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H Inagaki

Publications and source records attributed to H Inagaki.

At least 19 recordsLinked to original sources
PubMed2001

Novel peptidomimetics of the antifungal cyclic peptide Rhodopeptin: design of mimetics utilizing scaffolding methodology.

[reaction: see text]. Novel nonpeptide peptidomimetics of the antifungal cyclic peptide Rhodopeptin were designed utilizing hydantoin, benzimidazole, D-glucosamine, quinolone, and benzodiazepine units as scaffolds. The scaffolds were chosen on the basis of their potential to improve the physiochemical properties of the peptidomimetics as well as their ability to bear the requisite Rhodopeptin side-chain moieties with the proper three-dimensional orientation.

Antifungal Agents↗
PubMed2001

Novel peptidomimetics of the antifungal cyclic peptide Rhodopeptin: synthesis of mimetics and their antifungal activity.

[reaction: see text]. Novel peptidomimetics of the antifungal cyclic peptide Rhodopeptin were synthesized. As with the cyclic peptides, the presence of all three Rhodopeptin side chains was found to be indispensable for peptidomimetic activity. We discovered new compounds exhibiting greater antifungal activity and improved physiochemical properties in comparison to the parent compounds.

Alkanes↗
PubMed2001

API2-MALT1 fusion transcripts involved in mucosa-associated lymphoid tissue lymphoma: multiplex RT-PCR detection using formalin-fixed paraffin-embedded specimens.

Malignant lymphoma of mucosa-associated lymphoid tissue (MALT) type is a distinct clinicopathological disease entity in the category of extranodal marginal zone B-cell lymphoma. Recently, we and others have shown that the API2 gene on chromosome 11 and the MALT1 gene on chromosome 18 are fused as a result of t(11;18)(q21;q21) in MALT lymphomas. Here we report a detection assay that can be used for formalin-fixed, paraffin-embedded specimens. It consists of a multiplex one-tube reverse transcriptase-polymerase chain reaction (RT-PCR) followed by three parallel multiplex nested polymerase chain reactions. Eight variants of the fusion transcripts have been reported to date. When these variants were used as positive controls, all were successfully detected. The subsequent direct sequencing confirmed the results. Using this rapid and simple method, we could detect API2-MALT1 fusion transcripts in 5 of 15 (33%) archival cases of MALT lymphoma for a frequency comparable with those of RT-PCR assays using frozen materials. The lung was the preferential anatomical site of origin of MALT lymphomas harboring API2-MALT1 fusion. No fusion transcript was detected in any of 20 high-grade B-cell lymphomas. Our multiplex RT-PCR assay, which can be used for routinely-processed paraffin samples, should serve as a useful molecular tool for clarifying the clinicopathological significance of API2-MALT1 fusion in MALT lymphoma.

Adult↗
PubMed2001

Anti-fibrogenic effect of an angiotensin converting enzyme inhibitor on chronic carbon tetrachloride-induced hepatic fibrosis in rats.

The tissue renin-angiotensin system has recently been demonstrated to reduce fibrogenesis in various organs. However, little has been clarified regarding its role in hepatic fibrosis. The purpose of this study was to investigate the effect of angiotensin-converting enzyme inhibitors on liver fibrogenesis induced in rats by low-dose chronic carbon tetrachloride administration. We used lisinopril that is absorbed in its active form and not metabolized in the liver to avoid any influence by the administration of the chemical. Carbon tetrachloride was administered twice a week i.p. Twelve and 24 weeks after the start of treatment, expanded periportal fibrosis or portal-portal bridgings and severe fat deposition were observed in the rats treated with carbon tetrachloride alone, and these findings were significantly reduced with the simultaneous treatment with lisinopril. The hydroxyproline content of the liver was significantly lower in the lisinopril-treated group. Angiotensin II up-regulated mRNA of pro alpha (I) collagen and transforming growth factor-beta in isolated hepatic stellate cells. These results suggest that the local tissue renin-angiotensin system plays a role in rat hepatic fibrogenesis induced by chronic carbon tetrachloride administration and that hepatic fibrogenesis is significantly reduced by ACE inhibitors.

