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Biomedical subjects

K Higuchi

Publications and source records attributed to K Higuchi.

At least 127 records · Page 7Linked to original sources
PubMed1999

Association of the interleukin-4 receptor alpha chain with p47phox, an activator of the phagocyte NADPH oxidase in B cells.

Interleukin (IL)-4 plays an important role in IgE synthesis in B cells and in Th2 differentiation in T cells. IL-4 conducts its biological activities through binding to the IL-4 receptor (IL-4R) on the surface of target cells. IL-4R are thought to be composed of the IL-4R alpha chain (IL-4R alpha) and either the IL-2R gamma chain or the IL-13R alpha chain. We have previously shown that the membrane-proximal portion in the cytoplasmic domain of the human IL-4R alpha (hIL-4R alpha) is critical for proliferation, generation of germline epsilon transcript, and activation of STAT6, based on analyses of truncated hIL-4R alphas. In this study, we found that p47phox, an activator of the phagocyte NADPH oxidase, binds to this portion by the two-hybrid system. Furthermore, we observed the association of p47phox with the hIL-4R alpha in B cells derived from a normal donor. These results suggest that p47phox is involved in the signal transduction of IL-4 in B cells. However, activation of STAT6, CD23 expression, and IgE synthesis induced by IL-4 were not affected in p47phox-deficient patients, which raises the possibility that p47phox may be important in other signaling activities as well in B cells.

Amino Acid Sequence↗
PubMed1999

Low plasma levels of docosahexaenoic acid in patients with liver cirrhosis and its correction with a polyunsaturated fatty acid-enriched soft oil capsule.

Plasma levels of docosahexaenoic acid (DHA, C22:6 omega 3) were found to be decreased in 11 patients with alcoholic and non-alcoholic liver cirrhosis depending on the severity of liver damage. In this reduction, we found impaired metabolism of omega-3 long-chain polyunsaturated fatty acids in the cirrhotic liver and poor dietary intake of DHA to involved in the reduction of DHA plasma levels. The deficiency of this fatty acid, which is concentrated in the nervous tissues, may be related to the impaired neural function observed in hepatic encephalopathy of these patients. Oral DHA supplementation was supplied in the form of a polyunsaturated fatty acid-enriched soft oil capsule (omega 3/omega 6 ratio = 0.91, and P/S ratio = 1.87). Twelve capsules per day (containing 408 mg DHA, which corresponds to one-fourth of the DHA content in a normal daily diet) improved the DHA contents in the plasma phospholipid fractions of 5 alcoholic patients with low DHA levels.

Aged↗
PubMed1999

Inhibition by 16,16-dimethyl prostaglandin E2 of tumor necrosis factor-alpha and interleukin-1beta production and messenger RNA expression in human monocytes stimulated by Helicobacter pylori.

We investigated the effects of 16,16-dimethyl prostaglandin E2 on the production of tumor necrosis factor-alpha and interleukin-1beta in human monocytes stimulated with Helicobacter pylori. Monocytes isolated from human peripheral blood were incubated for 24 hr with the extract of H. pylori diluted 1:100 to 1:100,000 by volume, a combination of the extract and 16,16-dimethyl prostaglandin E2, or a vehicle alone. The extract stimulated the production of tumor necrosis factor-alpha and interleukin-1beta and the expression of their messenger RNA in a dose-dependent manner. 16,16-Dimethyl prostaglandin E2 inhibited the production of these cytokines and their messenger RNA in the presence of H. pylori at doses higher than 10(-6) M, predominantly with tumor necrosis factor-alpha. These data suggest that antiinflammatory effects of prostaglandins on gastric mucosa are in part related to their effects on inhibition of production of proinflammatory cytokines by monocytes.

16,16-Dimethylprostaglandin E2↗
PubMed1999

Sphingosylphosphorylcholine is a potent inducer of intercellular adhesion molecule-1 expression in human keratinocytes.

