Biomedical subjects

T Ohtsuka

Publications and source records attributed to T Ohtsuka.

At least 163 records · Page 9Linked to original sources

PubMed1997

Nailfold capillary abnormality and pulmonary hypertension in systemic sclerosis.

BACKGROUND: Patients with systemic sclerosis (SSC) show a capillary abnormality of nailfolds with controversial correlation with organ involvement. Our purpose was to study the correlation between this nailfold capillary abnormality and pulmonary hypertension in patients with SSC. METHODS: We studied the nailfold capillaries, using capillary microscopy, and the pulmonary arterial pressure, using right-heart catheterization, in 44 patients with SSC. Canonical discriminant analysis was used to define the capillary abnormality in patients with SSC, which was then compared with that of 40 normal controls. The correlations between the patterns of nailfold capillaries and the cardiopulmonary findings, including the pulmonary arterial pressure, were examined using Fisher's test. RESULTS: Thirty-two of 44 patients with SSC could be differentiated from normal controls by our definition of the SSC pattern. The SSC pattern correlated significantly with elevated pulmonary vascular resistance, as well as with pulmonary fibrosis, electrocardiographic abnormalities, decreased vital capacity, and decreased diffusing capacity for carbon monoxide. All SSC patients with pulmonary hypertension showed this SSC pattern. In patients with elevated pulmonary arterial pressure, capillary microscopy and diffusion capacity for carbon monoxide (DCCM) showed the highest rate of abnormalities. A limited-type SSC significantly correlated with DCCM and with anticentromere antibody, and the diffuse-type SSC with pulmonary fibrosis and anti-sci-70 antibody. CONCLUSION: Our data suggest that in patients with SSC, nailfold capillary abnormalities correlate with pulmonary arterial hypertension as well as with clinical and laboratory findings indicating pulmonary hypertension.

Adolescent↗

PubMed1997

Expression of interleukin-1 beta converting enzyme gene family and bcl-2 gene family in the rat brain following permanent occlusion of the middle cerebral artery.

Recent investigations have been suggesting that some neuronal subpopulations may die via programmed cell death after focal ischemic injury. To clarify the possible roles of the genes involved in the cell-death program, this study examined the expression of three members of the interleukin-1 beta converting enzyme (Ice) gene family (Ice, Nedd2, and Yama/CPP32) and two members of the bcl-2 gene family (bcl-2 and bcl-x) in the rat brain after permanent occlusion of the middle cerebral artery. Northern blot analysis revealed a transient induction of Nedd2 mRNA 8 h after the ischemic insult (3.8-fold) and an increase in Yama/CPP32 mRNA 16 to 24 h after the insult (5.8-fold at 24 h), whereas the expression of Ice remained constant. The expression of bcl-2 and bcl-x remained constant after the ischemic insult. Taking into account the key role of the Ice gene family in the execution of programmed cell death, the induction of Ice gene family might play a causative role in apoptotic cell death.

Animals↗

PubMed1997

Purification and calcium dependence of transglutaminases from sheep hair follicles.

To study the calcium sensitivity of sheep hair follicle transglutaminase, which was reportedly calcium-independent [H. W. Harding and G.E. Rogers, Biochemistry, 11, 2858-2863 (1972)], the enzyme was purified from a homogenate of merino sheep hair follicles and its calcium dependence was examined. As a result of purification, two types of transglutaminases (DEAE-unabsorbed and absorbed transglutaminase, DU-TG and DA-TG, respectively) were obtained. The molecular mass of DU-TG was 77 and 82 kDa by SDS-PAGE and gel filtration, respectively, while that of DA-TG was 40 and 80 kDa. Each enzyme was obviously calcium dependent and contained (a) cysteine residue(s) in the active site, like other known mammalian transglutaminases. Maximum activation of DU-TG and DA-TG was observed at 1 and 0.1 mM CaCl2, respectively.

Animals↗

PubMed1997

Regional myocardial stiffness measured by a new tactile sensor system.

