Search PubMed⌕ Search

Biomedical subjects

H Kurosawa

Publications and source records attributed to H Kurosawa.

At least 19 recordsLinked to original sources
PubMed2001

Carbon-carbon bond formation by electrophilic addition at the central carbon of the mu-eta(3)-allenyl/propargyl ligand on the Pd-Pd bond.

The mu-eta(3)-allenyl/propargyldipalladium complexes were synthesized by the reaction of the corresponding eta(1)-allenyl- or eta(1)-propargylpalladium complexes with Pd(2)(dba)(3). The X-ray diffraction analysis indicates that the dinuclear complex has a unique structure, in which two palladium, three carbon, two phosphorus, and one halogen atoms are in the same plane. These dinuclear complexes react with electrophiles, such as HCl or AcCl, at the central carbon of the mu-eta(3)-allenyl/propargyl ligand to give the mu-eta(3)-vinylcarbenedipalladium complexes. Intramolecular reaction proceeded smoothly to give cyclization products quantitatively. Addition of a catalytic amount of a palladium(0) complex dramatically accelerated the carbon-carbon bond formation. The MO calculations on the mu-eta(3)-allenyl/propargyl complexes indicated that the reaction proceeds via orbital control.

Journal Article↗
PubMed2001

Coordination of Lewis acid to eta(2)-enonepalladium(0) leading to continuous structure variation from eta(2)-olefin type to eta(3)-allyl type.

The reaction of alpha,beta-unsaturated carbonyl compounds, a palladium(0) complex, and Lewis acids led to the formation of a new class of complexes showing a wide variety of structures with eta(2)-type and eta(3)-type coordination of the carbonyl compounds. The reaction of Pd(PhCH=CHCOCH(3))(PPh(3))(2) with BF(3).OEt(2) or B(C(6)F(5))(3) quantitatively gave palladium complexes 1a,b having BX(3)-coordinated eta(2)-enonepalladium structure, as revealed by X-ray structure analysis of the B(C(6)F(5))(3) adduct 1b. On the other hand, the reaction of Pd(PhCH=CHCHO)(PPh(3))(2) with BF(3).OEt(2) or B(C(6)F(5))(3) gave distorted zwitterionic eta(3)-allylpalladium complexes 3a,b, where the Pd-carbonyl carbon distance in 3a (2.413(4) A) is much shorter than that (2.96(1) A) in 1b. The values of the P-P coupling constant and (13)C chemical shift for carbonyl carbon are useful criteria for predicting how the eta(3)-coordination mode contributes to the structure of the enone-palladium-Lewis acid system. Molecular orbital calculations on the series of model complexes suggest that orbital overlap in the highest occupied molecular orbital between the palladium and carbonyl carbon is enlarged by coordination of the Lewis acid to the carbonyl group. Palladium-catalyzed conjugate addition of R-M (R-M = AlMe(3), AlEt(3), ZnEt(2)) and its plausible reaction path are also reported.

Journal Article↗
PubMed2001

Enhancement of osteoclastic bone resorption and suppression of osteoblastic bone formation in response to reduced mechanical stress do not occur in the absence of osteopontin.

Reduced mechanical stress to bone in bedridden patients and astronauts leads to bone loss and increase in fracture risk which is one of the major medical and health issues in modern aging society and space medicine. However, no molecule involved in the mechanisms underlying this phenomenon has been identified to date. Osteopontin (OPN) is one of the major noncollagenous proteins in bone matrix, but its function in mediating physical-force effects on bone in vivo has not been known. To investigate the possible requirement for OPN in the transduction of mechanical signaling in bone metabolism in vivo, we examined the effect of unloading on the bones of OPN(-/-) mice using a tail suspension model. In contrast to the tail suspension-induced bone loss in wild-type mice, OPN(-/-) mice did not lose bone. Elevation of urinary deoxypyridinoline levels due to unloading was observed in wild-type but not in OPN(-/-) mice. Analysis of the mechanisms of OPN deficiency-dependent reduction in bone on the cellular basis resulted in two unexpected findings. First, osteoclasts, which were increased by unloading in wild-type mice, were not increased by tail suspension in OPN(-/-) mice. Second, measures of osteoblastic bone formation, which were decreased in wild-type mice by unloading, were not altered in OPN(-/-) mice. These observations indicate that the presence of OPN is a prerequisite for the activation of osteoclastic bone resorption and for the reduction in osteoblastic bone formation in unloaded mice. Thus, OPN is a molecule required for the bone loss induced by mechanical stress that regulates the functions of osteoblasts and osteoclasts.