We recently reported that the epidermis of patients with atopic dermatitis contains an abnormally expressed sphingomyelin deacylase that yields a large amount of sphingosylphosphorylcholine (SPC) rather than ceramide. In this study, we characterize inflammatory roles of newly discovered chemicals in the epidermis by elucidating biologic effects of SPC on intercellular adhesion molecules-1 (ICAM-I) expression by human keratinocytes in culture in comparison with other sphingolipids. Using fluorescence-activated cell sorter analysis, we found that SPC treatment at concentrations of 10-20 microM significantly enhanced the expression of ICAM-I by cultured human keratinocytes in a dose-dependent manner after incubation for 15-24 h, and, using northern blot analysis, that this was accompanied by increased expression of ICAM-1 mRNA within 4 h of incubation. Transforming necrosis factor-alpha (TNF-alpha) levels in the medium of keratinocytes treated at a 10 microM concentration of SPC were significantly increased by 200%. Furthermore, the SPC-induced ICAM-1 expression was partially abolished by the concomitant addition of anti-TNF-alpha, suggesting a partial autocrine involvement of TNF-alpha in ICAM-1 expression. Assay of mitogen-activated protein kinase revealed that 10 microM SPC induced a rapid activation of mitogen-activated protein kinase in human keratinocytes, including an increase in its phosphorylation within 5 min, which then declined to the baseline control level after 30 min. In contrast, sphingomyelin or sphingosine had no significant potential to activate mitogen-activated protein kinase at the same concentration. These findings suggest that SPC plays an important role in the inflammatory process of epidermis in skin diseases, such as atopic dermatitis, with high expression of sphingomyelin deacylase.

Calcium↗
PubMed1999

Influence of rebamipide on indometacin-induced gastric hemorrhage in rats under restraint stress.

The effect of rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid, CAS 11911-87-6) in preventing acute gastritis was examined in rats by stomach perfusion. Teprenone (CAS 6809-52-5), cimetidine (CAS 51481-61-9) and omeprazole (CAS 73590-58-6) were used as control drugs. Severe gastric hemorrhage was observed in conscious restrained rats, 1 h after treatment with indometacin (20 mg/kg i.p.). Pretreatment with rebamipide (3, 10 or 30 mg/kg s.c.) suppressed the hemorrhage induced by indometacin plus restraint stress, being more effective than teprenone or cimetidine. Pretreatment with omeprazole (30 mg/kg s.c.) did not suppress the gastric hemorrhage. Superoxide dismutase (30,000 U/kg s.c.) significantly decreased the hemorrhage. Anti-rat PMN (polymorphonuclear leukocytes), 1 ml/kg i.v., which caused depletion of circulating neutrophils, also suppressed the hemorrhage induced by indometacin plus restraint stress. Thus reactive oxygen species derived from neutrophils may play a role in the occurrence of the hemorrhage during acute gastritis induced by indometacin with restraint stress.

Acute Disease↗
PubMed1999

Aminoguanidine supplementation delays the onset of senescence in vitro in dermal fibroblast-like cells from senescence-accelerated mice.

The effects of aminoguanidine supplementation on senescence acceleration in vitro were examined in fibroblasts from the dorsal dermis of newborn SAMP11 (accelerated senescence-prone mice), and were compared to the effects in cell lines from SAMR1 (accelerated senescence-resistant) mice. Four millimolar aminoguanidine supplementation significantly delayed the senescence/crisis in cell lines from SAMP11 mice, but did not affect the senescence/crisis in cell lines from SAMR1 mice. Flow cytometric analysis of the DNA content of confluent cells revealed that aminoguanidine supplementation significantly decelerated the increase in the number of tetraploid cells until senescence/crisis. Although mean concentrations of lipid peroxides in the primary cultures did not differ significantly, considerably higher lipid peroxidation was observed in some SAMP11 cultures, and aminoguanidine supplementation reduced them to the levels in SAMRI cultures. These results strongly suggest that oxidative stress derived from polyamine catabolism may contribute to the senescence acceleration in vitro in cell lines from SAMP11 mice.

Animals↗
PubMed1999

Endoscopic resection of two granular cell tumours of the oesophagus.

