged 40 years or younger were treated with coronary intervention in our institution between 1983 and 1994. This young Japanese population had a strong predisposition to risk factors but did not have extensive disease. These patients underwent 50 elective interventional procedures for angina pectoris or old myocardial infarction and 6 direct balloon angioplasty procedures for acute myocardial infarction. The initial successful result was obtained in 41 of the 45 patients (91%). The mean follow-up was 43 +/- 35 months. Angiographic follow-up was available in 31 of the 41 eligible patients (76%). Angiographic restenosis was seen in 9 of these 31 patients (29%), and in 12 of the 38 lesions (32%) with initial successful intervention. There were no deaths among the successfully treated patients. Event-free survival rate without death, myocardial infarction, or coronary artery bypass surgery was 94%; however, event-free survival rate without death, myocardial infarction, coronary artery bypass surgery, or repeat intervention was 66% at 43 months. Ninety three percent of the eligible patients were free from angina at follow-up. These short- and long-term results suggest that young Japanese patients can be treated safely and effectively with coronary interventions.

Adult↗
PubMed1995

Gene expression of liver-specific proteins in hepatocyte spheroids in primary culture.

Adult rat hepatocytes assemble to form multicellular spheroids under non-adherent environments such as immobilized chondroitin sulfate-proteoglycan in primary culture. Previously, we demonstrated that hepatocyte spheroids exhibited various differentiated structures as observed in the liver tissue. It was also shown that hepatocyte growth was highly suppressed and several differentiated functions, including albumin production and gluconeogenesis, were well preserved in spheroids. To investigate the differentiated functions of cultured hepatocytes in relation to cell morphology, we compared the expression of the albumin and transferrin genes in spheroids with those in monolayers by Northern blot analysis. Production of these proteins in the culture medium was simultaneously examined by ELISA. Gene expression and protein production of both albumin and transferrin were better preserved in spheroids. We also examined changes in the expression of liver-specific genes in response to IL-6. Reduced mRNA levels of both albumin and transferrin was only found in spheroids and no change was observed in monolayers. These results suggest that the regulation of tissue-specific gene expression is better preserved in spheroids, in which hepatocytes are in close contact with each other.

Albumins↗
PubMed1995

Chronic lymphocytic leukemia associated with nephrotic syndrome and dermatomyositis.

Several types of autoimmune complications of chronic lymphocytic leukemia (CLL) have been previously reported. However, the tendency to develop autoantibodies is usually restricted to the hematopoietic system. We report a 68-year-old man who had developed dermatomyositis after ten years of chemotherapy for CLL. He also had secondary nephrotic syndrome at the onset of CLL. Subsequently, the patient died of perforation of the small intestine. The association of both nephrotic syndrome and dermatomyositis with CLL is very rare. We discuss the possibility of a casual relation.

Aged↗
PubMed1995

Effects of luteinizing hormone and follicle-stimulating hormone on the progesterone receptor induction in chicken granulosa cells in vivo.

Progesterone receptor (PR) is increased in the granulosa cells prior to ovulation. In order to investigate the factors that induce PR in granulosa cells, we examined whether the PR is induced in granulosa cells by the injection of chickens with ovine luteinizing hormone (oLH) or porcine follicle-stimulating hormone (pFSH) by Western blot analysis. In the oLH-stimulated birds, PR of 79 kDa and 110 kDa were recognized in the granulosa cells of the largest follicle, whereas a PR of 110 kDa was observed in those of the smaller follicles (the second and third largest follicles). No immunoreaction product was observed in the granulosa cells of both the largest and the smaller follicles in pFSH-stimulated birds. In the control birds that were injected with saline, no immunoprecipitate was recognized in the granulosa cells of the largest or smaller follicles. These results suggest that LH may be involved in the induction of PR in the granulosa cells prior to ovulation.

Animals↗
PubMed1995

Intensive chemotherapy with cisplatin, doxorubicin, cyclophosphamide, etoposide and granulocyte colony-stimulating factor for advanced thymoma or thymic cancer: preliminary results.