Journal Article↗
PubMed2001

Does infiltration of neutrophils in peritubular capillaries indicate humoral rejection? A case displaying a characteristic lesion of a significantly high amount of neutrophils in peritubular capillaries at 1-h graft biopsy during transplant operation.

We present a case report of a 50-yr-old Japanese woman with a significant accumulation of neutrophils in the peritubular capillaries (PTC) and severe acute tubular necrosis (ATN) at 1-h allograft biopsy during transplant operation from cadaver donor after a cardiac death. Significant accumulation of neutrophils in the PTC is usually valuable diagnostically for acute humoral rejection. However, the patient showed no clinical signs of acute rejection. A second graft biopsy performed on the fifth postoperative day (POD) revealed that both infiltration of neutrophils in PTC and ATN lesions were more aggravated. Neither clinical course nor other morphological findings were compatible with humoral rejection. After the third biopsy of POD 27 revealing acute vascular rejection of moderate degree, acute rejection therapy using methylprednisolone pulse therapy and OKT-3 therapy was performed. Consequently, after a period of delayed graft function requiring haemodialysis for approximately 4 wk, graft function was restored and serum creatinine decreased to 2 mg/dL. Later, we were able obtain information from a paired graft from the same donor. Significant accumulation of neutrophils in the PTC similar to our recipient was also noted in a 1-h biopsy specimen of the paired kidney. This confirmed that the accumulation of neutrophils in the PTC noted in two recipients was transmitted from the donor kidney. The pathogenesis and clinical significance of neutrophils in the PTC has been shrouded in mystery.

Biopsy↗
PubMed2001

Prognostic significance of p27 and Ki-67 expression in mucoepidermoid carcinoma of the intraoral minor salivary gland.

p27 and Ki-67, a universal cyclin-dependent kinase inhibitor and a proliferative cell marker, respectively, have been useful in predicting clinical aggressiveness in various human tumors. We studied clinicopathologic significance of these molecules in mucoepidermoid carcinoma of the intraoral minor salivary gland. Expression of p27 and Ki-67 was assessed immunohistochemically in primary mucoepidermoid carcinomas from 31 patients without distant metastasis at surgery. Correlation each of p27 and Ki-67 expression was analyzed with various clinicopathologic parameters including age, sex, primary tumor site, tumor size, nodal metastasis, clinical stage, and histologic grade. The latter was evaluated using a point-scoring scheme of Auclair et al. that consists of five histologic factors (intracystic component, neural invasion, necrosis, mitosis, and anaplasia). p27 expression was correlated inversely with histologic grade (P =.007), but with none of other factors. When the correlation of p27 expression was further examined with each of the histologic factors, it was correlated significantly with intracystic component, but not with neural invasion, necrosis, mitosis, or anaplasia. Ki-67 expression was correlated significantly with histologic grade only in the clinicopathologic factors (P <.0001), and in the histologic factors, with necrosis, mitosis, and anaplasia. Multivariate prognostic analyses were performed to identify independent risk factors for both disease-free and overall survivals. Large tumor size (P =.031, relative risk = 5.5) and low p27 expression (P =.012, relative risk = 5.2) were risk factors for worse disease-free survival. Low p27 expression (P =.015, relative risk = 15.2) was selected as a risk factor for worse overall survival. Other factors including age, sex, tumor site, nodal status, clinical stage, histologic grade, and Ki-67 did not emerge as independent risk factors in either prognostic analysis. These data suggest that p27 may be useful in estimating prognosis of the patients who have mucoepidermoid carcinoma of the intraoral minor salivary gland.

Adolescent↗
PubMed2001

Global intellectual deterioration in Alzheimer's disease and a reverse model of intellectual development: an applicability of the Binet scale.

Since intellectual deterioration in Alzheimer's disease (AD) might be considered to demonstrate a reverse of the intellectual development of children, we herein investigated the applicability of the Tanaka-Binet Intelligence scale (TB scale). This scale can assess the mental age (MA) and the lower-limit age (LLAge) values, and was reported to be correlated with the tasks determining Piaget's developmental stages of intelligence. Thirty AD patients and 30 age-matched normal control subjects were examined with the scale. We found that the mean MA values of the AD patients and controls were 97.4 and 150.3 months, respectively. In the control group, there were significant correlations between the MA and chronological age, and between the MA and years of education. In the AD patients, there was a significant correlation between the MA and the MMSE score. Regarding the LLAge for the AD patients, similar to the theory of Piaget, there was a tendency that they could be classified into three LLAge groups. We consider that the TB scale is useful in assessing the intellectual function in AD patients.

