Search PubMed⌕ Search

Biomedical subjects

H Tsutsui

Publications and source records attributed to H Tsutsui.

At least 127 records · Page 7Linked to original sources
PubMed1995

Corticosteroid enhances the experimental induction of osteonecrosis in rabbits with Shwartzman reaction.

Bacterial endotoxic reactions can cause osteonecrosis in humans by disseminated intravascular coagulation. The authors first used a combination of the Shwartzman reaction and corticoid injections in rabbits to develop a new animal model of osteonecrosis. This model showed a significantly higher incidence and wider area of osteonecrosis in the femur and humerus than that found in rabbits with either Shwartzman reaction or steroid injection alone. Osteonecrosis was observed in several foci that were distributed from the diaphysis to the epiphysis in both bones. Histologically, the bone marrow cells underwent necrosis, whereas the bone trabeculae demonstrated either empty lacunae or pycnotic nuclei of osteocytes. Exogenous steroids appeared to potentiate the Shwartzman reaction and the magnitude of osteonecrosis, perhaps by increasing endothelial damage and hypercoagulability of those intraosseous and extraosseous vessels that subsequently thrombosed. This model may not only be useful in clarifying the etiology and early pathogenesis of human osteonecrosis after corticoid therapy, but also in designing pharmaceuticals for prevention and early treatment.

Animals↗
PubMed1995

[Negative repressor THZif-1 of protooncogene c-myc].

A human recombinant cDNA clone that encoded 253 amino acids residues of a zinc-finger protein (THZif-1) was cloned by screening a cDNA library prepared from human promyelocytic leukemia HL60 cells with synthetic oligodeoxynucleotide probes that corresponded to the amino acid sequences of tryptic peptides derived from the DNA-binding protein specific for the nuclease-hypersensitive element (NHE) of the human c-myc gene. The predicted amino acid sequence of THZif-1 included a DNA-binding domain that contained five tandemly repeated zinc finger motifs. The three amino-terminal sets of zinc finger motifs, including the second finger, were found to be responsible for high-affinity interactions with the triple-helical conformation of NHE, as well as for high-affinity binding to the single-pyrimidine-rich strand of NHE in a sequence-specific manner. Cotransfection, trans-activation and in vitro transcription studies using the wild-type form and THZif-1 with a mutated second zinc finger motif demonstrated that the DNA-binding activity specific for H-form DNA of NHE was a prerequisite for the negative regulation of the expression of the c-myc gene.

Amino Acid Sequence↗
PubMed1995

Adenosine triphosphate stress echocardiography in the detection of myocardial ischemia.

The purpose of this study was to assess feasibility and safety in the diagnosis of coronary artery in the diagnosis of coronary artery disease and myocardial ischemia using adenosine triphosphate (ATP) stress echocardiography. ATP, a product of human myocardial tissue, is more potent than adenosine in increasing coronary blood flow. Like adenosine, ATP also has a short half-life (<10 s). Left ventricular echocardiograms were recorded during step-wise infusions of ATP in 86 patients who underwent coronary angiography and stress thallium 201 scintigraphy. No serious complications occurred with ATP infusion and most of the side effects were mild and transient. Significant coronary artery disease (>75% diameter stenosis) was present in 34 of 48 patients who had normal echocardiograms at rest. The sensitivity and specificity of ATP-induced wall motion abnormalities for coronary artery disease was 65% (22 of 34) and 100% (14 of 14), respectively. The sensitivity was 50% (10 of 20) in those with one-vessel disease and 86% (12 of 14) in those with multivessel disease (P < .05). In patients with normal echocardiograms at rest and without prior myocardial infarction, the sensitivity of ATP stress echocardiography for the detection of myocardial ischemia assessed by 201Tl single proton emission computed tomography was 58%, with a specificity of 76%, and a diagnostic accuracy of 66%. The sensitivity was 43% in those with one-vessel disease, and 86% in those with multivessel disease (P = .05). In patients with prior myocardial infarction, the sensitivity of ATP stress echocardiography for the detection of viable but jeopardized myocardium was 81%, with a specificity of 91%. The patients with well-developed collateral circulation had a higher incidence of developing wall motion abnormality than those without collaterals (70% v 40%, P < .01). ATP stress echocardiography is valuable for the assessment of coronary artery disease in patients with multivessel disease, coronary collaterals, and with prior myocardial infarction.

