ADAMTS13 Retards Progression of Diabetic Nephropathy by Inhibiting Intrarenal Thrombosis in Mice.

Objective: ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type I repeats-13) prevents microvascular thrombosis by cleaving prothrombogenic ultralarge von Willebrand factor (VWF) multimers. Clinical studies have found association between reduced ADAMTS13-specific activity, ultralarge VWF multimers, and thrombotic angiopathy in patients with diabetic nephropathy. It remains unknown, however, whether ADAMTS13 deficiency or ultralarge VWF multimers have a causative effect in diabetic nephropathy.

Lectin-like oxidized low density lipoprotein receptor 1-deficient mice show resistance to instability-induced osteoarthritis.

Objectives: The lectin-like oxidized low density lipoprotein (ox-LDL) receptor 1 (LOX-1)/ox-LDL system, which contributes to the pathogenesis of atherosclerosis, may be involved in the development of osteoarthritis (OA). However, the mechanisms by which the LOX-1/ox-LDL system contributes to OA development in vivo are unclear. In this study, we investigated the direct involvement of LOX-1/ox-LDL in OA development by using LOX-1-knockout (LOX-1(-)/(-)) mice in a joint instability-induced model of OA.

Parallel resetting of arterial baroreflex control of renal and cardiac sympathetic nerve activities during upright tilt in rabbits.

Since humans are under ceaseless orthostatic stress, the mechanisms to maintain arterial pressure (AP) against gravitational fluid shift are important. As one mechanism, it was reported that upright tilt reset baroreflex control of renal sympathetic nerve activity (SNA) to a higher SNA in anesthetized rabbits. In the present study, we tested the hypothesis that upright tilt causes a parallel resetting of baroreflex control of renal and cardiac SNAs in anesthetized rabbits.

Upright tilt resets dynamic transfer function of baroreflex neural arc to minify the pressure disturbance in total baroreflex control.

Maintenance of arterial pressure (AP) under orthostatic stress against gravitational fluid shift and pressure disturbance is of great importance. One of the mechanisms is that upright tilt resets steady-state baroreflex control to a higher sympathetic nerve activity (SNA). However, the dynamic feedback characteristics of the baroreflex system, a hallmark of fast-acting neural control, remain to be elucidated.

Baroreflex increases correlation and coherence of muscle sympathetic nerve activity (SNA) with renal and cardiac SNAs.

Despite accumulating data of muscle sympathetic nerve activity (SNA) measured by human microneurography, whether neural discharges of muscle SNA correlates and coheres with those of other SNAs controlling visceral organs remains unclear. Further, how the baroreflex control of SNA affects the relations between these SNAs remains unknown. In urethane and alpha-chloralose anesthetized, vagotomized, and aortic-denervated rabbits, we recorded muscle SNA from the tibial nerve using microneurography and simultaneously recorded renal and cardiac SNAs.

Heart-type fatty acid binding protein is a novel prognostic marker in patients with non-ischaemic dilated cardiomyopathy.

Objective: To determine whether concentrations of heart-type fatty acid binding protein (H-FABP) measured before hospital discharge predict critical cardiac events in patients with idiopathic dilated cardiomyopathy (DCM).

Patients: 92 consecutive patients with DCM were enrolled and followed up for four years.

Main Outcome Measures: Serum concentrations of H-FABP, brain natriuretic peptide (BNP), cardiac troponin T before hospital discharge and survival rate.

Resetting of the arterial baroreflex increases orthostatic sympathetic activation and prevents postural hypotension in rabbits.

Since humans are under ceaseless orthostatic stress, the mechanism to maintain arterial pressure (AP) under orthostatic stress against gravitational fluid shift is of great importance. We hypothesized that (1) orthostatic stress resets the arterial baroreflex control of sympathetic nerve activity (SNA) to a higher SNA, and (2) resetting of the arterial baroreflex contributes to preventing postural hypotension. Renal SNA and AP were recorded in eight anaesthetized, vagotomized and aortic-denervated rabbits.

FRETS-VWF73, a first fluorogenic substrate for ADAMTS13 assay.

A plasma metalloprotease, ADAMTS13, cleaves von Willebrand factor (VWF) multimers and downregulates their activity in platelet aggregation. Functional ADAMTS13 deficiency leads to the accumulation of hyperactive large VWF multimers, inducing a life-threatening disease, thrombotic thrombocytopenic purpura (TTP). Although measuring ADAMTS13 activity is important in TTP diagnosis, existing methods require time and skill.

Faster oscillometric manometry does not sacrifice the accuracy of blood pressure determination.

Faster oscillometry enables one to track rapid pressure changes. We therefore examined whether it was possible to shorten the measurement time without sacrificing accuracy. We accelerated and linearized cuff deflation and determined systolic and diastolic pressure values by the appearance and disappearance of oscillometric waves based on the interpolated cuff pressure-oscillometric wave amplitude relationship.

Association of a promoter variant of the haeme oxygenase-1 gene with hypertension in women.

Objective: To examine the relationship between the gene for haeme oxygenase (HO)-1 (HMOX-1) and human essential hypertension, because both the acute and systemic induction of HMOX-1 have been suggested to attenuate vascular tone and blood pressure.

Methods: We screened for sequence variations in HMOX-1 and conducted an association study, using these polymorphisms, in a large cohort (1998 individuals) representing the general Japanese population. RESULTS We sequenced HMOX-1 and found a T(-413)A polymorphism in the promoter region.

