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Biomedical subjects

T Mitsuhashi

Publications and source records attributed to T Mitsuhashi.

At least 37 records · Page 2Linked to original sources

Torsades de pointes ventricular tachycardia induced by mosapride and flecainide in the presence of hypokalemia.

We report a 68-year-old man who developed torsades de pointes ventricular tachycardia induced by combined use of mosapride and flecainide. He had a permanent pacemaker (DDD mode) implanted because of sick sinus syndrome (bradytachy syndrome) 6 years earlier. The patient had started taking mosapride for upper abdominal discomfort 2 weeks earlier. On admission, ECG showed prolongation of the QTc interval from 0.48 to 0.56 seconds and self-terminating torsades de pointes occurred. We considered that this proarrhythmia was induced by mosapride in combination with antiarrhythmic agents.

Aged↗

Circadian variation of autonomic nervous activity in patients with multivessel coronary spasm.

The present study investigated whether the circadian rhythm of sympathovagal activity is related to the severity of coronary spasm or multivessel coronary spasm. Heart rate variability was examined in 22 consecutive patients with vasospastic angina provoked by intracoronary injection of acetylcholine, who had either multivessel spasm (Group M, n=11 ) or single vessel spasm (Group S, n= 11), in 20 subjects without coronary artery disease (Group C) and 20 patients with effort angina who had organic coronary artery stenosis (Group E). The frequency domain indices were analyzed, including low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-0.4Hz), the latter being an index of efferent parasympathetic activity, and the ratio (L/H) as an index of sympathovagal balance. The circadian variation of the parameters was analyzed by its pattern and was quantified by the difference of the mean values between daytime and nighttime. Although the HF power increased during nighttime in Groups C and S, this increase was attenuated in Groups E and M. The circadian variation of the L/H ratio (ie, a drop during nighttime) was smaller in the S and M groups than in Groups C and E. Accordingly, in Group M, the circadian variation of both sympathetic and parasympathetic nervous activity was attenuated, but in Group S, the variation of sympathetic nervous activity, but not parasympathetic nervous activity, was decreased. These data suggest that relatively enhanced sympathetic nervous activity at night may be involved in the mechanism underlying multivessel coronary spasm.

Acetylcholine↗

Neurogenic pulmonary edema and large negative T waves associated with subarachnoid hemorrhage.

We describe a 72-year-old woman with hypertension who developed acute neurogenic pulmonary edema and giant negative T waves on electrocardiography (ECG) due to subarachnoid hemorrhage. The patient was alert and complained of precordial chest discomfort, dyspnea and shoulder stiffness. Echocardiography demonstrated normal left ventricle contraction with hypertrophy. Computed tomography (CT) and subsequent cerebral angiography revealed subarachnoid hemorrhage and saccular aneurysm at the anterior communicating artery. It is important to consider the possibility of subarachnoid hemorrhage when a patient shows pulmonary edema and ECG abnormalities even without typical clinical signs of subarachnoid hemorrhage.

Aged↗

Computer image analysis for prediction of carcass composition from cross-sections of Japanese Black steers.

Carcasses from Japanese Black steers were used to obtain prediction equations for carcass composition from information derived by computer image analysis of carcass cross-section images. The total weights of lean, fat, and bone were obtained from the left sides of 55 carcasses (Data Set I) and 18 carcasses (Data Set II) by physical dissection. The information such as total lean, fat, and bone areas in the cross-sections; muscle area, muscle circumference, short and long radius axis lengths, and direction of long radius axis; and geometric distance between any two muscle centers of gravity was obtained by scanning and image analysis of pictures of the cross-sections of the beef side at the 6th/7th rib interface. The coefficients of determination of the multiple regression equations estimated from Data Set I for kilograms of lean, fat, and bone were 0.76, 0.82, and 0.69, respectively, whereas for the percentages of lean, fat, and bone they were 0.57, 0.66, and 0.42, respectively. The multiple regression equations from Data Set I was applied to Data Set II in order to test the applicability of the prediction equations obtained. The correlation coefficients between the value predicted by the multiple regression equation and the measurement obtained by physical dissection for kilograms of lean, fat, and bone were 0.71, 0.72, and 0.70, respectively, whereas those for the percentages of lean, fat, and bone were 0.63, 0.44, and 0.29, respectively. The results indicate that the information obtained from the carcass cross-sections by the computer image analysis method can be used to predict carcass composition in Japanese Black steers.

