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Biomedical subjects

T Tamura

Publications and source records attributed to T Tamura.

At least 217 records · Page 12Linked to original sources

[Coronary flow after successful angioplasty in patients with acute myocardial infarction: comparison between coronary flow reserve by nicorandil and papaverine].

In order to evaluate coronary flow response to 2 different vasodilators, nicorandil and papaverine, in patients with myocardial infarction, we measured coronary flow reserve using a Doppler guide wire in infarct-related and non infarct-related arteries. The study group consisted of 28 patients with first acute myocardial infarction 3 weeks after successful coronary angioplasty within 6 hr after symptom onset. Twelve patients with atypical chest pain served as the control group. Coronary flow reserve induced by intracoronary papaverine(12 mg) was lower in infarct-related arteries than in non infarct-related arteries, but there were no differences in coronary flow reserve induced by intracoronary nicorandil(1 mg) between infarct-related and non infarct-related arteries. Coronary flow reserve induced by nicorandil was lower than that by papaverine in non infarct-related arteries and the control group. However, there were no differences between coronary flow reserve induced by nicorandil and papaverine in infarct-related arteries. Vasodilatory response induced by nicorandil was relatively preserved in infarct-related arteries compared with papaverine. These results suggest that impairment of coronary microvascular response in infarct myocardium varies in the different sites acted on by different vasodilator agents.

Angioplasty, Balloon, Coronary↗

[Phase I clinical trial design of anticancer agents--a Fibonacci and a modified Fibonacci sequence].

A Phase I clinical trial of an anticancer agent is the first evaluation in humans, and it is an important step in drug development. From the ethical point of view, the goal is to escalate to the maximum tolerated dose quickly, yet safely, to minimize the likelihood of treating patients at doses that are too low or high. It is expected that the contradictions between safety and efficacy in the Phase I clinical trials will be solved by developing methods. The modified Fibonacci sequence has been generally adopted for dose escalation, although it includes some problems. It is necessary to recognize that the method used for Phase I clinical trials for anticancer agents remains unsatisfactory, and that it is also necessary to develop more ethical and scientific methods.

Animals↗

[A case report of skeletal muscle metastasis of renal cell carcinoma effectively treated with interferon-alpha].

The skeletal muscle is a very rare site of metastasis in renal cell carcinoma. We report the third case of skeletal muscle metastasis of renal cell carcinoma effectively treated with interferon-alpha. The patient was a 74-year-old woman who had undergone radical nephrectomy on the left side for renal cell carcinoma on April 23, 1990, and had been observed as an outpatient. In June 1997, she was admitted with a diagnosis of metastasis in the left great adductor muscle and right sixth rib, as well as multiple lung metastasis. The metastatic lesion in the great adductor muscle decreased in size by more than 50% following concomitant intramuscular administration of natural interferon-alpha (nIFN-alpha). In the other metastatic lesions, nIFN-alpha-sensitive and resistant metastatic foci were intermingled. Thus, the primary focus in the present study was presumably composed of several clones with different sensitivities to nIFN-alpha.

Aged↗

Analysis of acceleration signals using wavelet transform.

In this study, we attempted to discriminate the acceleration signal for horizontal level and stairway walking using wavelet-based fractal analysis method. The acceleration signal was measured close to the center of gravity of the body, while the subjects walked continuously in the corridor and up and down the stairs. We used the wavelet-based fractal analysis method to discriminate walking pattern. The parameter H which is related directly to the fractal dimension was estimated by the wavelet coefficient and was changed into low value during walking upstairs. By manually setting the threshold level for individual, it was possible to discriminate walking upstairs from the other walking type. However, the common feature among subjects was not shown between level walking and walking downstairs.

Acceleration↗

[Gamma-interferon-induced cardiomyopathy during treatment of renal cell carcinoma: a case report].

