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T Hara

Publications and source records attributed to T Hara.

At least 469 records · Page 26Linked to original sources

Hydroxyapatite-coating on titanium arc sprayed titanium implants.

We developed a new titanium spray technique using an inert gas shielded arc spray (titanium arc spray). Hydroxyapatite (HA)-coating can be applied to the implant without any surface pore obstruction after the rough surface is made by this technique. Scanning electron microscopy (SEM) of various porous implant surfaces after HA-coating revealed that the bead and fiber metal-coated implants had either a pore obstruction or an uneven HA-coating. On the other hand, the titanium arc sprayed implant demonstrated an even HA-coating all the way to the bottom of the surface pore. In the first set of animal experiments (Exp. 1), the interfacial shear strength to bone of four kinds of cylindrical Ti-6A1-4V (Ti) implants were compared using a canine transcortical push-out model 4 and 12 weeks after implantation. The implant surfaces were roughened by titanium arc spray (group A-C) and sand blasting (group D) to four different degrees (roughness average, Ra = group A: 56.1, B: 44.9, C: 28.3, D: 3.7 microns). The interfacial shear strength increased in a surface roughness-dependent manner at both time periods. However, the roughest implants (group A) showed some failed regions in the sprayed layers after pushout test. In the second set of animal experiments (Exp. 2), four kinds of Ti implants; HA-coated smooth Ti (sHA) with Ra of 3.4 microns, bead-coated Ti (Beads), titanium arc sprayed Ti (Ti-spray) with Ra of 38.1 microns and HA-coated Ti-spray (HA + Ti-spray) with Ra of 28.3 microns were compared using the same model as that in Exp. 1. The interfacial shear strength of HA + Ti-spray was significantly greater than that of sHA and Beads at both time periods, and that of Ti-spray at 4 weeks. Although a histological examination revealed that HA-coating enhanced bone ingrowth, sHA showed the lowest shear strength at both time periods. SEM after pushout test showed that sHA consistently demonstrated some regional failure at the HA-implant substrate interface. HA + Ti-spray had many failed regions either at the HA-bone interface or within the bone tissue rather than at the HA-implant substrate interface. These results suggested that the HA-coated smooth surfaced implants had a mechanical weakness at the HA-substrate interface. Therefore, HA should be coated on the rough surfaced implants to avoid a detachment of the HA-coating layer from the substrate and thus obtain a mechanical anchoring strength to bone. HA-coating on this new type of surface morphology may thus lead to a solution to the problems of conventional HA-coated and porous-coated implants.

Alloys↗

Effect of an aldose reductase inhibitor on abnormalities of electroretinogram and vascular factors in diabetic rats.

The effect of an aldose reductase inhibitor, [5-(3-thienyl) tetrazol-1-yl] acetic acid (TAT), on the electroretinogram was determined in rats with streptozotocin-induced diabetes. Laboratory chow containing 0.05% TAT was given to rats for 2 months, while other diabetic rats were untreated. Groups of TAT-treated and untreated normal rats were also studied. Treatment with TAT produced significant improvement of the electroretinogram. TAT shortened the peak latencies of the b-wave oscillatory potentials, which were significantly prolonged in untreated diabetic rats (P < 0.0001 vs. untreated normal rats). This was accompanied by a significant decrease in the retinal sorbitol and fructose concentrations (by 46.5% and 25.7%, respectively). TAT treatment of diabetic rats also markedly reduced ADP-induced platelet aggregation and significantly increased the red blood cell 2,3-diphosphoglycerate level, accompanied by a marked reduction in sorbitol and fructose concentrations of platelet and red blood cells. There were significant correlations between the summed b-wave peak latencies and platelet aggregation or the 2,3-diphosphoglycerate level in diabetic rats. These findings suggest that an aldose reductase inhibitor, TAT, has therapeutic value for diabetic retinopathy.

2,3-Diphosphoglycerate↗

An experimental study of a combination method using a pedicle screw and laminar hook for the osteoporotic spine.