Aged↗
PubMed2001

More than 1,000 cases of total parathyroidectomy with forearm autograft for renal hyperparathyroidism.

Between March 1981 and December 2000, we performed 1,053 total parathyroidectomies with forearm autograft for advanced renal hyperparathyroidism (HPT). Based on histopathologic and pathophysiologic investigations, surgical treatment should be considered when parathyroid glands show nodular hyperplasia. Measuring parathyroid volume by ultrasonography was useful to detect nodular glands and to determine surgical indications. The clinical effect of parathyroidectomy on the symptoms and biochemical variables was striking. Skeletal deformity, progressive bone loss, and vessel calcification leading to high mortality risk could not be alleviated by even successful surgery, however. To prevent cardiovascular complications, parathyroidectomy should be performed in the relatively early stage of renal HPT. Total parathyroidectomy with forearm autograft is a suitable procedure for renal HPT, especially in patients who require long-term hemodialysis. For surgeons, it is important to remove all parathyroid glands, including supernumerary glands, at the initial operation and to choose adequate parathyroid tissue for the autograft to prevent persistent and recurrent HPT. Although the risk of graft-dependent recurrent HPT is not negligible, enlarged transplanted parathyroid tissue can be removed easily and noninvasively from the forearm under local anesthesia. There is no risk of hypofunction of the autograft.

Adult↗
PubMed2001

Osteoprotegerin levels before and after renal transplantation.

Osteoprotegerin (OPG) is a newly identified glycoprotein that belongs to the tumor necrosis factor receptor superfamily and regulates bone mass by inhibiting osteoclastic bone resorption. The regulatory mechanism of OPG is still unclear after successful renal transplantation (RTX), however, resulting in resolution of uremia. The present study was designed to clarify the potential role of OPG in uremia and after RTX under immunosuppressive therapy. We evaluated circulating OPG levels by measuring them before and after RTX (postoperative days 2, 14, and 28). Our protocol of immunosuppressive drugs was dual therapy using cyclosporine and steroids. Serum OPG was quantitated using enzyme-linked immunosorbent assay. After successful RTX, serum OPG levels decreased significantly on day 14 and day 28 compared with the baseline level (P < 0.05). Creatinine clearance dramatically increased until day 14 and decreased thereafter. Serum OPG declines for the first 2 weeks after RTX owing to functioning allograft and decreases again for the next 2 weeks because of steroids and possible immunosuppressive agents.

Adult↗
PubMed2001

Changes in major blood components after adopting the supine position during haemodialysis.

BACKGROUND: In Japan, haemodialysis (HD) is usually performed with patients in the supine position. However, the effects of changing posture on major blood components have not been investigated in HD patients. It is possible that several fluid components change rapidly when patients change from the upright to the supine position. We therefore investigated the effects of posture on blood component analysis. METHODS: A first blood sample was taken from 10 HD patients 5 min after they adopted a supine position; HD was begun immediately after sampling. Additional blood samples were collected 15 and 30 min later while patients remained in the supine position. On an alternate day, blood samples were taken from these same patients in the supine position, but not during HD. The same procedure was performed in 10 healthy volunteers. RESULTS: Haematocrit significantly decreased in patients undergoing HD at 15 and 30 min into the HD session. Similar decreases were observed in HD patients not undergoing HD and in normal control subjects. Haematocrit changes at 15 min were not significantly different between the three groups. Serum albumin concentrations decreased in the same way as haematocrit. Consequently, the reductions in haematocrit and albumin concentrations in HD patients during the HD session were not attributable to the HD procedure or to end-stage renal disease, but rather were due to the supine position and consequent haemodilution caused by redistribution of water from the extra- to the intravascular space. Finally, WBC counts decreased significantly at 15 min in both HD patient groups and in normal controls. The relative decrease at 15 min was significantly greater in HD patients undergoing HD (61.4% of baseline) than in those not undergoing HD (88.0%) or in normal controls (94.7%). These differences were probably due to previously reported WBC sequestration in the lungs during the early phase of HD. CONCLUSIONS: This study suggests that the change from the upright to the supine positions during HD causes changes in blood components that are critical for quality control determinations.