Adenosine Triphosphate↗
PubMed1994

Complete sequence of the Bacteroides fragilis YCH46 neuraminidase-encoding gene.

The nucleotide sequence of the Bacteroides fragilis neuraminidase-encoding gene (nanH) and its flanking regions was determined. The B. fragilis nanH open reading frame (ORF) of 1632 nucleotides encoded a neuroaminidase of 544 amino acid residues with a calculated molecular mass of 59.51 kDa. The amino acid sequence at the N-terminus of the deduced protein exhibited the common features of procaryotic signal sequences. The Asp box sequence, Ser-X-Asp-X-Gly-X-Thr-Trp, which is conserved among bacterial neuraminidases, was found at five positions in the deduced amino acid sequence. A single transcription start point was identified 88 nucleotides upstream of the nanH ORF. Northern blot analysis using an internal nanH probe revealed a single mRNA species with a length of 1.8 kb that could encode just the neuraminidase.

Amino Acid Sequence↗
PubMed1994

Native beta-adrenergic support for left ventricular dysfunction in experimental mitral regurgitation normalizes indexes of pump and contractile function.

BACKGROUND: It is generally accepted that the adrenergic nervous system provides inotropic support for the failing heart. However, the magnitude of this support has never been studied extensively. The present study was performed to test the hypothesis that the adrenergic nervous system is capable of maintaining indexes of pump and contractile function in the normal range despite significant innate myocardial depression. METHODS AND RESULTS: We used our model of experimental canine mitral regurgitation, which produces left ventricular dysfunction after 3 months of volume overload. We studied indexes of contractile function on and off beta-blockade at baseline and again on and off beta-blockade 3 months after chronic mitral regurgitation had induced significant contractile dysfunction. At baseline, acute beta-blockade caused insignificant reductions in the mass-corrected slope of the end-ejection stress-volume relation (EESVR), the end-systolic stiffness constant, and the ejection fraction-end-systolic stress and the mean velocity of circumferential fiber shortening (VCF)-end-systolic stress relations. After 3 months of chronic mitral regurgitation, all indexes of contractile function were normal in the unblocked state except for the VCF-stress relation, which was mildly reduced. However, after acute beta-blockade after 3 months of chronic mitral regurgitation, the EESVR fell to 303 +/- 27 versus 443 +/- 24 during acute beta-blockade before mitral regurgitation was created (P < .05), and the end-systolic stiffness constant was reduced to 2.54 +/- 0.15 versus 3.27 +/- 0.11 (P < .05). Only after beta-blockade was the ejection fraction-stress relation significantly reduced for dogs with chronic mitral regurgitation. The VCF-stress relation became markedly more abnormal. The viscosity-velocity relation of myocytes isolated from the ventricles of the dogs with mitral regurgitation confirmed that substantial innate contractile depression was present. CONCLUSIONS: After 3 months of chronic mitral regurgitation, the adrenergic nervous system was able to maintain most indexes of contractile function in the normal range despite significant depression in innate contractile function. Thus, in the absence of beta-blockade, significant innate contractile depression may be obscured by adrenergic support.

Animals↗
PubMed1994

Role of microtubules in contractile dysfunction of hypertrophied cardiocytes.

Cardiac hypertrophy in response to systolic pressure overloading frequently results in contractile dysfunction, the cause for which has been unknown. Since, in contrast, the same degree and duration of hypertrophy in response to systolic volume overloading does not result in contractile dysfunction, we postulated that the contractile dysfunction of pressure hypertrophied myocardium might result from a direct effect of stress as opposed to strain loading on an intracellular structure of the hypertrophied cardiocyte. The specific hypothesis tested here is that the microtubule component of the cytoskeleton is such an intracellular structure, which, forming in excess, impedes sarcomere motion. The feline right ventricle was either pressure overloaded by pulmonary artery banding or volume overloaded by atrial septotomy. The quantity of microtubules was estimated from immunoblots and immunofluorescent micrographs, and their mechanical effects were assessed by measuring sarcomere motion during microtubule depolymerization. We show here that stress loading increases the microtubule component of the cardiac muscle cell cytoskeleton; this apparently is responsible for the entirety of the cellular contractile dysfunction seen in our model of pressure-hypertrophied myocardium. No such effects were seen in right ventricular cardiocytes from normal or volume-overloaded cats or in left ventricular cardiocytes from any group of cats. Importantly, the linked microtubule and contractile abnormalities are persistent and thus may be found to have significance for the deterioration of initially compensatory cardiac hypertrophy into the congestive heart failure state.

