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Biomedical subjects

H Azuma

Publications and source records attributed to H Azuma.

At least 37 records · Page 2Linked to original sources
PubMed2001

17 Beta-estradiol increases nitric oxide and prostaglandin I2 production by cultured human uterine arteries only in histologically normal specimens.

These experiments were designed to investigate whether 17beta-estradiol (E2) modulates the endothelial function of perimenopausal human uterine arteries. After the artery specimen was cultured in the presence or absence of E2 at a physiologic concentration of 200 pg/ml, changes in isometric tension and cyclic nucleotide production were determined. Degree of intimal hyperplasia was assessed histologically and expressed as intima-to-media ratio. Acetylcholine produced an endothelium-dependent relaxation in six specimens (group I) of 12, which was inhibited by NG-nitro-L-arginine or indomethacin. However, the agonist failed to produce a definite relaxation in the remaining 6 (group II). The endothelium-dependent relaxation was significantly augmented after incubating with E2 only in group I specimens. Cyclic nucleotide production was significantly increased after E2 incubation only in group I specimens, whereas it was inhibited by NG-nitro-L-arginine or indomethacin. Histologic study revealed that the six specimens of group I had normal intima (intima-to-media ratio = 19.1+/-1.8%) and the remaining six of group II had intimal hyperplasia (intima-to-media ratio = 53.6+/-5.3%). Increased production of cyclic nucleotides occurred in uterine arteries with normal intima but not in arteries with intimal hyperplasia derived from perimenopausal women.

Adult↗
PubMed2001

Homozygous deletion mutation of the parkin gene in patients with atypical parkinsonism.

Autosomal recessive juvenile parkinsonism (AR-JP) is characterised by homogenous clinical features and selective degeneration of nigral neurons. Recent progress in molecular genetic analyses of AR-JP has led to the identification of a novel ubiquitin-like protein, parkin, whose precise function still remains to be elucidated. Two unrelated Japanese families had levodopa unresponsive parkinsonism complicated with cerebellar and pyramidal tract dysfunction. Genetic analysis of the parkin gene and mRNA in both families disclosed identical mutations with large deletions extending from exons 3 to 4. These results suggest that the parkin protein possesses an important function not only in the substantia nigra but also in extranigral neurons of the CNS and that the phenotype of multiple system dysfunction can also be a complication in patients with AR-JP due to variations in sites of or changes in functions by parkin mutation.

Blotting, Southern↗
PubMed2001

Nifedipine induces gingival overgrowth in rats through a reduction in collagen phagocytosis by gingival fibroblasts.

BACKGROUND: Nifedipine is used as a long-acting vasodilator, and a primary side effect is the induction of gingival overgrowth, which is characterized by an accumulation of collagenous components within the gingival connective tissue. To elucidate the mechanisms of nifedipine-induced gingival overgrowth, we investigated the effect of nifedipine on Type I collagen metabolism in the gingiva of rats. METHODS: Twenty-day-old rats were fed a powdered diet containing or lacking nifedipine for 3 to 55 days. Immunohistochemical analysis with anti-Type I collagen antibody was employed to examine the density of Type I collagen in the gingival connective tissue. Total RNAs were isolated from mandibular molar gingiva on days 0, 3, 15, 30, and 55, and reverse transcription polymerase chain reaction was performed to investigate the mRNA levels of Type I collagen. In addition, we performed a flow cytometric analysis with collagen-coated latex beads and cultured fibroblasts derived from rat gingiva to measure collagen phagocytosis. RESULTS: Immunohistochemical analysis revealed that Type I collagen was more prevalent in the connective tissue of nifedipine-treated gingiva than in controls on day 55. In the nifedipine-treated group, the expression of Type I collagen mRNA gradually decreased to 1.5% on day 55 compared to day 0. In the control group, Type I collagen mRNA also decreased to 32%; however, mRNA expression was significantly lower in the nifedipine-treated group than in the controls. When the rate of phagocytic cells derived from nifedipine-treated gingiva and controls was represented as the mean +/- SE of the percentage from 3 different experiments, the values were as follows: on day 15, 13.5 +/- 2.1% and 15.0 +/- 1.5%; on day 30, 12.2 +/- 4.3% and 34.5 +/- 6.7% in the nifedipine-treated and the control group, respectively, indicating that phagocytic cells were considerably fewer in the nifedipine-treated gingiva on day 30. This finding demonstrates that the decrease in phagocytosis caused by nifedipine appeared before the detection of severe macroscopic gingival overgrowth. CONCLUSION: These findings suggest that the decrease in collagen degradation due to lower phagocytosis is closely associated with the increase in Type I collagen accumulation in nifedipine-treated rat gingiva.

