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Biomedical subjects

T Ota

Publications and source records attributed to T Ota.

At least 55 records · Page 3Linked to original sources

Prediction of contractile reserve by cyclic variation of integrated backscatter of the myocardium in patients with chronic left ventricular dysfunction.

OBJECTIVE: To clarify whether assessment of the acoustic properties of the myocardium at rest can predict contractile reserve in patients with chronic left ventricular dysfunction. METHODS: 23 patients (mean (SD) age 63 (12) years) with chronic left ventricular dysfunction were studied. The magnitude of cardiac cycle dependent variation of integrated backscatter (CVIB) of the myocardium was measured at rest in the basal and mid segment of the septum and posterior wall of the left ventricle, using a real time two dimensional integrated backscatter imaging system. The results were compared with the percentage wall thickening and the wall motion at rest and during low dose dobutamine infusion. The wall motion was graded as normal, hypokinetic, or akinetic and contractile reserve was considered present when an akinetic or hypokinetic segment improved during dobutamine infusion. RESULTS: The CVIB at rest correlated with per cent wall thickening at rest and during dobutamine infusion (at rest, r = 0.61, p < 0.0001, during dobutamine, r = 0.76, p < 0.0001). Of the 76 segments examined, 27 showed contractile reserve. The mean CVIB at rest was significantly greater in segments with contractile reserve than in those without (p < 0.0001). CVIB above 3 dB at rest predicted segments with contractile reserve with a sensitivity and specificity of 81% and 60%, respectively (p < 0.0001). CONCLUSIONS: CVIB reflected not only myocardial contractility but also the functional capacity of the myocardium. It predicted segmental contractile reserve in patients with chronic left ventricular dysfunction.

Adult↗

A case of systemic lupus erythematosus complicated with multicentric reticulohistiocytosis (MRH): successful treatment of MRH and lupus nephritis with cyclosporin A.

We document the first case of a patient who manifested systemic lupus erythematosus (SLE) complicated with multicentric reticulohistiocytosis (MRH). Neither intravenous steroid nor cyclophosphamide (CY) pulse therapies were fully effective against multiple MRH-related tumors that appeared on the left ankle joint and interphalangeal joints of both hands. In contrast, treatment with cyclosporin A (CyA) resulted in a marked regression of these nodules within one month, together with a complete remission of both MRH and lupus nephritis. We propose CyA as an alternative choice for the treatment of MRH.

Adult↗

Novel method for assessing myocardial perfusion: visualization and measurement of intramyocardial coronary blood flow in the entire left ventricular wall using contrast enhanced, high frequency Doppler echocardiography.

Using a high frequency ultrasonic transducer, intramyocardial coronary blood flow (IM-CBF) can be visualized and evaluated during hemodynamic changes in the anterior wall and septum of the left ventricle (LV). We tested the hypothesis that detection and quantitative measurement of IM-CBF of entire LV segments are feasible using a high frequency ultrasonic transducer in conjunction with intravenous contrast injection in vivo. A 3 - 8 MHz transducer was used to image and measure IM-CBF in 10 anesthetized dogs. We obtained a color Doppler image of IM-CBF in the LV short-axis view after intravenous Levovist injection (25 mg/ml). The IM-CBF velocity was recorded using spectral Doppler in the antero-septal and infero-posterior wall of closed chest dogs and in the entire LV after opening the chest. A significant increase in IM-CBF velocity was observed in all LV regions after adenosine 5'- triphosphate (ATP) administration. After Levovist(TM) injection, the visualization of IM-CBF was improved and the spectral Doppler pattern of coronary flow velocity was clarified compared to baseline. IM-CBF was assessed in the antero-septal region of the LV before and after left anterior descending coronary artery occlusion. A high frequency ultrasonic transducer in conjunction with intravenous contrast injection improved IM-CBF visualization, enabling quantitative evaluation of the intramyocardial coronary circulation in the entire LV after coronary occlusion and hyperemia. This study may represent a step towards noninvasive assessment of myocardial perfusion before and after coronary reperfusion.

