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H Nawata

Publications and source records attributed to H Nawata.

At least 145 records · Page 8Linked to original sources
PubMed1999

[Donor leukocyte transfusion in a patient with relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation: analysis of natural killer cell activity and T-cell receptor repertoire in bone marrow T cells that exhibited graft-versus-leukemia activity].

Hematologic relapse of chronic myeloid leukemia developed in 37-year-old man 255 days after allogeneic bone marrow transplantation. The patient received a donor lymphocyte transfusion (DLT) twice at a dose of 5 x 10(6)/kg T cells. He achieved complete cytogenetic response (CCR) 14 weeks after DLT, and has remained in a CCR state for 17 months. Neither acute nor chronic graft-versus-host disease (GVHD) was observed. Natural killer (NK) cell activity was elevated. Also, analysis of the T cell receptor (TCR) repertoire disclosed oligoclonal expansion of T cells of the TCR V beta and J beta subfamilies. These observations provide evidence for the clonal expansion of allogeneic T cells that are capable of mediating antileukemic activity without causing GVHD.

Adult↗
PubMed1999

[Melatonin].

Explore the source record for details and available documents.

Humans↗
PubMed1999

Is endothelin-1 an aggravating factor in the development of acute pancreatitis?

OBJECTIVE: We have reported previously that cerulein-induced edematous pancreatitis would transform into hemorrhagic pancreatitis by administration of endothelin-1 in rats. In the present study, we tried to protect rat model from developing into hemorrhagic pancreatitis with BQ123 (an ETA receptor antagonist). METHODS: The rat model was made by 5-hour restraint water-immersion stress and two intraperitoneal injections of cerulein (40 micrograms/kg) at hourly interval. BQ123 (3 or 6 mg/kg) was administered intravenously 30 minutes before and 2 hours after the first cerulein injection. RESULTS: Acute hemorrhagic pancreatitis was induced in all rats treated with cerulin + stress. The score for pancreatic hemorrhage was 2.4 +/- 0.2 in this group. In the rats pretreated with BQ123, the score was reduced to 1.0 +/- 0.0, pancreas wet weight and serum amylase activity were significantly reduced, and histologic alterations in the pancreas lightened, also the local pancreatic blood flow improved without affecting the systemic blood pressure. CONCLUSIONS: These results suggest that endothelin-1 should play a role in aggravating the development of acute hemorrhagic pancreatitis, through its action on the pancreatic microcirculation.

Acute Disease↗
PubMed1998

Heterogeneity of anterograde fast-pathway and retrograde slow-pathway conduction patterns in patients with the fast-slow form of atrioventricular nodal reentrant tachycardia: electrophysiologic and electrocardiographic considerations.

OBJECTIVES: This study sought to define the electrophysiologic and electrocardiographic characteristics of fast-slow atrioventricular nodal reentrant tachycardia (AVNRT). BACKGROUND: In fast-slow AVNRT the retrograde slow pathway (SP) is located in the posterior septum, whereas the anterograde fast pathway (FP) is located in the anterior septum; however, exceptions may occur. METHODS: Twelve patients with fast-slow AVNRT were studied. To determine the location of the retrograde SP, atrial activation during AVNRT was examined while recording the electrograms from the low septal right atrium (LSRA) on the His bundle electrogram and the orifice of the coronary sinus (CS). Further, to investigate the location of the anterograde FP, single extrastimuli were delivered during AVNRT both from the high right atrium and the CS. RESULTS: The CS activation during AVNRT preceded the LSRA in six patients (posterior type); LSRA activation preceded the CS in three patients (anterior type), and in the remaining three both sites were activated simultaneously (middle type). In the anterior type, CS stimulation preexcited the His and the ventricle without capturing the LSRA electrogram (atrial dissociation between the CS and the LSRA), suggesting that the anterograde FP was located posterior to the retrograde SP. In the posterior and middle types, high right atrial stimulation demonstrated atrial dissociation, suggesting that the anterograde FP was located anterior to the SP. In the posterior and middle types, retrograde P waves in the inferior leads were deeply negative, whereas they were shallow in the anterior type. CONCLUSIONS: Fast-slow AVNRT was able to be categorized into posterior, middle and anterior types according to the site of the retrograde SP. The anterior type AVNRT, where an anteriorly located SP is used in the retrograde direction and a posteriorly located FP in the anterograde direction, appears to represent an anatomical reversal of the posterior type which uses a posterior SP for retrograde and an anterior FP for anterograde conduction. Anterior type AVNRT should be considered in the differential diagnosis of long RP (RP > PR intervals) tachycardias with shallow negative P waves in the inferior leads.

Adult↗
PubMed1998

Effect of eicosapentaenoic acid on glucose-induced diacylglycerol synthesis in cultured bovine aortic endothelial cells.

