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Biomedical subjects

H Moriyama

Publications and source records attributed to H Moriyama.

At least 91 records · Page 5Linked to original sources
PubMed1999

[A study on the concentration of eosinophil cationic protein in chronic sinusitis].

The relationship between eosinophil and chronic sinusitis was investigated by measuring the concentration of eosinophil cationic protein (ECP). In addition to the blood, a cytological brush was inserted into middle meatus to scrape the nasal membrane, and the concentration of ECP in the collected specimen was measured. There was a moderate degree of correlation between the blood eosinophil count and the ECP concentration in the blood (r = 0.543, p < 0.01). On the other hand, there was high degree of correlation between the number of EG2-positive cells and ECP of the nasal membrane in the middle meatus (r = 0.805, p < 0.001), reflecting the amount of ECP in the nasal mucous membrane. The ECP in 10 control group subjects and 14 patients with severe chronic sinusitis and nasal polyps was significantly lower than that in 14 patients with severe chronic sinusitis and asthma (p < 0.01). The ECP concentration of the nasal membrane in the middle meatus was significantly lower in patients showing a good postoperative course compared with patients showing a poor postoperative course following Endoscopic Sinus Surgery (p < 0.01). These findings suggest that eosinophils are closely related to the pathology and clinical course of chronic sinusitis, and that the ECP concentration of the nasal membrane in the middle meatus reflects the pathology of chronic sinusitis. The ECP concentration thus has potential as a prognostic indicator for chronic sinusitis.

Adult↗
PubMed1999

[Pathophysiology and treatment results of auditory ossicle damage due to earpick-induced trauma].

We examined 10 ears from 10 patients undergoing ossiculoplasty due to a diagnosis of earpick-induced traumatic ossiculodialysis. Surgical findings induced dialysis of the incudostapedial joint in 5 patients, however, dialysis of this articulation was infrequent. Abnormal stapes were observed in 9 patients, including 6 patients with foot plate invagination. Five patients had a concomitant perilymphatic fistula. Perilymphatic fistula was found in 5 of 6 patients with vertigo but not in patients with tinnitus. It is thought to be difficult to diagnose ossiculodialysis from a tympanogram alone; stapedius reflex could possibly be referred to at diagnosis. The auditory ossicle was reconstructed using the stapes head and foot plate in patients with normal foot plates. In patients with ossicular invagination, the position of the auditory ossicle was reduced and the perilymphatic fistula closed, with ossicular reconstruction as needed. The surgical results were satisfactory, and auditory acuity was improved in 90% of the patients.

Adult↗
PubMed1999

[Eustachian tube function of adhesive tympanum--pre and post operative evaluation].

We examined the eustachian tube function of 48 patients with adhesive tympanum who had undergone operations. Preoperative tubal openings were observed and determined in 57% of these cases by the dynamic movement of the tympanic membrane, 35% by the impedance method, and 74% by the sonotubometry and was found to be lower than in healthy subject. Furthermore the tubal opening duration in sonotubometry was significantly shortened in patients with adhesive tympanum as compared to healthy subjects. However, in a few cases of adhesive tympanum, tubal opening was prolonged remarkably, and indicated a mixed tendency of stenotic and patulous types. Postoperative tubal opening was not seen in 90.9% of the cases as determined by the inflation-deflation test. Mucociliary function was poor in 81.3% of the cases. No remarkable differences were seen between cases of total adhesion and those of posterosuperior quadrant adhesion by any method. The condition of the tympanic membrane and the tympanic cavity after operation, and the eustachian tube function were not correlated in some cases and indicated possible involvement of other factors.

Adolescent↗
PubMed1999

[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent head and neck cancer].