Numerous investigators have attempted to measure regional wall stress directly. However, the measurement systems and devices employed have been too complex for accurate quantification in situ. We have developed a new tactile sensor system for measuring accurately myocardial stiffness in situ and validated its use for estimation of myocardial contractile function. The tactile sensor was placed on the left ventricle of five mongrel dogs, (weighing 12-17 kg) and myocardial stiffness (g/mm2) was measured. Dobutamine (5.0 micrograms/kg/min) and propranolol (0.25 mg/kg) were sequentially administrated intravenously, and the change in myocardial stiffness was monitored. Myocardial stiffness followed a time course similar to that of left ventricular pressure, indicating a close relationship with wall stress. Baseline end-systolic stiffness in 5 dogs was 2.38 +/- 0.19 g/mm2. After administration of dobutamine, end-systolic stiffness increased to 3.26 +/- 0.32 g/mm2 (p < 0.01). After the administration of propranolol, end-systolic stiffness decreased significantly to 1.83 +/- 0.19 g/mm2 (p < 0.01), compared with the baseline values. Regional myocardial stiffness of a beating heart can be measured precisely using our new tactile sensor system. End-systolic stiffness is a useful index for accurate quantification of the regional myocardial contractile state.

Animals↗

PubMed1997

[Cushing's syndrome due to small cell lung cancer with ectopic production of adrenocorticotropic and parathyroid hormone].

A 72-year-old man was admitted to our hospital because of a tumor-like shadow on a chest X-ray film. At the initial examination, he had clinical signs of Cushing's syndrome: moon face, central obesity, and hypertension. A computed tomographic scan of chest showed an abnormal shadow in the lung (5 x 6 cm) with involvement of the right paratracheal and anterior tracheal lymph nodes, and a right-sided pleural effusion. Small cell lung cancer (extended disease; T2N2M6 stage IV) was diagnosed after a transbronchial biopsy. The concentrations of adrenocorticotropic hormone, cortisol, and parathyroid hormone in plasma were markedly elevated, and there was no circadian rhythm (336 pg/ml. more than 60.1 micrograms ml. and 805 pg/ml, respectively). Fluid obtained by thoracentasis had malignant cells, and the levels of adrenocorticotropic hormone and parathyroid hormone in the effusion (1120 pg/ml and 1810 pg/ml, respectively) were higher than those in serum, which indicates that these hormones were produced by the tumor cells. The patient received chemotherapy and responded well, but he died of respiratory failure 26 months later. The response rate to chemotherapy in elderly patients with lung cancer is said to be comparable to that in younger patients, but treatment may be difficult because of poor performance status and diminished physical capacity. Although patients with lung cancer complicated by Cushing's syndrome have a poor prognosis, this patient survived for more than 2 years after the disease was diagnosed.

Adrenal Cortex Hormones↗

PubMed1997

Tactile sensor method for thoracoscopic detection of intrapulmonary nodules.

We have developed a tactile sensor which can be used to quantify the hardness of objects and applied it to thoracoscopic surgery for the localization of small invisible nodules in the lung. The hardness properties of objects can be obtained as changes in the resonance frequency of the tactile sensor (delta f). When the sensor probe is moved over the lung surface, a delta f curve is depicted on the computer screen. When the sensor tip passes the area just above a target nodule, a spike is evoked in the delta f curve. In thoracoscopic surgery, tactile sensor was employed to detect a total or 42 nodules, 32 indeterminate and 10 metastatic, in 37 patients. All except two of these detected nodules, had been preoperatively demonstrated with computed tomography. Each nodule was detected successfully by recognizing the spot on the pleura, at which the spike of delta f curve was evoked, and resected thoracoscopically. All of the indeterminate nodules were diagnosed intraoperatively; 28 benign tumors and 4 primary carcinomas. In conclusion, our tactile sensor method can be a viable alternative for thoracoscopic detection of small and invisible pulmonary nodules.

Humans↗

PubMed1997

Nailfold capillary abnormalities in patients with Sjögren's syndrome and systemic lupus erythematosus.