Granular cell tumour of the oesophagus is rare and usually single. It is diagnosed by endoscopic appearance, results of endosonography, and histological examination of biopsy specimens. Although histological examination is required for diagnosis, it is difficult occasionally to obtain tumour samples by forceps because granular cell tumour is usually located in the submucosal layer. We report the case of a Japanese man with two granular cell tumours of the oesophagus. One lesion was diagnosed as a granular cell tumour by histological examination of a biopsy specimen, but the other was not. Endoscopic resection was performed to obtain the diagnosis and treat the lesions since some granular cell tumours are potentially malignant. Both tumours were completely resected endoscopically, and the diagnosis of granular cell tumour could be established by histological examination of resected tissue. Endoscopic resection is thus useful in the diagnosis and treatment of granular cell tumour of the oesophagus.

Adenocarcinoma↗
PubMed1999

Cloning of nicotianamine synthase genes, novel genes involved in the biosynthesis of phytosiderophores.

Nicotianamine synthase (NAS), the key enzyme in the biosynthetic pathway for the mugineic acid family of phytosiderophores, catalyzes the trimerization of S-adenosylmethionine to form one molecule of nicotianamine. We purified NAS protein and isolated the genes nas1, nas2, nas3, nas4, nas5-1, nas5-2, and nas6, which encode NAS and NAS-like proteins from Fe-deficient barley (Hordeum vulgare L. cv Ehimehadaka no. 1) roots. Escherichia coli expressing nas1 showed NAS activity, confirming that this gene encodes a functional NAS. Expression of nas genes as determined by northern-blot analysis was induced by Fe deficiency and was root specific. The NAS genes form a multigene family in the barley and rice genomes.

Alkyl and Aryl Transferases↗
PubMed1999

Expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in human bladder cancer.

We investigated the expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) in primary bladder cancer, its association with clinicopathologic findings, and their prognostic value. mRNA was extracted from 20 bladder cancer specimens and 6 normal bladder mucosal tissues. Relative amounts of PD-ECGF/TP mRNA were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and compared with the level of glyceraldehyde-3-phosphate dehydrogenase mRNA (used as an internal standard). PD-ECGF/TP expression was examined by immunohistochemistry in 85 patients who underwent cystectomy for bladder cancer. Serum PD-ECGF/TP levels were measured in 23 patients using a sandwich-type enzyme-linked immunosorbent assay. By RT-PCR analysis, expression of PD-ECGF/TP was found to be 7-fold higher in invasive tumors than in superficial tumors (P<0.01) and 9-fold higher than in normal bladder (P<0.01). Out of 85 transitional cell carcinoma tissue samples, 69 (81%) were evaluated as PD-ECGF/TP-positive by immunohistochemical staining. PD-ECGF/TP expression correlated significantly with tumor grade (P = 0.001), depth of invasion (P = 0.012), and lymphatic invasion (P = 0.01). No correlation was found between expression of PD-ECGF/TP and the number of tumors, tumor configuration, lymph node involvement, venous invasion, c-erbB-2 expression, or overall survival. We could not detect a significant serum level of PD-ECGF/TP in any patient. The results suggest that PD-ECGF/TP might give valuable information for bladder cancer management, though it may not be a good new tumor marker for bladder cancer.

Adult↗
PubMed1999

Complete regression of recurrent esophageal carcinoma with reduced expression of glutathione S-transferase-pi by treatment with continuous infusion of 5-fluorouracil and low-dose cisplatin infusion.

The mortality rate of recurrent esophageal carcinoma remains high because of its resistance to chemotherapy and radiation therapy. We present a patient with recurrent esophageal carcinoma, which dramatically disappeared after treatment with the combination of continuous infusion of 5-fluorouracil and low-dose cis-Diamminedichloroplatinum-II (cisplatin) infusion (FP therapy). Furthermore, we immunohistologically found that glutathione S-transferases (GST)-pi, a marker of resistance to cisplatin, was faintly expressed both in the endoscopical biopsy specimens of recurrent tumor and in the resected specimens of esophageal carcinoma and metastatic lymph nodes. FP therapy was suggested to be effective for recurrent esophageal carcinoma. Immunostaining for GST-pi might be a prospective marker for the sensitivity of esophageal carcinoma to FP therapy, particularly cisplatin.