A late phase II clinical study of RP56976 (docetaxel), a new anticancer agent for advanced/recurrent head and neck cancer, was conducted in 29 institutions all over Japan as a multi-institutional cooperative study. Docetaxel was administered by 1 to 2-hour intravenous infusion at a dose of 60 mg/m2 every 3 to 4 weeks. Of 63 patients eligible in this study, 59 were judged as complete cases. Complete response (CR) was observed in 1 patient, partial response (PR) in 13, no change (NC) in 25, and progressive disease (PD) in 20, for an overall response rate of 22.2% (14/63, 95% CI: 12.7-34.5%) in eligible cases, and 23.7% (14/59, 95% CI: 13.6-36.6%) in complete cases. Previously treated patients showed a 17.9% (10/56) response rate, whereas treatment--naive patients showed a 57.1% (4/7) response rate. Among 46 patients who received prior chemotherapy, one CR and 7 PR were observed with a 17.4% response rate. Major hematological toxicities were leucopenia in 95.1% (> or = grade 3, 59.7%) and neutropenia in 90.3% (> or = grade 3, 79.0%). Other severe toxicities (> or = grade 3) included anorexia in 9.7% (6 cases), diarrhea in 3.2% (2 cases), dyspnea in 3.2% (2 cases), and fatigue in 3.2% (2 cases). One patient had a grade 3 interstitial pneumonia; however, symptoms were resolved by the administration of corticosteroids. During this study, one patient died due to multiple organ failure (MOF) caused by disseminated intravascular coagulation (DIC), and this case was reported as a therapy-related death. Based on these results, docetaxel is an active agent for treatment of head and neck cancer.

Adenocarcinoma↗
PubMed1998

Local expression of immunoregulatory IL-12p40 gene prolonged syngeneic islet graft survival in diabetic NOD mice.

Local production of immunosuppressive cytokines will be one of the most suitable therapeutic strategies against organ-specific autoimmune diabetes. To establish such a new therapy, we constructed recombinant adenoviral vectors with inserted mIL-12p40 (Ad.IL-12p40) and mIL-10 (Ad.IL-10). Sufficient amounts of IL-12p40 and IL-10 were secreted by relevant adenovirus-transfected nonobese diabetic (NOD) islets. Shortly after transfection, 400 NOD islets transfected with Ad.IL-12p40 or Ad.IL-10 were transplanted under the renal capsule of a newly diabetic NOD mouse. NOD mice with IL-12p40-producing islet grafts kept normoglycemia in all of 14 grafted mice for over 4 wk after transplantation. In contrast, NOD mice with IL-10-producing islet grafts became diabetic in all of six grafted mice within 2 wk af-ter transplantation. Reverse transcription-PCR analysis revealed that local production of IL-12p40 led to the decrease of interferon-gamma and the augmentation of transforming growth factor-beta at the graft site. These results suggest that IL-12 plays an important role in the destruction of islet cells at the inflamed site of autoimmunity. Such a local blockade of IL-12 would be a useful gene therapy for human autoimmune diabetes.

Adenoviridae↗
PubMed1998

Studies on selectin blockers. 7. Structure-activity relationships of sialyl Lewis X mimetics based on modified Ser-Glu dipeptides.

We have previously found that heterochiral fucodipeptides, L-Ser-D-Glu (3a) and D-Ser-L-Glu (3b), exhibited up to 20-100 times more potency than a sialyl Lewis X (sLeX, 1) and a 3'-sulfated Lewis X analogue (2) toward E-selectin binding and have also proposed, from molecular dynamics calculation, that their strong activities would depend on a possible formation of the type II and/or type II' beta-turn of compounds 3a,b (Tsukida, T.; Hiramatsu, Y.; Tsujishita, H.; Kiyoi, T.; Yoshida, M.; Kurokawa, K.; Moriyama, H.; Ohmoto, H.; Wada, Y.; Saito, T.; Kondo, H. J. Med. Chem. 1997, 40, 3534-3541). To clarify our hypothesis, we synthesized several analogues of compounds 3a,b and investigated their structure-activity relationships. As a result, it was indicated that the type II and/or type II' beta-turn conformation would be a comparatively tight form and would play important roles in favorable binding to E-selectin. These findings indicate that sLeX mimetics with type II and type II' beta-turn dipeptides could be a useful methodology for the design of an active selectin blocker.

Dipeptides↗
PubMed1998

Abrogation of mitochondrial cytochrome c release and caspase-3 activation in acquired multidrug resistance.