Animals↗
PubMed2001

Role of a central muscarinic cholinergic pathway for relaxation of the proximal urethra during the voiding phase in rats.

PURPOSE: We examined the role of a central muscarinic cholinergic pathway in proximal urethral function during the voiding phase. MATERIALS AND METHODS: During isovolumetric bladder contraction we independently recorded proximal urethral pressure, external urethral sphincter activity, and hypogastric and pelvic nerve discharge in urethane anesthetized rats. We administered intravenous, intrathecal or intracerebral ventricular atropine sulfate and atropine methyl nitrate. Atropine sulfate crosses the blood-brain barrier, while atropine methyl nitrate does not. RESULTS: Filling the bladder with 0.5 ml saline induced rhythmic urethral relaxation accompanied by efferent burst discharges from the pelvic nerve. When administered intravenously, only atropine sulfate caused the dose dependent inhibition of urethral relaxation and efferent pelvic nerve discharge. Neither atropine sulfate nor atropine methyl nitrate affected the maximum firing rate of the external urethral sphincter or hypogastric efferent discharge. Intrathecal and intracerebral ventricular atropine sulfate and atropine methyl nitrate similarly inhibited urethral relaxation. CONCLUSIONS: These results suggest that excitation of the central muscarinic cholinergic pathway at a supraspinal or spinal site promotes proximal urethral relaxation during the voiding phase through the activation of efferent pathways in the pelvic nerves.

Animals↗
PubMed2001

Molecular mechanism of type I congenital heparin cofactor (HC) II deficiency caused by a missense mutation at reactive P2 site: HC II Tokushima.

We found a 66-year-old Japanese patient with type I congenital heparin cofactor (HC) II deficiency manifesting multiple atherosclerotic lesions. To investigate the molecular pathogenesis of our patient, we performed sequencing analysis and expressed recombinant human wild-type and mutant HC II molecules in COS-1 and CHO-K1 cells. Sequencing analysis following amplification of each of all 5 exons and its flanking region showed a single C to T transition at nucleotide position 12,854 in exon 5, which changed a Pro443 codon (CCG) to Leu codon (CTG). Because this mutation generates a new Bhv I site, the Bbv I digestion pattern of the PCR-amplified exon 5 fragments from each family member was analyzed. In all cases, the patterns were consistent with the activities and antigen levels of plasma HC I1 in those members. Transient transfection, metabolic labeling and pulse-chase experiments followed by immunoprecipitation analysis showed that the recombinant mutant HC II molecules were secreted from COS-1 cells in reduced amounts compared with the wild-type, and that an enhanced intracellular association of the mutant molecules with a chaperone, GRP78/BiP, was observed in CHO-K1 cells. Northern blot analysis indicated that the mutant HC I1 mRNA was transcribed at a similar level as that of wild-type. Immunohistochemical staining of the transfected cells revealed that COS-1 cells expressing the mutant HC II molecules were stained mainly in the perinuclear area. We conclude that the impaired secretion of the mutant HC II molecules, due to intracellular degradation, is the molecular pathogenesis of type I congenital HC II deficiency caused by a Pro443 to Leu mutation at reactive P2 site.

Aged↗
PubMed2001

[Von Hippel-Lindau disease associated with renal cell carcinoma and bilateral cystadenoma of the epididymis: a case report].

