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Biomedical subjects

T Sakamaki

Publications and source records attributed to T Sakamaki.

At least 55 records · Page 3Linked to original sources

Localized right ventricular structural abnormalities in patients with idiopathic ventricular fibrillation: magnetic resonance imaging study.

Lethal arrhythmias, including ventricular tachycardia and ventricular fibrillation, may occur in the absence of apparent morphological abnormalities. However, a recent study using magnetic resonance imaging (MRI) has suggested that localized, minor structural abnormalities of the right ventricle are responsible for right ventricular outflow tract ventricular tachycardia in a number of patients. We demonstrated regional wall thinning and systolic dyskinesia of the right ventricle by MRI in two patients with idiopathic ventricular fibrillation in whom other cardiac imaging modalities failed to show abnormalities. This finding implies that minor structural abnormalities do exist in patients with so-called idiopathic ventricular fibrillation.

Adult↗

Interleukin-6 secreted from human myxoma reduces murine viral myocarditis.

The effect of interleukin-6 (IL-6) secreted by a human atrial myxoma in vitro was investigated in C3H female mice with acute viral myocarditis. A culture medium containing IL-6 (100 ng/ml) and IL-8 (250 ng/ml), was prepared; viral myocarditis was induced by exposure to the encephalomyocarditis virus. Mice were assigned to four groups: 1) intraperitoneal (i.p.) injection of supernatant with IL-6 and IL-8 (0.2 ml/mice) given simultaneously with virus, 500 pfu for 4 days (Group 1); 2) i.p. injection of supernatant with IL-6 starting on Day 4 for 4 days in the same manner (Group 2); 3) i.p. injection of culture medium simultaneously with the virus (Group 3); and 4) i.p. injection of PBS in the same manner (Group 4). Uninfected control mice were administered medium only (Group 5) or supernatant with IL-6 and IL-8 (Group 6) for 4 days without virus. The survival rate on Day 14 in Group 1 was 90% significantly (p < 0.01) prolonged. The ratio of heart weight-to-day weight in the Group 1 was significantly (p < 0.01) lower. Histopathological examination revealed that cardiac necrosis and cellular infiltration in Group 1 was reduced compared with Group 3. Moreover, the radio of spleen weight/body weight in Group 1 was significantly (p < 0.01) higher than that of Group 3 and of Group 4. To confirm the effect of IL-6 or IL-8, mice were treated with recombinant IL-6 to IL-8 simultaneously with virus for 4 days. IL-6 treated mice survived significantly compared with IL-8 treated mice and untreated mice. The viral titer on day 4 of IL-6 treated mice was significantly lower than IL-8 treated or untreated mice. Thus, IL-6 derived from human myxoma improved the survival of murime viral myocarditis and reduced myocardial necrosis when the myxoma-derived IL-6 was administered simultaneously with the virus, due to eliciting cellular immunity in the spleen.

Animals↗

Molecular cloning and characterization of human non-smooth muscle calponin.

cDNA clones encoding a calponin isoform with 309 amino acids have been isolated from human heart. The deduced amino acid polypeptide (M(r) 33,697) showed a neutral isoelectric point of 7.1. The mRNA, expressed in cultured smooth muscle cells as well as in fibroblasts, vascular endothelial cells, and keratinocytes, contains a 3' untranslated region of 1.2 kilobases that includes an Alu repetitive sequence in the antisense direction. On the basis of the nucleotide sequence identity to an expressed sequence tag, HUM21ES93 [Cheng, J.-F., Boyartchuk, V., and Zhu, Y. (1994) Genomics 23, 75-84], the human neutral calponin gene is assigned to chromosome 21q11.1. The amino acid sequence indicates that this protein is the human equivalent of mouse calponin-h2 (94.8% identity) [Strasser, P., Gimona, M., Moessler, H., Herzog, M., and Small, J.V. (1993) FEBS Lett. 330, 13-18]. Three tandem repeats of 29 amino acids, a Vav-homologous region and an actin-binding sequence, originally identified in the basic calponin isoform, are conserved. There are two consensus phosphorylation sites for tyrosine kinase. An immunoreactive form of the neutral calponin appears to be localized with vinculin in the cell-to-cell junctions of cardiomyocytes. Mouse calponin-h2 is also expressed in both embryonic and adult heart. These results indicate that the human neutral calponin is a non-smooth muscle isoform, and may play a physiological role in cytoskeletal organization.

Adult↗

Femoral deformity in adults with developmental hip dysplasia.