Amino Acids↗
PubMed2001

Pulmonary thromboembolism after one and a half ventricle repair. Successful catheter-directed thrombolysis.

Acute pulmonary thromboembolism in a patient who had undergone bidirectional Glenn anastomosis was treated by percutaneous selective intravascular thrombolysis. A 20-year-old woman was diagnosed with pulmonary stenosis and right ventricular hypoplasia, complete occlusion of the left pulmonary artery secondary to a Blalock-Taussig shunt, and atrial septal defect. The patient developed thromboembolism of the subsegmental branches of the right pulmonary artery resulting in critical hemodynamic deterioration 2 weeks after undergoing one and a half ventricle repair (bidirectional Glenn shunt). The patient was treated with tissue plasminogen activator administered directly into the right pulmonary artery via an intravascular catheter. Progressive recanalization of the obstruction began immediately. Pulmonary angiography 3 months after thrombolytic therapy demonstrated patent subsegmental vessels. Early detection of the pulmonary thromboembolism and prompt intervention are crutial to relieving this fatal complication after a Fontan operation.

Adult↗
PubMed2001

Right ventricular dynamic cardiomyoplasty for the univentricular heart with pulmonary hypertension.

OBJECTIVES: We conducted an acute experimental study to test the feasibility of dynamic cardiomyoplasty in a setting of modified Fontan procedure for univentricular heart with pulmonary hypertension to obtain a possible proxy for high-risk Fontan candidates. METHODS: After electrical preconditioning of the left latissimuss dorsi for 6 weeks in 8 dogs, the right ventricular cavity was totally obliterated with concomittent closure of the tricuspid valve and right pulmonary artery. Modified Fontan circulation was established with the aortic homograft anastomosed between the right atrium and pulmonary trunk, incorporated with a pericardial pouch as a compression chamber (neoright ventricle) fixed onto the epicardial surface of the ventricle. After cardiopulmonary bypass termination, a latissimus dorsi was applied to wrap the pericardial pouch and ventricle clockwise and stimulated with a trained-pulse (25 Hz) at 1:1 synchronization ratio with cardiac beats. RESULTS: Profound right heart failure was noted during Fontan circulation in increased pulmonary vascular resistance (11 +/- 3.2 Wood units), whereas graft pacing showed significant augmentation of systolic pulmonary pressure by 54 +/- 12%, the mean pulmonary flow by 68 +/- 23%, and aortic pressure by 23 +/- 5% at a physiological range of central venous pressure (13.2 +/- 0.7 mmHg). Right heart function curve analysis confirmed marked augmentation of right heart performance, restoring almost normal pulmonary circulation. These functional benefits were sustained up to 4 hours in 4 animals until experiments were terminated. CONCLUSIONS: Dynamic cardiomyoplasty in a modified Fontan procedure is a viable surgical option for univentricular heart, not a Fontan candidate.

Animals↗
PubMed2001

Thoracoscopic lung volume reduction surgery for pulmonary emphysema patients with severe hypercapnia.

OBJECTIVES: We assessed whether hypercapnia patients with an extremely high level of PaCO2 > or = 60 mmHg were suitable candidates for lung volume reduction in the treatment of severe pulmonary emphysema. METHODS: Of 65 patients undergoing lung volume reduction surgery between May 1993 and August 1997, 6 (9.23%) who had a preoperative rest room air blood gas level of PaCO2 > or = 60 mmHg were selected for study. All patients underwent video-assisted thoracoscopic surgery. Of the 6 with severe hypercapnia, 5 underwent the unilateral procedure and 1 the bilateral procedure. RESULTS: All severe hypercapnia patients showed significant clinical improvement. When assessed at 3 to 6 months after lung volume reduction surgery, significant improvements were seen in mean forced expiratory volume in 1 second (preop: 0.44 +/- 0.04 L; postop: 0.74 +/- 0.20 L; p < 0.01), for a magnitude improvement of 69.8%, and in trapped gas volume (preop: 3.28 +/- 1.11 L; postop: 1.61 +/- 1.02 L; p < 0.05). Arterial blood gas analysis showed significant improvement in PaO2 from 51.1 +/- 6.68 mmHg to 69.8 +/- 7.87 mmHg (p < 0.001) with a decrease in PaCO2 from 70.4 +/- 9.41 mmHg to 46.9 +/- 3.44 mmHg (p < 0.01). Postoperative follow-up averaged 55 months (43-69 months). All but 1 patient remain alive and well. CONCLUSION: Patients with severe pulmonary emphysema accompanied by hypercapnia can gain relief and a better quality of life through volume reduction surgery and should not be excluded from surgical treatment simply based on this condition. Selection should involve a comprehensive view of the patient's condition that includes criteria such as the results of radiographic diagnosis and detailed pulmonary function tests.