Animals↗

Sperm motion analysis in rats treated with adriamycin and its applicability to male reproductive toxicity studies.

Adriamycin (ADR), an anticancer drug which induces testicular toxicity, was administrated to Slc:SD male rats at doses of 0.5, 1.0, and 2.0 mg/kg intravenously once a week for 4 weeks. The males treated with ADR were mated with untreated females, and sperm analyses (motion, count, and morphology) were performed. Sperm motion was analyzed by Hamilton-Thorne Sperm analyzer (HTM-IVOS) to investigate the useful parameters. Copulated females were necropsied at Day 13 of gestation, and reproductive status was evaluated. In ADR-treated groups, the testicular weight was dose-dependently decreased. Associated with this decrease was a depletion of the number of spermatogonia noted histopathologically at all dosage levels. Sperm morphological abnormalities, which were classified as tailless sperm and/or no-hook head sperm, were increased in both the 1.0 and 2.0 mg/kg groups. The males treated with ADR at 1.0 and 2.0 mg/kg had a decreased number of sperms per cauda epididymis. In sperm motion analysis, decreases in the percentage of motile sperm, percentage of progressive sperm, and sperm velocity (straight line velocity and curvilinear velocity) were noted at 2.0 mg/kg. Impaired fertility was noted at 2.0 mg/kg in the form of decreased numbers of implantations and live embryos, and an increased number of pre-implantation losses. In conclusion, ADR induced deterioration of sperm motion and sperm content, which were responsible for the adverse effect on male fertility. The most sensitive indicators to detect male reproductive toxicity induced by ADR were testicular weight and histopathological findings in the testis. Among the parameters generated by HTM-IVOS, the percentage of motile sperm, the percentage of progressive sperm, and sperm velocity are useful for assessing male fertility.

Animals↗

[Pulmonary hypertension associated with refractory hyperthyroidism: a case report].

A 25-year-old woman was admitted to our hospital with goiter. The diagnosis was Grave's disease. Diagnostic transthoracic echocardiography revealed a hyperdynamic stage of the heart with right ventricular dilation. Doppler echocardiography showed mild to moderate tricuspid regurgitation and elevated systolic right ventricular pressure. Right heart catheterization revealed high cardiac output (9.49 l/min) and pulmonary hypertension (57 mmHg) with increased pulmonary vascular resistance and total pulmonary resistance. No intracardiac shunts were detected. Since neither thiomazole nor propylthiouracil was effective and both caused side effects, she underwent subtotal thyroidectomy. After the surgery, pulmonary hypertension improved and cardiac output normalized, but without normalization of pulmonary vascular resistance and total pulmonary resistance. Reversible pulmonary hypertension may occur in patients with hyperthyroidism. Increased pulmonary blood flow and sustained high pulmonary artery resistance were suspected as the causes of pulmonary hypertension. In addition, pulmonary endothelial dysfunction as a result of sustained increased pulmonary blood flow could be another cause of pulmonary hypertension.

Adult↗

SEA0400, a novel and selective inhibitor of the Na+-Ca2+ exchanger, attenuates reperfusion injury in the in vitro and in vivo cerebral ischemic models.

The effect of the newly synthesized compound 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline (SEA0400) on the Na+-Ca2+ exchanger (NCX) was investigated and compared against that of 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea (KB-R7943). In addition, the effects of SEA0400 on reperfusion injury in vitro and in vivo were examined. SEA0400 was extremely more potent than KB-R7943 in inhibiting Na+-dependent Ca2+ uptake in cultured neurons, astrocytes, and microglia: IC50s of SEA0400 and KB-R7943 were 5 to 33 nM and 2 to 4 microM, respectively. SEA0400 at the concentration range that inhibited NCX exhibited negligible affinities for the Ca2+ channels, Na+ channels, K+ channels, norepinephrine transporter, and 14 receptors, and did not affect the activities of the Na+/H+ exchanger, Na+,K+-ATPase, Ca2+-ATPase, and five enzymes. SEA0400, unlike KB-R7943, did not inhibit the store-operated Ca2+ entry in cultured astrocytes. SEA0400 attenuated dose- dependently paradoxical Ca2+ challenge-induced production of reactive oxygen species, DNA ladder formation, and nuclear condensation in cultured astrocytes, whereas it did not affect thapsigargin-induced cell injury. Furthermore, administration of SEA0400 reduced infarct volumes after a transient middle cerebral artery occlusion in rat cerebral cortex and striatum. These results indicate that SEA0400 is the most potent and selective inhibitor of NCX, and suggest that the compound may exert protective effects on postischemic brain damage.