A 78-year-old woman with renal cell carcinoma and pulmonary metastasis presented with reversible cardiomyopathy induced by gamma(gamma)-interferon. She was treated with gamma-interferon twice a week since November 1996. She presented with severe acute congestive heart failure and gamma-interferon was immediately discontinued in December 1997. Left ventricular fractional shortening was 38% before admission, 12% on admission, and improved to 31% by 40 days after discontinuation of interferon together with administration of diuretics and angiotensin converting enzyme inhibitor. We restarted the same gamma-interferon regimen because it was effective against renal cell carcinoma after 47 days. She has remained well with no significant changes of cardiac function or renal cell carcinoma for almost one year.

Aged↗

Slowly growing cardiac tumor: a case of fibroelastoma.

Echocardiographic follow-up for 16 years in an asymptomatic patient with mitral stenosis showed very slow growth of a mass attached to the mitral valve. The tumor doubling time was estimated to be 3.6 years. Surgical excision of the mass was performed when the patient eventually developed dyspnea on exertion, and histopathological examination revealed papillary fibroelastoma. Echocardiographic follow-up and anti-coagulation may be sufficient treatment for asymptomatic patients with papillary fibroelastoma.

Echocardiography↗

[Angioimmunoblastic T-cell lymphoma presenting with rapidly increasing biclonal gammopathy].

A 59-year-old man was admitted to our hospital with high fever and dysphagia. Physical examination revealed a lingual tumor and swelling of the cervical and inguinal lymph nodes. A lymph node biopsy specimen revealed that the normal nodal architecture had been obliterated by infiltration of small, intermediate, and large pale lymphocytes. Arborous branching of high endothelial venules was also observed. Southern blotting analysis showed rearrangement of the T-cell receptor beta gene. A diagnosis of angioimmunoblastic T-cell lymphoma was made. Serial serum protein fractionation analysis showed rapidly increasing M-protein. Immunofixation electrophoresis indicated specific bands for IgG kappa and IgM lambda, confirming the presence of biclonal gammopathy. Biclonal gammopathy has rarely been reported in patients with angioimmunoblastic T-cell lymphoma. The relationship between the occurrence of biclonal gammopathy and the possible role of HHV-6, HHV-8 and EBV is discussed.

Humans↗

[A 90-day repeated dose oral toxicity study of magnesium chloride in F344 rats].

In order to examine the toxicity of magnesium chloride hexahydrate, four groups of 10 male and 10 female F344 rats received the compound by dietary supplementation at 2.5, 0.5, 0.1 or 0% for 90 days. No treatment-related death was observed during the study. Transient soft stool and sustained increase in water consumption were observed both in males and females of the 2.5% group and slight reduction in body weight gain was noted in the high-dose males. There were no toxic changes in food consumption, organ weights, hematology and biochemistry, and histopathological examinations in any treated-groups. Based on these results, the no-observed-adverse-effect-level was estimated to be 0.5%, and 2.5% is considered to be appropriate as highest dose for a 2-year carcinogenicity study.

Administration, Oral↗

Induced expression, localization, and chromosome mapping of a gene for the TBP-interacting protein 120A.

TBP-interacting protein 120A (TIP120A) is a novel eukaryotic transcriptional regulator and has been suggested to be involved in the general regulation of transcription because of its ability to potentiate transcription of all classes of genes and to interact with common transcriptional machineries. In the present study, we investigated the expression of the tip120a gene. TIP120A transcripts were expressed abundantly in the heart and liver, moderately in the brain and skeletal muscle, and only slightly in the spleen and lung. This ubiquitous expression pattern was similar to that of TBP. Gene expression of TIP120A in the rat liver was not stimulated by hepatocarcinogenesis or liver regeneration. TIP120A was thus suggested not to be a growth-related protein. On the other hand, in P19 mouse embryonal carcinoma cells, TIP120A expression was elevated upon retinoic acid treatment, which induces differentiation. Notably, the foci-like nuclear localization pattern of TIP120A was transformed into a speckle-like pattern. The level of TIP120A was also elevated in such stem-like cells as F9 and HL60 after each differentiation procedure, retinoic acid and DMSO, respectively. In HEp-2 cells, TIP120A was observed as a limited number of nuclear foci, and the localization coincided with that of the PML oncogenic domain. FISH detection revealed that the human tip120a gene was located at 12q14, the position to which a myopathic type scapuloperoneal syndrome locus also mapped. Our study suggests that, contrary to an early assumption, TIP120A is involved in tissue-specific and/or differentiation-related gene expression.

