Biomedical subjects

H Shirai

Publications and source records attributed to H Shirai.

At least 55 records · Page 3Linked to original sources

PubMed1999

Junctional amino acids determine the maturation pathway of an antibody.

We found that two distinct antibody maturation pathways exist in the immune response of C57BL/6 mice to (4-hydroxy-3-nitrophenyl)acetyl and that the junctional amino acid introduced by a process far preceding somatic hypermutation determined the pathway of affinity maturation. Antibodies belonging to each pathway clearly separated into two separate branches of a phylogenic tree. We also constructed a three-dimensional fitness landscape for antibody evolution by introducing the association constants of the antibodies into the phylogenic tree as the third axis, allowing us to comprehend the significance of junctional diversity in the "evolvability" of antibodies. Thermodynamic analyses of the antigen-antibody interactions suggested that a high conformational versatility in the antigen-combining site allows for the enhanced evolvability of antibodies.

Amino Acid Sequence↗

PubMed1999

The effect of diabetes mellitus on histopathological changes in the denture-supporting tissues under continuous mechanical pressure in rat.

The histopathological changes in denture-supporting tissues of streptozotocin-induced diabetes mellitus rat were studied in relation to continuous mechanical pressure exerted through an experimental denture base. The experimental dentures were designed to load continuous mechanical pressures (3.4, 1.5 or 0.5 kPa) to the hard palate of the molar region of a rat. From the results of this study, the following conclusions were drawn: the streptozotocin-induced diabetic condition (1) tended to prolong the appearance period of a shortened epithelial ridge, and weakened the phenomenon, (2) reduced the appearance period and severity of the compression of epithelium, (3) delayed the time of manifestation of the proliferative change in the recovery process of the shortened epithelial ridge, and weakened the phenomenon, (4) prolonged the appearance period of the compressed lamina propria mucosae, and enhanced the phenomenon, (5) reduced the number of osteoclasts, (6) lowered the threshold for induction of the osteoclastic bone resorption to between 1.5 and 0.5 kPa, (7) inhibited the appearance of osteoblast which follows the disappearance of osteoclasts, (8) did not induce any inflammatory change, and (9) tended to enhance the longitudinal change of the continuous mechanical pressure. The histopathological changes in the denture-supporting tissues of the streptozotocin-induced diabetes mellitus rat related highly to the longitudinal change of the continuous mechanical pressure exerted through the denture base. From the results of this study, it was suggested that the streptozotocin-induced diabetic condition lowers the tolerance of the denture-supporting tissues to continuous mechanical pressure.

Animals↗

PubMed1999

The effect of diabetes mellitus on histopathological changes in the tissues under denture base bearing masticatory pressure.

The effect of streptozotocin-induced diabetes mellitus on histopathological changes in tissues bearing masticatory pressure exerted through an experimental denture base has been studied in animal specimens. Experimental dentures, which prescribed the masticatory pressure by the amount of subsidence of the denture base (100, 50 or 13 microm), were constructed for the hard palate of the molar regions of rats. It was revealed that streptozotocin-induced diabetes mellitus (1) weakened the intercellular junctions in the epithelium and gradually enhanced this state with time, (2) lessened the atrophic and proliferative reactions in the epithelial ridge and prolonged their appearance period, (3) enhanced the compression of lamina propria mucosae and prolonged the appearance period of this reaction, (4) enhanced the inflammatory change and extended its appearance period, (5) lowered the threshold for the inflammatory reaction induced by the masticatory pressure, (6) increased the number of osteoclasts and prolonged the period of their presence, (7) lowered the threshold for osteoclastic bone resorption induced by the masticatory pressure, (8) inhibited the appearance of osteoblasts following the disappearance of osteoclasts and (9) accelerated the decline rate of masticatory pressure exerted to the denture supporting tissues. Therefore, it can be concluded that the streptozotocin-induced diabetes mellitus in the animals tested deteriorated the tolerance of the denture supporting tissues to masticatory pressure.

Alveolar Bone Loss↗

PubMed1999

Case of gonadoblastoma in a 9-year-old boy without physical abnormalities.

