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Biomedical subjects

H Moriyama

Publications and source records attributed to H Moriyama.

At least 19 recordsLinked to original sources
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

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↗
PubMed1998

Gene therapy for hepatic micrometastasis of murine colon carcinoma.

BACKGROUNDS/AIMS: Pit cells are located in the hepatic sinusoids and are organ-associated natural killer cells that contribute to immune surveillance in the liver. In the present study, the interleukin-2 gene was introduced into hepatocytes using an adenovirus vector to induce interleukin-2 production in an attempt to enhance the natural killer activity of pit cells, leading to inhibition of metastasis of colon carcinoma. METHODS: The recombinant adenovirus vector "Adex1CAmIL2" was constructed by inserting an expression unit which was composed of the CAG promotor (cytomegalovirus enhancer plus chicken beta-actin promotor), murine interleukin-2 cDNA, and a rabbit beta-globin polyadenylation signal. After administration of Adex1CAmIL2 to mice (4x10(7) pfu per animal), the expression of murine interleukin-2 in hepatocytes was examined by immunostaining and in situ hybridization, and the natural killer activity of hepatic mononuclear cells was measured. Inhibition of hepatic metastasis of colon carcinoma was examined after infusion of colon 38 tumor cells into the superior mesenteric vein. RESULTS: After administration of Adex1CAmIL2, interleukin-2 mRNA expression was demonstrated in hepatocytes until day 7, and the serum interleukin-2 level was increased. The natural killer activity of hepatic mononuclear cells was markedly enhanced for 7-10 days. Hepatic metastasis was inhibited by administration of Adex1CAmIL2 until day 7 after tumor cell inoculation. CONCLUSION: These results suggest that gene therapy using Adex1CAmIL2 could be potentially useful for inhibiting hepatic micrometastasis by enhancing the natural killer activity of pit cells.

Actins↗
PubMed1998

A study on epidermal proliferation ability in cholesteatoma.

With the objective of estimating proliferation ability of epidermis of middle ear cholesteatoma, the difference in proliferating cell nuclear antigen (PCNA) staining between the skin of the bone region of the external ear canal (control skin) and cholesteatoma epidermis and the effects on PCNA staining of subepidermal inflammatory cell infiltration of cholesteatoma were immunohistochemically studied using an antibody against PCNA. Transforming growth factor-alpha (TGF-alpha) is known to promote epidermal proliferation based on autocrine mechanism. But it is not clear that cholesteatoma epidermis is actually in the state of hyperproliferation under the effect of this growth factor. To estimate the effect of TGF-alpha on epidermal proliferation ability, the authors compared the location of PCNA and TGF-alpha in the same specimen. Unlike the control skin, not only epidermal basal cell layer and suprabasal cell layer, but also more superior layers were found to have high levels of PCNA staining in the epidermis of cholesteatoma. However, in the same cholesteatoma epidermal tissue, the PCNA staining was varied and the difference was ascribable to subepidermal cell inflammation. It appeared that the proliferation ability was high in regions where subepidermal inflammatory cell infiltration was severe. These differences in microenvironment are inferred to greatly affect proliferation ability of cholesteatoma epidermis.

Adult↗
PubMed1998

Infectivity and immunogenicity of SIVmac/HIV-1 chimeric viruses (SHIVs) with deletions in two or three genes (vpr, nef and vpx).

Two SHIVs with two or three genes deleted (SHIV-drn and SHIV-dxrn) were constructed. The inoculation of monkeys with SHIV-drn resulted in short-term viremia, but inoculation with SHIV-dxrn did not. At 68 weeks post-inoculation, the monkeys were reinoculated with a 100-fold higher dose of each SHIV, but none showed viremia. Killer cell activities against HIV-1 Env were detected in the SHIV-drn- and SHIV-dxrn-inoculated monkeys. Cross-reactive killer activity against HIV-1 Gag and SIVmac Gag was observed in one monkey. Antibodies were not detected in the SHIV-dxrn-inoculated monkeys, but the SHIV-drn-inoculated monkeys showed an anamnestic antibody reaction. These data indicate that SHIV-drn is infectious to and immuno-inducible in macaques but SHIV-dxrn is not.

AIDS Vaccines↗
PubMed1998

[Intraoperative coronary artery spasm treated by percutaneous cardiopulmonary support in a patient with left lung cancer].

A 53-year-old man with left lung cancer underwent left upper lobectomy and extended mediastinal lymphadenectomy. Shortly before the end of the operation, electrocardiogram showed elevation of ST wave and multiple ventricular premature contractures first, then ventricular fibrillations, and finally cardiac arrest. Coronary artery spasm was strongly suspected. The patient was resuscitated by cardiac massage and countershock immediately, however, such attacks repeated several times. As medication and cardiac pacing were not effective, percutaneous cardiopulmonary support (PCPS) was established. The hemodynamics was stabilized with PCPS. He was weaned off PCPS the next day. He was discharged and has had no attack so far. PCPS is an excellent modality for intraoperative coronary spasm which is uncontrollable by medicines and other methods.

Carcinoma, Squamous Cell↗
PubMed1997

Studies on selection blockers. 5. Design, synthesis, and biological profile of sialyl Lewis x mimetics based on modified serine-glutamic acid dipeptides.