Adipose Tissue↗

[A case of pseudomyxoma peritonei with a pancreatic cancer treated by the intraperitoneal administration of cisplatinum].

A 55-year-old woman underwent laparotomy with a diagnosis of pseudomyxoma peritonei associated with a pancreatic cancer. The peritoneal cavity was filled with much gelatinous material, which was removed as much as possible by suction and by hand. Distal pancreatectomy, appendectomy and bilateral oophorectomy were performed. The peritoneal cavity was washed by saline and 5% glucose solution followed by dispersion of 100 mg of cisplatinum. The intraperitoneal chemotherapy was performed once every two weeks after the operation through an indwelling catheter. Histological examination revealed a mucinous cystadenocarcinoma of the pancreas, causing pseudomyxoma peritonei. The patient is in a good health 4 years after the operation.

Adenocarcinoma↗

Lysozyme enhances renal excretion of advanced glycation endproducts in vivo and suppresses adverse age-mediated cellular effects in vitro: a potential AGE sequestration therapy for diabetic nephropathy?

BACKGROUND: Lysozyme (LZ), a host-defense protein, contains an 18 amino-acid domain with high affinity binding for sugar-derived proteins or lipids, called advanced glycation endproducts (AGE), that are implicated in diabetes- and age-dependent complications (DC). MATERIALS AND METHODS: A) The effects of LZ on AGE- removal were tested in vivo. LZ was injected (200 ug/day, i.p., X2 weeks) in non-obese diabetic (NOD), db/db (+/+) mice, and non-diabetic, AGE-infused Sprague-Dawley rats. B) LZ: AGE interactions with macrophage-like T1B-183 cells (Mf) and mesangial cells (MC) were tested in vitro. RESULTS: A) In NOD mice, LZ reduced the elevated basal serum AGE (sAGE) (p < 0.05), enhanced urinary AGE (uAGE) excretion by approximately 2-fold (p < 0.01), while it reduced albuminuria (UA), p < 0.005. In db/db mice, LZ infusion also reduced the elevated sAGE (p < 0.05), doubled uAGE excretion (p < 0.05), and decreased UA (p < 0.01). In addition, LZ maintained normal sAGE in normal rats infused with AGE-BSA, as it doubled the urinary AGE (uAGE) clearance (p < 0.01). B) LZ stimulated the uptake and degradation of (125) I-labeled AGE-BSA and (25) I-human serum AGE by Mf, while suppressing AGE-induced TNFalpha and IGF-I production. In MC, LZ suppressed the AGE-promoted PDGF-B, alpha1 type IV collagen, and tenascin mRNA levels, and restored the AGE-suppressed expression and activity of MMP-9, but not MMP-2. CONCLUSION: LZ may act to: a) accelerate renal in-vivo AGE clearance, b) suppress macrophage and mesangial cell- specific gene activation in vitro, and c) improve albuminuria due to diabetes. These data suggest that LZ by sequestering AGEs may protect against diabetic renal damage.

Animals↗

Importance of hypercoagulability over hyperglycemia for vascular complication in type 2 diabetes.

To critically evaluate the relative importance of coagulation abnormalities over other clinical variables for micro- and macrovascular diabetic complications, prothrombin fragment (F1+2), thrombin-antithrombin III complex (TAT), fibrin degradation product d-dimer, and alpha2 plasmin inhibitor complex were determined in 101 stable, relatively well controlled patients with Type 2 diabetes (the mean HbA1c, age and duration of diabetes, 7.1%, 61 and 7.5 years, respectively). First, incidence and severity of diabetic micro- and macroangiopathies were progressively increased with the severity of coagulation abnormalities. Next, correlation of the four values with the presence of micro- and macrovascular complications, respectively, was analyzed by the multiple logistic regression analysis, with the inclusion of other variables such as age, duration of diabetes, HbA1c, blood pressure, and urinary albumin excretion. With the presence of microangiopathies, F1+2 and systolic blood pressure were significantly related, with the relationship being very strong for the former (P=0.003) and weak for the latter (P=0.035). On the other hand, with the presence of macroangiopathies, F1+2 (P=0.003), TAT (P=0.002), duration of diabetes (P=0.015), and age (P=0.013) were related. Other clinical variables were not significantly related with the presence of complications. Coagulation and fibrinolytic abnormalities are stronger determinants of the presence of diabetic vascular complications than other clinical variables including the degree of glycemia, in stable, relatively well controlled patients with Type 2 diabetes.

Adult↗

Structure of the pig sterol 14alpha-demethylase (CYP51) gene and its expression in the testis and other tissues.