BACKGROUND: A 9-year-old boy was admitted to Jikei University Hospital complaining of gradual enlarging of the left scrotal contents. METHODS/RESULTS: Physical examination was significant for bilateral descended testicles. No abnormalities were detected in the testicles or along the spermatic cords. Scrotal ultrasound showed that hyperechoic shadows were recognized in the central area of the left testicle. Subsequent testicular biopsy and histopathological examination showed intratubular malignant germ cells in the testicular tubules. One week later, left orchiectomy was performed. CONCLUSIONS: Histopathological evaluation revealed gonadoblastoma. Gonadoblastoma, a rare gonadal neoplasm, is composed of germ cells and sex cord derivatives and usually occurs in phenotypically female patients with gonadal dysgenesis. To date, only three cases of gonadoblastoma have been reported in anatomically normal male patients with scrotal testicles. We report on a case of gonadoblastoma unaccompanied by a germ cell tumor in a physically normal male.

Child↗

PubMed1999

[Usefulness of percutaneous sclerosing treatment for low-flow vascular lesions].

Peripheral vascular lesions may occur as a result of various clinical problems, cosmetic or dysfunctional causes, or bleeding. In severe cases, coagulopathy and congestive heart failure may occur. Although the efficacy of transarterial embolization (TAE) for arterial vascular lesions is well known, TAE has no effect on low-flow vascular lesions (venous malformations, venous angiomas, and venous components of arteriovenous malformation). Therefore, in such cases, a percutaneous approach is the best method, and we consider sclerotherapy to be the most useful conservative treatment. The primary objective of this study was to confirm the efficacy of percutaneous sclerosing treatment for peripheral low-flow vascular lesions. Lesions were classified on the basis of state of blood flow and morphologic features, and infiltration was classified on the basis of angiographic features and magnetic resonance imaging (MRI) findings. In sclerosing treatment, we used 5% solutions of polidocanol, absolute ethanol, and N-butyl-2-cyanoacrylate (NBCA) as sclerosing agents. Each type of lesion, static or slow-flow, cystic, or localized, showed remarkable improvement after sclerosing treatment with only polidocanol. However, for moderate-to-fast-flow lesions, another sclerosing agent (absolute ethanol/NBCA) was needed. With diffuse infiltrative lesions, surgical repair might be needed, but we recognize the usefulness of sclerosing treatment for functional or cosmetic improvement in these cases.

Adolescent↗

PubMed1999

3D-pharmacophore analyses of aldose reductase inhibitory spiroquinazolinones.

In order to get an insight for designing novel inhibitors of aldose reductase, we analyzed relationships between structures of spiroquinazolinones and their inhibitory activities against rabbit aldose reductase by comparative molecular field analysis and molecular modeling of the enzyme-inhibitor complex. It was revealed that the following interactions were operative for the enhancement of inhibitory activity; 1) the hydrophobic interaction between substituents at the 6'- and 7'-position of quinazolinone and the hydrophobic residues such as Trp20, Val47, Tyr48, Tyr121 and Phe122; 2) the electrostatic interaction formed between electronegative substituents at the 6'-position and the side chain of Gln49; 3) the complementary fit of sterically small 6'-substituents to the active site.

Aldehyde Reductase↗

PubMed1999

[Experimental study of intraarterial injection of polidocanol as an embolic agent].

The treatment of hemangiomas and vascular malformations in the soft tissue presents several difficult problems. Transarterial embolization and/or percutaneous sclerosing therapy are useful for such lesions, but the effectiveness of these therapies is often partial, and serious problems like ulceration and tissue necrosis may occur. Therefore, we examined the efficacy of intraarterial injection of polidocanol solution as an embolic agent for hemangiomas and vascular malformations using the rabbit kidney. Three embolic agents were compared with polidocanol solution (polidocanol 3%, n = 5; absolute ethanol, n = 5; n-butyl-2 cyanoacrylate: NBCA, n = 5; polyvinyl alcohol: PVA, n = 5). All embolizations were followed by angiography and resection after a week. Results showed that absolute ethanol (n = 5), NBCA (n = 4) and PVA (n = 1) embolized completely. In the specimens, this led to cell necrosis throughout the kidney. In contrast, polidocanol (n = 5) obstructed neither the main trunk of the renal artery nor the peripheral capillary arteries following angiography. In the specimens, the inner medulla of the kidney suffered necrosis. However, residual tissue with massive fibrotic change was seen. These results suggest the efficacy of "embolosclerosing" treatment for capillary vascular lesions and the possibility of alleviating complications from such therapy.

Animals↗

PubMed1998

Conformational sampling of CDR-H3 in antibodies by multicanonical molecular dynamics simulation.