STUDY DESIGN: Using human cadaver spines, the authors compared the effect of using a combination of pedicle screw and laminar hook on the same vertebra with that of using a pedicle screw alone in reference to bone mineral density of the vertebra under nondestructive cyclic loading. OBJECTIVES: To quantify stiffness obtained by pedicle screw alone and by the combination method and to clarify a relationship between stiffness obtained by each instrumentation method and bone mineral density of the vertebra. SUMMARY OF BACKGROUND DATA: The use of pedicle screws apparently improves the union rate of spinal fusion. Instrumentation failures sometimes occur, however, such as loosening or loss of correction of the spine, especially in patients with osteoporosis. Some augmentation method in instrumentation is necessary to overcome bone fragility in the osteoporotic spine. METHODS: Thirteen cadaver lumbar vertebrae were used for this study. Bone mineral density was measured by dual-energy X-ray absorptiometer. After separating each vertebrae, the pedicle screw was screwed into a vertebra. Five cycles of cephalocaudal loading were performed to the shank of the screw with a cross-head speed of 3 mm/min under a maximum load control of 29.4 N using an Instron type testing machine, and the stiffness obtained with the pedicle screw (Kj) was calculated from the load-deformation curve. Then, a laminar hook was set and connected to the screw via a rod. Mechanical testing was performed in the same way, and the stiffness obtained with the combination method (Kf) was determined. Kj and Kf were compared using the paired t test. The relationship between Kj, Kf, or the stiffness improvement ratio ([Kf-Kj]/Kj) by the combination method and bone mineral density was analyzed by linear regression analysis. RESULTS: Stiffness obtained by the combination method was significantly greater than that obtained by pedicle screw alone (89.8 +/- 35.0 N/mm by the combination method, 60.2 +/- 19.6 N/mm by pedicle screwing alone; P < 0.0001). Stiffness, whether obtained by pedicle screw alone or by the combination method, was positively correlated with bone mineral density (with pedicle screw alone, R2 = 0.614, P < 0.0001; with the combination method, R2 = 0.645, P < 0.0001). However, there was no significant correlation between stiffness improvement ratio and bone mineral density. CONCLUSION: Instrumentation stiffness obtained by the combination method was significantly greater than that obtained by the use of pedicle screw alone. There was no significant correlation between the improvement ratio by the combination method and bone mineral density. These results suggest that the combination method is valuable irrespective of the presence of spinal osteoporosis.

Aged↗

Site-directed mutagenesis of active site contact residues in a hydrolytic abzyme: evidence for an essential histidine involved in transition state stabilization.

Specific molecular interactions involved in catalysis by antibody 6D9 were investigated by site-directed mutagenesis. The catalytic antibody 6D9, which was generated against a transition state analog (III), hydrolyzes a non-bioactive chloramphenicol monoester derivative (I) to produce chloramphenicol (II). Construction of a three-dimensional molecular model of 6D9 and sequence comparison within a panel of related antibodies suggested candidates for catalytic residues, His (L27d), Tyr (L32), Tyr (H58) and Arg (H100b); these were targeted for the site-directed mutagenesis study. The Y-H58-F and R-H100b-A mutants possessed catalytic activities comparable to that of the wild-type, and the Y-H58-H and Y-L32-F mutant displayed an approximately fivefold decrease in k(cat)/Km. In the transition state analysis, the plots of logK(TSA) versus log(k(cat)/Km) for the mutants are linear, with a slope of approximately 1.0, indicating that the entire hapten-binding energy in the mutants is also utilized to bind the transition state and to accelerate the catalysis. In addition, a dramatic change in the catalytic activity was observed when the histidine residue (27d) in the CDR1 light chain was replaced with alanine. The H-L27d-A mutant had no detectable catalytic activity. This mutation led to a large, 40-fold reduction in transition state binding, with no change in substrate binding. Coupled with the previous kinetic studies and chemical modifications of the intact 6D9 antibody, this mutagenesis study has demonstrated that His L27d plays an essential role in stabilization of the transition state, the mechanism of catalysis by the 6D9 antibody.

Amino Acid Sequence↗

Involvement of a common 10-amino-acid segment in the cytoplasmic region of CD40 but different MAP kinases in different CD40-mediated responses.

CD40-mediated signals can induce cell aggregation, proliferation and rescue from apoptosis in WEHI231. To define which segment of cytoplasmic domain of CD40 and how signals are involved in those events, we generated mutant CD40 transfectants. We demonstrated the same 10 amino acid segment that could bind to tumor necrosis factor receptor associated factor-2 and -3 mediated all those responses. However, activation pattern of mitogen activated protein kinases was different. Immunoglobulin M-mediated apoptosis was inhibited by CD40-mediated signal that activated c-Jun aminoterminal kinase synergistically. While, CD40 stimulus through the 10 amino acid segment alone that induced cell aggregation and proliferation resulted in activation of extracellular signal-regulated protein kinase 2.

Amino Acid Sequence↗

p53 induced by ionizing radiation mediates DNA end-jointing activity, but not apoptosis of thyroid cells.

