Search PubMed⌕ Search

Biomedical subjects

H Moriyama

Publications and source records attributed to H Moriyama.

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

Transient insulin autoantibody expression independent of development of diabetes: comparison of NOD and NOR strains.

NOD mice spontaneously develop anti-insulin autoantibodies associated with the subsequent development of diabetes. NOD mice that express insulin autoantibodies at 8 weeks of age have a diabetes risk exceeding 90%, while mice that do not express autoantibodies by 16 weeks have a risk of less than 20%. NOD female mice expressed insulin autoantibodies more often than male mice (13/15+ vs. 6/15+). Autoantibodies characteristically developed between 8 and 20 weeks and then for most mice became negative at diabetes onset in NOD mice. In the diabetes-free strain NOR mice, spontaneous expression of insulin autoantibodies was observed in less mice (female 8/15+, male 3/10+) compared to NOD mice. The expression of autoantibodies was transient in NOR mice and followed the same time-course as for NOD mice and they were all negative by 28 weeks (without progression to diabetes). No correlation was found in NOR mice between the levels of autoantibodies and insulitis. The program of insulin autoantibody expression is regulated over approximately 5 months for both NOD and NOR mice with only NOD mice developing diabetes, indicating that depending upon genetic combination, the presence of insulin autoantibodies does not always predict diabetes development. In addition, this data is not consistent with the hypothesis that the time-course of autoantibodies simply reflects the destruction of beta-cells with development of diabetes.

Animals↗
PubMed2001

Studies on selectin blocker. 9. SARs of non-sugar selectin blocker against E-, P-, L-selectin bindings.

As a part of study of selectin blockers, we have already reported that a non-sugar selectin antagonist (3) was successfully discovered using a computational screening (Hiramatsu, Y.; Tsukida, T.; Nakai, Y.; Inoue, Y.; Kondo, H. J. Med. Chem. 2000, 43, 1476). To investigate the SARs of compound 3 against E-, P-, and L-selectins, we synthesized the derivatives of compound 3 and evaluated their inhibitory activities toward selectin bindings. The structural diversity of compound 3 contained the following: (1) a modification of the spacer unit (4--7), (2) a modification of the tail unit (8--11), (3) a modification of the head unit (12--18). As a result, it was found that a non-sugar based selectin blocker (3) could be a potential lead compound for E-, P-, and L-selectin blockers and some of the derivatives showed broad and/or selective inhibitory activities toward the E-, P-, and L-selectins. In addition, it was found that the experimental evidence well supported that the computational screening using 3D-pharmacophore model could be useful methodology to find out a new lead for the several type of selectin blockers, which included a broad and/or a selective inhibitor.

Benzamides↗
PubMed2001

Polymorphism in RANTES chemokine promoter affects extent of sarcoidosis in a Japanese population.

RANTES, a member of C-C chemokine, is known to be produced at sites of granulomatous reactions in the lung of sarcoidosis. RANTES is a potent eosinophil and lymphocyte attractant with particular preference for CD45RO+ T cells and eosinophils. Polymorphism of the RANTES promoter has recently been shown to be related to allergic and infectious diseases; atopic dermatitis, asthma, and polymyalgia rheumatica. Considering that this might affect sarcoidosis, we studied polymorphism of the RANTES gene in 114 patients with sarcoidosis and 136 healthy control subjects. Their genotypes were determined using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Although no difference in the genotype distribution between healthy control subjects and sarcoidosis patients was identified, the difference in the frequencies of the patients with three or more organ involvement was significant (P<0.01) with the frequency of those in AA genotype being elevated (P<0.05). BAL findings in 48 out of 114 patients who underwent bronchoscopy were reviewed. The CD4/8 ratio of lymphocytes in bronchoalveolar lavage fluid in the patients with AA genotype was significantly increased (P<0.05). From the results, we suggest that in RANTES gene polymorphism the homozygous A allele might be a genetic risk factor for extent disease of sarcoidosis.

Bronchoalveolar Lavage Fluid↗
PubMed2001

Embryological consideration of drainage of the left testicular vein into the ipsilateral renal vein: analysis of cases of a double inferior vena cava.

