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Biomedical subjects

T Tamura

Publications and source records attributed to T Tamura.

At least 703 records · Page 39Linked to original sources
PubMed1993

Dietary folate requirement determined for channel catfish, Ictalurus punctatus.

Juvenile channel catfish, Ictalurus punctatus, were fed semipurified basal diets containing 0, 0.2, 0.5, 1.0, 4.0 or 10.0 mg/kg of folic acid or 10 g/kg of succinylsulfathiazole in aquaria for 15 wk. Fish fed the sulfonamide showed higher mortality, lower weight gain, lower thrombocyte counts, higher hemocytoblast and neutrophil counts, and lower liver folate concentrations than did control fish (0 folic acid), indicating that significant intestinal bacterial synthesis of folate occurs in channel catfish. There were positive quadratic regressions of weight gain, hematocrit, erythrocyte and leukocyte numbers, and positive linear regressions of plasma and liver folate on dietary folic acid concentrations. Broken-line analysis showed that the dietary requirements for folic acid for optimum weight gain, hematocrit, and erythrocyte and leukocyte numbers were 1.01, 1.17, 1.12 and 1.15 mg/kg, respectively. Plasma and liver concentrations of folate associated with normal growth and hematopoiesis were 22.9 nmol/L and 20.0 nmol/g, respectively. Ratios of leukocytes and lymphocytes to erythrocytes were maximal in fish fed 4.0 mg folic acid/kg, indicating that immunocompetence may increase as the dietary dose exceeds that required for normal growth. Anemia in folate-deficient channel catfish was characterized by pale livers, spleens, gills and kidneys, and by poikilocytosis, anisocytosis, pyknosis, cytoplasmic clearing, increased numbers of hemocytoblasts, macrocytosis, and binucleated erythrocytes or "spectacle" cells.

Animals↗
PubMed1993

Purification and characterization of the 26S proteasome complex catalyzing ATP-dependent breakdown of ubiquitin-ligated proteins from rat liver.

An ATP/ubiquitin-dependent proteasome complex with an apparent sedimentation coefficient of 26S was purified from rat liver to near homogeneity by an improved method based on procedures reported previously. Two electrophoretically distinct forms of the 26S complex, named 26S alpha and 26S beta, with very similar subunit compositions were found not only in purified preparations but also in crude extracts, indicating that the 26S proteasome is present as two isoforms. The 26S proteasome was shown to degrade multi-ubiquitinated, but not unmodified, lysozymes in an ATP-dependent fashion, to have ATPase activity supplying energy for proteolysis, and to contain isopeptidase activity to generate free ubiquitin Mg2+/ATP-dependently. The 26S proteasome also catalyzed the ATP-independent hydrolyses of three types of fluorogenic peptides with basic, neutral, and acidic amino acids at their cleavage sites, respectively. These peptides are also good substrates for the 20S proteasome, but their degradation by the free 20S proteasome and by its assembled form in the 26S complex differ markedly, suggesting a functional difference between the two forms of proteasomes. Electrophoretic and immunochemical analyses showed that the large 26S complex was composed grossly of two different structures: a core 20S proteasome with multicatalytic proteinase functions and an associated part possibly with a regulatory role. These two structures both consisted of multiple polypeptides with molecular masses of 21-31 and 35-110 kDa, respectively. The subunit multiplicity of the rat 26S proteasome closely resembled that of the human counterpart, showing only minor species-specific differences in certain components. The assembly of this multi-component complex was found not to involve a sulfhydryl bond. Electrophoretic peptide mapping with lysyl-endopeptidase indicated the non-identity of the multiple subunits of the 26S proteasome. From these structural and functional characteristics, the 26S proteasome, which is widely distributed in mammals, is suggested to be a new type of multi-molecular complex catalyzing the soluble energy- and ubiquitin-dependent proteolytic pathway.

Adenosine Triphosphate↗
PubMed1993

Stabilization of lysozyme by the introduction of Gly-Pro sequence.