It is unknown whether primary Sjögren's syndrome (pSS) and systemic lupus erythematosus (SLE) have the same nailfold capillary abnormality, although they show similarity in several clinical, immunological and genetic aspects. Microscopy of the nailfold capillaries was undertaken in the two diseases and the observed parameters were compared with age- and sex-matched controls using analysis of variance. pSS and SLE showed a different frequency in their clinical and laboratory findings, except for the presence of anti-SS-A/B antibodies. All nailfold capillary parameters showed significantly higher values than those of corresponding normal controls, although between pSS and SLE there was no significant difference. The results may indicate that pSS and SLE are part of a spectrum of disorder.

Adult↗

PubMed1997

Thoracoscopic implantation of a pacemaker lead: experimental study.

We have performed five thoracoscopic pacemaker lead implantations into the porcine myocardium. A small opening, approximately 2 cm in diameter, was made thoracoscopically in the pericardium overlying the apex of the left ventricle, avoiding phrenic nerve injury. Three screw-in type or two stab-in type standard sutureless unipolar epicardial electrodes were introduced through a trocar, and then screwed or stabbed into the myocardium near the apex of the left ventricle, avoiding the coronary vessels. Hemorrhage and arrhythmia were negligible during the procedures. Electrical tests of the pacing threshold and lead impedance after implantation of the leads revealed acceptable values in each lead. We conclude that thoracoscopic implantation of pacemaker leads is feasible, and may be used as a minimally invasive option when conventional transvenous techniques are unavailable or contraindicated.

Animals↗

PubMed1996

Different effects of various phospholipids on Ki-Ras-, Ha-Ras-, and Rap1B-induced B-Raf activation.

We have recently purified a Ki-Ras- and Ha-Ras-dependent extracellular signal-regulated kinase kinase from bovine brain and identified it as B-Raf protein kinase complexed with 14-3-3 proteins (Yamamori, B., Kuroda, S., Shimizu, K., Fukui, K., Ohtsuka, T., and Takai, Y. (1995) J. Biol. Chem. 270, 11723-11726). Moreover, we found that Rap1B as well as Ki-Ras and Ha-Ras stimulate the B-Raf activity. Since B-Raf contains a cysteine-rich domain originally found in protein kinase C as a domain responsible for interaction with phosphatidylserine (PS) and diacylglycerol or 12-O-tetradecanoylphorbol-13-acetate, we have examined here the effect of these compounds on the Ki-Ras-, Ha-Ras-, and Rap1B-induced activation of bovine brain B-Raf. Bovine brain PS enhanced Ki-Ras-stimulated B-Raf activity. Phosphatidic acid was slightly active, but other phospholipids, such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol (PI), PI-4-monophosphate, PI-4,5-bisphosphate, and PI-3,4,5-trisphosphate, were inactive. However, none of the above phospholipids affected the Ha-Ras-stimulated B-Raf activity, whereas PI, PS, phosphatidylethanolamine, and phosphatidic acid inhibited the Rap1B-stimulated B-Raf activity. Phosphatidylcholine or PI-4-monophosphate did not show any effect on the Rap1B-stimulated B-Raf activity. Synthetic PS with two unsaturated fatty acids, such as 1,2-dioleoyl-PS or 1,2-dilinoleoyl-PS, showed the same effect toward the Ki-Ras- and Rap1B-stimulated B-Raf activities, but synthetic PS with two saturated fatty acids, such as 1, 2-distearoyl-PS, was inactive. 12-O-Tetradecanoylphorbol-13-acetate did not affect the stimulatory or inhibitory effect of PS on the Ki-Ras- and Rap1B-stimulated B-Raf activities, respectively. PS did not affect the Ki-Ras-, Ha-Ras-, or Rap1B-independent basal B-Raf activity or the mitogen-activated protein kinase kinase or extracellular signal-regulated kinase activity. These results indicate that various phospholipids differently affect Ki-Ras-, Ha-Ras, and Rap1B-induced B-Raf activation.

Animals↗

PubMed1996

Expression of heat shock proteins in the developing rat retina.