Antimetabolites, Antineoplastic↗
PubMed1999

Five-year evaluation of implants placed at extraction and with dehiscences and fenestration defects augmented with ePTFE membranes: results from a prospective multicenter study.

BACKGROUND: Barrier membranes have been used to promote bone ingrowth on implants with dehiscences and fenestrations. Membranes also have been used to protect defects adjacent to implants placed at the time of extraction. The concept of guided bone regeneration relates to preferentially allowing cells from bone to migrate into various defects while excluding fibrous tissue and epithelium. The purpose of these procedures is to enhance bone-to-implant contact at the treated sites and to prevent mucosal complications. PURPOSE: The purpose of this article is to report clinical outcomes for implants placed at the time of extraction and augmented with expanded polytetrafluoroethylene (ePTFE) and followed for 5 years. The outcomes for implants with dehiscences and fenestrations augmented with ePTFE barriers and followed up to 5 years also are reported. METHODS AND MATERIALS: Four treatment centers participated in this study (Tucson, Gothenburg, Spokane, and Leuven). In the extraction group, teeth were removed for varying reasons, and Brånemark implants were placed and stabilized within the host bone. Defects present at the coronal implant aspect were covered with ePTFE barrier membranes. Flaps were rotated to cover the membrane-treated sites. If exposure of the material occurred prior to second-stage surgery, the membranes were removed. Barriers remaining unexposed were removed at second-stage surgery. The implants were followed up to 5 years. In the fenestration and dehiscence group, implants with exposed threads were augmented with ePTFE barrier membranes. The barriers were removed at appropriate intervals, and the patients were followed up to 5 years. Radiographic measurements were made from nonstandardized periapical radiographs at abutment connection and 1, 3, and 5-year follow-up visits. RESULTS: Forty patients participated in the extraction group. They received a total of 49 implants. Three implants failed prior to loading. The 5-year cumulative survival rates for implants placed at the time of extraction were 93.9% and 93.8%, respectively, for maxillary and mandibular implants. The average maxillary mesial and distal marginal bone loss (1-5 yr) was 0.3 mm (standard deviation [SD] = 1.5) and 0.3 mm (SD = 1.0). In mandibles, the average mesial and distal bone loss (1-5 yr) was -0.2 mm (SD = 0.5) and -0.05 mm (SD = 0.6), respectively. The dehiscence and fenestration group included 44 patients. Twenty-six were followed for up to 5 years. Eight patients experienced total implant failure. For dehiscences and fenestrations, the cumulative survival rates were 76.8% and 83.8% for maxillary and mandibular implants, respectively. The average maxillary mesial and distal bone loss (1-5 yr) was 0.4 mm (SD = 0.8) and 0.2 mm (SD = 0.9), respectively. In mandibles, the average mesial and distal marginal bone loss was 0.3 mm (SD = 0.9) and 0.3 mm (SD = 0.8), respectively. CONCLUSIONS: Implants placed at the time of extraction and augmented with ePTFE barrier membranes have favorable long-term predictability. On the other hand, long-term evaluation of implant dehiscences and fenestrations augmented with barrier membranes indicates that they have less favorable 5-year survival rates. Membrane augmentation of these may be questioned.

Adolescent↗
PubMed1999

Identification of amino acid residues of the T-cell epitope of Mycobacterium tuberculosis alpha antigen critical for Vbeta11(+) Th1 cells.

Stimulation of Mycobacterium tuberculosis-primed lymph node cells from C57BL/6 mice with alpha antigen (also known as antigen 85B and MPT59) induced cell proliferation, production of interleukin 2 and gamma interferon, and expansion of Vbeta11(+) CD4(+) T cells in conjunction with antigen-presenting cells in an I-A(b)-restricted manner. Using a series of 15-amino-acid peptides that overlapped each other by 5 amino acids and spanned the mature alpha antigen, we identified the antigenic epitope for alpha antigen-specific Vbeta11(+) Th1 cells. That peptide (peptide-25), which corresponds to amino acid residues 240 to 254 of alpha antigen, contains a motif that is conserved in I-A(b) and requires processing by antigen-presenting cells. Using peptide-25-reactive Vbeta11(+) T-cell clones and substituted peptide-25 mutants, we determined which amino acid residues within peptide-25 were critical for T-cell receptor (TCR) recognition. Our results showed that the amino acid residues at positions 245, 246, 248, 250, and 251 are important for recognition of TCRVbeta11 and that residues at positions 244, 247, 249, and 252 are I-A(b) contact residues. We also observed that active immunization of C57BL/6 mice with peptide-25 can lead to decreased bacterial load in the lungs of M. tuberculosis H37Rv-infected mice. These results should provide us with a useful tool for delineating the regulation of Vbeta11(+) Th1-cell development during M. tuberculosis infection and for developing a vaccine inducing a Th1-dominant immune response.