Three mutant lysozymes where the Asp101-Gly102 sequence of lysozyme was converted to Asp101-Pro102, Gly101-Pro102 and Pro101-Gly102 were prepared to investigate the effect of proline residues on the stabilization of proteins. The free energy changes of lysozymes for the unfolding in aqueous solution at pH 5.5 and 35 degrees C were 10.0, 10.1, 11.0 and 7.7 kcal/mol for wild type, Asp101Pro102, Gly101Pro102 and Pro101Gly102 lysozyme respectively. When the energy level in the unfolded state of wild type lysozyme was fixed at a standard level, the energy levels in the folded state of Asp101Pro102 and Pro101Gly102 lysozymes were found to be higher than that of wild type lysozyme on the basis of delta GD(H2O) and entropy losses of their polypeptide chains in the unfolded state. The presence of some strain in the folded state of these lysozymes was supported by both the calculation of conformational energy for a trans-L-prolyl residue [Schimmel, P.R. and Flory, P.J. (1968) J. Mol. Biol., 34, 105-120] and the analysis of structures of energy-minimized mutant lysozymes. Therefore, it is concluded that the formation of the Gly-Pro sequence is effective in avoiding possible strain in the folded state of a protein caused by the introduction of proline residue(s).

Amino Acid Sequence↗
PubMed1993

Effect of sex on left ventricular pump function in patients with anterior wall myocardial infarction treated with primary angioplasty.

BACKGROUND: The prognosis of acute myocardial infarction (AMI) is distinctly worse in postmenopausal women than in age-matched men. Unstable angina before AMI is reported to protect left ventricular pump function during the left ventricular remodeling process in patients who have undergone successful percutaneous transluminal coronary angioplasty (PTCA). We postulate that left ventricular pump function may be different in postmenopausal women and age-matched men with unstable angina before AMI and successful PTCA. METHODS: Twenty-three postmenopausal women (aged 63 +/- 7 years) and 31 age-matched men (aged 65 +/- 6 years) with unstable angina before AMI and successful PTCA were investigated using radionuclide angiography in the late hospital phase. RESULTS: Global ejection fraction (EF), regional EF of the non-infarcted area, and the ratio of systemic arterial systolic blood pressure to left ventricular end-systolic volume (P:V ratio) were lower in women compared with those in men. Global EF, regional EF of the non-infarcted area, and the P:V ratio in women with left ventricular end-diastolic volume (EDV) > or = 140 ml were significantly lower than in those with a left ventricular EDV of less than 140 ml, but no significant differences were noted in these indexes with regard to left ventricular EDV in men. CONCLUSION: Sex may play an important role in the left ventricular remodeling process in postmenopausal women, especially those with a dilated left ventricle.

Aged↗
PubMed1993

Guidelines for analysis and reporting of clinical trials in oncology.

When analyzing and reporting the results of clinical trials, investigators should follow a simple approach. The purpose of a trial is to estimate an effect or treatment difference, which if present would have clinical utility when treating new patients. Procedures or methods that do not facilitate precisely and impartially estimating and reporting the treatment effect are likely to mislead investigators. Most often in clinical trials, investigators are interested in estimates of risk ratios (specifically odds or hazard ratios) between the treatment groups or levels of a prognostic factor. These simple ideas suggest that the most useful results from clinical trials will be estimated risk ratios and their confidence limits. Especially in cancer, where disease progression, recurrence, and death are common events following treatment, estimates of risk difference are very relevant. Hypothesis tests and associated P-values, although often (or exclusively) reported, are of lesser utility because they do not fully summarize the data. These recommendations may be seen by some investigators to be contrary to accepted practice. It is true that they are somewhat contrary to common practice but their general acceptance is evident in many journals and presentations by clinical trial methodologists. Despite some disagreement among statisticians regarding the need for adjustment of analyses for imbalanced prognostic factors, it is helpful to see if treatment effects change after accounting for imbalances. When this occurs, it may be of clinical interest. Although we discourage analyses that exclude any patients who meet the eligibility criteria, some circumstances will require that this be done (e.g., when a patient refuses to participate after randomization). Investigators should report, and emphasize as primary, those analyses that include all eligible patients. It is our hope and belief that analysis and reporting of trial results along the guidelines suggested here will result in impartial and useful information for journal readers.