Animals↗
PubMed1994

Effects of chronic beta-adrenergic blockade on the left ventricular and cardiocyte abnormalities of chronic canine mitral regurgitation.

The mechanism by which beta blockade improves left ventricular dysfunction in various cardiomyopathies has been ascribed to improved contractile function of the myocardium or to improved beta-adrenergic responsiveness. In this study we tested two hypotheses: (a) that chronic beta blockade would improve the left ventricular dysfunction which develops in mitral regurgitation, and (b) that an important mechanism of this effect would be improved innate contractile function of the myocardium. Two groups of six dogs with chronic severe mitral regurgitation were studied. After 3 mo both groups had developed similar and significant left ventricular dysfunction. One group was then gradually beta-blocked while the second group continued to be observed without further intervention. In the group that remained unblocked, contractile function remained depressed. However, in the group that received chronic beta blockade, contractile function improved substantially. The contractility of cardiocytes isolated from the unblocked hearts and then studied in the absence of beta receptor stimulation was extremely depressed. However, contractility of cardiocytes isolated from the beta-blocked ventricles was virtually normal. Consistent with these data, myofibrillar density was much higher, 55 +/- 4% in the beta-blocked group vs. 39 +/- 2% (P < 0.01) in the unblocked group; thus, there were more contractile elements to generate force in the beta-blocked group. We conclude that chronic beta blockade improves left ventricular function in chronic experimental mitral regurgitation. This improvement was associated with an improvement in the innate contractile function of isolated cardiocytes, which in turn is associated with an increase in the number of contractile elements.

Adrenergic beta-Antagonists↗
PubMed1994

Autologous blood transfusion with recombinant erythropoietin treatment. 22 arthroplasties for rheumatoid arthritis.

12 anemic and 10 non-anemic patients with rheumatoid arthritis were treated with recombinant human erythropoietin (rHuEPO) before arthroplasty. The patients received 400-800 units/kg of rHuEPO subcutaneously once a week. Autologous blood was collected after the hemoglobin concentration was increased by 5 percent or more. All but one of the patients responded to the treatment. They were given 1-3 units of autologous blood, and underwent the operation without homologous blood transfusion. The mean duration of the treatment was 1 month. In 1 patient with severe anemia, additional transfusion with 2 units of blood was necessary during the operation. In all patients, there was a tendency for the hemoglobin response ratio to rHuEPO to correlate negatively with the initial CRP levels. The treatment did not affect the patients' clinical rheumatologic condition and there were no adverse effects. These results demonstrated that the treatment with subcutaneous rHuEPO is both effective and non-toxic and can therefore eliminate the need for homologous blood transfusion in anemic patients undergoing arthroplasty for rheumatoid arthritis.

Adult↗
PubMed1994

Use of M4PO and oxygen-17 in the study on hydroxyl radical generation in the hypoxanthine-xanthine oxidase reaction.

To determine whether hydroxyl radicals (.OH) are generated in the hypoxanthine (HPX)-xanthine oxidase (XOD) reaction, we examined the electron paramagnetic resonance (EPR) spectra of the spin adducts formed. In the EPR study, we used 3,3,5,5-tetramethyl-1-pyrroline-N-oxide (M4PO) as a spin trap, sodium formate (HCOONa) as a .OH scavenger, and oxygen-17 gas as an oxygen source. In the HPX-XOD reaction, both M4PO-OOH and M4PO-OH were observed in the reaction products. The formation of M4PO-OH was independently inhibited by HCOONa resulting in the formation of M4PO-CO2- and in no effects on the formation of M4PO-OOH. With oxygen-17 gas as an oxygen source in the HPX-XOD reaction, both M4PO-17OOH and M4PO-17OH were observed in the reaction products. These results indicate that M4PO-OH is not produced by decomposition of M4PO-OOH and .OH is actually generated during the HPX-XOD reaction.

Cyclic N-Oxides↗
PubMed1994

[Recombinant human erythropoietin (KRN5702) therapy for autologous blood transfusion in patients with rheumatoid arthritis undergoing joint replacement surgery--a multicenter phase II clinical trial].