Hyperglycemia has been postulated to increase diacylglycerol (DAG) level through de novo synthesis pathway and subsequently activate protein kinase C (PKC) in vascular cells, possibly leading to vascular dysfunction associated with diabetes. In this study, we examined the effect of eicosapentaenoic acid (EPA) on high glucose-induced increase in DAG level in cultured aortic endothelial cells (ECs). In ECs, total DAG level was significantly increased in the cells cultured with high glucose levels (400 mg/dl) compared with the cells with normal glucose levels (100 mg/dl). The addition of EPA completely prevented high glucose-induced increase in total DAG level. In contrast, other common fatty acids such as palmitate and oleate significantly stimulated DAG syntheisis, although arachidonate did not affect it. High glucose level significantly stimulated the incorporation of 3H-palmitate into DAG, while it did not affect the incorporation of 3H-arachidonate into DAG. The addition of EPA completely prevented the high glucose-induced increase in 3H-palmitate incorporation into DAG, while it did not affect the 3H-arachidonate incorporation. These findings suggest that EPA can prevent high glucose induced-increase in DAG level in ECs, probably by specifically inhibiting de novo synthesis at the step of acylation. EPA may be one of the candidates for clinical agents normalizing activation of DAG-PKC pathway in diabetic vascular tissues and preventing vascular complications associated with diabetes.

Animals↗
PubMed1998

Chromogranin B (secretogranin I), a neuroendocrine-regulated secretory protein, is sorted to exocrine secretory granules in transgenic mice.

Chromogranin B (CgB, secretogranin I) is a secretory granule matrix protein expressed in a wide variety of endocrine cells and neurons. Here we generated transgenic mice expressing CgB under the control of the human cytomegalovirus promoter. Northern and immunoblot analyses, in situ hybridization and immunocytochemistry revealed that the exocrine pancreas was the tissue with the highest level of ectopic CgB expression. Upon subcellular fractionation of the exocrine pancreas, the distribution of CgB in the various fractions was indistinguishable from that of amylase, an endogenous constituent of zymogen granules. Immunogold electron microscopy of pancreatic acinar cells showed co-localization of CgB with zymogens in Golgi cisternae, condensing vacuoles/immature granules and mature zymogen granules; the ratio of immunoreactivity of CgB to zymogens being highest in condensing vacuoles/immature granules. CgB isolated from zymogen granules of the pancreas of the transgenic mice aggregated in a mildly acidic (pH 5.5) milieu in vitro, suggesting that low pH-induced aggregation contributed to the observed concentration of CgB in condensing vacuoles. Our results show that a neuroendocrine-regulated secretory protein can be sorted to exocrine secretory granules in vivo, and imply that a key feature of CgB sorting in the trans-Golgi network of neuroendocrine cells, i.e. its aggregation-mediated concentration in the course of immature secretory granule formation, also occurs in exocrine cells although secretory protein sorting in these cells is thought to occur largely in the course of secretory granule maturation.

Animals↗
PubMed1998

Novel mutation of the DAX1 gene in a patient with X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism.

X-linked adrenal hypoplasia congenita (AHC) is characterized by primary adrenal insufficiency and is frequently associated with hypogonadotropic hypogonadism (HHG). Mutations of the DAX1 gene have been reported in patients with AHC and HHG. We found a novel DAX1 mutation in our patient. Sequence analysis of the patient's DAX1 demonstrated a 1-bp (G) deletion at codon 49 in exon 1. The mutation shifts the reading frame, resulting in completely different amino acid sequences from codon 49 to the premature stop codon at 84. The G was present at this position in the sequences of the father and 2 younger brothers. Direct sequence and single-strand conformation polymorphism analyses of polymerase chain reaction fragments revealed that the mutation at codon 49 was heterozygously present in the mother's DAX1 gene. The codon 84 is located in the first half of the DNA binding domain, and the mutation site is closer to the N-terminus than those in previously reported cases. The onset of adrenal insufficiency in the neonatal period as seen in our patient has also been reported in other patients with different DAX1 mutations, especially in a patient with DAX1 protein lacking 11 amino acids at the C-terminus. Therefore, it is less likely that position of termination codons correlate to clinical manifestations.

Adrenal Glands↗
PubMed1998

Prevention of diabetes-induced abnormal retinal blood flow by treatment with d-alpha-tocopherol.