A cDNA coding sterol 14alpha-demethylase (CYP51), which was isolated from a pig liver cDNA, contained a 1,512 bp open reading frame and a 758 bp 3'-untranslated region. The deduced amino acid sequence was 94% identical to those of human and rat CYP51s. The pig CYP51 gene spanned about 21 kb and was divided into 10 exons. The sites of exon-intron junctions were completely identical to those in the human and rat CYP51 genes. Five GC boxes, but not a TATA box, were found in the 5'-flanking region of the gene, and cyclic AMP and sterol responsive elements were also found in this region. The main transcription start site determined with the 5'-RACE method with poly(A)(+) RNA from the liver and testis was located at 143 nucleotides upstream from the initiation codon in both tissues. Northern blot analysis revealed that an approximately 2.4 kb mRNA, which is produced through the use of a polyadenylation signal (AATAAA) located at 740 nucleotides downstream of the stop codon, was expressed in all the tissues examined in pigs: The mRNA levels were much higher in the liver and testis than in the kidney, lung, and epididymis. Furthermore, after the onset of spermatogenesis, a smaller size of mRNA (about 1.8 kb) was found in the testis but not in the epididymis. The 1.8 kb mRNA was produced through the use of an unusual polyadenylation signal (AAGAAA) located at 28 nucleotides downstream of the stop codon.

3' Untranslated Regions↗

Is there any difference between intermediate-acting and long-acting calcium antagonists in diurnal blood pressure and autonomic nervous activity in hypertensive coronary artery disease patients?

Recently, there have been some reports indicating that calcium antagonists induce a reflex increase in sympathetic activity, triggering cardiac events, especially in coronary artery disease (CAD) patients. In this study, we assessed heart rate (HR) variability (HRV) using power spectral analysis of the 24-h RR interval in 25 hypertensive outpatients with CAD treated with nifedipine. We compared blood pressure (BP), HR, and HRV variation in the same patients substituting benidipine (long-acting) for nifedipine (intermediate-acting). There were no significant differences in 24-h, daytime, nighttime, and morning BP between the nifedipine phase and the benidipine phase. HRV parameters (LF: low frequency power, HF: high frequency power, LF/HF ratio) also showed no significant differences in 24-h, daytime, nighttime, and morning LF, HF, and LF/HF ratio between the nifedipine phase and the benidipine phase. Blood pressure, HR, and HRV parameters, except the LF component from 2 to 4 h after nifedipine administration (the most effective duration), showed no differences compared to before administration. The LF component after the nifedipine administration was lower than before administration. In conclusion, in hypertensive patients with CAD, whose BP levels were well-controlled by twice-daily use of intermediate-acting nifedipine, switching from nifedipine to a long-acting calcium antagonist, benidipine, maintained well-controlled BP levels to a similar degree, but it may not have additional benefit in sympatho-vagal balance.

Autonomic Nervous System↗

A giant intramural gastric hematoma successfully treated by transcatheter arterial embolization.

We describe a case of intramural gastric hematoma with hemorrhagic shock caused by the formation of a large hematoma. Computed tomographic and angiographic examinations confirmed the presence of active bleeding into the hematoma. Transcatheter arterial embolization (TAE) was performed for hemostasis. To our knowledge, although 21 cases of intramural gastric hematoma have been reported in the literature, this is apparently the first case treated by TAE. We conclude that TAE is a safe and effective treatment option for intramural gastric hematoma confirmed to be associated with active bleeding into the hematoma.

Aged↗

Hyperthyroidism presenting as dysphagia.

A 65-year-old man presented with hyperthyroidism associated with thyrotoxic dysphagia. Treatment with thiamazole improved his symptoms promptly. Although dysphagia is a rare manifestation of thyrotoxicosis, it should be emphasized that the possibility of hyperthyroidism must be discussed in unexplained dysphagia because it is readily treatable.

Aged↗

[Morphology and immunophenotyping in hematological malignancies].