In order to evaluate the effect of recombinant human erythropoietin (rHuEPO) on autologous blood transfusion in patients with rheumatoid arthritis (RA), we performed a phase II clinical trial in 65 RA patients undergoing elective surgery. rHuEPO was administered subcutaneously once a week and after observing erythropoiesis, autologous blood was collected. Fifty-seven of the 58 patients who completed treatment responded to rHuEPO and could donate more than 400 ml of autologous blood. Among them, 23 out of 28 patients undergoing total hip arthroplasty, 27 out of 28 undergoing total knee arthroplasty and 1 out of 1 undergoing spinal surgery did not need homologous blood transfusion perioperatively. During rHuEPO treatment, no significant changes of clinical parameters of RA activity were observed. Two patients discontinued the treatment because of mild and transient side effects. These results indicate that subcutaneous rHuEPO is safe and effective in eliminate the need for homologous blood transfusion, even in anemic RA patients undergoing elective orthopedic surgery.

Adult↗
PubMed1994

The effects of complete versus incomplete mitral valve repair in experimental mitral regurgitation.

Severe mitral regurgitation (regurgitant fraction 0.75 +/- 0.02) was created in eight dogs by our closed-chest chordal rupture technique. After 3 months of chronic mitral regurgitation all indices of contractile function were depressed. Mitral valve repair was then attempted. Postoperative regurgitant fraction was reduced compared with the preoperative value in all eight dogs. Concomitantly, forward cardiac output increased in all dogs and pulmonary capillary wedge pressure fell in all dogs. However, in some dogs, significant regurgitation persisted despite repair. Postoperative regurgitant fraction ranged from 0% to 60%. Postoperative residual regurgitant fraction was related significantly to postoperative cardiac output (r = 0.99), pulmonary capillary wedge pressure (r = 0.77), ejection fraction (r = 0.75), and two indices of contractile function--the mass-corrected end-systolic stress volume relationship (r = 0.87) and end-systolic stiffness (r = 0.93). In general, these parameters returned to their normal values before mitral regurgitation when postoperative regurgitant fraction was less than 30%. Myocytes isolated from the ventricles at the end of study also demonstrated normal contractile function when regurgitant fraction was less than 30%.

Animals↗
PubMed1993

Cytoskeletal role in the contractile dysfunction of hypertrophied myocardium.

Cardiac hypertrophy in response to systolic pressure loading frequently results in contractile dysfunction of unknown cause. In the present study, pressure loading increased the microtubule component of the cardiac muscle cell cytoskeleton, which was responsible for the cellular contractile dysfunction observed. The linked microtubule and contractile abnormalities were persistent and thus may have significance for the deterioration of initially compensatory cardiac hypertrophy into congestive heart failure.

Actin Cytoskeleton↗
PubMed1993

Network of cytokine and arachidonic acid cascade in acute hepatic failure.

When heat-killed Propionibacterium acnes (P. acnes) was intravenously injected into mice and 7 days later a small amount of lipopolysaccharide (LPS) endotoxin was administered, most of the mice died of massive liver necrosis. In this liver injury model, cytokines, immunomediators, and eicosanoids, inflammatory products, were produced by Kupffer cells and liver-infiltrated macrophages, which were thought to participate, directly or indirectly, in the induction of liver cell damage. Furthermore, these two networks seemed to regulate each other. Thus, this regulatory mechanism might play an important role in the induction of liver cell injury.

Animals↗
PubMed1993

Electrically stimulated contraction accelerates protein synthesis rates in adult feline cardiocytes.

Cardiocytes were induced to contract via electrical field stimulation with an 8 V/cm electrical square-wave pulse of 5 ms at 0.125-2.0 Hz for up to 6 h. Protein synthesis rates were measured as rate of incorporation of [3H]-phenylalanine into total cell protein. Rates of protein synthesis were accelerated 43 +/- 4%, P < 0.001, by 4 h. The acceleration of total protein synthesis showed a frequency dependence between 0.125 and 0.5 Hz. In addition to accelerating rates of total protein synthesis, electrical stimulation of contraction accelerated fractional rates of synthesis of myosin heavy chain by 42 +/- 8%, P < 0.05. Protein synthesis rates were not accelerated upon electrical stimulation using subthreshold voltages. Addition of 100 ng/ml of actinomycin D had no effect on the ability of electrical stimulation of contraction to accelerate protein synthesis. To uncouple excitation-contraction coupling, 2,3-butanedione monoxime (BDM) was used to block actin-myosin cross-bridge interactions. BDM significantly decreased the ability of electrical stimulation to accelerate protein synthesis rates.