We present a case report of von Hippel-Lindau disease associated with renal cell carcinoma and bilateral cystadenoma of the epididymis. A 26-year-old man appeared with painless tumors of the bilateral scrotal contents. Ultrasonography and other radiographic examinations including computed tomographic scan and dripinfusion pyelography showed multiocular tumors in the bilateral epididymis and a right renal tumor 3 cm in diameter. The tumors of the bilateral epididymis were surgically resected and of the right renal tumor enucleated. Histopathological examination revealed cystadenoma of the epididymis and renal cell carcinoma (clear cell carcinoma, G1, pT1a). He has not received adjuvant therapy, and is doing well with no evidence of metastatic disease 2 years after surgery.

Adult↗
PubMed2000

Comparison of sensitivity to ultraviolet B irradiation between human lymphocytes and hematopoietic stem cells.

To investigate the clinical applicability of prophylaxis of post-transplant graft-versus-host disease by UV-B irradiation of stem cell preparations, the UV-B sensitivities of human lymphocytes and primitive hematopoietic progenitors were compared. The mononuclear cell fractions (MNC) derived from human cord blood and granulocyte-colony-stimulating factor-mobilized peripheral blood were used. After UV-B irradiation, lymphocyte proliferation ability, hematopoietic colony-forming cells, and apoptotic cells were analyzed. At a dose of 33 J/m(2), significant differences were observed in the residual percentages of hematopoietic progenitors and lymphocyte functions [ANOVA, F (5,46) = 19.4; P <.0001], and the difference between CFU-C (85.2% + 24.0%; n = 8) and MLR (12.7% + 12. 6%; n = 10) was significant (P <.0001). There were no significant differences in the residual percentages of CFU-C, HPP-CFC, and LTC-IC. Percentages of annexin V-positive cells in the total MNC and the CD34(+) cell population in MNC after UV-B irradiation were 69.8% and 18.7%, respectively. In conclusion, there was a range of UV-B doses over which T lymphocytes were inactivated but hematopoietic progenitors, including HPP-CFC and LTC-IC, were preserved.

Annexin A5↗
PubMed2000

Analysis of soluble interleukin 6 receptor in cerebrospinal fluid in inflammatory and non-inflammatory conditions.

The objective of this study was to investigate the pathophysiological roles of soluble interleukin 6 receptor (sIL-6R) in cerebrospinal fluid (CSF). CSF was obtained from patients suspected with meningitis. Eight patients without any meningeal signs or symptoms were enrolled as controls. An additional 34 CSF samples were collected to measure both biologically active and immunoreactive sIL-6R. All CSF samples were proven to be aseptic. IL-6 and sIL-6R were measured using specific ELISAs. Patients were divided into three groups on the basis of cell number in CSF; inflammatory group (cell number >5 microl, mean 241+/-363.1, n=61); non-inflammatory group (cell number < or =5 microl, mean=2.1+/-1.7, n=12) and controls (cell number < or =5 microl, mean=0.3+1.7, n=8). Among these three groups, the differences in protein (F (2,78)=8.274, P<0.0001) and IL-6 concentration (F (2,78)=6.475, P<0.001) were statistically significant but those of sIL-6R concentration were not. There were only weak correlations between log (sIL-6R) versus log (cell number) (r=0.23, P=0.0375), log (protein) (r=0.239, P=0.0358) and log (IL-6) (r=0.27, P=0.0167). Amounts of immunoreactive and biologically active sIL-6R were closely correlated (r=0.62, n=34, P<0.005). It was concluded that sIL-6R is present constitutively in CSF and its level may not increase significantly in inflammatory conditions; infiltrating cells in CSF are not the main source of sIL-6R; and sIL-6R in CSF can bind IL-6.

Case-Control Studies↗
PubMed2000

Differences in binding of glucocorticoid receptor to DNA in chronic renal graft rejection.