The diversity in the lengths and the amino acid sequences of the third complementarity determining region of the antibody heavy chain (CDR-H3) has made it difficult to establish a relationship between the sequences and the tertiary structures, in contrast to the other CDRs, which are classified by their canonical structures. Enhanced conformational sampling of two different CDR-H3s was performed by multicanonical molecular dynamics (multicanonical MD) simulation while restricting the base structures, with and without the other surrounding CDR segments. The results showed that the multicanonical MD sampled a much larger conformational space than the conventional MD, independent of the initial conformations of the simulations. When the other CDRs surrounding the CDR-H3 segments were included in the calculations, the predominant conformations at 300 K corresponded to the X-ray crystal structures. When only the single CDR-H3 loops were considered with the restricted base structures, a greater number of different conformations were sampled as putative loops, but only a small number of stable conformations appeared at 300 K. Analyses of the resultant conformations revealed a structural role for the glycine, when it is located at position three residues before the last residue of CDR-H3 (Gly-X-X-last residue), coincident with the statistical tendencies of many antibody crystal structures. This reflects the general consistency between the energetically stable conformations and the empirically observed conformations. The current method is expected to be applicable to the structural modeling and the design of antibodies, especially for the inherently flexible loops.

Algorithms↗

PubMed1998

The effect of diabetes mellitus on histopathological changes in the tissues under denture base and without mechanical pressure.

Histopathological changes in the tissues under a denture base were studied with respect to the difference between diabetic and normal rats. Diabetes mellitus was induced in Wistar rats by streptozotocin. The experimental denture base was designed to make contact with the palatal mucosa without any continuous nor masticatory pressure. Histopathological observation periods were 1, 2, 4, 8, 12 and 20 weeks after the insertion of the denture base. Histopathological examination revealed that only the transient slight proliferative reaction observed in mucosal epithelium under a denture base in normal non-diabetic rats, was lessened by induced diabetes mellitus. Moreover, covering the palatal mucosa with a denture base without any continuous nor masticatory pressure and with the maintenance of mucosal cleanliness under it and of the denture itself, did not cause any inflammatory change or bone resorption in the tissues under the base.

Acrylic Resins↗

PubMed1998

Isolation of anti-glutathione antibodies from a phage display library.

We have isolated anti-glutathione antibodies from a human synthetic phage antibody scFv library (Nissim,A., Hoogenboom,H.R., Tomlinson,I.M., Flynn,G., Midgley,C., Lane,D. and Winter,G., 1994, EMBO J., 13, 692-698). Glutathione (GSH) conjugates with carrier proteins, such as bovine serum albumin (BSA), keyhole limpet hemocyanin (KLH) and human lysozyme (LZM), were used as antigens. After four cycles of panning and affinity chromatography, clones that recognized GSH-conjugated proteins, but not BSA, KLH or LZM, were isolated. The isolated phage antibodies and the soluble scFv fragments were characterized by immunoblotting, and the nucleotide sequences of the VH segments of selected clones were determined. The binding of several isolates to GSH-BSA was competitively inhibited by GSH in an ELISA. These observations have demonstrated that antibodies against GSH, a tripeptide, can be isolated from the library. We constructed the tertiary models of several scFv fragments and discussed the mechanism of antigen binding sites.

Antibodies, Viral↗

PubMed1998

Threshold for bone resorption induced by continuous and intermittent pressure in the rat hard palate.

Osteoclastic bone resorption under the denture base has been considered to be influenced by mechanical force exerted through the denture base. However, no scientific evidence has been shown concerning whether osteoclastic bone resorption is a pressure-threshold-regulated phenomenon or merely a proportionally pressure-dependent phenomenon. In this study, a clear statistical criterion as an objective standard for the evaluation of histopathological bone resorption was established, and the relationship between the amount of continuous or intermittent compressive pressure exerted on the rat hard palate and induced osteoclastic bone resorption was studied based on this criterion. Eighty-five male rats of the Wistar strain, 15 weeks of age, were fitted with experimental dentures which were designed to exert a defined amount of continuous or intermittent compressive pressure on the intermolar region of the hard palate. No bone resorption was observed when continuous compressive pressure was < or = 1.96 kPa or when intermittent compressive pressure was < or = 9.8 kPa. In contrast, continuous compressive pressure > or = 6.86 kPa or intermittent compressive pressure > or = 19.6 kPa caused significant bone resorption in all rats studied. From these results, it was revealed that osteoclastic bone resorption under the denture base was a pressure-threshold-regulated phenomenon, and that the thresholds exist for the induction of bone resorption under the denture base by both continuous and intermittent compressive pressure, respectively. It was also clearly revealed from the results that the threshold for continuous compressive pressure is lower than that for intermittent compressive pressure.