The right gonadal vein (GV=testicular vein in men, ovarian vein in women) usually drains into the inferior vena cava (IVC) while the left gonadal vein drains into the left renal vein (RV). This anatomical difference induces relatively weak haemodynamics in the left testicular vein (TV) and is considered to be a cause of a left varicocele. In textbooks on embryology, it has been documented that bilateral supracardinal veins (=origin of right and left IVC) and the subcardinal sinus (=origin of RVs and GVs) symmetrically develop during early embryogenesis. However, persistence and regression of the right and left supracardinal veins, respectively, results in drainage of the left GV into the ipsilateral RV. A double IVC (DIVC) commonly originates from a failure of disappearance of the left supracardinal vein. Although there have been a considerable number of case reports on DIVC, little attention has been paid to the anatomy of the left GV in such cases. We report here an autopsy case, a 72-year-old Japanese man, with a DIVC. This case belongs to type BC of McClure and Butler's classification. In this case, it was observed that the right TV drained into the confluence of the right IVC with the ipsilateral RV, while the left TV drained into the left RV in spite of the presence of the left IVC. This case indicates that the embryonic anastomosis point between the subcardinal sinus and the supracardinal vein on the left side is different from that on the right side. Statistical analysis of many case reports of DIVC also suggests that the bilateral supracardinal veins tend to asymmetrically anastomose with the subcardinal sinus during embryogenesis. These data imply that drainage of the left GV into the ipsilateral RV leads to regression of the left supracardinal vein but also to asymmetrical anastomosis between the supracardinal veins and the subcardinal sinus.

Aged↗
PubMed2001

RNA-dependent RNA polymerase activity associated with endogenous double-stranded RNA in rice.

RNA-dependent RNA polymerase (RdRp) activity was detected in the crude microsomal fraction of rice cultured cells that contain a 14 kbp double-stranded RNA (dsRNA). RdRp activity is maximal in the presence of all four nucleotide triphosphates and Mg2+ ion and is resistant to inhibitors of DNA-dependent RNA polymerases (actinomycin D and alpha-amanitin). RdRp activity increases approximately 2.5-fold in the presence of 0.5% deoxycholate. Treatment of purified microsomal fraction with proteinase K plus deoxycholate suggests that the RdRp enzyme complex with its own 14 kb RNA template is located in vesicles. The RdRp enzyme complex was solubilized with Nonidet P-40 and purified by glycerol gradient centrifugation, then exogenous RNA templates were added. Results indicate that exogenous dsRNA reduces RNA synthesis from the endogenous 14 kb RNA template.

Cells, Cultured↗
PubMed2001

Crystal structures of mutants of Thermus thermophilus IPMDH adapted to low temperatures.

Random mutagenesis on thermophilic 3-isopropylmalate dehydrogenases (IPMDH; EC 1.1.1.85) produced mutant enzymes which adapt to low temperatures. These mutants had higher activity at lower temperatures than the wild-type enzyme without losing high thermostability. Here we report three structures of the mutants of Thermus thermophilus IPMDH determined by X-ray diffraction which was adapted to a low-temperature environment. Two of them have unstable coenzyme binding states and the other one probably has a stable substrate binding state. The present research suggests that the adaptation is correlated with the binding of either coenzyme or the substrate.

3-Isopropylmalate Dehydrogenase↗
PubMed2001

Molecular biological diagnosis of congenital and acquired cholesteatoma on the basis of differences in telomere length.

OBJECTIVE: To establish a molecular biological basis for differentiation of congenital and acquired cholesteatoma. STUDY DESIGN: The time of onset was estimated for congenital cholesteatoma and for acquired cholesteatoma by comparing the telomere length and the telomerase activity in the tissues of both diseases with the values of those parameters in normal external ear canal skin. METHODS: The telomere length was determined by extracting DNA from each tissue and then applying the Southern blot technique to hybridize it with a 32P-labeled telomeric oligonucleotide (TAAGGG)8 probe. The telomerase activity was analyzed by a modification of the polymerase chain reaction-based telomeric repeat amplification protocol. RESULTS: The telomere length in congenital cholesteatoma tissue was shorter than the length in normal external ear canal skin from the same patient, whereas in acquired cholesteatoma tissue the telomere length was almost the same as in the normal external ear canal skin. Some of the acquired cholesteatoma tissue specimens and normal external ear canal skin specimens were positive for telomerase activity, but all of the specimens of congenital cholesteatoma tissue were negative for telomerase activity. No correlation was found between the presence of telomerase activity and the telomere length. CONCLUSIONS: The present results indicate that congenital cholesteatoma manifests at an earlier time compared with acquired cholesteatoma, and the results can be thought to support the theory that congenital cholesteatoma originates from vestigial fetal tissue or aberrant tissue. In addition, the finding that telomerase activity was weak in the congenital cholesteatoma tissue suggests the possibility that vestigial fetal tissues and aberrant tissues are naturally eliminated in normal subjects as a result of apoptosis.