Acyltransferases↗
PubMed1999

Acanthosis nigricans with severe obesity, insulin resistance and hypothyroidism: improvement by diet control.

We report on a 27-year-old man with acanthosis nigricans (AN) associated with severe obesity, insulin resistance and hypothyroidism. A very low-calorie diet treatment decreased his weight and then ameliorated the insulin-resistant state. These effects were followed by remarkable improvement of the AN prior to the correction of the hypothyroidism. This confirms that AN may be mainly attributed to insulin resistance rather than hypothyroidism per se.

Acanthosis Nigricans↗
PubMed1999

[Development and assessment of the pharmaceutical management and guidance services for inpatients considering clinical value and economy].

We developed pharmaceutical management and guidance services for inpatients in a ward of circulatory medicine, considering clinical and economical standpoints. In these services, pharmacists deliver drugs prescribed for inpatients with individual drug information papers, explain to them about their drugs using information papers and give counsel. Since most of the patients were aged people, developing many kinds of diseases and taking many kinds of drugs, they had many problems such as lack of knowledge of the effects of drugs. First, we surveyed views of patients, physicians and nurses on these services. Consequently, all of them advised us that "pharmacists should explain to patients about the prescribed drugs using information papers." The patients preferred pharmacists as expositors of drugs to physicians or nurses. The physicians considered that "pharmacists have to attach importance to clinical information and package-inserts of drugs and explain to patients about drug information using pamphlet in response to the understanding of patients." The nurses wanted to cooperate with pharmacists in "improving medication compliance." On the basis of these views, we improved our services. Next, we made a survey of patients' knowledge about their drugs. We found that in the patients the level of knowledge concerning "ways," "effects" and "reasons" of taking drugs and that of "compliance" and "satisfaction in taking drugs" were improved through these services. The patients reentered in the hospital kept a high level. The ratio of patients taking drugs by themselves increased. Last, we also applied this method to wards of "blood and collagen diseases" and "pediatrics." The demand for these services increased smoothly. We compared these services based on our method with all other services by hospital pharmacists from the viewpoint of economy. We found that only our service method was beneficial.

Drug Therapy↗
PubMed1999

[Fibrous dysplasia of the skull presenting interesting neuroradiological findings].

A case of fibrous dysplasia of the frontal bone in a 51 year-old male is described. He was admitted to our hospital with a hard, painless growing mass in the left frontal region. A symmetrical protrusion of his forehead has been observed since several years before. Neurological examination and laboratory data revealed no abnormalities. Skull x-rays demonstrated two different lesions. One showed a ground glass appearance in the supraorbital region, and the other showed a radiolucent lesion with marginal sclerosis crossing the left coronal suture CT scan revealed an intradiploic multilocular mass. T1 and T2 MR images showed an abnormal low-intensity mass, and heterogeneous gadolinium-enhancement was noticed in both lesions. Selective external carotid angiography showed tumor stain in the left coronal mass fed by middle meningeal and superficial temporal arteries mimicking intraosseous meningioma. On the other hand, a supraorbital hyperostotic lesion showed no apparent vascularity. An operation was performed on the left coronal lesion to verify the nature of the progressively enlarging mass, which was histologically confirmed to be a fibrous dysplasia rich in numerous vessels. Postoperative course was uneventful. Correlation with clinical activity and enhancement pattern was not known, however, careful observation is required in hypervascular fibrous dysplasia such as was observed in this case.

Cerebral Angiography↗