Adult↗
PubMed2001

Clonality assay of hematopoietic disorders: significance of the buccal epithelium as non-hematopoietic control and of 95% rejection limit as a novel criterion for monoclonality.

In clonality assays using X chromosome inactivation patterns (XCIPs), several factors such as constitutive and acquired XCIP skewing, lack of appropriate controls for hematopoietic diseases including multilineage disorders, and ambiguous criteria for monoclonality, have complicated determination of clonality. To address these issues, we studied the significance of the buccal epithelium as a non-hematopoietic control and the usefulness of the 95% rejection limit as a criterion for monoclonality. Sixty-nine females informative for human androgen receptor gene (HUMARA) were divided into "young," "middle-aged" and "elderly" groups. When XCIP correlation between the buccal epithelium, peripheral granulocytes, and peripheral lymphocytes was analyzed, the buccal epithelium showed a good correlation with granulocytes and lymphocytes in "young" and "middle-aged" groups, whereas the correlation was poor for the "elderly" group. For all age groups, there was an excellent correlation between granulocytes and lymphocytes. When we performed clonality assay for seven "young" and "middle-aged" patients with various leukemic phases using buccal epithelium as a non-hematopoietic control, all cases were accurately evaluated with the aid of a novel criterion, the 95% rejection limit. Our findings suggest that the buccal epithelium may constitute an effective control, especially when a non-hematopoietic control is required, and that the 95% rejection limit may serve as a statistically-defined criterion for monoclonality.

Adult↗
PubMed2001

Effects of contractile activity on mitochondrial transcription factor A expression in skeletal muscle.

Mitochondrial transcription factor A (Tfam) is a nuclear-encoded gene product that is imported into mitochondria and is required for the transcription of mitochondrial DNA (mtDNA). We hypothesized that conditions known to produce mitochondrial biogenesis in skeletal muscle would be preceded by an increase in Tfam expression. Therefore, rat muscle was stimulated (10 Hz, 3 h/day). Tfam mRNA levels were significantly elevated (by 55%) at 4 days and returned to control levels at 14 days. Tfam import into intermyofibrillar (IMF) mitochondria was increased by 52 and 61% (P < 0.05) at 5 and 7 days, respectively. This corresponded to an increase in the level of import machinery components. Immunoblotting data indicated that IMF Tfam protein content was increased by 63% (P < 0.05) at 7 days of stimulation. This was associated with a 49% (P < 0.05) increase in complex formation at the mtDNA promoter and a 65% (P < 0.05) increase in the levels of a mitochondrial transcript, cytochrome-c oxidase (COX) subunit III. Similarly, COX enzyme activity was elevated by 71% (P < 0.05) after 7 days of contractile activity. These results indicate that early events in mitochondrial biogenesis include increases in Tfam mRNA, followed by accelerations in mitochondrial import and increased Tfam content, which correspond with increased binding to the mtDNA promoter region. This was accompanied by increased mitochondrial transcript levels and elevated COX activity. These data support the role of Tfam as a regulatory protein involved in contractile activity-induced mitochondrial biogenesis.

Animals↗
PubMed2000

Synthesis and antifungal activity of rhodopeptin analogues. 1. Modification of the east and south amino acid moieties.

Structure-activity relationships of the east and south amino acid modified analogues of rhodopeptins, novel antifungal cyclic tetrapeptides isolated from Rhodococcus species Mer-N1033, have been investigated. It was observed that a basic amino acid moiety (lysine or ornithine) as the east amino acid and a hydrophobic and bulky neutral amino acid (i.e., gamma-methylleucine) as the south amino acid were indispensable structure motifs for antifungal activity of rhodopeptin analogues.

Amino Acids↗
PubMed2000

Nkx3.1, a murine homolog of Ddrosophila bagpipe, regulates epithelial ductal branching and proliferation of the prostate and palatine glands.