Hyperglycemia in diabetes mellitus has been shown to activate diacylglycerol (DAG)-protein kinase C (PKC) pathway in the vascular tissues, possibly altering vascular function. We have characterized the effects of vitamin E (d-alpha-tocopherol) on activation of PKC and DAG levels in retinal tissues of diabetic rats, and correlated its effects to retinal hemodynamics using video-based fluorescein angiography (VFA). Comparing streptozotocin-induced diabetic rats to controls, membranous PKC specific activities were increased by 71% (p < 0.05). Western blot analysis showed that the membranous PKC beta II isoform was significantly increased by 133 +/- 45% (p < 0.05). Intraperitoneal injection of d-alpha-tocopherol (40 mg/kg) every other day prevented the increases in membranous PKC specific activity and PKC beta II protein shown by immunoblots. Similar to PKC activities, total DAG levels were increased in the retina and were normalized by d-alpha-tocopherol treatment. Physiologically, abnormalities of retinal blood hemodynamics, as measured using VFA, which previously have been reported to be associated with increases of DAG and PKC levels in the diabetic rats, were prevented by d-alpha-tocopherol treatment in diabetic rats. The direct effect of d-alpha-tocopherol on total DAG and [3H]-palmitate incorporation into DAG were also examined using cultured bovine retinal endothelial cells (REC). Exposure of REC to 22 mM glucose for three days increased total DAG and [3H]-palmitate labeled DAG levels by 35 +/- 8% and 50 +/- 8%, respectively (p < 0.05). The presence of d-alpha-tocopherol (50 micrograms/ml) prevented the increase of both total DAG and [3H]-palmitate labeled DAG levels in cells exposed to 22 mM glucose. These findings suggested that the mechanism of the d-alpha-tocopherol's effect appears to be mediated by the normalization of the hyperglycemia-induced activation of the DAG-PKC pathway which leads to the normalization of abnormal retinal blood flow seen in diabetes mellitus.

Animals↗
PubMed1998

Effect of high glucose concentrations on prostacyclin-stimulating factor mRNA expression in cultured aortic smooth muscle cells.

Prostacyclin (PGI2) is a potent vasoactive prostanoid regulating vascular tone. We recently purified and cloned a PGI2-stimulating factor (PSF), which stimulates PGI2 production by vascular endothelial cells (ECs). Previous study demonstrated that PSF is predominantly located in vascular smooth muscle cells (SMCs) and present in serum. PSF may act on vascular ECs to regulate PGI2 synthesis for maintaining vessel wall homeostasis. Decreased PSF production in the vessel wall may result in an imbalance of prostanoid synthesis, leading to the development of vascular lesions such as diabetic angiopathy. In the present study, to investigate the regulatory mechanisms of PSF gene expression, we examined the effect of high glucose concentrations on PSF mRNA expression in cultured bovine aortic SMCs. Expression of PSF mRNA was significantly decreased to 66+/-6% of control value (p < 0.01), when the glucose level was raised from 5.5 to 27.8 mmol/l. We also examined the effect of osmolarity on PSF mRNA expression by addition of an appropriate dose of mannitol to the culture medium. We confirmed that high glucose concentration itself reduced the expression of PSF mRNA and glucose had much more effect than the osmolarity control. The expression of PSF mRNA was significantly decreased to 72+/-5% of control value (p < 0.05) by a protein kinase C (PKC) activator, phorbol-12-myristate-13-acetate (PMA). The decreased expression of PSF mRNA in the presence of high glucose or PMA was restored by co-incubation with a PKC-specific inhibitor (GF109203X). These results suggest that PSF gene expression in vascular SMCs may be decreased via a specific effect of high glucose concentrations. High glucose-induced activation of PKC is suggested to participate partly in the regulation of PSF gene expression.

Animals↗
PubMed1998

Oxidative stress measurement by in vivo electron spin resonance spectroscopy in rats with streptozotocin-induced diabetes.

Enhanced oxidative stress in diabetic patients may contribute to the pathogenesis of diabetic angiopathy. We have recently developed a method to determine the electron spin resonance (ESR, electron paramagnetic resonance; EPR) of reactive oxygen species and free radicals in vivo, using the nitroxide derivative, carbamoyl-PROXYL as a probe. In this study, diabetes was induced in Wistar rats by streptozotocin (STZ) injection (65 mg/kg, body weight, intravenously). Two, 4, and 8 weeks later, the animals received carbamoyl-PROXYL (300 nmol/g, intravenously), and ESR was measured at the upper abdominal level at a frequency of 300 MHz. The intensity of the carbamoyl-PROXYL ESR signal decreased gradually after the injection, and the spin clearance rate was determined over the first 5 min. At all time points, the spin clearance rate was significantly greater in the diabetic rats than in control rats. Moreover, the spin clearance rate in the diabetic rats was significantly correlated with urinary malondialdehyde (MDA) levels, which serve as a marker for lipid peroxidation. Daily treatment with 4 units neutral protamin Hagedorn (NPH) insulin for 4 weeks reduced the spin clearance rate in the diabetic rats. Simultaneous injection of carbamoyl-PROXYL and superoxide dismutase reduced the spin clearance rate in the diabetic rats in a dose-dependent manner. Injection of the antioxidant alpha-tocopherol (40 mg/kg, intraperitoneally) for 2 weeks restored the spin clearance rate in the diabetic rats without concomitant glycaemic restoration. These results suggest that a diabetic state enhances the generation of free radicals in vivo, and that both glycaemic control and antioxidant treatment can reduce this oxidative stress. Non-invasive in vivo ESR measurement may be useful for evaluating oxidative stress in diabetes.

Animals↗