Aniline Compounds↗

Real-time, volumetric echocardiography: usefulness of volumetric scanning for the assessment of cardiac volume and function.

BACKGROUND: A novel imaging system has been introduced which uses a dedicated two-dimensional echo probe for rapid beam forming to scan a pyramidal volume in real time. Real-time volumetric echocardiography has the potential to determine accurate cardiovascular anatomy, volume and function in the beating heart without reconstructions. The results of animal and human studies using volumetric echocardiography are evaluated for the potential for clinical applications. IMAGING METHODOLOGY: A new type of ultrasound imaging, high-speed volumetric scanning based on phased array principles permits real-time three-dimensional, volumetric echocardiography (real-time 3-DE). The system requires no off-line reconstruction techniques, thus enabling dynamic three-dimensional visualization and quantification of the heart in real time using a transthoracic approach. Real-time 3-DE uses a 2-D matrix phased array transducer. Image formation employs 16:1 parallel processing to scan a pyramidal volume composed of multiple steering directions in the azimuth dimension and in the elevation dimension. The finished transducer is mounted in a hand-held case with a circular aperture of 16 mm diameter. The array consists of approximately 1,600 elements, operating at 2.5 MHz. Real-time 3-DE permits simultaneous, multiple plane display of two sector arcs (B-scans) and C-scan (parallel to the transducer face or inclined) on a single monitor, conveying the three-dimensional nature of the ultrasound data. This system also allows these planes to be angled for extra diagnostic flexibility. The motion of all the structures during the cardiac cycle can be evaluated in dynamic mode. METHODS: Real-time 3-DE was assessed for accuracy of volume measurement by measuring the volume of balloons of different size and shape, and the hearts of 15 closed chest dogs with myocardial contrast enhancement, and compared to the volumes measured by left ventricular angiography in the dogs. Real-time 3-DE was used to evaluate the endocardial border determination of the entire left ventricle by injecting contrast agent in 12 patients. The endocardial border determination of each segment was scored, and the endocardial border score index calculated. Both real-time 3-D images and cine magnetic resonance imaging (MRI) were performed in 16 patients to assess the accuracy of volume measurement of the left ventricle in humans. The endocardial border of the left ventricle was manually traced, and the volumes calculated by Simpson's rule. RESULTS: The volumes measured by real-time 3-DE correlated well with the true volumes for different sizes of balloon and for asymmetric balloons. The end-diastolic volume and end-systolic volume linear correlation of real-time 3-DE versus angiography measurements using manual tracing in vivo also gave a good correlation (r = 0.97, p < 0.001; r = 0.92, p < 0.01). Fifty-eight of 192 segments were rated as good at baseline and 143 rated as good after Levovist injection. Endocardial border determination was improved by Levovist injection in 100 of 137 segments (74.6%). The endocardial border score index was significantly higher after Levovist administration than at baseline (p < 0.003). The end-diastolic volume and end-systolic volume of the left ventricle measured by real-time 3-DE in humans correlated well with those measured by MRI (end-diastolic volume: r = 0.97, p < 0.001; end-systolic volume: r = 0.96, p < 0.001). CONCLUSIONS: Transthoracic real-time, volumetric echocardiography opens a new and exciting field of echocardiography. The results of these studies demonstrate that this system can accurately measure the ventricular volume and function without use of geometric assumptions. This volumetric mode or V-mode scanning is a new imaging modality that provides a practical methodology to investigate important clinical and research questions.