We evaluated 443 outpatients and inpatients in Keio University Hospital between 1994 and 1999. Morphologic features from peripheral blood and bone marrow aspiration were evaluated in our hematology laboratory, using Wright-Giemsa, peroxidase staining films and other cytochemistry. Immunophenotype was determined by cell surface antigen analysis by laser flow cytometry, FACscan, using various monoclonal antibodies. Information on cytogenetic and molecular genetic characteristics can be also integrated for diagnosis. One hundred fifty patients were diagnosed with acute leukemia, in which 59 cases were ALL and 91 cases were AML. Seventy-four cases were MDS, 76 cases were myeloproliferative disorders, 21 cases were CLL related disorders, 104 patients were malignant lymphoma, and 18 cases were multiple myeloma. The ratio of male to female was 1.7. The probability of diagnostic rate by Immunophenotyping was estimated by Discriminant analysis in 189 patients, using multivariate analysis of immunophenotype compared to morphology. The average probability by immunophenotypic analysis for diagnostic rate was 91.7%, in which the probability for NHL was very high of 97.1%. Thus, morphologic and immunophenotypic analysis is most essential and basic approach in laboratory hematology, from the perspective of rapid and precise diagnostic methods. Recent advance appreciates the rapid contribution for diagnosis by immunophenotypic analysis. Furthermore, Tele-hematology would contribute the standardization for morphologic method in the near future.

Bone Marrow Cells↗

A novel technique for myomectomy. Intranodal surgery with an electromechanical tissue borer.

OBJECTIVE: To investigate the possibility of clinical application of a new technique for myomectomy that involves morcellating the myoma within the myometrium with a new instrument that minimizes invasion of the myometrium and abdominal wall. STUDY DESIGN: In a pilot clinical study, myomectomy was performed on five women with uterine myomas and a normal menstrual cycle using a microwave coagulator and electromechanical tissue borer of our invention. The length of the surgical incisions in the abdominal wall and myometrium, operating time and blood loss were measured. RESULTS: The mean length of the surgical incisions was 6.3 cm in the abdominal wall and 3.5 cm in the myometrium. The mean operating time was 167 minutes, and the mean blood loss was 312 mL. The length of the incisions in the abdominal wall and myometrium per centimeter of the maximal diameter of the myoma was 0.78 and 0.42 cm, respectively. The incision tended to become smaller in successive operations. CONCLUSION: This new technique of myomectomy significantly reduced invasion of the abdominal wall and uterus.

Adult↗

DNA binding and interaction with the nuclear receptor corepressor of thyroid hormone receptor are required for ligand-independent stimulation of the mouse preprothyrotropin-releasing hormone gene.

A negative thyroid hormone response element (TRE) in the mouse preprothyrotropin-releasing hormone (TRH) gene was previously mapped within the proximal promoter element between -83 and +53 that contained a TRE half-site motif at -57 (-57TGACCT-51). In transfection experiments, the promoter activity is stimulated by unliganded thyroid hormone receptor (TR) and T3 reverses the basal promoter stimulation. In this study, we determined whether the direct binding of TR to the TRE half-site in the mouse TRH gene is required for the ligand-independent stimulation using a transient transfection assay into CV-1 cells and electrophoretic mobility shift assays (EMSA). In addition, the role of a corepressor protein for the ligand-independent stimulation was examined using a putative splicing variant of the nuclear receptor corepressor (N-CoRI). Point mutations introduced into the TRE half-site at -57 eliminated the binding of TR and the stimulatory effect of unliganded TR. Two mutant TRs lacking DNA-binding activity and two CoR box mutant TRs showed no stimulation in the wild-type TRH promoter. The cotransfected N-CoRI potentiated the ligand-independent stimulation by the wild-type TR, but did not compensate for the impaired function of the CoR box mutant TR. In EMSA, TR strongly bound as homodimers and weakly as heterodimers with retinoid X receptor (RXR) to the element containing the TRE half-site at -57. Binding of TR to the TRE half-site was essential to form homo- and heterodimers, and the RXR binding site appeared to be located downstream of the TRE half-site. In vitro translated N-CoRI preferentially bound TR homodimers over TR/RXR heterodimers. These results collectively suggest that the DNA-bound TR/corepressor complex might be directly involved in the ligand-independent stimulation of the mouse TRH gene promoter.

Animals↗

Inhibition of advanced glycation endproduct formation by acetaldehyde: role in the cardioprotective effect of ethanol.