Clinical Trials as Topic↗
PubMed1993

Systemic sclerosis terminating as systemic necrotizing angiitis.

We report a 57-year-old woman with systemic sclerosis (SSc) who died suddenly, following a haemoptysis. At post-mortem, systemic necrotizing angiitis of small vessels was observed in several organs. Necrotizing angiitis has been reported as a rare complication of systemic sclerosis, and is usually lethal.

Connective Tissue Diseases↗
PubMed1993

Potent inhibitory action of the gastric proton pump inhibitor lansoprazole against urease activity of Helicobacter pylori: unique action selective for H. pylori cells.

The gastric proton pump inhibitor lansoprazole, its active analog AG-2000, and omeprazole dose dependently inhibited urease activity extracted with distilled water from Helicobacter pylori cells; the 50% inhibitory concentrations were between 3.6 and 9.5 microM, which were more potent than those of urease inhibitors, such as acetohydroxamic acid, hydroxyurea, and thiourea. These compounds also inhibited urease activity in intact cells of H. pylori and Helicobacter mustelae but did not inhibit ureases from other bacteria, such as Proteus vulgaris, Proteus mirabilis, and Providencia rettgeri. The mechanism of urease inhibition was considered to be blockage of the SH groups of H. pylori urease, since SH residues in the enzyme decreased after preincubation with lansoprazole and glutathione or dithiothreitol completely abolished the inhibitory action. The SH-blocking reagents N-ethylmaleimide and idoacetamide were also examined for their inhibition of the urease activity; their 50% inhibitory concentrations were 100- to 1,000-fold higher than those of lansoprazole. These results suggest that lansoprazole and omeprazole can potently and selectively inhibit H. pylori urease and that inhibition may be related to earlier findings indicating that these compounds have selective activity against HP growth.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1993

Purification of a factor which provides a costimulatory signal for gamma interferon production.

A protein factor which induces high levels of gamma interferon (IFN-gamma) in resting splenic nonadherent cells was isolated from the sera of mice with generalized inflammation caused by endotoxic shock. The factor was highly purified by ammonium sulfate precipitation followed by ion-exchange column chromatography on DEAE-Sepharose, molecular sieving on Ultrogel AcA 44, and hydrophobic column chromatography with phenyl-Sepharose. It was further purified to apparent homogeneity by polyacrylamide gel electrophoresis. It induced IFN-gamma production in a dose-dependent manner in the presence of interleukin-2, monoclonal anti-CD3 antibody (anti-CD3 MAb), or concanavalin A (ConA) in spleen cells deprived of plastic plate- and nylon wool-adherent cells. Anti-CD3 MAb induced the highest level of production of the three. The factor, interleukin-2, anti-CD3 MAb, or ConA alone induced a trace of or no detectable IFN-gamma in these cells. The factor also exhibited an accessory function during proliferation in these cells in the presence of a suboptimal dose of ConA. However, the factor failed to stimulate IFN-gamma production when staphylococcal enterotoxin A, a superantigenic T-cell mitogen, was employed. Treatment with pronase or heat abolished these activities. These studies confirm the existence of a soluble protein factor which is able to exhibit a novel accessory function in IFN-gamma production in resting T or natural killer cells. It will be of interest to compare this factor with the recently cloned human natural killer stimulatory factor (NKSF/IL-12).

Animals↗
PubMed1993

Mapping of the bone morphogenetic protein 1 gene (BMP1) to 8p21: removal of BMP1 from candidacy for the bone disorder in Langer-Giedion syndrome.