A study was conducted to evaluate the impact of cisplatin, doxorubicin, cyclophosphamide and etoposide (PACE) with granulocyte colony-stimulating factor (G-CSF) on advanced thymoma or thymic cancer. Between August 1989 and December 1994, 14 patients with invasive, metastatic or recurrent thymoma or thymic cancer were treated with cisplatin (80 mg/m2, on day 1), doxorubicin (45 mg/m2, on day 1), cyclophosphamide (800 mg/m2, on day 1) and etoposide (80 mg/m2, on day 1-3) with G-CSF (90 micrograms/m2, on day 5-18) at the National Cancer Center Hospital, Tokyo. Courses were repeated every 3 or 4 weeks for a maximum of 4 cycles. Twelve patients were treated with 2 or more courses of PACE. Two patients were treated with only one course, one refused and another required emergency thoracic radiotherapy after one course of PACE. Six patients had partial responses (3 thymomas and 3 thymic cancers) but there were no complete remissions (response rates, 42.9%; 95% confidence interval, 17.7% to 71.1%). Moderate hematological toxicities were observed: grade 3 or 4 leukopenia, neutropenia, anemia and thrombocytopenia in 10, 13, 8 and 6 patients, respectively. Six patients developed infections that required antibiotics. Surgical resection or thoracic radiotherapy after PACE treatment was performed in 2 and 7 patients, respectively. The overall median survival time was 14.7 months (range, 5.9 to 59.7 months). For 9 patients who had received no prior treatment before chemotherapy, the median survival time was 8.9 months, and one patient survived for 4 years and is still alive. In conclusion, PACE with G-CSF frequently produces objective remissions in patients with advanced thymoma or thymic cancer. A large-scale intergroup study is necessary to determine the impact of this regimen on advanced thymoma and thymic cancer.

Adult↗
PubMed1995

Effects of parathyroidectomy on left ventricular mass in patients with hyperparathyroidism.

The effects of parathyroidectomy on left ventricular muscle volume and mechanical performance were evaluated echocardiographically in 24 patients with secondary hyperparathyroidism due to chronic renal failure and in 7 with primary hyperparathyroidism. Intraventricular septum and posterior wall thickness, left ventricular end-diastolic diameters, shortening fraction, ejection fraction, and left ventricular mass index were measured by M mode recording by the parasternal short axis view prior to parathyroidectomy as baseline and repeated 12 months after parathyroidectomy. Serum basal carboxyterminal parathyroid hormone levels in patients with secondary hyperparathyroidism (34.4 +/- 13.7 ng/ml) were significantly higher than in those with primary hyperparathyroidism (3.4 +/- 5.1 ng/ml; p < 0.0001). At 12 months after parathyroidectomy, intraventricular septum and posterior wall thickness, left ventricular end-diastolic diameter and left ventricular mass index were reduced from 11.8 +/- 3.1 mm, 10.9 +/- 1.7 mm, 53.8 +/- 6.3 mm, 200.8 +/- 57.1 g/m2 to 10.0 +/- 2.1 mm (p < 0.05), 9.8 +/- 1.9 mm (p < 0.05), 50.7 +/- 7.2 mm (p < 0.05), 149.6 +/- 38.7 g/m2 (p < 0.0001), in patients with secondary hyperparathyroidism. In patients with primary hyperparathyroidism, all echocardiographic parameters remained in the normal range and did not show any significant changes before or after parathyroidectomy. From this study, parathyroid hormone at extremely high concentrations as seen in secondary hyperparathyroidism appears to be a cardiotoxic substance. Therefore, all patients with secondary hyperthyroidism should be examined by echocardiography and parathyroidectomy should be considered if myocardial hypertrophy is present.

Adult↗
PubMed1995

[Videofluorographic analysis of the swallowing disorders in spinocerebellar degeneration].

Clinical and videofluorographic (VF) studies of swallowing were performed in 11 patients with spinocerebellar degeneration (SCD). Eight patients had a subjective symptom of dysphagia. In VF study, seven patients represented abnormal findings in an oral phase such as residue on the tongue (2 patients), reduced tongue control (3 patients), uncontrolled bolus or premature loss of liquid (6 patients), and piecemeal deglutition (4 patients). Seven patients showed abnormality in a pharyngeal phase such as vallecular residue after swallow (5 patients), residue in pyriform sinuses after swallow (4 patients), delayed onset of laryngeal elevation (5 patients), and aspiration during swallow (5 patients). Aspiration was more obvious when barium liquid was swallowed. When the patients aspirated, techniques such as the chin down posture and the supraglottic swallow were tried in 4 of the 5 patients with the evidence of aspiration. The aspiration was prevented in 2 patients. It was suggested that in SCD the change in the form and volume of food is recommended for prevention of aspiration and that the rehabilitation techniques such as the chin down posture and the supraglottic swallow may also improve the dysphagia.

Adult↗
PubMed1995

Divergent structural requirements exist for calcitonin receptor binding specificity and adenylate cyclase activation.

