Search PubMed⌕ Search

Biomedical subjects

T Hara

Publications and source records attributed to T Hara.

At least 541 records · Page 30Linked to original sources

Non-RGD domains of osteopontin promote cell adhesion without involving alpha v integrins.

Osteopontin (OPN) is an integrin-binding secreted protein that contains an Arg-Gly-Asp (RGD) amino acid sequence and binds to various cell types via RGD-mediated interaction with the alpha v beta 3 integrin. We have identified a cell line whose binding to OPN does not require RGD or alpha v interactions. We compared the ability of two murine cell lines, L929 fibroblastic cells and B16-BL6 melanoma cells, to interact with OPN (from human milk, and recombinant human and mouse OPN) as well as recombinant OPN prepared to include either the N-terminal or C-terminal halves but lacking the RGD sequence. Both cell lines adhered to GRGDS peptides coupled to BSA, and these interactions were inhibited by addition of GRGDS (but not GRGES) peptides or a monoclonal antibody specific to the alpha v integrin subunit. Adhesion of L929 cells to OPN was also dependent on the RGD sequence and the alpha v integrin subunit. However, the binding of B16-BL6 cells was not inhibited by either GRGDS peptides or the anti-alpha v antibody. B16-BL6 (but not L929) cells were also able to adhere to and spread on both N-terminal and C-terminal OPN proteins that lack the RGD sequence, and these interactions were not inhibited by either GRGDS peptides or anti-alpha v antibody. Together these results indicate that B16-BL6 cells can adhere to OPN by interactions that are independent of either the RGD sequence or the alpha v integrin subunit, and suggest that some cells can interact with additional, non-RGD binding sites in OPN.

Amino Acid Sequence↗

Function and signal transduction mediated by the interleukin 3 receptor system in hematopoiesis.

Interleukin 3 (IL-3) promotes development of hematopoietic cells through activation of the IL-3 receptor (IL-3R) complex consisting of alpha and beta subunits. The alpha subunit binds IL-3 with low affinity and forms a high-affinity receptor with the common beta subunit (beta c). The beta c subunit does not bind any cytokine by itself but is involved in the formation of high-affinity functional receptors for IL-5 and GM-CSF. As the alpha subunits provide the specificity to cytokines and beta c plays a major role in signal transduction, IL-3, GM-CSF and IL-5 exhibit similar functions when they act on the same cells. Surprisingly, no apparent hematological defect other than a reduced number of eosinophils was found in knock-out mice lacking an entire function of IL-3, GM-CSF and IL-5; this indicates a remarkable functional overlap with other cytokine systems for hematopoiesis. Binding of the cytokines to the receptor induces activation of the JAK2 tyrosine kinase that associates with beta c and triggers the signaling events. The membrane proximal region of beta c is responsible for activation of JAK2 and STAT5, as well as for induction of c-myc. The signals induced by this region are required for cell-cycle progression and DNA synthesis. Activation of the Ras pathway requires the distal region of beta c and is involved in the suppression of apoptosis. Proliferation of hematopoietic cells requires signals for both DNA synthesis and anti-apoptosis. In this review, we describe the recent findings of the function and signal transduction mediated by the IL-3R system.

Animals↗

Detection of chromosomal abnormalities of chromosome 12 in uterine leiomyoma using fluorescence in situ hybridization.

Fifty uterine leiomyomas were examined using conventional cytogenetic method and fluorescence in situ hybridization (FISH) for detection of chromosomal abnormalities of chromosome 12. Of the 50 tumors, nine were examined using FISH on the non-cultured samples. Two (4.0%) of 50 tumor samples examined showed chromosomal abnormalities of chromosome 12 by the conventional cytogenetic analysis. For FISH, the whole-chromosome painting probe and D12Z3 probe specific for the centromeric region were used. Of the 50 cultured samples, 10 showed structural aberrations and four showed numerical aberrations of chromosome 12 by FISH analysis. Of the nine non-cultured samples, four showed structural abnormalities of chromosome 12, all of which also showed structural abnormalities of chromosome 12 on the cultured samples. These results indicate that chromosomal abnormalities of chromosome 12 are important in the biology of at least some types of uterine leiomyoma, and that FISH is a useful complement to the conventional cytogenetic analysis in the study of solid tumors.

Chromosome Aberrations↗

The fertilizing ability of human epididymal sperm.