Expression of three heat shock proteins (HSPs), HSP70, HSP90, and immunoglobulin heavy chain binding protein (Bip) was examined in the developing rat retina using Northern blot analysis. The expression of the inducible form of HSP70 remained uniformly low throughout the perinatal period until P5 and increased rapidly at P7. On the other hand, the constitutive form of HSP70, HSP90, and Bip were expressed constitutively in the rat retina throughout the developmental stage except P3-P5, at which a transient decrease of the expression was observed. The increase of inducible HSP70 mRNA at P7 may correspond to the functional maturation of photoreception in the visual nervous system and may be one of the stress responses to photostimulation. The potential roles of each HSP during development of the rat visual system are discussed.

Animals↗

PubMed1996

Analysis of the T-cell activation signaling pathway mediated by tyrosine kinases, protein kinase C, and Ras protein, which is modulated by intracellular cyclic AMP.

T-cell receptor (TCR) triggering by an anti-CD3 antibody or phytohemagglutinin (PHA) as well as the treatment with phorbol myristate acetate (PMA), a direct activator of protein kinase C (PKC), induces activation of Ras in T-lymphocytes (Downward, J. et al. (1990)) Nature 364, 719-723). In this paper, we studied the role of Ras in the process of TCR-mediated T-cell activation using a human lymphomic Jurkat cell line. The stimulatory effect of TCR cross-linking on Ras activation was inhibited by herbimycin A, a specific inhibitor of protein tyrosine kinases (PTKs), whereas PMA-induced Ras activation was not affected. On the other hand, calphostin C, a specific inhibitor of PKC, blocked not only PMA-induced, but also TCR-mediated formation of Ras.GTP. Furthermore, down-regulation of PMA-sensitive PKC severely impaired the activation of Ras in response to TCR-stimulation. Tyrosine-phosphorylation and translocation to the particulate fraction of phospholipase C-gamma 1 (PLC-gamma 1) were observed upon T-cell activation. Subcellular localization of PKC was also changed when the cells were stimulated with an anti-CD3 antibody or PMA. While TCR-stimulated translocation of PKC was observed only transiently, PMA-induced translocation of PKC was more sustained. These results suggest that the activation of PLC-gamma 1 by PTK and subsequent activation of PKC are important for TCR-mediated Ras activation in Jurkat cells. An activated form of Ras enhanced the activation of interleukin 2 (IL-2) promoter by TCR stimulation or PMA treatment, although the activated Ras by itself was insufficient for IL-2 promoter activation. On the other hand, a dominant-inhibitory Ras diminished almost completely the activation of IL-2 promoter induced by PMA plus calcium ionophore, indicating that Ras is essential for transduction of T-cell activation signals. Cholera toxin (CTX), which directly activates Gs alpha, is shown to inhibit the activation of IL-2 promoter. TCR-mediated Ras activation, tyrosine phosphorylation and translocation of cellular proteins including ZAP-70, PLC-gamma 1 , and PKC. An activated Gs alpha mutant as well as dibutylyl cAMP (dBcAMP) also showed similar inhibitory effects.

Cell Compartmentation↗

PubMed1996

Activation of brain B-Raf protein kinase by Rap1B small GTP-binding protein.

Rap1 small GTP-binding protein has the same amino acid sequence at its effector domain as that of Ras. Rap1 has been shown to antagonize the Ras functions, such as the Ras-induced transformation of NIH 3T3 cells and the Ras-induced activation of the c-Raf-1 protein kinase-dependent mitogen-activated protein (MAP) kinase cascade in Rat-1 cells, whereas we have shown that Rap1 as well as Ras stimulates DNA synthesis in Swiss 3T3 cells. We have established a cell-free assay system in which Ras activates bovine brain B-Raf protein kinase. Here we have used this assay system and examined the effect of Rap1 on the B-Raf activity to phosphorylate recombinant MAP kinase kinase (MEK). Recombinant Rap1B stimulated the activity of B-Raf, which was partially purified from bovine brain and immunoprecipitated by an anti-B-Raf antibody. The GTP-bound form was active, but the GDP-bound form was inactive. The fully post-translationally lipid-modified form was active, but the unmodified form was nearly inactive. The maximum B-Raf activity stimulated by Rap1B was nearly the same as that stimulated by Ki-Ras. Rap1B enhanced the Ki-Ras-stimulated B-Raf activity in an additive manner. These results indicate that not only Ras but also Rap1 is involved in the activation of the B-Raf-dependent MAP kinase cascade.