Animals↗

[Intramedullary spinal cord metastasis of lung adenocarcinoma causing Brown-Séquard Syndrome].

A 36-year-old woman admitted to our hospital because of numbness in the left limbs and weakness in the right arm, and was subsequently given a diagnosis of intramedullary spinal cord metastases from lung cancer. The patient had lung adenocarcinoma with metastases to the brain, spine and lymph nodes. Occipital craniotomy, radiation therapy and chemotherapy were performed on the lesions in the year following June 1994. In June 1995, however, she complained of numbness in the left limbs and weakness in the right arm. Compatible with her neurological manifestation, MRI demonstrated tumors in the right side of the cord at the spinal level of C3-4 and C7-Th1, both of which were of high density in T2-enhanced conditions with enhancement by gadolinium-diethylenetriamine pentaacetic acid. No invasion from spinal metastasis was detected by CT, scintigraphy or MRI. We therefore diagnosed her manifestation as Brown-Séquard syndrome caused by intramedullary spinal cord metastatic tumors of lung adenocarcinoma. In order to avoid paraplegia and dysfunction of the bladder and bowel, radiation therapy of the cord lesions with total dose of 44 Gy was performed. Her neurologic manifestation was improved, restoring her quality of life, as the tumor size estimated by MRI decreased. Four months later, however, she died of lung adenocarcinoma that developed accompanied with severe peritonitis carcinomatosa and multiple metastases.

Adenocarcinoma↗

Optic cup enlargement followed by reduced optic nerve head circulation after optic nerve stimulation.

PURPOSE: To investigate changes in optic nerve head (ONH) circulation, visual evoked potentials (VEPs), and ONH cupping after stimulation of the optic nerve. METHODS: Electrodes were fixed above the optic chiasma in rabbits under general anesthesia. Screw-type electrodes for VEP recording were fixed on the dura. ONH circulation, intraocular pressure (IOP), and blood pressure (BP) were measured after the passage of a current of 0.1 mA for 0.1 second (weak stimulation), 1 mA for 1 second (moderate), 5 mA for 10 seconds (strong), or 25 mA for 10 seconds (severe). Normalized blur (NB), indicative of tissue blood flow and velocity, was measured in the ONH after each stimulation, by using a laser speckle circulation analyzer. Changes in VEP and ocular fundus were also recorded. The ratio of cup area (CA) to disc area (DA) was measured before and 4 weeks after stimulation. After all experiments, the ONH was histologically examined. RESULTS: Weak stimulation increased NB in ONH for 10 minutes, whereas strong or severe stimulation significantly decreased NB for a longer time, in a dose-dependent manner. BP showed no significant change, except with severe stimulation. IOP was not significantly changed. VEP amplitude was reduced 30 minutes after strong stimulation. The CA-to-DA ratio was significantly increased 4 weeks after strong stimulation. In some rabbits, disc hemorrhage occurred, followed by enlargement of disc cupping, with slight gliosis. CONCLUSIONS: Electrical stimulation of the optic nerve changed ONH circulation and VEPs and increased disc cupping. This technique warrants further investigation as an experimental model for normal-tension glaucoma.

Animals↗

[A case of cerebellar glioblastoma with massive cerebellar hemorrhage].

A case is reported of glioblastoma multiforme (GM) of the cerebellum associated with an intracerebellar hemorrhage. A 54-year-old male was admitted to our hospital with sudden onset of headache and nausea. CT scan showed right intracerebellar hemorrhage. The patient received conservative therapy and was discharged without any neurological deficits. However a second cerebellar hemorrhage attacked him ten days after discharge. His level of consciousness deteriorating, he underwent suboccipital craniectomy and the hematoma with the surrounding elastic tissues was excised. There were no findings suggesting hemorrhage within the tumor on the preoperative neuroimagings, but histological examination confirmed GM with massive hemorrhage. To our knowledge, only 2 cases of cerebellar GM with massive hemorrhage have been reported in the literature. Our case indicates cerebellar GM should be taken into account as a possible cause of cerebellar hemorrhage.