PURPOSE: Membrane cofactor protein (MCP), CD46, whose primary function is to protect host cells from homologous complement, has been presumed to serve as a sperm adhesion molecule for oocytes. The purpose of this study was to clarify the relationship between the properties of MCP expressed on epididymal sperm and their fertilizing ability in a recently developed strategy for assisted reproduction. METHODS: We collected ejaculated sperm from normal subjects and epididymal sperm from vasectomized subjects and patients with congenital absence of the vas deferens. Western blotting and cofactor activity assay were performed to investigated the structural and functional properties of MCP. RESULTS: Epididymal spermatozoa which showed a reduced fertilizing ability tended to react poorly with antibodies against MCP and also showed low cofactor activity, indicating weak complement regulatory activity compared to that of ejaculated spermatozoa. CONCLUSIONS: MCP is sufficiently expressed in ejaculated sperm in men with a normally developed epididymis but is diminished in epididymal sperm from men with congenital or acquired obstruction of the vas deferens.

Antigens, CD↗

Effects of propionyl-L-carnitine and insulin on the electroretinogram, nerve conduction and nerve blood flow in rats with streptozotocin-induced diabetes.

The effect of an analogue of L-carnitine, propionyl-L-carnitine, on the electroretinogram, motor nerve conduction velocity and nerve blood flow was determined in rats with streptozotocin-induced diabetes, and was compared with the effects of insulin alone or combined therapy. Oral administration of propionyl-L-carnitine (3 g/kg daily for 4 weeks) significantly increased caudal nerve motor conduction velocity and sciatic nerve blood flow in diabetic rats. There were no differences in the effects of insulin (8-10 U daily for 4 weeks), propionyl-L-carnitine and combined therapy. Although propionyl-L-carnitine significantly shortened the peak latency of the electroretinogram b-wave in diabetic rats, its effect was far weaker than that of insulin or combined therapy, with combined therapy producing the greatest improvement. These effects of propionyl-L-carnitine were accompanied by a decrease of serum lipid levels, an increase of the sciatic nerve carnitine content, and no changes of the tissue (nerve and retinal) sorbitol and myo-inositol concentrations. In contrast, insulin significantly reduced the tissue sorbitol content and markedly increased myo-inositol. These findings suggest that propionyl-L-carnitine may improve diabetic neuropathy and retinopathy without influencing the polyol pathway, and that this beneficial effect may be mediated through the amelioration of microcirculation and tissue carnitine content, thus probably increasing fatty acid oxidation.

Animals↗

Ampullary somatostatinoma in a patient with von Recklinghausen's disease.

We report a case of somatostatinoma of the ampulla of Vater associated with von Recklinghausen's disease in a 44-year-old woman. On admission the patient was jaundiced, and percutaneous Cholangio-drainage was performed. Cholangiography revealed stenosis of the common bile duct at the lower end Duodenoscopy showed a yellowish tumor of the ampulla of Vater, and the biopsy specimens showed no malignant cells. Pylorus-preserving pancreaticoduo-denectomy was performed. Histologically, the tumor was composed of small round cells with a solid or trabecular pattern and with multiple psammoma bodies. Immunohistochemical examination showed that the tumor cells stained for somatostatin. Genomic examination showed neither K-ras nor p53 gene mutations of the resected specimen.

Adult↗

A new method for theoretical analysis of static indentation test.

A new mathematical method was developed to study the indentation problem of an infinite elastic layer overlaid on a rigid foundation. Rigid, flat-ended cylindrical or spherical indenters are pressed onto the upper surface of the elastic layer causing a small deformation mode. Shear stresses between the indenter and the layer are assumed negligible and the layer is assumed to be either bonded or unbonded to the rigid foundation. The problem is equivalent to a mixed boundary-value problem of the theory of elasticity. Instead of using the Fredholm integral equation reported in the literature, the new approach obtained closed-form solutions through an infinite series. Convergence can be achieved using less than 10 terms of the series.

Algorithms↗

Soluble CD46 (membrane cofactor protein, MCP) in human reproductive tract fluids.