Aged↗
PubMed2001

Electron microscopic and cytochemical studies of peroxidase-negative acute nonlymphoblastic leukemia.

Cytochemical and ultrastructural studies of 42 patients with acute nonlymphoblastic leukemia (ANLL) lacking myeloperoxidase as detected by light microscopy were performed. These ANLL patients were classified into minimally differentiated acute myeloid leukemia (AML-M0) (26 cases), mixed-lineage leukemia (9 cases), and acute undifferentiated leukemia (AUL) (7 cases). Ultrastructural morphology revealed blasts from AML-M0 as very immature myeloid cells, blasts from mixed-lineage leukemia as having partially lymphoid cell features, and blasts from AUL as undifferentiated blasts with myeloid nature to some extent. Ultrastructurally, myeloperoxidase activity was positive in 81% of AML-M0 patients and less positive in the mixed-lineage leukemia and AUL patients. The DNA in the nuclei of the AML-M0 blasts was dispersed, as was observed in the immature myeloid cells. Some of the blasts from the mixed-lineage leukemia patients showed condensation of DNA, resembling blasts from acute lymphoblastic leukemia (ALL). The distribution of periodate-reactive glycoconjugates revealed that glycogen particles were absent or, if present, very scanty in AML-M0. Most of the blasts from the AUL patients lacked glycogen particles, and the blasts from those with mixed-lineage leukemia contained clustered glycogen particles, as was observed in the blasts from all patients. These findings disclosed that three subtypes of immature ANLL showed different cytochemical and ultrastructural features in accordance with their immunophenotypical classification.

Adolescent↗
PubMed2001

Spatiotemporal distribution of GAP-43 in the developing rat spinal cord: a histological and quantitative immunofluorescence study.

In the rat spinal cord we studied developmental changes in spatiotemporal expression of the growth-associated protein GAP-43, which is known to play an important role in neural development, axonal regeneration, and modulation of synaptic function. GAP-43 was expressed predominantly in the white matter at embryonic day 13 to postnatal day 7, evenly in the white and gray matter at the 2nd to the 3rd postnatal week, and predominantly in the gray matter after the 5th postnatal week. The shifting of predominance was quantitatively assessed. On the basis of histological findings and quantitative assessment of GAP-43 immunoreactivity, it appears likely that the development proceeds from the phase of mostly axonal elongation during the embryonic period and the 1st postnatal week, via the phase of axonal elongation and formation of end arbors and synaptic organization during the 2nd to the 4th postnatal week, to the phase of final maturation of synaptic organization. GAP-43 was continuously expressed through adulthood in neuropil of the gray matter, the pyramidal tract, and the dorsal portion of the lateral funiculus that was identified as serotonergic by confocal laser scanning microscopic studies. The continuous expression may imply perpetual remodeling in these structures even in adulthood.

Animals↗
PubMed2001

Renal protective effects of chronic exercise and antihypertensive therapy in hypertensive rats with chronic renal failure.

OBJECTIVES: Patients with chronic renal failure are restricted to mild physical activity and tend to a lack of exercise. However, there have been few reports regarding the influence of chronic exercise on the progression of renal disease. Similarly, there are few animal models concerned with the effect of exercise training on improving renal function. Therefore, we assessed the renal effects of moderate chronic treadmill exercise in a remnant kidney model of spontaneously hypertensive rats (SHR) with chronic renal failure. We also assessed the effects of exercise and antihypertensive therapy on renal function. DESIGN AND METHODS: Eight-week-old SHR were subjected to 5/6 nephrectomy by removal of the left kidney and excision of two-thirds of the right kidney. The rats were divided into four groups: (i) no exercise (Non-EX); (ii) moderate exercise with treadmill running (20 m/min, 0 grade incline for 60 min) (EX); (iii) EX with an angiotensin converting enzyme (ACE) inhibitor, enalapril (2 mg/kg per day, i.p.); and (iv) EX with an angiotensin receptor antagonist, losartan (5 mg/kg per day, i.p.), for 4 weeks. RESULTS: Chronic EX significantly attenuated the increase in proteinuria (P < 0.01) and significantly protected against increases in the index of glomerular sclerosis (IGS). Both enalapril and losartan with EX significantly decreased blood pressure (P < 0.001), and further decreased the IGS. In the stepwise multiple regression analysis, only antihypertensive drug remained in the model as a significant predictor of IGS (P < 0.0001). In contrast, exercise, antihypertensive drug and mean systolic blood pressure (weeks 1-4) remained in the model as a significant predictors of mean proteinuria (weeks 1-4) (all P < 0.0001). CONCLUSIONS: These results suggest that exercise does not worsen renal function and has renal-protective effects in this model of rats. Moreover, the antihypertensive therapy has additional renal-protective effects in this model of rats.