Quantitative computed tomography and 3 dimensional modeling were used to portray the deformity of the proximal femur in 24 Japanese adults with low subluxations to high dislocations secondary to developmental dysplasia of the hip. Periosteal and canal bony contours were extracted, 3 dimensional models generated, and morphologic parameters were calculated for each femur. Three dimensional illustrations of the average deformity and variability were created. Morphologic parameters were not found to be statistically correlated with the degree of the disease. Interestingly, the major axis of the canal contours of the proximal femur was found to be aligned with the plane of the femoral neck (anteversion), regardless of the degree of anteversion. Thus, the amount of version correctable in an uncemented prosthesis is limited, and at times may require a special prosthesis, overreaming, undersizing and cementing, or an osteotomy. Additionally, the proximal medial curvature of the dysplastic femurs was straighter than that of normal femurs. This necessitated a corresponding reduction in the proximal medial curvature of a conventional uncemented prosthesis to match the medial curvature of the individual femur and the average developmentally dysplastic femur. This objective description of the developmentally dysplastic femur corroborates clinical observations, highlights some unrecognized findings, provides a rationale for planning reconstructions, and aids in the design of prostheses for adult patients with this deformity.

Adult↗

Rate of nitric oxide release in the lung and factors influencing the concentration of exhaled nitric oxide.

The level of nitric oxide (NO) in exhaled air fluctuates in normal individuals depending on the physiological conditions. We evaluated the effects of duration of exhalation and breath-holding on the exhaled concentrations of NO in 16 normal human volunteers. Exhaled gas corresponding to vital capacity was collected in 6-liter Tedlar bags and analyzed by chemiluminescence. The NO concentration in exhaled gas increased significantly in proportion to the duration of exhalation [P = 0.009 +/- 0.011 (SD)] and was increased after breath-holding. There was no significant difference in the exhaled NO concentration among 10-s phases of a 30-s exhalation, as determined from multiple breath collections. The NO released from the airways is presumably unaffected by fluctuation of exhalation speed. The NO release rate, calculated from a single regression analysis between the NO concentration and the duration of exhalation, was 39 +/- 29 pmol/s, a value which was about fourfold greater in nine patients with bronchial asthma.

Adult↗

Long-term effects of doxazosin, an alpha 1-blocker, on serum lipids in hypertensive patients.

Nowadays practical antihypertensive therapy involves not only simple normalization of blood pressure but also a reduction of the risks of cardiovascular disease. In this multicenter open-label study, the long-term effects of doxazosin, an alpha 1-adrenergic receptor blocker, on serum lipids were prospectively investigated in 253 patients with essential hypertension. They were treated with doxazosin for 1 year. The averaged the blood pressure was maintained at levels lower than 150/90 mmHg throughout 1 year, but heart rate did not increase. After 3 months of doxazosin therapy, total and low density lipoprotein-cholesterol levels in serum were significantly reduced by 3.3% and 3.4%, respectively, and these levels were maintained throughout the study period. This effect of doxazosin on serum lipids was especially prominent in patients with hypercholesterolemia. In addition, the lipid profile of these patients was favorably altered even when other antihypertensive drugs or lipid-lowering drugs had already been used or were used concurrently. These results constitute useful information for physicians who treat hypertension with alpha 1-blockers to reduce the overall risk of cardiovascular disease.

Adrenergic alpha-2 Receptor Antagonists↗

Lack of inhibitory effect of dexamethasone on exhalation of nitric oxide by healthy humans.

Nitric oxide (NO) is present in the breath exhaled from healthy humans. The location and subtype of the NO synthase responsible for the expired NO are unknown. As dexamethasone inhibits the induction of NO synthase, we evaluated the effect of administering dexamethasone (4 mg/day for 2 days) on the amount of NO exhaled by eight healthy men. The amount of NO showed a significant linear correlation with the duration of exhalation, allowing the rate of NO release to be calculated. The rate of NO release was 0.047 +/- 0.023 nmol/s before drug administration. There was no significant change in the release rate at the end of the 2-day administration of drug or at 5 days after cessation. Serum concentrations of interferon-gamma and interleukin-1 beta were unaffected by the administration of dexamethasone. These results suggest that the NO released from the human airway under normal conditions is not generated by the action of inducible NO synthase.

Adult↗

N omega-hydroxyagmatine: a novel substance causing endothelium-dependent vasorelaxation.

Agmatine (Agm), a decarboxylated L-arginine, has been suggested to be an endogenous clonidine-displacing substance in the brain. We hypothesed that Agm enzymatically produces nitric oxide (NO) through N omega-hydroxyagmatine (OHAgm) similar to the well-known endogenous NO generation from L-arginine through N omega-hydroxy-L-arginine, because Agm possesses a guanidyl function in its molecule. OHAgm was originally synthesized from delta-aminopentanoic acid in 36% overall yield. Agm and the synthetic OHAgm were examined using rat aortic rings whether they could cause endothelium-dependent vasorelaxation or not. These substances equally elicited vasorelaxations. The relaxations were completely abolished by a NO synthase inhibitor, N omega-nitro-L-arginine methyl ester, or endothelium denudation. These results suggested that Agm and OHAgm are alternative precursors for NO generated by NOS and that OHAgm may be an endogenous substance distributable in the brain.