Although chronic rejection is the most common reason for late allograft loss, its pathophysiology and etiology are unclear. Attempts to prevent chronic rejection are now focused on the modulation of transcriptional regulation. We evaluated the ability of glucocorticoid receptors (GR) to bind to the DNA binding site in peripheral blood mononuclear cells (PBMC) of five patients with chronic rejection and seven without it. Using an electrophoretic mobility shift assay, we measured the amount of nuclear glucocorticoid receptor capable of binding to its specific DNA recognition sequences, termed glucocorticoid response elements (GRE). GR binding was significantly greater in control patients than in those with chronic rejection (P < 0.01). The retarded band was almost undetectable in two patients with chronic rejection even though they were taking more prednisolone than the seven control patients, all of whom had clearly identifiable retarded bands. These results suggest a decreased ability of GR to bind to GRE in chronic rejection, resulting in a reduced ability to block key proinflammatory promoter sites. This reduced binding may be one molecular basis of chronic rejection.

Adult↗
PubMed2000

Effective improvement of the cerebral vasospasm after subarachnoid hemorrhage with low-dose nitroglycerin.

In the rabbit subarachnoid hemorrhage (SAH) model, the sensitivity of spastic basilar arteries to nitric oxide (NO) was enhanced whereas the endothelial function to release/produce NO became impaired, as described previously. We assumed from these results that low-dose NO might selectively dilate spastic arteries without influencing normal or systemic blood vessels; therefore, we investigated whether exogenous low-dose NO effectively improves cerebral vasospasm. Low-dose NO was derived from a small size of the tape containing nitroglycerin, which is not invasive and is clinically available. The experimental SAH was induced by injecting autologous blood into the cisterna magna of the rabbit. Experiments were performed on the following three groups: (a) SAH group with nitroglycerin tape (nitroglycerin group), (b) SAH group with placebo tape (placebo group), and (c) saline group injected with saline instead of blood. The tape containing 0.675 mg nitroglycerin was applied once daily for 2 days onto the skin area of the rabbit's ear. Angiograms were performed once before cisternal injection of blood and/or saline and again on day 2. On day 2 the basilar artery was isolated and sliced into 2-mm ring preparations. Relaxations of the basilar artery to acetylcholine, sodium nitroprusside, and calcium ionophore A23187, as well as the contractile responses to serotonin and endothelin- 1, were measured. The diameter of the basilar artery on day 2 was reduced to 69.6+/-2.2% (n = 7) before the injection of autologous blood. The angiographic vasospasm of the basilar artery was partially but significantly (p<0.0001) improved to the percentage diameter of 89.4+/-1.4% (n = 7) by the application of low-dose nitroglycerin, which did not affect the systemic blood pressure and heart rate. In the basilar artery preparations harvested from SAH rabbits on day 2, the impaired acetylcholine-induced endothelium-dependent relaxation was partially but significantly (p<0.001) improved in the nitroglycerin group. However, this group remained unaffected in the increased sensitivity to nitroglycerin and the contractile responses to serotonin and endothelin-1. Low-dose nitroglycerin tape effectively improved the cerebral vasospasm after SAH without any significant changes in the systemic circulation and would be one of the useful and noninvasive treatments for cerebral vasospasm. The results seem to be partially affected by the effective dilation of the spastic artery and the improvement of the impaired endothelium-dependent relaxation with low-dose NO.

Administration, Cutaneous↗
PubMed2000

Effect of a novel immunosuppressant, FTY720, on allograft survival after renal transplant in rats.