Fifteen cosmids containing sequences from the human bone morphogenetic protein 1 gene (BMP1) were isolated from a cosmid library. The probe was a 483-bp DNA obtained by the reverse transcriptase-PCR method using primers designed according to the reported BMP1 sequence. When the positive cosmids were tested for chromosome fluorescence in situ hybridization, all showed signals at 8p21. The results indicated that BMP1 is not responsible for Langer-Giedion syndrome, whose putative gene has been assigned to 8q24.

Base Sequence↗
PubMed1993

Ventriculoarterial coupling during low-level exercise testing after myocardial infarction.

To evaluate the change of ventriculoarterial coupling during low-level exercise in patients after myocardial infarction, the ratio of systolic blood pressure to left ventricular end-systolic volume (P/V ratio) and the ratio of systolic blood pressure to stroke volume (effective arterial elastance) were investigated using radionuclide angiography in 73 consecutive patients with a negative predischarge exercise test. The patients were divided into three groups according to their resting left ventricular ejection fraction: group A (n = 12) > or = 60%; group B (n = 32) 41-59%; group C (n = 29) < or = 40%. The ejection fraction increased significantly during exercise in all three groups. There was no significant difference in the change of the P/V ratio during exercise between groups A and B, but it was significantly smaller in group C. The effective arterial elastance increased during exercise in group A, did not change in group B, and decreased in group C. Thus, the augmentation of myocardial contractility was an important factor related to the increase in ejection fraction during exercise in patients with normal or slightly reduced cardiac function, whereas the decrease in effective arterial elastance was important in patients with poor cardiac function.

Adult↗
PubMed1993

Molecular structure of 20S and 26S proteasomes.

Eukaryotic proteasomes are unusually large protein complexes with characteristic sets of subunits and have been classified into two isoforms with apparent sedimentation coefficients of 20S and 26S, respectively. The 20S proteasome (previously named the multicatalytic proteinase complex) is a cylindrical particle with a molecular weight (MW) of approximately 750 kD. It is a dimeric assembly of two symmetrical discs, each consisting of 7 alpha-type subunits and 7 beta-type subunits, having the molecular organization alpha n[1-7)beta n[1-7)beta n[1-7)alpha n[1-7), where 'n' indicates the number of heterogeneous 7 subunits with MWs of 21-32 kD. The alpha-type and beta-type subunits constitute a unique multi-gene family encoding previously unidentified, but homologous, polypeptides that have been conserved during evolution. Interestingly, some beta-type subunits with catalytic functions appear to be replaced by very homologous, but distinct, gene products that might be generated by gene duplication in response to extracellular signals, such as gamma-interferon, suggesting that the 20S proteasome exists in cells as a heterogeneous population with functional diversity. The 26S proteasome is a eukaryotic ATP-dependent protease, selectively degrading various cellular proteins with specific degradation signals such as a multi-ubiquitin chain. It is a cylindrical caterpillar-shaped complex with a MW of about 2,000 kD. The 26S proteasome is a symmetrical assembly of a central 20S proteasome and a large terminal polypeptide complex with an apparent sedimentation coefficient of 22S. The terminal 22S subset consists of multiple components with MWs of 30-110 kD, which possibly have regulatory functions, and contains multiple ATPases, a de-ubiquitinating enzyme and the recognition molecule(s) for the target proteins. Thus the 26S proteasome is a multi-molecular assembly, consisting of the 20S proteasome and the 22S regulatory subunit complex.

Adenosine Triphosphatases↗
PubMed1993

Macrophage colony-stimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors.