Epidemiological studies suggest that there is a beneficial effect of moderate ethanol consumption on the incidence of cardiovascular disease. Ethanol is metabolized to acetaldehyde, a two-carbon carbonyl compound that can react with nucleophiles to form covalent addition products. We have identified a biochemical modification produced by the reaction of acetaldehyde with protein-bound Amadori products. Amadori products typically arise from the nonenzymatic addition of reducing sugars (such as glucose) to protein amino groups and are the precursors to irreversibly bound, crosslinking moieties called advanced glycation endproducts, or AGEs. AGEs accumulate over time on plasma lipoproteins and vascular wall components and play an important role in the development of diabetes- and age-related cardiovascular disease. The attachment of acetaldehyde to a model Amadori product produces a chemically stabilized complex that cannot rearrange and progress to AGE formation. We tested the role of this reaction in preventing AGE formation in vivo by administering ethanol to diabetic rats, which normally exhibit increased AGE formation and high circulating levels of the hemoglobin Amadori product, HbA1c, and the hemoglobin AGE product, Hb-AGE. In this model study, diabetic rats fed an ethanol diet for 4 weeks showed a 52% decrease in Hb-AGE when compared with diabetic controls (P < 0.001). Circulating levels of HbA1c were unaffected by ethanol, pointing to the specificity of the acetaldehyde reaction for the post-Amadori, advanced glycation process. These data suggest a possible mechanism for the so-called "French paradox," (the cardioprotection conferred by moderate ethanol ingestion) and may offer new strategies for inhibiting advanced glycation.

Acetaldehyde↗

Differential regulation of ligand-dependent and ligand-independent functions of the mouse retinoid X receptor beta by alternative splicing.

RXR is involved in two distinct signal transduction pathways. RXR activates transcription ligand-dependently on RXRE and behaves as a positive heterodimer partner with permissive receptors; while it behaves as a ligand-independent silent partner with nonpermissive receptors. We studied the functions of a unique isoform of mouse RXRbeta2 (mRXRbeta2E) which has an in-frame four-amino-acid insertion in the ligand binding domain. mRXRbeta2E did not bind 9-cis RA with high affinity and did not activate transcription on RXRE. However, mRXRbeta2E formed heterodimers with TR, VDR, RAR, and LXR, and enhanced transcriptional activity of the nonpermissive VDR to the same extent as mRXRbeta2. With the permissive LXR, mRXRbeta2E did not show 9-cis RA-dependent transactivation and inhibited mRXRbeta2 activity. Thus, although mRXRbeta2E can perform ligand-independent functions of RXR, it cannot mediate the ligand-dependent functions of RXR, indicating that alternative splicing plays an important role in the differential regulation of these two important functions of RXR.

Alitretinoin↗

Lipid-lowering therapy corrects endothelial cell dysfunction in a short time but does not affect hypercoagulable state even after long-term use in hyperlipidemic patients.

Lipid-lowering therapy reduces cardiac events to an extent that is disproportionate to the small degree of regression of coronary atherosclerosis observed among hyperlipidemic patients. We prospectively investigated the effects of lipid reduction using simvastatin on the endothelial dysfunction and hypercoagulability found in hyperlipidemic patients. We measured levels of coagulation factors [factor VII (FVII) coagulant activity (FVIIc), FVII antigen (FVIIAg), activated FVII (FVIIa), and fibrinogen], and markers of coagulation activation [prothrombin fragment 1 + 2 (F1 + 2)] and endothelial cell dysfunction [von Willebrand factor (vWF)] in 20 hyperlipidemic patients, 20 hypertensive patients, and 20 normotensive normolipidemic controls. The levels of FVIIa, FVIIc, FVIIAg, F1 + 2, and vWF were all higher in hyperlipidemic patients, but only FVIIa, F1 + 2, and vWF levels were higher in hypertensive patients than in controls. We measured the above parameters in 13 hyperlipidemic patients before and after 1, 3, 6, 12 and 24 months of simvastatin therapy and compared these values with those in 15 hypertensive patients at baseline and after 12 and 24 months. The median (25th-75th percentile) level of total cholesterol was decreased from 259 (255-278) to 206 (176-220) mg/dl after 1 month of simvastatin therapy and this reduction persisted for 2 years. The plasma level of vWF [136% (113-158%)] was not changed after 1 month of administration of simvastatin [132% (115-153%)], but was decreased after 3 months of treatment [114% (96-128%), P<0.01]. This decrease also persisted for 2 years during simvastatin therapy and both of these reductions were significant, compared with levels in hypertensive patients. In contrast, levels of fibrinogen, FVIIc, FVIIAg, FVIIa, and F1 + 2 did not change throughout the 2 years of simvastatin therapy. We conclude that lipid reduction using simvastatin corrects endothelial cell dysfunction but not hypercoagulability in hyperlipidemic patients. The improvement in endothelial cell function brought about by lipid-lowering therapy might contribute to the reduction in cardiac events within a relatively short time period in hyperlipidemic patients.

Blood Coagulation↗