To understand the effects of ionizing radiation on thyroid cells, we investigated the role of p53 in mediating apoptosis and in DNA repair following in vivo and in vitro irradiation of thyroid cells. In vitro exposure of human thyroid cells to ionizing radiation of up to 5-8 Gy failed to induce apoptosis in primary cells. The same results were obtained when the thyroid gland was irradiated in the intact rat. To explore the mechanism of failure of the wild-type p53 in inducing apoptosis in thyroid cells, we investigated the expression of apoptosis-related genes, bax, bcl-2 and fas/APO-1 following irradiation or induction of temperature-sensitive p53. The expression of Bax, Bcl-2 and Fas/APO-1 in human primary cultured thyroid cells did not change after irradiation. To further confirm the results, we established a clonal cell line (tsFRO) in which a temperature sensitive p53 (Val138) expression vector was stably transfected to a thyroid carcinoma cell line lacking endogenous p53. Incubation of tsFRO cells at the permissive temperature for three days, however, did not induce apoptosis although G1 arrest was noted. Although enhanced expression of the bax mRNA level was observed, the expression of Bax, Bcl-2 and Fas/APO-1 protein did not change by shifting tsFRO cells to permissive temperature as well as irradiated primary cells. Furthermore, DNA end-jointing ability was examined by transfection of linearized luciferase plasmid into tsFRO cells. Increased luciferase activity occurred when the cells were cultured at the permissive temperature, indicating that the wild-type p53 enhances DNA end-jointing activity. Our results indicate that the wild-type p53 does not lead to apoptosis but facilitates DNA end-jointing in thyroid cells. These results may reflect specific responses in thyroid cells following irradiation.

Animals↗

Abnormal expansion of peripheral gamma delta T cells in patients with neurologic disorders.

The proportions and the variable region usages of peripheral gamma delta T cells were investigated in 205 patients with various neurologic disorders. Flow cytometric analysis was performed with monoclonal antibodies against C delta, V delta 1, V delta 2. V delta 1-J delta 1/J delta 2, and V gamma II (9) epitopes. Further analysis was carried out with reverse transcription-polymerase chain reaction (RT-PCR) using variable region-specific primers. The proportion of gamma delta T cells in 33 patients with cerebral palsy (CP) (mean +/- SD; 11.1 +/- 11.0%) was significantly higher than that in 35 normal controls (5.6 +/- 2.6%) (p < .01). Of 205 patients, persistent gamma delta T cell expansion over 15% was observed in 15 patients (M/F = 13/2). Nine of these 15 were patients with CP. Six of the 9 with CP had neither perinatal nor postnatal events related to the neurologic abnormalities. None of the 9 with CP had active infections or autoimmune disorders that could induce gamma delta T cell expansion. Of the 15, 13 had V gamma II/V delta 2-dominant expansion and 2 showed V delta 1-dominant expansion. Unusual expansions of V delta 4 and V delta 6, which were not usually found in peripheral blood, were detected by RT-PCR in one case with CP and V delta 1-dominant expansion. This study showed subclinical immunologic abnormalities with marked and persistent gamma delta T cell expansion in patients with neurologic disorders, especially CP. These results might indicate the existence of neuroimmunologic disorder(s).

Adolescent↗

Primary malignant fibrous histiocytoma of the descending colon.

We herein present the case of a 50-year-old woman with malignant fibrous histiocytoma arising from the descending colon and localizing in the colonic wall. Malignant fibrous histiocytoma of the large bowel is a very rare tumor. A total of 18 cases, including our case, have been reported in the world medical literature so far and we also reviewed these cases. In our case, combined adjuvant chemotherapy was administered after a complete resection had been performed. No clinical signs of local recurrence or distant metastasis were found at 7 years after the operation.

Antineoplastic Combined Chemotherapy Protocols↗

A morphometric comparison of trabecular structure of human ilium between microcomputed tomography and conventional histomorphometry.

Recently, an imaging technique using microcomputed tomography (micro-CT) has emerged as a method for nondestructively assessing the microarchitecture of unprocessed surgical bone biopsy specimens. Using micro-CT, two-dimensional (2D) axial images were obtained from undecalcified transiliac bone biopsies which were taken from 15 patients with various metabolic bone diseases. Total area, bone area, and bone perimeter were determined, from which the bone volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp) were calculated semiautomatically and instantaneously. To evaluate the validity of this technique as a useful tool, the results were compared with those obtained from conventional histomorphometry. There were significant correlations between the two techniques for all parameters, with correlation coefficients ranging from 0.759 (Tb.N, P < 0.005) to 0.949 (BV/TV, P < 0.0001). Different resolutions seem to lead to major differences in perimeter values measured by the two methods. These factors may explain why the correlation coefficients of Tb.N and Tb.Th estimated from the perimeter and area is lower than that of BV/TV. Our results show that the micro-CT based on 2D images is a useful tool for imaging and nondestructively quantifying the microarchitecture of trabecular bone in unprocessed surgical bone specimens.