Animals↗
PubMed1993

Effects of chronic mitral regurgitation on diastolic function in isolated cardiocytes.

We have previously shown that chronic mitral regurgitation (MR) increases the rate of left ventricular early diastolic filling. These changes in chamber diastolic function were felt to be secondary to alterations in left ventricular loading conditions. Therefore, cellular diastolic function measured in cardiac muscle cells (cardiocytes) isolated from animals with chronic MR (absent alterations in loading conditions) was expected to be normal. However, chronic MR caused a decrease in sarcomere lengthening rate. The purpose of the current study was to define the mechanisms causing this decreased sarcomere lengthening rate in chronic MR cardiocytes and to explain the apparent dichotomy between chamber and cellular diastolic properties. Accordingly, sarcomere motion was measured using laser diffraction techniques in enzymatically isolated cardiocytes from seven control dogs and 11 dogs with chronic MR (produced by closed-chest transection of the mitral chordae). In the MR cardiocytes, there were abnormalities in cellular systolic function (decreased extent and velocity of shortening) and in cellular diastolic function (decreased velocity of sarcomere lengthening). Because studies in papillary muscles have shown that there is a direct relation between abnormal diastolic function (decreased velocity of muscle lengthening) and abnormal systolic function (decreased extent of muscle shortening), it was unclear whether the changes in cellular relaxation rate observed in chronic MR merely reflected a concomitant decrease in the extent of shortening or instead reflected an impairment in intrinsic relaxation properties. To make this distinction, the relation between relaxation velocity (measured as peak sarcomere lengthening rate) and sarcomere shortening extent was examined in MR cardiocytes and compared with that in control cardiocytes. There was a direct relation between sarcomere relaxation velocity and sarcomere shortening extent in both control and MR cardiocytes. Over a wide range of shortening extent, the slopes and y intercepts of this relation were similar in control and MR cardiocytes (slope, 27.7 sec-1 in control cells versus 28.1 sec-1 in MR cells; y intercept, -1.1 microns/sec in control cells versus -1.7 microns/sec in MR cells; p = NS). At any common shortening extent, relaxation velocity was the same in control and MR cardiocytes. To prove that this relation could detect abnormalities in the intrinsic myocardial relaxation process, interventions known to produce primary alterations in the intrinsic myocardial relaxation process were examined: the effects of hypothermia (30 degrees C) and isoproterenol (10(-6) M) on the relaxation velocity-shortening extent relation were studied in normal and MR cardiocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

[A double-blind dose ranging study of weekly subcutaneous administration of rHuEPO (KRN5702) on post-phlebotomy anemia of patients scheduled for predeposit autologous blood transfusion (multicenter late PhII study)].

Preoperative blood reservation for autologous blood transfusion generally causes anemia. We performed a double blind controlled study to determine the optimal dose of subcutaneous rHuEPO (recombinant human erythropoietin, KRN5702) for preventing preoperative anemia due to blood reservation. Patients received KRN5702 subcutaneously once a week in a doses of 12000, 24000 or 36000 IU by a double blind technique. After storage of 1200 ml of their own blood right before surgery, their hemoglobin (Hb) averaged about 1 and was about 0.5 g/dl lower than the level before administration of KRN5702 in doses of 12000 and 24000 IU, respectively. This fall was significant. In patients receiving KRN5702 in a dose of 36000 IU, the level of Hb rose instead of a fall; Hb immediately before surgery was 1.1% higher than that before administration which, however, was not significant. This elevation indicates a possibility of abnormal elevation of Hb at this dose. The mean Hb value right before surgery was significantly lower in patients receiving 12000 IU KRN5702 than in patients of the other two groups. The recovery rate of Hb was an indicator to reflect improvement of anemic conditions, and increased as the dose increased after the blood reservation. The rate in the 12000 IU group was significantly lower than that in the other two groups; there was not much difference between the other two rates. We estimated that to reserve 1200 ml of autologous blood, 24000 IU of KRN5702 is adequate but not excessive. One patient receiving 24000 IU showed side effects including an elevation of body temperature, rash, and edema.

Adult↗