CD46 (membrane cofactor protein, MCP) is a cell surface complement regulatory protein which may have an additional role in human sperm-egg interaction. A soluble form (sCD46) has also been detected in a number of biological fluids, most notably seminal plasma. The present study has employed a monoclonal antibody-based ELISA to assay sCD46 in reproductive tract fluids in normal and pathological conditions. Large amounts of sCD46 were detected in seminal plasma of both fertile and infertile men (combined mean, 4859 ng/ml). Vasectomized men had lower levels (mean, 2421 ng/ml), indicating contributory sources both before and after the vas deferens ligation site. Pre-colostrum also contained relatively high quantities (mean, 445 ng/ml), whereas breast milk (mean, 117 ng/ml), peritoneal fluid (mean, 154 ng/ml) and follicular fluid (mean, 107 ng/ml), as well as uterine (mean, 208 ng/ml), umbilical (mean, 166 ng/ml) and peripheral (mean, 206 ng/ml) blood plasma, had sCD46 levels within a comparable range. Amniotic fluid had low sCD46 concentrations (mean, 22 ng/ml). In endometriosis, peritoneal fluid levels of sCD46 were significantly raised (mean, 199 mg/ml). These results indicate distinctive fluid compartmentalisation of sCD46 consistent with a biological function in human reproductive tract fluids.

Amniotic Fluid↗

Attenuation of cardiotoxicity of daunomycin using a complex with heparin.

Daunomycin (DM) is one of the most important antitumor agents. However, the cardiotoxicity of DM limits it's clinical use. We have made an ionic complex with heparin to decrease the cardiotoxicity. Cardiotoxicities of DM and DM-heparin complex were compared in hamsters. On the electrocardiogram (ECG), two of the four hamsters given DM showed the serious abnormality, bidirectional ventricular premature contraction, while the hamsters given DM-heparin or saline had no abnormalities. On pathological examination, cardiac tissue in hamsters given DM showed deposition of basophilic materials, mild eosinophilic change of myofibrils and microvascuolization, whereas no change was observed in hamsters given DM-heparin complex or saline. Acute toxic effects on survival rates and body weights were more profound in DM-infused mice than in DM-heparin-infused mice. DM and DM-heparin complex showed similar anticancer activity both in vivo and in vitro. Thus, the present study suggests that the DM-heparin complex may attenuate the cardiotoxicity of DM without affecting it's antitumor effect in humans.

Animals↗

Accommodation in primate eyes after implantation of refilled endocapsular balloon.

PURPOSE: To restore accommodation after crystalline lens removal. METHODS: The crystalline lens of one eye of each of four primates was removed by phacoemulsification. Each operated-on eye underwent endocapsular silicone balloon implantation followed by filling with an organosilicone mixture. Seven months postoperatively, the anterior chamber depth and refractive power changes were measured before and after topical application of 4% pilocarpine. RESULTS: In the refilled eyes, the average anterior chamber depth reduction was 0.50 mm and the average maximal myopic change was 6.74 diopters. CONCLUSION: After lens removal, measurable accommodation was restored in the eyes with the endocapsular balloon filled with an organosilicone mixture.

Accommodation, Ocular↗

Changes in bacterial strains before and after cataract surgery.

PURPOSE: To investigate the rate of contamination of conjunctival smears and anterior chamber aspirates at the conclusion of cataract surgery, and the relation between the types of bacterial strain in the conjunctival sac and anterior chamber at the conclusion of surgery and in preoperative samples from the conjunctival sac of the same eye. METHODS: The bacterial strains in conjunctival smears 1 week preoperatively and in conjunctival smears and anterior chamber aspirates at the conclusion of surgery from 58 consecutive eyes of 48 patients were examined. The patients underwent cataract surgery by phacoemulsification and aspiration followed by intraocular lens (IOL) implantation. All surgeries were broadcast simultaneously by closed-circuit television to the patients' families who were in a separate waiting room. RESULTS: At the conclusion of surgery, six eyes (10.3%) were contaminated: one anterior chamber aspirate (1.7%) and five conjunctival smears (8.6%). Only two (33%) of the six contaminated eyes at the conclusion of surgery had the same bacterial strain as the preoperative conjunctival smears. CONCLUSION: The percentage of culture-positive anterior chamber aspirates at the conclusion of phacoemulsification surgery and intraocular lens implantation was only 1.7%, despite a concurrent televised broadcast accompanied by an intraoperative microphone-transmitted explanation by the surgeon. Sixty-seven percent of the bacterial strains at the conclusion of surgery did not match those found preoperatively in the same eye.

Aged↗

Liposomal induction of a heat-stable macrophage priming factor to induce nitric oxide in response to LPS.