Adolescent↗
PubMed2001

Design, X-ray crystallography, molecular modelling and thermal stability studies of mutant enzymes at site 172 of 3-isopropylmalate dehydrogenase from Thermus thermophilus.

The relationship between the structure and the thermostability of the 3-isopropylmalate dehydrogenase from Thermus thermophilus was studied by site-directed mutation of a single Ala residue located at the domain interface. The crystal structures of three mutant enzymes, replacing Ala172 with Gly, Val and Phe, were successfully determined at 2.3, 2.2 and 2.5 A resolution, respectively. Substitution of Ala172 by relatively 'short' residues (Gly, Val or Ile) enlarges or narrows the cavity in the vicinity of the C(beta) atom of Ala172 and the thermostablity of the enzyme shows a good correlation with the hydrophobicity of the substituted residues. Substitution of Ala172 by the 'longer' residues Leu or Phe causes a rearrangement of the domain structure, which leads to a higher thermostability of the enzymes than that expected from the hydrophobicity of the substituted residues. Mutation of Ala172 to negatively charged residues gave an unexpected result: the melting temperature of the Asp mutant enzyme was reduced by 2.7 K while that of the Glu mutant increased by 1.8 K. Molecular-modelling studies indicated that the glutamate side chain was sufficiently long that it did not act as a buried charge as did the aspartate, but instead protruded to the outside of the hydrophobic cavity and contributed to the stability of the enzyme by enhancing the packing of the local side chains and forming an extra salt bridge with the side chain of Lys175.

3-Isopropylmalate Dehydrogenase↗
PubMed2001

A stabilized flavonoid glycoside in heat-treated Cassia alata leaves and its structural elucidation.

Heat-treated leaves of Cassia alata were studied for any change in chemical constituents using sun dried leaves as the reference standard. A high concentration of a constituent was observed in the heat-treated leaves. Spectroscopic studies revealed the structure of the constituent as kaempferol 3-gentiobioside, which has not yet been detected in the Cassia species. In a stability study disappearance of kaempferol 3-gentiobioside was noted in the sun dried leaves while there was little or no change in the kaempferol 3-gentiobioside concentration in the heat-treated leaves when incubated in an aqueous solution, suggesting a possible presence of enzymatic activities in the sun dried leaves. Therefore, heat-treatment may be a good method to stabilize kaempferol 3-gentiobioside in Cassia alata leaves.

Cassia↗
PubMed2001

Peptide and major histocompatibility complex-specific breaking of humoral tolerance to native insulin with the B9-23 peptide in diabetes-prone and normal mice.

NOD mice spontaneously develop anti-insulin autoantibodies and diabetes. A dominant peptide recognized by T-cell clones from NOD mice is insulin B-chain peptide B9-23. When administered subcutaneously to NOD mice, this peptide decreases the development of diabetes. In this study, we evaluated the autoantibody response to native insulin after administration of the B9-23 peptide. In NOD mice, administration of the B9-23 peptide in incomplete Freund's adjuvant enhanced their insulin autoantibody response with a higher level and longer persistence. Induction of insulin autoantibodies with the B9-23 peptide was observed in non-diabetes-prone BALB/c mice and NOR mice within 2 weeks of administration, but this was not observed in C57BL/6 mice. A series of A-chain, other B-chain, and proinsulin peptides did not induce insulin autoantibodies. Induced anti-insulin autoantibodies could not be absorbed with the peptide alone but could be absorbed with native insulin. The B13-23 peptide (one of two identified epitopes within B9-23) when administered to BALB/c mice, induced autoantibodies, whereas peptide B9-16 did not. Induction of autoantibodies mapped to the major histocompatibility complex (MHC) rather than to the background genes. Both splenocytes with I-A(d)/I-E(d) or I-A(g7)/I-E(null) presented the B9-23 peptide to NOD islet-derived T-cell clones. Finally, administration of the B9-23 peptide to BALB/c mice, even without adjuvant, could induce insulin autoantibodies. Our results indicate that B-cell tolerance to intact insulin is readily broken with the presentation of the B9-23 insulin peptide, depending on the host's specific MHC.