3T3 Cells↗

PubMed1996

Conversion of chlorophyll b to chlorophyll a via 7-hydroxymethyl chlorophyll.

Chlorophyll b is synthesized from chlorophyll a by the oxidation of the methyl group on the ring B of the tetrapyrrole ring to the formyl group. Previously, we reported that chlorophyllide b could be converted to chlorophyll a in isolated cucumber etioplasts indicating the conversion of chlorophyll b to chlorophyll a. To identify the intermediate molecule, we used barley etioplasts instead of cucumber. Chlorophyll a and an additional pigment were found after incubation of chlorophyllide b with isolated barley etioplasts. The pigment has the same retention time and absorption spectrum as 7-hydroxymethyl chlorophyll, which has the hydroxymethyl group on ring B instead of the formyl group of chlorophyll b. Authentic 7-hydroxymethyl chlorophyll was prepared by reduction of chlorophyll b by NaBH4. Chlorophyll a accumulated during the incubation of 7-hydroxymethyl chlorophyllide with etioplasts. These findings indicate that chlorophyll b is converted to chlorophyll a via 7-hydroxymethyl chlorophyll. Chlorophyll b and 7-hydroxymethyl chlorophyll accumulated within a short period of incubation of chlorophyllide b with etioplasts. However, chlorophyll a accumulated with a concomitant decrease of chlorophyll b and 7-hydroxymethyl chlorophyll. These observations also suggest that chlorophyll b is converted to 7-hydroxymethyl chlorophyll and then to chlorophyll a. Both steps required ATP.

Carbon Radioisotopes↗

PubMed1996

Glucocorticoid-mediated gene suppression of rat cytokine-induced neutrophil chemoattractant CINC/gro, a member of the interleukin-8 family, through impairment of NF-kappa B activation.

The glucocorticoid dexamethasone inhibited the production of the rat cytokine-induced neutrophil chemoattractant CINC/gro, a counterpart of human melanoma growth-stimulating activity that belongs to the interleukin-8 (IL-8) family, in the normal rat kidney epithelial cell line NRK-52E stimulated with interleukin-1 beta (IL-1 beta), lipopolysaccharide, or tumor necrosis factor alpha. The accumulation of CINC/gro mRNA induced by these activators was also decreased comparably by dexamethasone. A nuclear run-on assay revealed that dexamethasone decreased the IL-1 beta-induced transcription of the CINC/gro gene. The half-life of CINC/gro mRNA transcripts did not change significantly after exposure to dexamethasone, suggesting that this glucocorticoid acts mainly at the transcriptional level. Transfection with luciferase expression vectors containing 5'-deleted and mutated CINC/gro gene sequences demonstrated that the 5'-flanking region containing the NF-kappa B binding site is involved in the IL-1 beta- and dexamethasone-induced activation and repression of the CINC/gro gene expression, respectively. Furthermore, a tandem repeat of the NF-kappa B sequence in the CINC/gro gene conferred the inducibility by IL-1 beta and suppression of luciferase activity by dexamethasone. In an electrophoretic mobility shift assay, dexamethasone diminished the IL-1 beta-induced formation of NF-kappa B complexes, which consisted of p65 and p50. Western blotting revealed that dexamethasone inhibited the IL-1 beta-induced translocation of p65 from the cytoplasm into the nucleus, while the nuclear level of NF-kappa B p50 remained almost unchanged. In addition, the degradation of I kappa B-alpha induced by IL-1 beta was not inhibited by dexamethasone. These results indicated that the suppression of the CINC/gro gene transcription by glucocorticoid occurs through the impairment of NF-kappa B activation, possibly by interference with the translocation of NF-kappa B p65 from the cytoplasm into the nucleus, thereby suppressing transactivation of the CINC/gro gene.