The basis of the high potency of salmon calcitonin (sCT) in radioligand binding competition and cAMP accumulation studies with cloned calcitonin (CT) receptors from rats, pigs, and humans was examined using two sets of CT analogues, i.e., chimeric sCT/human CT (hCT) analogues and analogues of sCT with differing capacities to form an amphipathic alpha-helix. In competition for 125I-sCT binding the following relative specificities were observed for the chimeric peptides: rat C1a CT receptor, sCT > or = (1-16)hCT/(17-32)sCT (ACT-15) > (1-16)sCT/(17-32)hCT (ACT-27); rat C1b CT receptor, sCT >> ACT-15 > ACT-27; hCT receptor, sCT = ACT-15 > ACT-27; porcine CT receptor, sCT > ACT-27 > ACT-15. In contrast, in ligand-induced cAMP accumulation studies the relative efficacies were as follows: rat C1a CT receptor, sCT = ACT-15 > ACT-27; rat C1b CT receptor, sCT = ACT-15 > ACT-27; hCT receptor, sCT = ACT-15 > or = to ACT-27; porcine CT receptor, sCT = ACT-15 = ACT-27. The data demonstrate that residues present in the carboxyl-terminal half of sCT are more important for binding competition with the rat C1a, rat C1b, and human CT receptors, whereas residues in the amino-terminal half of sCT are more important for binding competition with the porcine CT receptor. Carboxyl-terminal sCT residues are also important for full potency in adenylate cyclase activation with the rat C1a and rat C1b CT receptors but are less important for activation via the hCT receptor. The disparity in the relative potencies of the peptides in studies of binding competition and cAMP accumulation is suggestive of significant differences in the relative affinities of the peptides for active and inactive conformations of the CT receptor. The use of sCT analogues with varying capacities to form alpha-helices also revealed divergence in the responses of different receptors. This was most apparent for the stimulation of cAMP production by the rat receptor isoforms C1a and C1b. In cells expressing the C1a receptor, the helical analogues sCT and des-Ser2-sCT were equipotent with [Gly8]-des-Leu19-sCT and des-1-amino-[Ala1,7,Gly8]-des-Leu19 sCT, analogues that have reduced or absent helical structure, respectively. In contrast, the nonhelical analogues were 100-1000-fold less potent than sCT and des-Ser2-sCT at the C1b receptor. In general, reduction in the ability of sCT analogues to form helix structures had a greater impact on the potency of the analogues in competition for 125I-sCT binding than in cAMP accumulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenylyl Cyclases↗
PubMed1995

[Regulation of gene expression and recent advance on transcription studies].

Gene expression is governed by multiple cellular processes including transcription, splicing, and translation. Among them, transcriptional regulation is the main regulatory mechanism. Transcription process can be divided into pre-initiation, initiation, elongation and termination, and transcriptional regulation is especially governed through the pre-initiation step. Eukaryotic RNA polymerase alone is not able to initiate specific transcription, but general transcription factors (GTFs) is required for this reaction. In pre-initiation step, many GTFs and RNA polymerase gather at the core promoter of a gene, and form a large initiation complex. There are another class of factors: transcription regulatory factors (TRFs) responsible for the regulation such as tissue-specific/timing-specific transcription and induction/repression of transcription. TRFs directly bind to cis-acting DNA elements which are generally referred enhancers (for activation) or silencers (for repression), and regulate the rate of formation of initiation complex. A TRFs can be divided into at most 4 domains: domains for binding to DNA, regulation of transcription, interaction to other proteins and ligand binding. A number of TRFs can be categorized into rather small numbers of families such as b-zip, Zn-finger, etc. which have a characteristic combination with functional motifs. The third class of transcription factor is referred as a mediator/coactivator, that binds to both TRFs and GTFs, and can transduce the regulatory signal from enhancer to promoter. We can describe many biological processes by a term of transcriptional regulation, such as carcinogenesis, development, morphogenesis, infection and immunity, cell growth and hormone action, etc. However, further studies on chromain/nuclear matrix structure, molecular anatomy of transcription factors, and network of transcription factors are required for understanding of the relationship between biological processes and transcriptional regulation.

DNA-Binding Proteins↗
PubMed1995

[5-FU concentrations in the blood and tumor tissue after 5'-DFUR or UFT administration in the patients with uterine cervical cancer].