Cerebellar Diseases↗

The molecular characterization and tissue distribution of the human cysteinyl leukotriene CysLT(2) receptor.

Cysteinyl leukotrienes (CysLTs), slow-reacting substances of anaphylaxis, are lipid mediators known to possess potent proinflammatory action. Pharmacological studies using CysLTs indicate that at least two classes of G protein-coupled receptors (GPCRs), named CysLT(1) and CysLT(2), exist; the former is sensitive and the latter is resistant to the CysLT(1) antagonists currently used to treat asthma. Although the CysLT(1) receptor gene has been recently cloned, the molecular identity of the CysLT(2) receptor has remained elusive. Here we show that the pharmacological profile of an orphan GPCR (PSEC0146) is consistent with that of the CysLT(2) receptor. In human embryonic kidney 293 cells that express the PSEC0146 cDNA, leukotriene C(4) (LTC(4)) and leukotriene D(4) (LTD(4)) induce equal increases in intracellular calcium mobilization; these increases are not affected by CysLT(1) antagonists. Additionally, [(3)H]LTC(4) specifically binds to membranes from COS-1 cells transiently transfected with PSEC0146. Large amounts of the PSEC0146 mRNA are found in human heart, placenta, spleen, and peripheral blood leukocytes but not in the lung and the trachea. Pharmacological feature and expression studies will eventually lead to a better understanding of the classification of CysLT receptors, possibly leading to a reconsideration of the pathological and physiological role of CysLTs.

Animals↗

[Hyperferritinemia and diseases].

Ferritin is the principal iron storage protein participating in iron metabolism. As serum ferritin levels often reflect the amount of storage iron in the body, physicians have measured serum ferritin in order to evaluate iron deficiency or overload. Although a rise in serum ferritin concentration occurs in iron overload, hyperferritinemia without it has been reported in some inflammatory diseases and malignancies. Some cytokines have been reported to be responsible for the elevation of ferritin production. Studies on serum isoferritin in adult Still's disease and other diseases, especially measurements of the proportion of glycosylated ferritin, have been widely accepted. Pathophysiological properties of the increased serum ferritin are not clear. However, we should be aware that the hyperferritinemia is not a result, but is profoundly participating in the disease process.

Biomarkers↗

Statistical analysis of the 5' untranslated region of human mRNA using "Oligo-Capped" cDNA libraries.

We constructed 34 types of human "full-length enriched" and "5'-end enriched" cDNA libraries based on the "Oligo-Capping" method. We randomly picked and sequenced 10,000 clones from these libraries. BLAST analysis showed that about 50% of the cDNAs were identical to known genes. Among them, we selected 954 species of cDNA that should represent the entire sequence from the mRNA start sites. Compared with previously reported sequences, they were on average 45 bp longer in the 5'-end. Using these cDNA data, we statistically analyzed the sequence features of the 5'UTR. The average length of the 5'UTR was 125 bp, and there was little correlation with the corresponding mRNA length (correlation coefficient = 0.26). Of the 954 species of 5'UTR, 459 contained no in-frame terminator codon, which is against the common belief. Two hundred seventy-eight species contained at least one ATG codon upstream of the initiator ATG codon. We identified 569 upstream ATGs, in total, 63% of which adequately satisfied Kozak's criteria. These findings are contrary to the typical translation initiation model, which states that translation is initiated from the "first" ATG codon.

5' Untranslated Regions↗

Molecular cloning of mouse thioredoxin reductases.