The mechanism of action of macrophage colony-stimulating factor (M-CSF) in osteoclast development was examined in a co-culture system of mouse osteoblastic cells and spleen cells. In this co-culture, osteoclast-like multinucleated cells (MNCs) were formed within 6 d in response to 10 nM 1 alpha,25(OH)2D3 added only for the final 2 d of culture. Simultaneously adding hydroxyurea for the final 2 d completely inhibited proliferation of cultured cells without affecting 1 alpha,25(OH)2D3-stimulated MNC formation. Autoradiographic examination using [3H]-thymidine revealed that osteoclast progenitors primarily proliferated during the first 4 d, whereas their differentiation into MNCs occurred predominantly during the final 2 d of culture in response to 1 alpha,25(OH)2D3. When anti-M-CSF antibody or anti-M-CSF receptor antibody was added either for the first 4 d or for the final 2 d, the MNC formation was similarly inhibited. In co-cultures of normal spleen cells and osteoblastic cells obtained from op/op mice, which cannot produce functionally active M-CSF, the lack of M-CSF either for the first 4 d or for the final 2 d failed to form MNCs in response to 1 alpha,25(OH)2D3 added for the last 2 d. These results clearly indicate that M-CSF is indispensable for both proliferation of osteoclast progenitors and their differentiation into mature osteoclasts.

Animals↗
PubMed1993

Comparison of adaptation to the home culture of Japanese children and adolescents returned from overseas sojourn.

A questionnaire based on the MMPI was administered to Japanese children aged between 6 and 18 years who had returned from an overseas sojourn of more than one year's duration (N = 1941) and a matched control group who had no overseas experiences (N = 1354). Overall females had more difficulty with friends, and scored higher on both psychological and physical symptoms. The older children had more complaints about life in Japan, difficulty with friends and physical and psychological problems. The differences between the returnee and control group were less in the age range between 7 and 9, but the overseas experience seemed to have positive effects between the ages of 10 to 15. The longer the children stayed overseas, the more they had complaints about life in Japan and difficulty with friends, and less negative attitudes towards overseas life. Children who had multiple overseas experiences had more problems such as anxiety, depression and mental complaints. Children's developmental stages and the amount of exposure to the foreign culture are therefore important determinants of their readjustment. The expectations of parents and the home culture to the returnee children, gender, and emphasis on academic achievement, must also be taken into account.

Acculturation↗
PubMed1993

Phase I study of CPT-11 and etoposide in patients with refractory solid tumors.

PURPOSE: To determine the maximum-tolerated dose (MTD) and acceptable dose level of a cytotoxic regimen of CPT-11, a new camptothecin derivative, in combination with etoposide (VP-16) and to describe the principal toxicities associated with it. PATIENTS AND METHODS: Patients with refractory solid tumors received VP-16 and CPT-11 daily for 3 consecutive days (days 1 through 3) every 3 or 4 weeks. Groups entered the trial at escalating CPT-11/VP-16 dose levels of 40/60, 60/60, 60/80, and 80/60 mg/m2. Thirty-four patients entered this study, of whom 33 were assessable for toxicity and 22 for therapeutic efficacy. RESULTS: Granulocytopenia was so severe that this regimen required supportive therapy with recombinant human granulocyte colony-stimulating factor (G-CSF). The majority of the patients experienced a 5% weight loss and diarrhea was the dose-limiting toxicity. The MTDs were 60/80 and 80/60 mg/m2 administered on days 1 through 3. Five of seven previously untreated patients with non-small-cell lung cancer (NSCLC) achieved partial responses (PRs) to this therapy, as did two with NSCLC who had received prior chemotherapy, two with head and neck cancer, and one with an adenocarcinoma (primary tumor unknown). CONCLUSION: The recommended dose of CPT-11/VP-16 for this regimen with G-CSF is 60/60 mg/m2 on days 1 through 3 every 3 to 4 weeks. We suggest that the combination of topoisomerase I and II inhibitors is likely to be an effective treatment strategy. The activity of this regimen against NSCLC is particularly encouraging and should be evaluated in a phase II trial.

Adult↗
PubMed1993

Hyponatremia and osmoregulation of thirst and vasopressin secretion in patients with adrenal insufficiency.