Animals↗
PubMed2001

Morphometric nerve fiber analysis and aging process of the human inferior alveolar nerve.

We studied morphometric nerve fiber analysis and the aging process of the inferior alveolar nerve (IAN). Human IANs were resected at the mandibular foramen. The preparation of sections involved fixation, washing, dehydration, embedding, sectioning and staining as described in our previous reports. We estimated the total number of myelinated axons in the IAN being average 26,200, the transverse area of those being average 37.1 microns 2, the average perimeter of those being 23.0 microns, the average circularity ratio of those being 0.85, respectively. According to these results, the IAN did not demonstrate notable age-relation change in any measured item. The IAN differed from not only our previous data on the human motor peripheral nerves but also those on the human sensory peripheral nerves. With regard to the aging process, the IAN indicated morphological features compared with other peripheral nerves.

Aged↗
PubMed2001

[A case report of allergic fungal sinusitis caused by Penicillium sp. and Cladosporium sp].

We report a case of allergic fungal sinusitis (AFS) caused by Penicillium sp. and Cladosporium sp. in a 57-year-old man satisfying the following diagnostic criteria: (1) chronic rhinosinusitis revealed by computed tomographic scan, (2) Japanese cedar pollinosis for 3 years, (3) positivity for Penicillium sp. and Cladosporium sp. by a skin test, (4) increased immunoglobulin E (IgE) specific to these fungi, (5) increased total IgE, (6) nasal polyps with severe eosinophilic invasion, (7) allergic mucin revealed by histopathological examination, (8) fungal hyphae revealed by histopathological examination and (9) detection of Penicillium sp. and Cladosporium sp. revealed by fungi culture. The patient was treated by endoscopic sinus surgery. Four weeks after surgery, nasal polyps recurred, but his condition was improved by oral administration of steroids and nebulizer treatment with steroids and fluconazole. Total IgE, specific IgE and eosinophil count in the peripheral blood decreased, apparently reflecting this improvement. After obtaining the patient's consent, we conducted an allergen provocation test, which is as highly diagnostic as a skin test, to test for an antigen causing type I hypersensitivity. The immediate phase response was positive, indicating that type I hypersensitivity intermediated by IgE was involved in AFS.

Cladosporium↗
PubMed2001

[CT screening of vertebrarterial circulatory disorder].

The frequency of MR angiography (MRA) used to diagnose vertebrobasilar insufficiency appears high. Findings of abnormality by MRA show cases with maldescription of hemivertebral artery. In such cases, it is unclear whether these are due to anaplasia of the vertebral artery or to the existence of morbid constriction, thus requiring confirmation by a vertebral arteriography (VAG). We observe the vascular morphology of vertebral artery by Computed tomography (CT) scanning for screening circulatory disorders. In photography and CT scan reading, the region was severally photographed between foramen magnum and aortic arch by plain CT and contrast CT at a slice of 5 mm. The constrictive region of the vertebral artery was estimated by comparing plain and contrast CT. Subjects were 34 clinical cases of vascular maldescription in the vertebrobasilar artery, nearly no blood vessel description, or blood vessel winding or inclination. We determined the constrictive morbid state of the vertebral or subclavian artery and cervical vertebra deformity. In findings of maldescription by MRA, it was suggested that discrimination is feasible to a certain degree, whether the vertebral artery has a morbid constrictive region or due to anaplasia. Our results suggest that screening by CT scanning may be more efficient than that by MRA.

Aged↗
PubMed2001

[A case of pulmonary inflammatory pseudotumor with hypergammaglobulinemia, elevated ANA, and uveitis].

A 63-year-old man presented with a chronic myeloproliferative disorder complicated with left pneumonia. His pneumonia was cured with antibiotics, but a nodular lesion remained in his chest radiographs together with hypergammaglobulinemia, a high titer of anti-nuclear antigen, and uveitis with secondary glaucoma. Specimens obtained by transbronchial lung biopsy showed a mixed accumulation of plasma cells, lymphocytes, and histiocytes as well as a spindle cell proliferation diagnosed as pulmonary inflammatory pseudotumor. The specimen did not show any recombination indicative of a heavy or a light chain of immunoglobulin in Southern blotting analysis. Oral prednisolone treatment improved the pulmonary nodular lesion, the abnormal laboratory data, and the uveitis. These findings suggest that much of the gammaglobulin produced by plasma cells in the inflammatory pseudotumor caused a variety of clinical symptoms.

Administration, Oral↗