In order to verify the antitumor activity of fluorinated pyrimidine drugs, we conducted an investigation of the clinical pharmacology with two drugs, 5'-DFUR and UFT. Total 21 cases of cervical cancer were alloted randomly into 5'-DFUR group (daily dose 800 mg for 3 days) consisting of 11 patients and UFT group (daily dose 600 mg for 3 days) consisting of 10 patients, the unchanged substances (5'-DFUR in the 5'-DFUR group and tegafur concentrations in the UFT group) and 5-FU concentrations in serum and tissues were measured 6 hours after administration of the drugs. The 5'-DFUR concentration in the 5'-DFUR group was not detected in serum and less than a detectable limit for all of cancerous tissues, normal cervical tissues, and lymph nodes. The tegafur concentrations in the UFT treated group was 13.8 +/- 7.0 micrograms/ml for serum, 10.4 +/- 6.4 micrograms/g for cancerous tissues, 14.1 +/- 7.3 micrograms/g for normal cervical tissues, and 4.5 +/- 4.2 micrograms/g for lymph nodes. The 5-FU concentrations in the 5'-DFUR treated group were 0.018 +/- 0.046 micrograms/g for cancerous tissues, but less than a detectable limit for serum and normal cervical tissues. On the other hand, in the UFT group, 0.271 +/- 0.247 micrograms/g for a cancerous tissue, 0.035 +/- 0.018 micrograms/ml for serum, 0.125 +/- 0.073 micrograms/g for normal cervical tissues, showing significantly high values (p < 0.01, p < 0.001, and p < 0.01, respectively) compared to those in the 5'-DFUR treated group. These results suggest that UFT is a promising drug for the treatment of cancer of the uterine cervix.

Administration, Oral↗
PubMed1995

Image analysis of nail fold capillaries in patients with Raynaud's phenomenon.

Videograph images of nail fold capillaries in patients with Raynaud's phenomenon were analyzed, and capillary patterns were defined using standardized canonical discriminant analysis. Of sixty-eight patients with Raynaud's phenomenon, forty-nine (72 percent) showed a systemic sclerosis pattern and nineteen (28 percent) showed a normal pattern. The systemic sclerosis type capillary pattern significantly correlated not only with secondary Raynaud's syndrome but also with sclerodactyly, telangiectasia, and antinuclear antibody. This study confirms the value of nail fold capillary microscopy as a noninvasive technique for the examination of the cutaneous microcirculation in vivo. We should continue to evaluate the patients with Raynaud's phenomenon who showed systemic sclerosis pattern abnormality to determine if these patients would show a progression to systemic sclerosis or not.

Adolescent↗
PubMed1995

[Effects of carbon monoxide produced during laparoscopic surgery].

One of the complications of laparoscopic surgery is carbon monoxide (CO) production under the use of electro-cautery. We studied 11 patients undergoing laparoscopic urological surgery. The concentrations of CO in peritoneal cavity and carboxyhemoglobin (HbCO) in arterial blood were measured before the operation under laparoscopy, during the use of electro-cautery and after the operation. The concentration of CO in peritoneal cavity reached 78 ppm during the use of electro-cautery but the HbCO level was unchanged. In the study on laparoscopic cholecystectomy (LC) performed previously, we had found no change of HbCO. The increase of CO on LC was more pronounced than in the present study. The concentration of CO in peritoneal cavity might be more dependent on the intensive use of electro-cautery than on operation time. Additionally the frequency of the insertion and extraction of the instruments through the trocar could have influenced it. CO could also be produced in the carbon dioxide cylinder. It should be investigated since it might contaminate the operating room.

Adult↗
PubMed1995

Clinical pharmacokinetics and pharmacodynamics of paclitaxel: a 3-hour infusion versus a 24-hour infusion.

The present study was conducted to compare the pharmacokinetics and pharmacodynamics (PD) of paclitaxel between Phase I trials of 3- and 24-h infusions and to determine the most informative pharmacokinetic parameter to describe the PD. Twenty-seven patients were treated in a Phase I study of paclitaxel by a 3-h infusion at one of six doses: 105, 135, 180, 210, 240, and 270 mg/m2. Pharmacokinetic data were obtained from all patients. Paclitaxel concentrations were measured in the plasma and urine using HPLC. The pharmacokinetics and PD were compared with those of a Phase I trial of paclitaxel by a 24-h schedule previously performed. The maximum tolerated dose of paclitaxel by a 3-h infusion was determined to be 240 mg/m2. The major toxicities were granulocytopenia, neuromuscular toxicities, and hypotension. Apparent differences in pharmacodynamic relationships for the change in granulocytes with dose, peak concentration, and areas under the concentration versus time curve were observed between the 3- and 24-h schedules. However, the relationship between the duration of plasma concentration above 0.05 microM and the change in granulocytes could be fitted to the same sigmoid maximum effect model in either schedule (P < 0.01). There were no clear relationships between peripheral neuropathy or hypotension and any pharmacokinetic parameters. The pharmacokinetics and PD of paclitaxel were schedule dependent. The duration of plasma concentration above 0.05 microM could be a common pharmacokinetic parameter predicting granulocytopenia for both schedules.

Agranulocytosis↗