Acquired multidrug resistance to anti-cancer agents has been associated with overexpression of the P-glycoprotein and other members of the ATP-binding cassette superfamily. The present studies demonstrate that SCC-25 cells selected for resistance to the alkylating agent cisplatin (CDDP) overexpress the anti-apoptotic Bcl-xL protein. In contrast to parental cells, the SCC-25/CDDP-resistant variant failed to exhibit activation of caspase-3, cleavage of protein kinase C delta, and other characteristics of apoptosis in response to CDDP. Similar results were obtained when SCC-25/CDDP cells were exposed to the structurally and functionally unrelated antimetabolite 1-beta-D-arabinofuranosyl-cytosine (ara-C). Other cells selected for resistance to doxorubicin or vincristine also exhibited overexpression of Bcl-xL and failed to respond to CDDP and ara-C with activation of caspase-3. The results further demonstrate that multidrug-resistant cells exhibit a block in the release of mitochondrial cytochrome c into the cytosol and that this effect is dependent on overexpression of Bcl-xL. The demonstration that lysates from the resistant cells respond to the addition of cytochrome c with activation of caspase-3 confirms that the block in apoptosis is because of inhibition of mitochondrial cytochrome c release. These findings demonstrate that cells respond to diverse classes of anti-cancer drugs with overexpression of Bcl-xL and that this response represents another mechanism of acquired multidrug resistance.

Antineoplastic Agents↗
PubMed1998

Studies on selectin blockers. 6. Discovery of homologous fucose sugar unit necessary for E-selectin binding.

We describe a mimic of the sugar unit of the E-selectin ligand, sialyl Lewis X (sLeX). Carbohydrates are entering the realm of rational drug design, aided by the growing understanding of the structure-function relationships. We investigated a new methodology of preparing sLeX mimetics and developed a potent E-selectin blocker characterized by beta-turn dipeptides. Another characteristic point of this E-selectin blocker is that the six-membered fucose ring was replaced with a five-membered fucose ring. Interestingly, it was found that the five-membered fucose ring could also bind to a calcium ion on the E-selectin, which could be an important role of the six-membered fucose ring. Especially, the L-Ser-D-Glu and D-Ser-L-Glu derivatives 3a,b showed 65-90-fold more potent inhibitory activities than the sulfated LeX analogue 1. In addition, molecular dynamics (MD) studies indicated that the 2- and 3-OH groups of the six-membered fucose ring, which were necessary for the calcium binding, overlapped well with the 2- and 3-OH groups of the five-membered fucose ring. These new findings could be useful for the design of new types of selectin blockers.

Carbohydrate Sequence↗
PubMed1998

Various types of HIV mixed infections in Cameroon.

In order to assess the incidence of HIV mixed infection as well as to clarify the molecular epidemiology of HIV in central Africa, we investigated 43 HIVs obtained from 211 Cameroonian AC, ARC, and AIDS patients in 1994 and 1995. Part of the pol region and part of the env region were phylogenetically analyzed. The genotypes observed were varied: of 43 specimens, 28 (65%) were subtype A, 1 (2%) was subtype B, 2 (5%) were subtype D, 3 (7%) were subtype F, and 2 (5%) were group O. Of the remaining 7 specimens, 3 were mixed infections with HIV-1 subtypes A and C, HIV-1 subtypes C and F, and HIV-2 subtype A and HIV-1 subtype A; 1 was a mixed infection with HIV-1 subtypes A and D and the highly divergent group O (triple infection); another 3 appeared to consist of mosaic genomes (A/G, A/E, and B/A recombinant). These data show that various types of mixed infection, such as between different subtypes of HIV-1 group M, between HIV-1 and HIV-2, and even between HIV-1 groups O and M, were confirmed at a rather high frequency (approximately 10%). The mixed infection is particularly significant where there is a greater variety of HIV-1 subtypes circulating, since it results in new genetic diversity generated by intersubtype recombination.

Adolescent↗
PubMed1998

Crystallization and preliminary X-ray studies on the hyperstable 3-isopropylmalate dehydrogenase from the thermoacidophilic archaeon Sulfolobus sp. strain 7.

3-Isopropylmalate dehydrogenase from the thermoacidophilic archaeon, Sulfolobus sp. strain 7, has been crystallized by the vapor-diffusion method. The crystals were grown from a solution containing ammonium sulfate, 2-methyl-2,4-pentanediol and magnesium chloride. The crystallization requires 2-methyl-2,4-pentanediol to avoid twinning of the crystals. The crystal belongs to the orthorhombic system with the space group P2221 and unit-cell dimensions a = 67.9, b = 93.3 and c = 134.1 A.