FTY720 was developed by chemical modification of ISP-1 which was purified from culture filtrates of an ascomycete, Isaria sinclairii. We evaluated the effect of FTY720 on allograft survival using a rat renal transplantation model in which Wistar King Aptekman Hokkaido rats (WKAH, RT1(K)) served as the organ donor and Lewis rats (LEW, RT1(l)) as the recipient. WKAH renal allografts were acutely rejected by the untreated LEW recipients at a mean graft survival +/- SD of 7.2 +/- 0.4 days (n = 5). Consecutive oral administration of FTY720 following transplantation significantly prolonged allograft survival in a dose-dependent manner over the range of 0. 05-3 mg/kg/day. The mean allograft survival of the recipients treated with FTY720 at a doses of 0.05, 0.1, 0.5, 1, and 3 mg/kg/day was 12.2 +/- 3.3 (n = 5, p < 0.05, vs. untreated host), 11.2 +/- 2.4 (n = 5, p < 0.05, vs. untreated host), 13.6 +/- 0.9 (n = 5, p < 0.01, vs. untreated host), 14.6 +/- 1.7 (n = 5, p < 0.01, vs. untreated host) and 20.2 +/- 0.8 days (n = 5, p < 0.01, vs. untreated host). In the recipients treated with FTY720 (3 mg/kg/day), the number of peripheral blood lymphocytes significantly decreased. From the results of the flow cytometric study, FTY720 significantly diminished the percentage of interleukin-2 receptor (IL-2R)-positive cells in the allografts (6.34 +/- 0.81% in the untreated recipients vs. 3.10 +/- 0.86% in the recipients treated with FTY720, p < 0.05). As to the CD4/CD8 ratio of splenic cells and graft infiltrate, there was no significant difference between the untreated hosts and the recipients treated with FTY720. In conclusion, FTY720 significantly extended rat renal allograft survival and the immunosuppressive effects of FTY720 may be due to a reduction in not only the number of peripheral lymphocytes but also the percentage of IL-2R-positive cells in the allografts.

Animals↗
PubMed2000

A patient with cyclic neutropenia complicated by severe persistent neutropenia successfully delivered a healthy baby.

We describe a 24-year-old pregnant woman complicated by cyclic neutropenia (CN), who was successfully treated with granulocyte-colony stimulating factor (G-CSF). Her white blood cell (WBC) and neutrophil count fluctuated from 2,600 to 4,600/microl, and 26 to 2,530/microl, respectively. The peak neutrophil count gradually decreased as pregnancy advanced, resulting in the disappearance of its cyclicity. At 39 weeks of pregnancy when the neutrophil count became 84/microl, the patient was started on G-CSF and her neutrophil count increased to 1,550/microl on the fourth day after delivery. She delivered a healthy baby without any complications at 39 weeks of pregnancy.

Adult↗
PubMed2000

[Reliability of electrogustatory threshold--electrogustometry using CNV].

CNV (contingent negative variation), an event-related potential, is induced when an oncoming imperative stimulus (S2) is anticipated after recognition of a warning stimulus (S1). With this in mind, we assessed the usefulness of electrogustometry using CNV as an objective gustatory test with an electric gustatory stimulus as a warning stimulus, S1. A gustatory test was performed on a total of 100 sides of the tongue in 50 subjects. Excluding no response cases on 5 sides in 5 subjects, the CNV threshold was successfully determined on 95 sides in 50 subjects. When the CNV threshold values obtained and the conventionally measured subjective threshold values were compared, a very high correlation was demonstrated between the two thresholds, with a correlation coefficient of 0.961. To assess the reliability of the CNV threshold, three additional measurements on 5 sides in 5 subjects with normal subjective threshold values were performed on different days, and the CNV threshold value variation among the three measurements in all 5 subjects never exceeded 13 microA. Separately, subjective threshold and CNV threshold values were compared in 4 patients with facial palsy (hence with gustatory abnormality) who consented to a follow-up examination. The difference between the subjective threshold and CNV threshold values in all 4 patients never exceeded 10 microA. These findings demonstrate that the reliability of the CNV threshold is satisfactory. Next, a gustatory imitation experiment was performed to assess the usefulness of electrogustometry using CNV as a means of detecting gustatory abnormality malingering. The experiment was performed on a total of 6 subjects: 3 physicians with knowledge of CNV (knowledge group) and 3 others with no knowledge of CNV (no-knowledge group). The differences between the imitated threshold and the subjective threshold values in all of these subjects never exceeded 10 microA, and the difference between imitated threshold and CNV threshold values never exceeded 13 microA. Comparison between the knowledge group and the no-knowledge groups showed that the imitated threshold values were very close to the subjective threshold and CNV threshold values. Based on the above results, it was concluded that gustometry using CNV is useful and can serve well as a method of objective evaluation of gustatory sensation. The results also suggested that it will be useful in diagnosing malingering.