Animals↗

PubMed1996

Enhanced susceptibility to transglutaminase reaction of alpha-lactalbumin in the molten globule state.

The susceptibility of alpha-lactalbumin to transglutaminase reactions was studied using an enzyme from Streptoverticillium which can catalyze the reactions irrespective of the presence or absence of Ca2+. Transglutaminase-catalyzed polymerization of alpha-lactalbumin in the native state occurred to a very limited extent. Transformation from the native state to the molten globule state brought about by Ca(2+)-removal from holo-alpha-lactalbumin enhanced the polymerization of the protein catalyzed by transglutaminase. The incorporation of Carbobenzoxy-Gln-Gly into alpha-lactalbumin through the enzyme reaction was investigated to determine the amounts of lysine residues which are present at molecular surface and available to the enzyme. There was no significant difference in the amount of available lysine residues between the native and the molten globule molecule. However, the amount of surface glutamine residues incorporated with monodansylcadaverine by transglutaminase was remarkably higher in the molten globule state than that in the native state. The monodansylcadaverine-incorporated site of alpha-lactalbumin in the molten globule state was identified as Gln-54 by amino-acid sequence analysis of fluorescence-labeled peptides separated from chymotryptic digests of the protein. Possible reason for selective labeling of Gln-54 in molten globule alpha-lactalbumin was proposed.

Amino Acid Sequence↗

PubMed1996

Granulomatous mastitis diagnosed and followed up by fine-needle aspiration cytology, and successfully treated by corticosteroid therapy: report of a case.

A 36-year-old woman presented to our hospital with a rapidly growing lump in her left breast. Fine-needle aspiration (FNA) cytology of the mass revealed many epithelioid cells admixed with multinucleated Langhans-type giant cells, neutrophils, lymphocytes, and stromal cells, leading to a diagnosis of granulomatous mastitis. This report describes the clinical course of this patient in whom granulomatous mastitis was successfully treated with corticosteroid therapy. Special reference is made to the usefulness of FNA cytology in the diagnosis and follow-up of this disease.

Adult↗

PubMed1996

Excellent survival in a subgroup of patients with intrapulmonary metastasis of lung cancer.

BACKGROUND: Recently, intrapulmonary metastases in non-small cell lung cancer have been considered to have less influence on prognosis than extrapulmonary metastases. We report a subgroup found among patients with intrapulmonary metastases showing a good prognosis. METHOD: A retrospective study was performed on 236 consecutive patients with non-small cell lung cancer who underwent surgical resection of their tumors. Intrapulmonary metastases were found histopathologically in 50 of them, and their clinicopathologic features were investigated. RESULTS: Analysis of postsurgical results revealed a subgroup of patients showing excellent prognosis (n = 15). They had well-differentiated adenocarcinomas with bronchioloalveolar spread and pT1-2 N0, without vascular or lymphangitic invasion. Their actuarial 5-year survival rate was 100%, with a mean survival interval to date of 28 months. However, none of the other 35 patients survived for 5 years, with a mean survival interval to date of 11 months. CONCLUSIONS: We have clarified that patients with histopathologically diagnosed intrapulmonary metastases from non-small cell lung cancer do not constitute a homogeneous group. Pulmonary metastases with good prognosis, which are considered to be hematogenous metastases, may be benign lesions such as adenomatous or atypical adenomatous hyperplasias mimicking malignant tumors.

Adenocarcinoma↗

PubMed1996

Tuberculous pseudoaneurysm of the thoracic aorta.

Tuberculous pseudoaneurysm has been reported to be a fatal, but rare complication of tuberculosis. We report a case of a 68-year-old man who underwent successful surgical treatment for a tuberculous pseudoaneurysm of the thoracic aorta with bronchial communication, and review previous reports of patients who also underwent operation for similar lesions, focusing especially on the pathway of infection to the aorta.

Aged↗