Animals↗

PubMed1997

Organogels Formed by N-Benzyloxycarbonyl-l-alanine 4-Hexadecanoyl-2-nitrophenyl Ester and Related Compounds

Organogels of low molecular weight compounds, N-benzyloxycarbonyl-l-alanine 4-hexadecanoyl-2-nitrophenyl ester (BLAHN) and related compounds, in methanol and cyclohexane solvents were studied by FT-IR, circular dichroism (CD), transmission electron microscope (TEM), and scanning electron microscope (SEM). The gels exhibited a thermally reversible sol-to-gel phase transition, which gave the thermodynamic parameters for the transition. The FT-IR spectroscopic results suggested that the intermolecular hydrogen bonding between N-H and C=O of urethane bond played a vital role in gelation. The aggregates for gelation were mainly assembled by pi-pi interaction, dipole-dipole interaction, and the hydrophobic interaction as well as hydrogen bonding for BLAHN. The comparison of CD spectra of BLAHN, N-benzyloxycarbonyl-d-alanine 4-hexadecanoyl-2-nitrophenyl ester (BDAHN), and related molecules indicated that the self-aggregation of gelator molecules gradually proceeds and the component molecules are cooperatively organized to form a chiral aggregate. The three-dimensional interlocking structures and tree-branched structures responsible for the immobilization of fluid were observed by TEM and SEM. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗

PubMed1997

A domain for G protein coupling in carboxyl-terminal tail of rat angiotensin II receptor type 1A.

To delineate domains essential for Gq protein coupling in the C-terminal region (C-tail) of rat angiotensin II (Ang II) receptor type 1A (AT1A), we modified the putative cytosolic regions of the receptor by truncation or alanine substitution and determined resultant changes in the guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) effect on Ang II binding and inositol trisphosphate production by the agonist. Independently, we studied the effect of synthetic C-tail peptides (P-5) and its alanine substitution analogs on [35S]GTPgammaS binding to Gq. Effects of GTPgammaS on Ang II binding (shift to a low affinity form) and inositol trisphosphate production in the deletional mutant receptor 1-317 AT1A was similar to wild type AT1A, whereas in shorter C-terminal deletion mutants 1-309, 1-311, 1-312, 1-313 AT1A, and substitutional mutants Y312A, F313A, and L314A these activities were markedly reduced. The binding of [35S]GTPgammaS to Gq was promoted by the synthetic C-terminal peptide P-5 but not when mutated at Tyr312, Phe313, or Leu314. Results indicate that Tyr312, Phe313, and Leu314 in cytosolic carboxyl-terminal region of rat AT1A are essential for coupling and activation of Gq.

Amino Acid Sequence↗

PubMed1997

Enhanced induction of apoptosis of human gastric carcinoma cells after preoperative treatment with 5-fluorouracil.

BACKGROUND: It has been reported that anticancer drugs induce apoptosis, thus it is considered that apoptosis may be important in cancer chemotherapy. The authors examined whether the administration of 5-fluorouracil (5-FU) enhanced apoptosis of gastric carcinoma cells, and investigated the relationship between apoptosis and the expression of Ki-67 and the Bax gene. METHODS: Twenty patients with gastric carcinoma were divided into 2 groups. Ten patients received continuous intravenous 5-FU at 500 mg/body weight/day for 7 days preoperatively whereas the other 10 did not receive any chemotherapy or radiotherapy, and served as controls. For detection of apoptotic cells, apoptotic indices were examined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling (TUNEL) method. The expression of Ki-67 and the Bax gene were examined by immunohistochemical staining. RESULTS: Apoptosis of gastric carcinoma cells increased significantly to 6.1 +/- 3.6% in the 5-FU-treated group compared with the controls (3.2 +/- 1.8%; P < 0.05). The level of expression of Ki-67, a marker of cell proliferation, was inversely correlated with the extent of TUNEL staining that was specific for apoptosis. The percentage of cells that were immunopositive for Ki-67 fell to 50.8 +/- 7.3% of the apoptotic area in the 5-FU-treated group compared with 57.5 +/- 6.9% in the controls (P < 0.05). There was no significant correlation between frequency of apoptotic cells and the level of expression of the Bax gene. CONCLUSIONS: The authors demonstrated enhanced apoptosis in gastric tumors after continuous intravenous infusion of 5-FU for 7 days. This result suggests that it may be possible to evaluate the effects of chemotherapy by detecting apoptotic cells.