To clarify the mechanism underlying abnormal vasopressin (AVP) secretion in glucocorticoid deficiency, we examined the response of AVP secretion to osmotic stimulus produced by 5% saline infusion and analyzed the possible causative factors in seven patients with hypoosmolal hyponatremia resulting from adrenal insufficiency. In all patients, urinary sodium excretion persisted with urine osmolality exceeding plasma osmolality, and plasma AVP levels relative to plasma osmolality were elevated. Blood urea nitrogen, plasma creatinine, and PRA ranged from low to normal. All patients had nausea or vomiting, three had hypotension, and two had hypoglycemia; however, the primary cause of increased AVP secretion was attributed to none of these stimuli. After 5% saline infusion, patterns of changes in plasma AVP levels in individual patients were variable: levels decreased with increasing plasma osmolality in two patients and remained unchanged in the other five patients. Despite hyponatremia and absence of hypovolemia, thirst was present in the five patients, who responded normally to questions. This abnormality in AVP secretion and thirst was corrected after glucocorticoid replacement with normalization of plasma sodium concentrations and osmolality. Thus, glucocorticoid deficiency in man results in a clinical picture almost indistinguishable from that of the syndrome of inappropriate secretion of antidiuretic hormone. Persistent AVP secretion in this pathological state is due to a loss of hypotonic suppression of the osmostat for AVP release, which may be occasioned primarily by glucocorticoid deficiency per se and aggravated secondarily by multiple nonosmotic stimuli including nausea, hypotension, and hypoglycemia.

Adrenal Insufficiency↗
PubMed1993

Effect of the leukotriene receptor antagonist ONO-1078 on extravascular lung water after coronary ligation in dogs.

To determine whether or not leukotrienes are associated with pulmonary edema after coronary ligation in dogs, we studied the effects of a specific leukotriene C4/D4 antagonist, ONO-1078, on extravascular lung water, as measured by the thermal-dye double indicator dilution method (Extravascular thermal volume, ETV). Six dogs served as a sham control (group 1). The proximal left anterior descending coronary artery was ligated for 45 min in 6 dogs (group 2), and in 6 others the coronary artery was ligated after pretreatment with ONO-1078 (1 mu/kg/min) (group 3). ETV and pulmonary arterial pressure were measured at control and 45 min after coronary ligation. In group 1, no significant change was found in ETV. Although there was no significant increase in pulmonary arterial pressure after coronary ligation, ETV significantly increased in groups 2 and 3. ETV increased more in groups 2 and 3 than in group 1, but there was no significant difference between groups 2 and 3. Thus, ONO-1078 did not effectively prevent the accumulation of extravascular lung water after coronary ligation, indicating that leukotrienes are not important mediators of pulmonary edema after myocardial ischemia.

Animals↗
PubMed1993

Use of biplane transesophageal echocardiographic guide in radiofrequency catheter ablation of Wolff-Parkinson-White syndrome with left side Kent bundle.

We report 2 patients with Wolff-parkinson-White Syndrome, who underwent radiofrequency (RF) catheter ablation under observation by biplane transesophageal echocardiography. One of the patients had Kent bundle in the lateral wall of the left ventricle, and the tip of the catheter could be easily confirmed with transverse views. Since perforation was observed where the valve was attached to the posterior leaflet of the mitral valve during the 39th administration of RF energy, ablation was discontinued. The other patient had Kent bundle in the posterior septum of the left ventricle. The tip of the catheter could be easily confirmed with sagittal views. Ablation was successful after the 4th administration of RF energy, but particulate contrast echoes appeared from the site of the tip of the electrode which had been used for ablation during the 4th RF delivery. When the delivery of RF energy was discontinued, the contrast echo disappeared, and a thrombus was found at the tip of the removed catheter. TEE in RF catheter ablation was helpful for confirming the site of the tip of the catheter and for early detection of complications.

Adult↗