Adult↗

Possible association of infertility with sperm-specific abnormality of CD46.

Three infertile patients fulfilling normal or subnormal criteria on routine semen analysis showed abnormal sperm CD46 (membrane cofactor protein of complement) by SDS-PAGE/immunoblotting analysis using a panel of monoclonal antibodies. The sperm CD46 isoform has been reported to be associated with sperm-egg interaction. These three patients expressed normal CD46 isoforms on their lymphocytes and granulocytes. Sperm-specific abnormalities in these proteins thus parallel male infertility, suggesting a new category of infertility, probably due to aberrations in the molecules related to sperm-egg interaction.

Acrosome↗

Intracranial calcifications, epilepsy, and optic atrophy associated with metaphyseal dysplasia: a case report.

A 15-year-old boy presenting with epilepsy, optic atrophy and intracranial calcifications was diagnosed as having metaphyseal dysplasia by bone X-ray examinations. The patient had no laboratory data suggesting other metabolic or endocrinologic disorders. In addition, CT scans showed unique intracranial calcifications of the corpus callosum and periventricular and subcortical white matter, which were distinct from those of previously reported disorders. This case may represent a unique subset or a new type of metaphyseal dysplasia associated with intracranial calcifications and central nervous system symptoms.

Adolescent↗

Time resolved study of effect of chlorpromazine on mobility of cytochrome P-450 and phospholipids in the inner membrane of adrenocortical mitochondria.

The effects of chlorpromazine on the mobility of cytochrome P-450 and the fluidity of lipid membranes have been investigated in bovine adrenocortical submitochondrial particles (SMP). Rotational diffusion of the cytochrome was measured by observing the decay of absorption anisotropy, ra(t), after photolysis of the heme.CO complex by a vertically polarized laser flash. Analysis of ra(t) was based on a 'rotation-about-membrane-normal' model. The anisotropy decayed within 2 ms to a time independent value r3. The presence of chlorpromazine decreased the mobile population of cytochrome P-450 from 28 to 23%. The rotational relaxation time phi a of the mobile population (approximately 1100 microseconds) was, however, not significantly changed by chlorpromazine. The lipid fluidity was examined by observing time-resolved fluorescence anisotropy, rf(t), of 1,6-diphenyl 1,3,5-hexatriene (DPH). The anisotropy rf(t) decayed within 70 ns to a time independent value r infinity. The motion of DPH was analyzed based on a 'wobbling-in-cone' model. The presence of chlorpromazine decreased the cone angle from 42 degrees to 39 degrees, while the rotational relaxation time phi f (approximately 2 ns) was not significantly changed by the presence of chlorpromazine. These results demonstrate that chlorpromazine decreased the mobility of not only lipids but also membrane proteins.

Adrenal Cortex↗

Catecholamine and renin-angiotensin response during controlled hypotension induced by prostaglandin E1 combined with hemodilution during isoflurane anesthesia.

STUDY OBJECTIVE: To evaluate the catecholamine and renin-angiotensin response during controlled hypotension combined with hemodilution in the clinical setting. DESIGN: Randomized, prospective study. SETTING: Inpatient surgery at Nagasaki Rosai Hospital. PATIENTS: 30 ASA physical status I and II female patients scheduled for total hip arthroplasty. INTERVENTIONS: Patients were randomly divided into three groups. Group A (N = 10) received hemodilution alone. Group B (N = 10) received controlled hypotension alone. Group C (N = 10) received hemodilution plus controlled hypotension. Hemodilution was carried out after induction of anesthesia, in which drawn blood was replaced with 6% hydroxyethyl starch, and the final hematocrit value was approximately 22%. Controlled hypotension was induced with prostaglandin E1 (PGE1) to maintain mean arterial blood pressure at 55 mmHg for 80 minutes. MEASUREMENTS AND MAIN RESULTS: Measurements included plasma renin activity (RA) and plasma concentrations of angiotensin-II (AG-II), aldosterone (AS), norepinephrine (NE), and epinephrine (EP). These indices were measured before hemodilution, after hemodilution, 80 minutes after starting hypotension, and 60 minutes after recovery from hypotension. Hemodilution alone caused no significant change in the values throughout the time course. Controlled hypotension alone caused significant increases in plasma concentrations of NE (+295%) and EP (+203%) at 80 minutes after starting hypotension, whereas it caused no change in plasma RA and plasma concentrations of AG-II and AS. Hemodilution plus controlled hypotension caused significant increases in plasma RA (+271%) and plasma concentrations of AG-II (+188%), AS (+199%), NE (+279%), and EP (+184%) at 80 minutes after starting hypotension. CONCLUSION: The combination of hemodilution and PGE1 induced controlled hypotension causes significant responses, especially in a renin-angiotensin-aldosterone system under isoflurane anesthesia.