We have rationally designed a sLe(x) mimetic based on molecular modeling, synthesized type II and type II' beta-turn dipeptides (3a,b), and evaluated their biological profiles both in vitro and in vivo. Against E-selectin-sLe(x) binding, the type II beta-turn dipeptide L-Ser-D-Glu 3a (IC50, 13 microM) and the type II' beta-turn dipeptide D-Ser-L-Glu 3b (IC50, 5.5 microM) were 20-100-fold more potent blockers than sLe(x) (1; IC50, 600 microM) and a 3'-sulfated Le(x) analog (2; IC50, 280 microM). On the other hand, other stereoisomers, such as L-Ser-L-Glu 3c and D-Ser-D-Glu 3d, were very weak blockers, with IC50 > 1000 microM for both 3c,d. Against the P- and L-selectins, despite much different stereochemistry of compounds 3a-d, the dipeptides 3a-d were all more potent blockers than either sLe(x) or compound 2. Interestingly, compound 3b provided significant in vivo efficacy against an immunoglobulin E-mediated skin reaction in a mouse model. These findings indicate that sLe(x) mimetics with type II and type II' beta-turn dipeptides could be useful in the design of an active selectin blocker in vitro and/or in vivo.

Animals↗
PubMed1997

c-fos expression in the trigeminal sensory complex and pontine parabrachial areas following experimental tooth movement.

Ortodontic tooth movement causes continuous pain. However, it does not appear immediately, usually appearing after the application of orthodontic force to the teeth. Mechanically induced inflammatory responses in the periodontal membrane are assumed to be related to the mechanism of the later pain sensation. In the present study, we investigated Fos-like immunoreactivity in the trigeminal sensory complex and pontine parabrachial areas 24 h after the commencement of experimental tooth movement. An orthodontic elastic module was unilaterally inserted between upper molars. Following experimental tooth movement, Fos-like immunoreactive neurons appeared ipsilaterally in the trigeminal subnucleus caudalis and bilaterally in the lateral parabrachial nucleus. These results indicate that experimental tooth movement evokes delayed and continuous nociception after application of orthodontic force to the teeth and that the nociceptive information would be conveyed to the ipsilateral trigeminal subnucleus caudalis and further processed, at least in part, to the lateral parabrachial nucleus.

Animals↗
PubMed1997

The crystal structure of zinc-containing ferredoxin from the thermoacidophilic archaeon Sulfolobus sp. strain 7.

The crystal structure of ferredoxin from the thermoacidophilic archaeon Sulfolobus sp. strain 7 was determined by multiple isomorphous replacement supplemented with anomalous scattering effects of iron atoms in the Fe-S clusters, and refined at 2.0 A resolution to a crystallographic R value of 0.173. The structural model contains a polypeptide chain of 103 amino acid residues, 2 [3Fe-4S] clusters, and 31 water molecules; in this model, the cluster corresponding to cluster II in bacterial dicluster ferredoxins loses the fourth iron atom although it may originally be a [4Fe-4S] cluster. The structure of the archaeal ferredoxin consists of two parts: the core fold part (residues 37-103) and the N-terminal extension part (residues 1-36). The "core fold" part has an overall main-chain folding common to bacterial dicluster ferredoxins, containing two clusters as the active center, two alpha-helices near the clusters, and two sheets of two-stranded antiparallel beta-sheet (the terminal and central beta-sheets). The "N-terminal extension" part is mainly formed by a one-turn alpha-helix and a three-stranded antiparallel beta-sheet. The beta-sheet in the N-terminal extension is hydrogen-bonded with the terminal beta-sheet in the core fold to form a larger beta-sheet. The distinct structural feature of this archaeal ferredoxin lies in the zinc-binding center where the zinc ion is tetrahedrally ligated by four amino acid residues (His 16, His 19, and His 34 from the N-terminal extension, and Asp 76 from the core fold). The zinc ion in the zinc-binding center is located at the interface between the core fold and the N-terminal extension, and connects the beta-sheet in the N-terminal extension and the central beta-sheet in the core fold through the zinc ligation. Thus, the zinc ion plays an important role in stabilizing the structure of the present archaeal ferredoxin by connecting the N-terminal extension and the core fold, which may be common to thermoacidophilic archaeal ferredoxins.

Amino Acid Sequence↗
PubMed1997

Macrophage differentiation and expression of macrophage colony-stimulating factor in murine milky spots and omentum after macrophage elimination.

To elucidate the differentiation mechanisms of macrophages in the murine omentum, we studied the repopulation of these cells and the expression of macrophage colony-stimulating factor (M-CSF) in the milky spots and omental tissues in mice depleted of macrophages following administration of liposome-encapsulated dichloromethylene diphosphonate (clodronate). The macrophages in the omentum were spindle or dendritic in shape, expressed several macrophage-specific antigens and Ia antigen, and phagocytized intraperitoneally injected carbon particles. In the milky spots, macrophages and macrophage precursors were detected, and the number of precursors increased after elimination of macrophages by intraperitoneal injection of liposome-encapsulated clodronate. Macrophage precursors in the milky spots proliferated, moved to the omentum, and transformed into dendritic-shaped macrophages. Expression of M-CSF mRNA extracted from the milky spots was markedly enhanced at 2 and 3 days after macrophage depletion. Localization of M-CSF protein and mRNA was observed in the stromal cells of the milky spots. In osteopetrosis (op/op) mutant mice that are defective in the production of functional M-CSF omental macrophages were absent. These results indicate that M-CSF locally produced in the milky spots plays an important role in providing a microenvironment for development and differentiation of omental macrophages.

Animals↗