Antimetabolites, Antineoplastic↗

PubMed1997

MRI in carcinomatous encephalitis.

We report a rare case of miliary brain metastases presenting with symptoms similar to encephalitis ("carcinomatous encephalitis"). Contrast-enhanced MRI demonstrated miliary metastases more distinctly than other imaging methods and reproduced the pathological features.

Adenocarcinoma↗

PubMed1997

Appropriate osteotomy site and number in limb lengthening.

The effects of the placement of osteotomy site on osteogenesis during monofocal and bifocal lengthening were investigated in 47 immature rabbits allocated to 4 groups according to osteotomy site: (1) monofocal in the proximal diaphysis; (2) monofocal in the distal diaphysis; (3) bifocal in the proximal and distal diaphysis; and (4) bifocal in the proximal diaphysis. The right tibia was distracted at an overall rate of 1.0 mm per day for 15 days. These groups were compared by assessment of soft radiograph findings and torsional strength 2 and 6 weeks after the end of distraction. Microangiography was done in 5 rabbits in the bifocal proximal and distal group. The proximal distracted site showed favorable bone regeneration compared with the distal site, and torsional strength was significantly greater in the proximal than in the distal osteotomy group. Less bone formation and lower torsional strength were observed in the bifocal proximal diaphysis group, with short intermediate segment, than that in the other bifocal group, with long intermediate segment. The nutrient artery in the latter group was preserved in the intermediate segment and reanastomosed to the metaphyseal arteries. These results suggest that the proximal diaphysis is more suitable for the osteotomy site than is the distal diaphysis. In a 2-level osteotomy, the inflow site of the nutrient artery should be included within the intermediate segment.

Animals↗

PubMed1997

[Intraoperative interstitial microwave therapy for recurrent hepatocellular carcinoma of the caudate lobe: a case report].

Microwave tissue coagulation (MTC) therapy was given patients with recurrent hepatocellular carcinoma (HCC) of the caudate lobe of the liver, in which radical surgery for deteriorated liver function was impossible. A total of 40 MTC sessions was applied to two tumors under laparotomy. MTC was administered for 20 seconds in each session. Microwave energy output was 70 watts for 15 mm needle-electrodes and 100 watts for 30 mm electrodes. Alpha-fetoprotein levels in serum had decreased after surgery. Abdominal computed tomography showed no blood flow whatsoever in tumors undergoing MTC. There are fewer limits to the sites and angles for insertion of electrodes under laparotomy. Thus, the surgical approach provides access to all parts of the liver for treatment. We conclude that intraoperative MTC is highly effective in tumor necrosis, and can be a useful local treatment for nonresectable HCC.

Carcinoma, Hepatocellular↗

PubMed1997

[An increase in cerebrospinal fluid ubiquitin in human global brain ischemia--a prognostic marker for anoxic-ischemic encephalopathy].

The prognostic value of ubiquitin levels in cerebrospinal fluid (CSF) was studied in human global brain ischemia (anoxic-ischemic encephalopathy). Twenty four samples were collected from 13 patients who were resuscitated from cardio-pulmonary arrest and survived for at least 1 day. The outcome was classified according to the Glasgow Outcome Scale (GOS1-5). The ubiquitin levels (normal: 14.3 +/- 1.1 ng/ml, mean +/- S.E.M.) in neurologically symptomatic patients (GOS1-4) were 151 +/- 32.5 ng/ml on day 1-2 and elevated to 1,960 +/- 849 ng/ml on day 3-4. The Spearman's rank correlation of ubiquitin levels on day 3-4 and the GOS was -0.855, showing a better correlation than CSF neuron-specific enolase levels (r = -0.846). Ubiquitin is a heat shock protein associated with the degradation of abnormal cellular proteins. Thus, the elevation of CSF ubiquitin levels represents both its overproduction by a cytoprotective response to brain ischemia and its leakage from the damaged tissue. The present study suggests that the measurement of CSF ubiquitin level is useful for the early prognostic assessment of global brain ischemia.

Adult↗