3-Isopropylmalate Dehydrogenase↗
PubMed1998

Application of a fine thread beam to the structure analysis of a hemihedrally twinned crystal of hydroxylamine oxidoreductase.

Accurate diffraction intensity data have been collected from a twinned P6(3) crystal of the 24-haem protein hydroxylamine oxidoreductase, from a nitrifying chemoautotrophic bacterium Nitrosomonas europaea, using synchrotron radiation at station BL6A of the Photon Factory. Estimation of the twinning fraction and deconvoluted intensity data, including native and heavy-atom derivative data, gave an improved Patterson function. Four diffraction data sets were collected from one crystal and an estimation of the twinning fraction to confirm the phenomena was undertaken. The successfully detwinned data sets were utilized in the structure analysis of the present enzyme. The mechanism of twinned-crystal formation is also discussed.

Journal Article↗
PubMed1998

Ion chromatography on anion exchangers modified with mucopolysaccharides.

Anion exchangers modified with mucopolysaccharides, such as chondroitin sulfates and heparin, were used for the stationary phase in ion chromatography. Unusual retention behavior of anions was observed for the modified stationary phases. A 50-microM concentration of tartaric acid could separate inorganic anions in a reasonable time. The retention of analytes could be changed by changing the eluent composition.

Chromatography, Ion Exchange↗
PubMed1998

Rapid determination of vitamins A and E in serum with surfactant as a diluent by column-switching high-performance liquid chromatography.

The rapid and simple determination of fatty vitamins (vitamins A and E) in serum by high-performance liquid chromatography with a column-switching technique was investigated. The dilution of serum with an aqueous solution containing surfactant and organic solvent and the use of an aqueous solution with organic solvent as a sample pretreatment were an effective means of improving the sample recovery. To prevent sample decomposition during storage, the addition of an antioxidant reagent into the diluent was required. Under the optimal conditions, the relative standard deviation (R.S.D.) values against the standard samples were 1.12% (16.7 I.U./dl), 0.25% (333 I.U./dl) for vitamin A, and 1.02% (0.43 microgram/ml), 0.45% (8.5 micrograms/ml) for vitamin E, respectively. The relative coefficients (r2) between the sample amounts in serum and the peak areas were 1.0000 in the range from 16.7 to 667 I.U./dl (for vitamin A) and 0.9998 from 0.434 to 17.46 micrograms/ml (for vitamin E). The recoveries of vitamins from spiked serums were ca. 100% (vitamin A) and ca. 86% (vitamin E), respectively. By the combination of an on-line deproteination column and diluting solution, the simple and rapid determination of fatty vitamins could be routinely achieved in 18-min intervals.

Chromatography, High Pressure Liquid↗
PubMed1998

Close correlation between mutations of E2F4 and hMSH3 genes in colorectal cancers with microsatellite instability.

Defects in mismatch repair function can lead to the microsatellite instability (MI+; replication error) phenotype in certain human cancers. We previously reported that MI+ tumor-specific repeat number alteration at 13 consecutive trinucleotide (CAG) repeats within a coding exon of the E2F4 gene is a possible target of the defective repair pathway. Additional investigations revealed that E2F4 mutations are common (11 of 17 cases, 65%, mostly deletions) in a subset of human colorectal cancers with extensive MI+ phenotype, with respect to the proportion of loci affected and that most of these E2F4-mutated tumors (9 of 11, 82%) were accompanied by frameshift mutations in a polyadenine stretch within the seventh exon of the hMSH3 gene, a known mismatch repair gene that is responsible for repair of mismatch loops of two to four nucleotides. However, neither of these mutations was detected in 15 tumors with a lower incidence of MI+ loci. Similar repeat number alterations were less frequent in CAG repeats from other genes in all of the MI+ tumors we examined. These results indicate the presence of a novel cascade of mutational events that may be involved in acquisition of the malignant phenotype of human colorectal cancers with genetic instability.

Colorectal Neoplasms↗
PubMed1998

Cell proliferation and apoptosis in human middle ear cholesteatoma.