Adolescent↗
PubMed2000

Genetic and molecular pathogenesis of hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by vascular dysplasia and hemorrhage. The pathogenesis regarding heterogeneity of vascular malformations in patients with HHT has been obscure, although it has become possible to partially explain the pathogenesis from the identification of two distinct genes, endoglin and ALK-1. Endoglin and ALK-1 are type III and type I TGF-beta receptors, respectively, and are exclusively expressed on vascular endothelial cells. Binding of TGF-beta to the type II TGF-beta receptor on endothelial cells, which is accelerated in the presence of endoglin, phosphorylates type I TGF-beta receptors, ALK-5 and ALK-1, and phosphorylated ALK-5 and ALK-1 activate the downstream proteins Smad2/3 and Smad1/5, respectively. These activated Smad proteins dissociate from the type I TGF-beta receptor, bind to Smad4, and enter the nucleus to transmit TGF-beta signaling by regulating transcription from specific gene promoters involved in angiogenesis. Therefore, a balance between these two signaling pathways via ALK-5 and ALK-1 plays an important role in determining the properties of endothelial cells during angiogenesis. Mutations of endoglin and ALK-1 genes are genetic pathogenesis of HHT type 1 and HHT type 2, respectively. To date, at least 29 and 17 different kinds of mutations in endoglin and ALK-1, respectively, have been found, including missense, nonsense, frameshift, and deletion mutations. The precise mechanisms of vascular abnormalities elicited by these mutations observed in HHT patients are still uncertain, although elucidation of the mechanism of intracellular signal transduction and the change in targeted gene expressions using mutant recombinant endoglin or ALK-1 proteins and knockout mice will enable us to understand the genetic and molecular pathogenesis of HHT and to effectively treat patients with HHT.

Activin Receptors↗
PubMed2000

[Prognostic significance of chromosome analysis in childhood acute lymphoblastic leukemia. Children's Cancer and Leukemia Study Group (CCLSG)].

We analyzed the prognostic significance of chromosomal findings in children with acute lymphoblastic leukemia (ALL), treated according to the Children's Cancer and Leukemia Study Group protocols between 1987 and 1993. Patients were classified into 5 groups according to chromosome number. The patients with a hyperdiploid(> 50) karyotype(13%) had the best prognosis [4-year event-free survival (EFS): 83 +/- 6%], while those with a pseudodiploid karyotype (24%) had the worst prognosis(4-year EFS: 52 +/- 6%) (log-rank, p = 0.03). However, multivariate analysis revealed that the ploidy classification had no prognostic significance in terms of EFS. When patients were classified according to chromosome abnormalities, those with any type of translocation had a worse outcome (4-year EFS: 33 +/- 9%) than those with hyperdiploidy(> 50), normal diploidy, and other abnormalities(log-rank, p < 0.0001). Multivariate analysis revealed that chromosome abnormalities were an independent prognostic factor (relative risk 3.98; p < 0.0001). Patients with t(1; 19) had an EFS similar to that of patients with chromosome abnormalities other than translocations or normal diploidy. We conclude that chromosomal findings have prognostic significance, although some chromosome abnormalities lost their statistical significance after modern intensified chemotherapy. Childhood ALL should be further stratified according to chromosome classification.

Child↗
PubMed2000

No increased risk of thrombosis in heterozygous congenital dysplasminogenemia.

To assess the risk of thrombosis in congenital dysplasminogenemia, we studied 10 unrelated families with this disorder. The probands were excluded from the analysis of data to prevent bias in the selection of subjects. Positive thrombotic histories were found in 1 of the 25 family members determined to have heterozygous congenital dysplasminogenemia and in 2 of their 41 biochemically unaffected relatives. The percentages of family members with no history of thrombosis up to a given age among subjects with and without congenital dysplasminogenemia were analyzed by the Kaplan-Meier method. No significant difference between the 2 groups was observed by generalized Wilcoxon test (P = .32) or Cox-Mantel test (P = .62). These findings suggest that heterozygous congenital dysplasminogenemia is not associated with an increased risk of thrombosis.

Adolescent↗