Aged↗

A novel protein that participates in nonself discrimination of malignant cells by homologous complement.

The human complement (C) system protects an individual against substances of nonself origin, including xenografts and microbial pathogens. Human cells express C-regulatory proteins, CD46 and CD55, thereby circumventing attack by C3, a major effector of C. Nevertheless, certain malignant cells, particularly those undergoing apoptotic stress, can activate homologous C, overcoming the regulatory actions of CD46 and/or CD55. The molecular mechanisms whereby malignant cells are tagged by homologous C3 remain largely unknown. We identified a novel gene product that converts human cells into targets for homologous complement. Only malignant cells and cell lines exposed to Fas or X-irradiation stimuli produced this protein, designated M161Ag, which was an unglycosylated 43-kDa protein. Analysis of cloned cDNAs indicated that this molecule was a secretory protein containing five amino acids encoded by TGA codons. Its functions were unique in that once secreted from the tumor cells, it bound back to the surface of these cells and activated homologous complement (C3) via the alternative pathway, allowing for C3 deposition on the membrane. This molecule may offer new insight into innate immunity; surveillance of tumor cells by complement is a common feature in the human immune system.

Amino Acid Sequence↗

Defective response to thrombopoietin and impaired expression of c-mpl mRNA of bone marrow cells in congenital amegakaryocytic thrombocytopenia.

Congenital amegakaryocytic thrombocytopenia (CAMT) is an uncommon disorder in newborns and infants, characterized by isolated thrombocytopenia and megakaryocytopenia in the first year without physical anomalies. The defect of thrombopoiesis is not well understood. Recently, thrombopoietin (TPO), the ligand for the c-mpl receptor, was cloned. Accumulating evidence from in vitro and in vivo studies indicate that TPO plays a key role in the regulation of megakaryocytopoiesis. In this study we examined the effect of TPO on megakaryocyte colony formation from a patient with CAMT using a plasma-containing methylcellulose clonal culture. The in vitro results demonstrated a defective response to TPO in megakaryocyte colony formation from bone marrow mononuclear cells (MNC) of the patient. although interleukin-3 (IL-3) but not stem cell factor (SCF) induced only a small number of megakaryocyte colonies. These findings indicated that thrombocytopenia in CAMT could not be corrected by administration of TPO in vitro. Additionally, clonal cultures containing SCF, IL-3, IL-6 and erythropoietin showed decreased numbers of erythroid and myelocytic progenitors in the bone marrow of the patient. The serum TPO level measured by enzyme-linked immunosorbent assay was significantly higher than that in healthy controls. By PCR, marrow MNC from healthy children and from a patient with essential thrombocytosis expressed c-mpl mRNA, whereas no c-mpl mRNA was detected in marrow MNC from the patient with CAMT. There was no difference in the CD34 expression and c-kit mRNA between the CAMT patient and healthy children. The results of this study suggest that the pathophysiology in CAMT may be a defective response to TPO in haemopoietic cells through impaired expression of c-mpl mRNA.

Bone Marrow↗

Effect of continuous pressure on histopathological changes in denture-supporting tissues.

The histopathological changes in denture-supporting tissues were studied in relation to continuous pressure exerted through an experimental denture base. The experimental dentures were designed to load continuous pressures (1.5, 3.4 or 4.9 kPa) to the palate of molar region of rat. Histopathological changes caused by the continuous pressure were observed, and the intensity of the pressure was also estimated. A high correlation was observed between the histopathological changes under the denture base and the intensity of the continuous pressure. In groups exposed to 4.9 and 3.4 kPa, the continuous mechanical pressure caused bone resorption; in 1.5 kPa group, no evidence of bone resorption was observed. The epithelium and lamina propria mucosa under the denture base, which were compressed by the continuous pressure, recovered histopathologically depending on the decrease of the pressure caused by bone resorption; no quantitative recovery of the absorbed bone tissue was observed. No inflammatory change was induced by the continuous pressure. From the histopathological results observed in this study, the possibility of the existence of a threshold for bone resorption induced by continuous pressure was suggested.

Acrylic Resins↗