OBJECTIVE: To compare the pattern of proliferation and apoptotic cell death in cholesteatoma tissues with that in normal skin. PARTICIPANTS: The cholesteatoma tissue samples were excised from 10 patients during surgery. Normal skin specimens collected from the external ear canal of 6 of the 10 patients were used as controls. RESULTS: In all cholesteatoma tissue samples, apoptotic cells were not seen in the basal cell layer, but they were observed in the suprabasal, prickle, and granular cell layers. In skin specimens obtained from normal external ear canal skin, in which the suprabasal cell layer was comparatively small, similar kinetics of apoptotic cell death were observed. Immunohistochemical analysis using a monoclonal antibody to proliferation cell nuclear antigen demonstrated the presence of proliferating cells in the basal and suprabasal cell layers of the normal external ear canal skin, whereas in the cholesteatoma tissue samples, large numbers of proliferation cell nuclear antigen-positive cells were also observed in the prickle and granular cell layers. CONCLUSIONS: Proliferation in cholesteatoma epidermal cells is not uncontrolled, as it is in malignant tumors. Our results demonstrate an increase in the rate of proliferation and apoptotic cell death in cholesteatoma epidermis.

Adult↗
PubMed1998

Mode of migration of normal lymphocytes inside murine testis.

BACKGROUND: Previous studies have shown that in murine experimental autoimmune orchitis (EAO), lymphocytes preferably infiltrate into (1) the testicular capsule near the rete testis, (2) the subcapsular interstitium away from the rete testis, and (3) the interstitium surrounding the tubuli recti and rete testis. Therefore, these three sites might provide tissue environments in which specific lymphocytes can easily gain access to testicular autoantigens. However, there is another possibility that infiltrating lymphocytes in the testis spontaneously accumulate at these three sites via the lymphatic flow inside this organ during EAO. METHODS: To examine this possibility, normal lymphocytes were locally injected into the peripheral testis regions of recipient mice. Testes were then collected at various times for investigating the chronological pattern of lymphocytic migration inside the testes at a light microscopic level. RESULTS: The injected lymphocytes first stayed in the lymphatic space around the seminiferous tubules and then moved to the subcapsular lymphatic space away from the rete testis. The lymphocytes accumulated under the testicular capsule and then gradually infiltrated into the adjacent capsular tissue. In the capsule, the cells surrounded the arteriolae and then accumulated in the capsular tissue near the rete testis. Thereafter, the cells finally left the testes through the lymphatics running in the spermatic cords. In the course of the lymphocytic drainage, it was noted that the injected lymphocytes appeared not to pass through the testicular interstitium around the tubuli recti and rete testis. CONCLUSIONS: The regional distributions of the testicular lymphocytes imply that the lymphatic flow in the testis may somewhat influence murine EAO pathology characterized by lymphocytic accumulation in (1) the testicular capsule near the rete testis and (2) the subcapsular interstitium away from the rete testis. However, the pathology exhibiting lymphocytic accumulation in (3) the interstitium around the tubuli recti and rete testis is independent on the intratesticular lymph flow.

Animals↗
PubMed1998

Administration of IL-4 prevents autoimmune diabetes but enhances pancreatic insulitis in NOD mice.

The present study demonstrated that the administration of recombinant interleukin-4 (rIL-4) prevented overt diabetes in nonobese diabetic (NOD) mice whose T cells produced relatively low amounts of IL-4. However, massive insulitis was observed in rIL-4-treated NOD mice. The flow cytometric analysis of islet-infiltrating T cells revealed that the number of CD45RBlowCD4+ T cells was significantly increased by in vivo administration of rIL-4. By measuring the cytokine production of splenic T cells after stimulation, it was shown that CD45RBlowCD4+ T cells predominantly produced IL-4 and IL-10 but produced less IL-2 and interferon-gamma (IFN-gamma). A semiquantitative reverse-transcriptase polymerase chain reaction assay revealed a higher expression of IL-4 and IL-10 mRNA and an apparent decrease in IFN-gamma mRNA in the islets of NOD mice which were administered rIL-4. These results suggested that autoreactive CD45RBlowCD4+ T helper 2 (Th2)-like cells which developed following rIL-4 administration were predominant in the infiltrate of the islets, and overt diabetes was prevented. On the other hand, when splenocytes from rIL-4-treated NOD mice were transferred to irradiated NOD recipients, along with splenocytes from diabetic NOD mice, all of the recipient mice became diabetic within 8 weeks after transfer. Considered together, a supplement of rIL-4 administered to NOD mice may protect against autoimmune diabetes by facilitating the development of Th2-like autoreactive T cells in the islets.

Animals↗