We screened clones for thioredoxin reductase genes with a degenerate PCR-based strategy and have isolated two novel cDNA clones from a mouse thymocyte cDNA library. These encode two distinct thioredoxin reductases (TrxR1 and TrxR2) with 499 and 527 amino acid (aa) residues and calculated molecular masses of 54.5 kDa and 56.8 kDa respectively. These proteins share 90% and 50% aa sequence identity with those of previously cloned human TrxR, containing the redox-active cysteines, FAD binding domain, and the selenocysteine (SeCys) insertion sequence, which is composed of a putative stem-loop sequence located in the 3'-untranslated region (UTR). TrxR2 showing less homology to human TrxR has a mitochondrial translocation signal and a mitochondrial prepeptide protease cleavage site in the N-terminal domain. Transient expression experiments of each gene as fusion proteins with Xpress-tagged protein in NIH 3T3 cells indicated that TrxR1 was localized in the nucleus and cytoplasm and TrxR2 in the mitochondria. Furthermore, we mapped the TrxR1 gene to chromosome 10 (placed 1.71 cR from D10Mit42, lod>3.0) and the TrxR2 gene to chromosome 16 (placed 22.56 cR from D16Mit34, lod>3.0). Thus, the mouse has at least two distinct nuclear genes for TrxR that have different translocation sites in the cell.

3T3 Cells↗

Evolution of vertebrate immunoglobulin variable gene segments.

Evolution of Ig V gene segments are generally characterized by (a) evolution by "the birth and death process" and (b) diversifying selection. However, the detailed evolutionary pattern of V gene segments varies among species due to the fact that the humoral immune system itself has changed during vertebrate evolution. The change in somatic diversification system coupled with the change in lymphocyte development has imposed a significant impact on the evolution of Ig genes. In order to understand the evolution of immunological genes it is important to view it in the context of the evolution of the entire immune system itself.

Animals↗

Development of chimeric molecules for recognition and targeting of antigen-specific B cells in pemphigus vulgaris.

Pemphigus vulgaris (PV) is an autoimmune blistering disease characterized by circulating pathogenic IgG antibodies against desmoglein 3 (Dsg3). The purpose of this study was to develop chimeric molecules for specific recognition and elimination of autoimmune B cells in PV. Mouse hybridoma cell lines producing anti-Dsg3 antibody (5H10, 12A2) were developed as an in vitro model system for targeting B cells. Dsg3-GFP, a baculoprotein containing the entire extracellular domain of Dsg3 fused with green fluorescence protein, recognized and targeted the hybridoma cells through their surface immunoglobulin receptors in an antigen-specific way. The epitopes of these monoclonal antibodies were mapped on the amino terminal EC1 and part of EC2, a region considered functionally important in cadherins. Chimeric toxin molecules containing the mapped region (Dsg3deltaN1) and modified Pseudomonas exotoxin were produced in bacteria (Dsg3deltaN1-PE40-KDEL, PE3 7-Dsg3deltaN1-KDEL) and tested in vitro on hybridoma cell lines. The chimeric toxins, but not Dsg3deltaN1 alone, showed dose-dependent toxic activity with a reduction in hybridoma cell number to 40-60% of toxin-negative control cultures, compared with little or no effect on anti-Dsg3-negative hybridoma cells. Furthermore, these toxins showed toxic effects on anti-Dsg3 IgG-producing B cells from Dsg3deltaN1-immunized mice, with a 60% reduction in cell number compared with Dsg3deltaN1 alone. Thus, specific recognition and targeting of antigen-specific B cells in PV was demonstrated; this strategy may hold promise as a future therapeutic option for PV and other autoimmune diseases.

ADP Ribose Transferases↗

Correlation dimension of the human sleep electroencephalogram.

Sleep electroencephalogram (EEG) was analyzed by nonlinear analysis. Polysomnography of a healthy male subject was analyzed and the correlation dimension was calculated. The mean correlation dimensions decreased from stage 'awake' to stages 1, 2 and 3, and increased during rapid eye movement (REM) sleep. These results were also seen at every sleep cycle. During each sleep cycle the correlation dimensions decreased for slow wave sleep, then increased for REM sleep. The mean correlation dimension of the sleep EEG in the second half of the night was significantly higher than those in the first half of the night. A significant change was seen both during REM sleep as well as in sleep stage 2. Nonlinear analysis may be a useful method in the analysis of the entire sleep electroencephalogram.

Adult↗