Agmatine↗

Enhancement in accessibility to macrophages by modification of mucin-type carbohydrate chains on a tumor cell line: role of a C-type lectin of macrophages.

We investigated the role of mucin-type (O-linked) carbohydrate chains of tumor target cells in the recognition by macrophages through a Gal/GalNAc-specific calcium-dependent lectin. Binding of a soluble form of this lectin to P815 mastocytoma cells was increased by treatment with benzyl-GalNAc, which presumably inhibited the extension of mucin-type carbohydrate chains. The levels of cell surface expression of GalNAc residues were elevated after benzyl-GalNAc treatment, as revealed by the binding of Vicia villosa agglutinin B4 and Dolichos biflorus agglutinin. Adhesion of treated P815 cells to this lectin immobilized on plastic surfaces also increased. Furthermore, the binding of P815 cells to macrophage-like RAW 264.7 cells and to peritoneal macrophages also increased after the same treatment. We concluded that elevated levels of cell surface terminal GalNAc in mucin-type carbohydrate chains increased accessibility of P815 cells to macrophages through Gal/GalNAc-specific calcium-dependent lectins.

Acetylgalactosamine↗

Transesophageal echocardiographically detected atherosclerotic aortic debris in a patient with systemic embolism following coronary angiography.

Transesophageal echocardiography (TEE) has enabled detection of the cardiac source of systemic emboli. We report the case of a patient who manifested systemic, multiple embolization in the kidney, skin, and upper gastrointestinal tract following coronary angiography. TEE allowed visualization of the atherosclerotic debris in the thoracic aorta. The clinical picture of the patient was consistent with that of cholesterol embolism. We recommend that patients with extensive atherosclerotic disease should undergo TEE before cardiac catheterization or other invasive procedures involving the aorta are carried out.

Aorta, Thoracic↗

Magnetic resonance imaging of cardiac hemangiopericytoma.

We report a patient with hemangiopericytoma, a rare soft tissue sarcoma, involving the left ventricle. T1- and T2-weighted magnetic resonance imaging (MRI) revealed a high signal mass invading the left ventricular wall. A biopsied specimen obtained from the metastatic subcutaneous tumor in the right popliteal fossa showed pathologic findings consistent with hemangiopericytoma.

Adult↗

Effect of renal perfusion pressure on renal interstitial hydrostatic pressure and sodium excretion. Role of vasopressin V1 and V2 receptors.

Renal interstitial hydrostatic pressure (RIHP) has recently been cited as an important mediator of pressure natriuresis. Our objective was to determine the roles of vasopressin V1 and V2 receptors in mediating the effects of renal perfusion pressure (RPP) on RIHP and sodium excretion (UNaV). The effects of RPP on renal hemodynamics, RIHP, and UNaV were assessed in control Wistar rats (n = 10) and in rats pretreated with intravenous infusion of the specific nonpeptide vasopressin V1 antagonist OPC-21268 (100 micrograms.kg-1.min-1; n = 8) and the V2 antagonist OPC-31260 (40 micrograms.kg-1.min-1; n = 10). Increasing RPP from 95 to 118 mm Hg in control rats increased RIHP (6.4 +/- 1.0 to 9.9 +/- 1.3 mm Hg), UNaV (0.29 +/- 0.03 to 0.52 +/- 0.05 muEq.min-1.g-1), urine flow rate (UFR) (5.2 +/- 0.3 to 7.6 +/- 0.6 microL.min-1.g-1), and the fractional excretion of sodium (FENa). In rats pretreated with V1 antagonist, similar results were obtained for urine osmolality and the responses of RIHP, UNaV, UFR, and FENa to RPP. V2 antagonist reduced urine osmolality (392 +/- 47 compared with 979 +/- 88 mOsm.kg-1 in control rats) and enhanced the responses of UNaV (0.43 +/- 0.08 to 1.32 +/- 0.32 microEq.min-1), UFR (17.8 +/- 3.2 to 29.2 +/- 3.8 microL.min-1.g-1), and FENa to RPP, but the RIHP response resembled that observed in the control and V1 antagonist groups. Renal blood flow and glomerular filtration rate did not differ among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Recombinant human erythropoietin stimulates tubular reabsorption of sodium in anesthetized rabbits.