Angiotensin Receptor Antagonists↗
PubMed2001

The E2A-HLF oncoprotein activates Groucho-related genes and suppresses Runx1.

The E2A-HLF fusion gene, formed by the t(17;19)(q22;p13) chromosomal translocation in leukemic pro-B cells, encodes a chimeric transcription factor consisting of the transactivation domain of E2A linked to the bZIP DNA-binding and protein dimerization domain of hepatic leukemia factor (HLF). This oncoprotein blocks apoptosis induced by growth factor deprivation or irradiation, but the mechanism for this effect remains unclear. We therefore performed representational difference analysis (RDA) to identify downstream genetic targets of E2A-HLF, using a murine FL5.12 pro-B cell line that had been stably transfected with E2A-HLF cDNA under the control of a zinc-regulated metallothionein promoter. Two RDA clones, designated RDA1 and RDA3, were differentially upregulated in E2A-HLF-positive cells after zinc induction. The corresponding cDNAs encoded two WD40 repeat-containing proteins, Grg2 and Grg6. Both are related to the Drosophila protein Groucho, a transcriptional corepressor that lacks DNA-binding activity on its own but can act in concert with other proteins to regulate embryologic development of the fly. Expression of both Grg2 and Grg6 was upregulated 10- to 50-fold by E2A-HLF. Immunoblot analysis detected increased amounts of two additional Groucho-related proteins, Grg1 and Grg4, in cells expressing E2A-HLF. A mutant E2A-HLF protein with a disabled DNA-binding region also mediated pro-B cell survival and activated Groucho-related genes. Among the transcription factors known to interact with Groucho-related protein, only RUNX1 was appreciably downregulated by E2A-HLF. Our results identify a highly conserved family of transcriptional corepressors that are activated by E2A-HLF, and they suggest that downregulation of RUNX1 may contribute to E2A-HLF-mediated leukemogenesis.

Amino Acid Sequence↗
PubMed2001

Role of GABA within the nucleus tractus solitarii in the hypoxic ventilatory decline of awake rats.

The purpose of this study was to examine our hypothesis that gamma-aminobutyric acid (GABA) in the nucleus tractus solitarii (NTS) may be related to the hypoxic ventilatory decline (HVD) and that chemoreceptor stimulation was essential to activate this mechanism. We used unanesthetized, freely moving rats in this study. An in vivo microdialysis technique was used to measure the extracellular GABA concentration ([GABA]o), and an in vivo microinjection technique was used to examine the effects of the GABA agonists and antagonists on the ventilation during hypoxia. The GABA agonists injected into the NTS attenuated the ventilation during hypoxia. By hypoxic exposure, [GABA]o was increased during the HVD. However, by carotid body denervation (CBD), this GABA increase was abolished. Although GABA antagonists microinjected into the NTS during the HVD phase significantly increased the depressed ventilation, this effect on the ventilation was abolished by CBD. These results suggest that the GABA in the NTS has a pivotal role in the HVD and that this mechanism is not activated without chemoreceptor stimulation.

Animals↗
PubMed2001

Expression of Bcl-2 family reduces apoptotic hepatocytes after excessive hepatectomy.

Excessive hepatectomy often causes fatal hepatic failure, but the mechanism is unknown. We used a novel protocol of partial 90 and 95% hepatectomy (PHx) to investigate this mechanism in 2 groups of rats. The 90% PHx rats survived, but the 95% PHx animals died of hepatic failure. In the latter, cytokine (interleukin-6, tumor necrosis factor-alpha) levels and the apoptotic hepatocyte count increased, and there were few mitotic cells. By contrast, in the 90% PHx rats, the mitotic cell count increased, and more anti-apoptotic Bcl-xL protein was expressed. These results demonstrate that expression of Bcl-xL protein as an anti-apoptotic factor or regeneration factor contributes to survival after 90% PHx. Using an adenovirus vector, the human bcl-2 gene (hbcl-2) was therefore transfected to DA rat livers where it was efficiently expressed, and then 95% PHx was performed. Liver damage was decreased and the apoptotic cell count decreased too, but the rats died. We concluded that transfection of the hbcl-2 gene partly prevents cytotoxicity (apoptosis), but cannot ensure survival. Thus, some other factor is required (e.g., a regeneration stimulator) to maintain life in these models.

Animals↗