Changes in functional and histological distributions of nitric oxide synthase caused by chronic hypoxia in rat small pulmonary arteries.

1. Chronic hypoxia (CH) increases lung tissue expression of all types of nitric oxide synthase (NOS) in the rat. However, it remains unknown whether CH-induced changes in functional and histological NOS distributions are correlated in rat small pulmonary arteries.

Stretch-induced cell damage in sarcoglycan-deficient myotubes.

Sarcoglycans (SGs) are components of the dystrophin-glycoprotein complex, genetic defects in which cause skeletal muscle dystrophy and cardiomyopathy in humans and animals. To obtain insight into the roles of SGs, we characterized properties of myotubes prepared from cells of the rat L6 line or primary myoblast cultures of rat gastrocnemius muscle that were made SG-deficient by treatment with antisense oligodeoxynucleotides (AS-ODNs). Immunoblot and immunoprecipitation analyses revealed that dystrophin and its remaining associated proteins were tightly associated in these cells despite SG deficiency.

Analysis of serum lipid levels in Japanese men and women according to body mass index. Increase in risk of atherosclerosis in postmenopausal women. Research Group on Serum Lipid Survey 1990 in Japan.

Relatively low serum lipid levels are thought to be an important factor contributing to the low incidence of ischemic heart diseases (IHD) in Japanese. It has been proven that obesity or overweight constitutes a basal condition for several risk factors in atherosclerosis. The purpose of this study is to obtain data on serum lipids and lipoprotein profiles in relation to body mass index (BMI), which will enable us to compare the nature and weight of metabolic risk factors in atherosclerosis between Japanese and people in Western countries.

Northern blot analysis to quantify gene expression in vascular diseases.

To understand the molecular mechanisms of vascular diseases, studies are designed to process gene function from the discovery of relevant genes to examination of their expression and association with disease. Once a gene has been cloned, Northern blot analysis can directly monitor the gene expression at the mRNA level. Therefore, it is the most expedient strategy for investigating the potential relationship between specific gene expression and disease.

Transient oxygen uptake response to exercise characterizes functional capacity of the cardiocirculatory system in patients with chronic heart failure: a random stimulus approach.

The transient response of oxygen uptake (VO2) to submaximal exercise, known to be abnormal in patients with cardiovascular disorders, can be useful in assessing the functional status of the cardiocirculatory system, however, a method for evaluating it accurately has not yet been established. As an alternative approach to the conventional test at constant exercise intensity, we applied a random stimulus technique that has been shown to provide relatively noise immune responses of system being investigated. In 27 patients with heart failure and 24 age-matched control subjects, we imposed cycle exercise at 50 W intermittently according to a pseudo-random binary (exercise-rest) sequence, while measuring breath-by-breath VO2.

Vasodilator effects of adrenomedullin on small pulmonary arteries and veins in anaesthetized cats.

1. This study was conducted to determine adrenomedullin (AM) action sites in the pulmonary vascular bed and the relation between its vasodilator effects and vascular tone. Moreover, an examination was made into whether calcitonin gene-related peptide (CGRP) receptors mediate pulmonary vasodilatations induced by AM.

Direct observations of sympathetic cholinergic vasodilatation of skeletal muscle small arteries in the cat.

1. The aim of this study was to examine the actual changes of the internal diameter (i.d.

A point mutation (Arg271-->Cys) of a homozygote for dysfunctional prothrombin, prothrombin Obihiro, which has a region of high sequence variability.

The molecular defect of a congenitally dysfunctional form of prothrombin, prothrombin Obihiro, was identified in a patient with a severe bleeding tendency. He showed reduced fibrinogen clotting activity, despite a normal prothrombin antigen level. Nucleotide sequencing of amplified DNA revealed a C-->T change at nucleotide 7311 of exon VIII of the prothrombin gene.

Factor IX Bm Kiryu: a Val-313-to-Asp substitution in the catalytic domain results in loss of function due to a conformational change of the surface loop: evidence obtained by chimaeric modelling.

Factor IX Kiryu is a naturally occurring mutant of factor IX that has 2.5% coagulant activity, even though normal plasma levels of factor IX antigen are detected. Factor IX Kiryu was purified from a patient's plasma by immunoaffinity chromatography with a calcium-dependent anti-factor IX monoclonal antibody column.

Estimation of 2-D blood flow velocity map from cine-angiograms: algorithm using overlapping block set and illustration of vortex flow in abdominal aneurysm.

To derive blood flow dynamics from cine-angiograms (CAGs), we have developed an image-processing algorithm to determine a two-dimensional blood flow velocity map projected on CAGs. Each image data of CAG is divided into a set of overlapping blocks, and it is assumed that the contrast medium in each block moves only to its 'adjacent blocks' between two serial frames. Based on this assumption, a 'fundamental equation' and the 'maximum flow constraints' are derived.

Differential regional responses of myocardial interstitial noradrenaline levels to coronary occlusion.

Objective: The aim was to investigate the influence of coronary occlusion on myocardial interstitial noradrenaline levels in the ischaemic and non-ischaemic regions, using the dialysis technique.

Methods: In nine anaesthetised cats, regional ischaemia was produced by occlusion of the left anterior descending coronary artery for 90 min. Using the dialysis technique, dialysates were sampled from both the ischaemic region and the nonischaemic left circumflex coronary artery region.

Contractile effects of perivascularly applied vasopressin on the pial artery of the cat brain.

1. The effects of perivascularly applied vasopressin on the diameter of pial arteries (control 298 +/- 14 S.E.