Animals↗

Capsids of tricorn protease studied by electron cryomicroscopy.

Tricorn protease from the archaeon Thermoplasma acidophilum acts "downstream" of the proteasome; in conjunction with its aminopeptidase cofactors it converts peptides generated by the proteasome into free amino acids. The basic functional unit of Tricorn is a homohexamer of the 121-kDa subunit, 20 of which can assemble further to form an icosahedral capsid with a molecular mass of 14.6 MDa. We have used electron cryomicroscopy to determine the structure of the Tricorn capsids to a resolution of 1.3 nm.

Archaeal Proteins↗

FMIP, a novel Fms-interacting protein, affects granulocyte/macrophage differentiation.

Hematopoietic cell growth, differentiation, and commitment to a restricted lineage are guided by a set of cytokines acting exclusively on cells expressing the corresponding cytokine receptor. The macrophage colony stimulating factor (M-CSF, also termed CSF-1) and its cognate receptor, the tyrosine kinase c-Fms, are essential for monocyte and macrophage development. The underlying molecular mechanism, however, is poorly understood. Here we identified a novel Fms-interacting protein (FMIP, MW 78 kDa) which binds transiently via its N-terminal 144 residues to the cytoplasmic domain of activated Fms-molecules. Binding of FMIP was paralleled by rapid tyrosine phosphorylation within the binding domain which drastically reduced its ability to associate with Fms. Binding was specific as evidenced by co-immunoprecipitation and association with recombinant GST-Fms fusion proteins. No binding was observed with the tyrosine phosphorylated cytoplasmic domains of c-Kit, TrkA, c-Met, and the insulin receptor. The role of FMIP in hematopoietic differentiation was studied in the bipotential myeloid progenitor cell line, FDC-P1Mac11. Overexpression of FMIP prevented M-CSF induced macrophage differentiation. Instead, cells differentiated into granulocytes. Our data suggest that the level of FMIP expression could form a threshold that decides about differentiation either into macrophages or into granulocytes.

Amino Acid Sequence↗

Orexins, orexigenic hypothalamic neuropeptides, suppress the pulsatile secretion of luteinizing hormone in ovariectomized female rats.

It is well known that feeding disorders are deeply related to reproductive dysfunction, and some feeding regulatory factors may modulate the reproductive function. We examined the effect of orexins, the newly discovered orexigenic hypothalamic neuropeptides, on the pulsatile secretion of LH to clarify their influence on the reproductive function. We administered orexins or saline into the third ventricle of bilaterally ovariectomized (OVX) rats, and measured the serum LH concentration by RIA in blood samples drawn every 6 min for 2 hours to analyze the pulsatile secretion. In the orexin-treated groups, the mean LH concentration and the pulse frequency were significantly reduced (p < 0.01), but the pulse amplitude did not differ significantly. These data indicate that orexins suppress the pulsatile secretion of LH by influencing GnRH neurons at the hypothalamic level.

Animals↗

Bioactivity of orally administered unnatural isomers, [6R]-5-formyltetrahydrofolate and [6S]-5,10-methenyltetrahydrofolate, in humans.