Nkx3.1 is a homeobox gene related to Drosophila bagpipe. Nkx3.1 is an early marker of the sclerotome and a subset of vascular smooth muscle cells, and at later stages, this gene is expressed in the prostate, palatine glands, kidney, and restricted regions of the central nervous system. In the present study, we determined the chromosomal localization of Nkx3.1 and examined the function of Nkx3. 1 in vivo by using gene targeting technique. Interestingly, Nkx3.1 mapped to the central region of the mouse chromosome 14 and was linked to Nkx2.6, a murine homolog of Drosophila tinman. Homozygous mutant mice for Nkx3.1 were viable and fertile, and the phenotype was, unexpectedly, confined to the prostate and palatine glands. The homozygous mutant mice exhibited defective branching morphogenesis of the prostate and palatine glands. Moreover, epithelial cells of the mutant prostate and palatine glands showed significant hyperplasia. No abnormalities were detected in the sclerotome, blood vessels, kidney, or brain. These results indicate that Nkx3.1 plays a critical role in epithelial branching and proliferation in the prostate and palatine glands. However, we did not observe prostate cancer in homozygous mutant mice up to 2 years of age. Therefore, involvement of NKX3.1 in carcinogenesis in men needs to be carefully determined by further investigation.

Animals↗
PubMed2000

Differential expression of dihydropyrimidinase-related protein genes in developing and adult enteric nervous system.

Dihydropyrimidinase-related proteins (DRPs) are involved in axonal outgrowth and pathfinding. However, little is known about their significance in the enteric nervous system (ENS), the largest and most complex division of the peripheral nervous system. Using in situ hybridization (ISH) and northern blotting, we examined mRNA expression of DRP-1-4 transcripts in the developing and adult mouse digestive tract and in the adult human colon. ISH detected the mouse DRP-3 transcript in the developing ENS on embryonic day (E)12 and at the later stages as well as in the adult intestine. Mouse DRP-1 and -2 transcripts appeared at E14. DRP-2 transcript was also detected in the adult intestine although DRP-1 expression was lower in the adult. DRP-4 gene was not expressed in the ENS during development or adulthood whereas the signal was apparent in the developing and adult central nervous system (CNS). The DRP expression pattern in the human colon was similar to that of the mouse large intestine. Northern blot analysis showed that DRPs were differentially expressed in the mouse and human intestines, supporting the results of ISH. These data suggest that DRPs play a role not only in the CNS but also in the ENS.

Adult↗
PubMed2000

Induction of hepatic stellate cell proliferation by LPS-stimulated peripheral blood mononuclear cells from patients with liver cirrhosis.

We studied hepatic stellate cell proliferation in vitro. Peripheral blood mononuclear cells (PBMC) from patients with chronic active hepatitis C (CAH) and liver cirrhosis (LC) were cultured for 24h in the presence or absence of Escherichia coli lipopolysaccharides (LPS). Hepatic stellate cell proliferation induced by the culture supernatants was measured, and interleukin-1 (IL-1) and IL-6 levels in the culture supernatants were quantified. Culture supernatants of LPS-stimulated PBMC from LC patients induced rat hepatic stellate cell proliferation by almost 2.8-fold (stimulation index, 2.83 +/- 1.41) compared with when the cells were cultured without addition of PBMC culture supernatants. Production of IL-1beta was significantly higher in the culture supernatants of both CAH and LC patients than in those of ten healthy controls (P < 0.01 and P < 0.05, respectively). But there was no significant correlation between IL-1 production and the induction of hepatic stellate cell proliferation by the culture supernatants. Although there were no significant differences in IL-6 production by LPS-stimulated PBMC among healthy controls and CAH and LC patients, we observed a significant correlation between IL-6 production and the induction of hepatic stellate cell proliferation in the culture supernatants of LC patients. Rat hepatic stellate cells themselves produced IL-6, and treatment with IL-6 antisense oligodeoxynucleotides suppressed the cell proliferation, suggesting that IL-6 is an autocrine growth factor for hepatic stellate cells. The addition of human recombinant IL-6 (hrIL-6) augmented rat hepatic stellate cell proliferation, indicating that excessive IL-6 may further facilitate cell proliferation. These findings suggest that a cytokine cascade including IL-6 may participate in hepatic stellate cell proliferation in LC patients when they are exposed to endotoxin.

Animals↗