To determine whether recombinant human erythropoietin (rHuEPO) exerts a direct vasoconstrictive effect on renal arteries or affects renal function, we measured renal hemodynamics and renal function during a 30-min intrarenal infusion of rHuEPO in anesthetized rabbits without renal failure. Intrarenal infusion of rHuEPO at a rate of 100 U/min did not alter mean arterial pressure, renal blood flow, or renal vascular resistance, as compared with controls treated with vehicle. There were no significant rHuEPO-associated changes in glomerular filtration rate, filtration fraction, or arterial hematocrit. However, urine volume, urinary excretion of sodium and potassium, and fractional sodium excretion were significantly reduced by intrarenal infusion of rHuEPO. These observations indicate that rHuEPO has no direct effects on mean arterial pressure or renal hemodynamics, but that it stimulates net tubular sodium reabsorption, and reduces urine volume and urinary excretion of sodium and potassium in anesthetized rabbits without renal failure.

Animals↗

Reduced natriuretic response to increased renal interstitial hydrostatic pressure in Dahl salt-sensitive rats during volume expansion.

Renal interstitial hydrostatic pressure (RIHP) plays a key role in the link between renal hemodynamics and the rate of the tubular reabsorption of sodium and water. Our objective was to determine whether the natriuretic response to a rise in RIHP induced by acute saline infusion would be altered in prehypertensive, Dahl salt-sensitive (DS) rats. We compared the effects of an acute saline load (2.5 ml/100 g BW over 30-min) on RIHP and urinary sodium excretion in Dahl salt-resistant (DR) (n = 11) and DS rats (n = 11) maintained from birth on a low-sodium diet. Baseline mean arterial pressure, glomerular filtration rate rate, and urinary sodium excretion did not differ between DR and prehypertensive DS rats. Urine flow rate and urinary sodium excretion increased significantly in both groups following saline loading. Increases were significantly (p < 0.05) less in the prehypertensive DS rats (0.32 +/- 0.07 to 3.62 +/- 0.79 microEq/min) than in the DR rats (0.71 +/- 0.22 to 6.30 +/- 1.35 microEq/min). RIHP also increased significantly in both groups, but did not differ significantly in DR (7.3 +/- 1.1 to 9.7 +/- 1.7 mmHg) vs. DS rate (7.9 +/- 1.0 to 9.8 +/- 1.3 mmHg). At an equal mean arterial pressure, DS rats showed a reduced natriuretic capacity after an acute saline load, prior to the development of hypertension. Renal tubular sensitivity to the increased RIHP that was induced by an acute saline load was blunted in prehypertensive DS rats.

Animals↗

Creatine phosphokinase-linked immunoglobulin associated with hypokalemic myopathy.

We present three women with hypokalemic myopathy in whom serum creatine phosphokinase (CPK) was bound to serum immunoglobulin (macro-CPK). In all three cases, CPK isozyme electrophoresis demonstrated an extra CPK band between CPK-MM and CPK-MB. The bound immunoglobulins were identified as IgA/A-kappa and lambda, IgA-lambda and IgA-kappa and lambda, respectively. In all cases, histological examination of the biopsied muscles revealed necrotic and/or regenerating fibers. In each patient, potassium replacement therapy returned the macro-CPK as well as the marked elevations of serum muscle enzymes to normal. Taken together with other recent reports, our findings suggested that CPK-immunoglobulin binding may be related to the emergence of pathophysiology of hypokalemic myopathy.

Aged↗

Identification of Ro(SSA) 52 kDa reactive T cells in labial salivary glands from patients with Sjögren's syndrome.

OBJECTIVE: To identify the self-antigens recognized by autoreactive T cells in labial salivary glands from patients with Sjõgren's syndrome (SS). METHODS: T cells lines were established from infiltrating T cells in the labial salivary glands from 6 patients with SS, using interleukin 2 and phytohemagglutinin. Bulk cultured T cells and T cell lines were examined for the proliferative response to recombinant Ro(SSA) 52 kDa and SSB proteins. The usage of T cell receptor (TCR) V beta and V alpha genes from Ro(SSA) 52kDa reactive T cells was analyzed by family polymerase chain reaction. The sequences of complementary determining region 3 of TCR V beta genes were also examined. RESULTS: Three of 6 bulk cultured T cells and 4 of 16 T cell lines showed a significant proliferative response to Ro(SSA) 52 kDa protein. All T cell lines represented CD4+ alpha beta T cells by flow cytometry analysis. All 4 RO(SSA) 52 kDa reactive T cell lines utilized the V beta 2 gene and 3 lines used the V beta 13 gene, suggesting preferential usage of the V beta 2 and the V beta 13 genes in Ro(SSA) 52 kDa reactive T cells. Junctional sequences of TCR V beta genes from Ro(SSA) 52 kDa reactive T cell lines showed the conserved amino acid sequences in CDR3 region. CONCLUSION: These findings support the notion that Ro(SSA) 52 kDa is a possible autoantigen recognized by autoreactive T cells and that limited epitope is present on the Ro(SSA) 52 kDa antigen.

Amino Acid Sequence↗