It has been assumed that humans cannot utilize 5,6,7,8-tetrahydrofolates with the unnatural configuration at carbon 6, since these folates are enzymatically and microbiologically inactive. We hypothesized that orally administered unnatural [6R]-5-formyltetrahydrofolate or [6S]-5,10-methenyltetrahydrofolate is bioactive in humans. Subjects were given independent oral doses of these unnatural folates and of a natural [6S]-5-formyltetrahydrofolate. Plasma, before and after the dose for 4 h, and 2 h urine were collected. Areas under the curve for the change in plasma folate concentrations were measured microbiologically and urinary folates were measured using HPLC. Based on findings of plasma and urinary folates, the unnatural folates were estimated to be 14-50% active as compared to [6S]-5-formyltetrahydrofolate. The major plasma and urinary folate was [6S]-5-methyltetrahydrofolate in all experiments. In urine, a [6S]-5-formyltetrahydrofolate peak was observed only after a [6S]-5-HCO-H4folate dose and peaks of unnatural [6S]-10-formyltetrahydrofolate and 5-formyltetrahydrofolate were identified after a [6R]-5-formyltetrahydrofolate dose. A possible pathway that explains our findings is discussed. This pathway includes the oxidation of the unnatural [6S]-10-formyltetrahydrofolate to 10-formyl-7,8-dihydrofolate which can be further metabolized by 5-amino-4-imidazolecarboxamide-ribotide transformylase producing dihydrofolate. Dihydrofolate can then be metabolized to [6S]-5-methyltetrahydrofolate by well-established metabolism.

Administration, Oral↗

Histologic types of lung carcinoma and related family history of anatomic sites and histologic types of cancers.

BACKGROUND: Familial factors are suggested to play roles in lung carcinogenesis, but may well be different for each histologic cell type. METHODS: Information regarding smoking, past medical history, and family history of malignant diseases among first-degree relatives was collected from a total of 1188 patients with primary lung carcinoma (participants) who were treated in the thoracic oncology ward at the National Cancer Center Hospital, Tokyo, Japan. These data were analyzed for associations with the histologic type of the lung carcinoma. The main outcome measures were the relative risk of developing a malignancy, at any site or at certain specific sites, in first-degree relatives of participants who had a specific histologic type of lung carcinoma compared with the relative risk in those first-degree relatives of participants with other cell types. RESULTS: Participants with multiple malignant lesions reported significantly more first-degree relatives with a malignancy than those without multiple tumors (P = 0.008 by the Wilcoxon rank sum test). There was no statistically significant correlation between age, gender, smoking history, or histologic tumor type in the participant and the overall family history of malignancy. Site specific analyses revealed that participants with adenocarcinoma reported a family history of colorectal carcinoma, and those with squamous cell carcinoma reported a family history of head and neck carcinoma, more frequently than other participants (P = 0.041 and 0. 001, respectively, by chi-square analysis). CONCLUSIONS: The data from the current study suggest an association between familial factors and histologic type of lung carcinoma. Genetic factors to determine individual susceptibility to lung carcinogenesis should be investigated according to each histologic type.

Adenocarcinoma↗

Association of the rat heterogeneous nuclear RNA-ribonucleoprotein F with TATA-binding protein.

Heterogeneous nuclear ribonucleoprotein F (hnRNP-F) has been shown to be a pre-mRNA splicing factor. Recent studies have uncovered the coordination of synthesis of pre-mRNA and its processing, including post-transcriptional modification and splicing. Here, we present evidence for an association between a splicing factor, hnRNP-F, and TATA-binding protein (TBP), which is an essential factor needed for transcription initiation. An affinity detection experiment revealed hnRNP-F in the preparation of TBP-interacting proteins. HnRNP-F was associated with TBP in nuclear extracts and was capable of direct binding to TBP in vitro. These results suggest that hnRNP-F is associated with TBP in the cell. HnRNP-F was observed in abundance in the thymus, spleen and testis, and its distribution pattern was similar to that of TBP, implying a functional coordination of transcription and splicing. We assume that the splicing machinery is associated with the transcription apparatus as a prerequisite prior to transcriptional elongation.

Animals↗