PURPOSE: The effects of liposomes on nitric oxide (NO) production from mouse peritoneal macrophages following intraperitoneal injection of liposomes were investigated. METHODS: Mouse peritoneal macrophages were collected following intraperitoneal injection of liposomes and cultured with and without lipopolysaccharide (LPS). Peritoneal washing fluid was also collected from the mice injected with liposomes. NO production was evaluated by measuring the concentration of nitrite in the macrophage culture supernatant by Griess reagent. RESULTS: NO production stimulated by LPS was observed in peritoneal macrophages obtained from the liposome-treated mice, but liposomes did not active macrophages directly to induce NO in response to LPS. NO production was higher in the liposomes composed of phosphatidylcholine than that of negatively charged liposomes composed of phosphatidylserine. Peritoneal washing fluid obtained from mice injected with liposomes has a capacity to induce NO production in the macrophages from naive mice. This capacity was not diminished by heat-treatment at 100 degrees C for 5 min. CONCLUSIONS: Peritoneal macrophages were activated to produce NO in response to LPS following intraperitoneal injection of liposomes. They did not activate macrophages directly, and the induction of heat-stable macrophage priming factor, but not cytokines, is suggested.

Animals↗

Third ventriculostomy for symptomatic syringomyelia using flexible endoscope: case report.

Using a flexible endoscope, we performed a third ventriculostomy to treat a patient with communicating syringomyelia accompanied by enlarged cerebral ventricles. Her clinical improvement was rapid and dramatic. Postoperative magnetic resonance scan demonstrated shrinkage of the cervical syrinx as well as the ventricles. This simple and safe flexible endoscopic third ventriculostomy could be a treatment of choice for communicating syringomyelia accompanied by enlarged cerebral ventricles.

Adult↗

Human UDP-galactose translocator: molecular cloning of a complementary DNA that complements the genetic defect of a mutant cell line deficient in UDP-galactose translocator.

We have cloned a cDNA that codes for a putative human UDP-galactose translocator (UGT) protein. The cDNA contained an open reading frame of 1,179 base pairs encoding a novel protein of 393 amino acids. Introduction of the open reading frame sequence into a UGT-deficient mouse cell line, Had-1, complemented the genetic defect of the mutant, namely the inability to transport UDP-galactose from the cytosol to the Golgi lumen, as judged from the lectin-sensitivity spectrum of the transformant. To our knowledge, this is the first mammalian nucleotide-sugar translocator whose cDNA sequence has been described.

Amino Acid Sequence↗

Effect of occlusal pressure on the histopathological changes in denture supporting tissues.

Histopathological changes in the denture supporting tissues in relation to the occlusal pressure exerted through an experimental denture base were studied. An experimental denture, which prescribed the occlusal pressure by the amount of subsidence of the denture base (100, 50 and 13 microns), was constructed for the palate of the molar region of rat. Histopathological changes caused by the occlusal pressure were observed, and the intensity of the pressure was also estimated. In the 100 microns subsidence group, compression of epithelium and lamina propria mucosae, inflammatory change and bone resorption were caused by the occlusal pressure. In the 50 microns subsidence group, compression of epithelium and lamina propria mucosae and bone resorption were observed, while in the 13 microns subsidence group, no evidence of inflammatory change and bone resorption were observed. The epithelium and lamina propria mucosae recovered histopathologically depending on the gradual decrease of the occlusal pressure resulting from bone resorption, whereas no quantitative recovery of the resorbed bone tissue was observed in the 100 and 50 microns subsidence groups. From the results observed in this study, a high correlation was observed between the histopathological changes under a denture base and the intensity of the occlusal pressure, and the possibility of the existence of the threshold for bone resorption induced by occlusal pressure was suggested.

Acrylic Resins↗

Phylogenetic tree-based epidemiological analysis of hepatitis C virus transmission in a region of Japan with a high prevalence of infection.

Local clustering of hepatitis C virus (HCV) infection has been demonstrated in various regions in Japan. HCV genotypes have now been compared between infected individuals from districts of Saga prefecture with either a high (H district) or low (L district) prevalence of HCV-seropositivity. The prevalence of HCV genotype 1b was significantly higher (P < 0.001) in the H district (45/50; 90%) than in the L district (19/36; 52.8%). A phylogenetic tree was constructed based on the genomic sequences of viral isolates from 20 patients infected with genotype 1b in the H district. Almost all these HCV strains clustered in the same regions of the tree. With regard to risk factors for HCV transmission, the percentage of patients with a history of surgery was significantly higher in the H district than in the L district (58 versus 33.3%; P < 0.05). Of 20 patients infected with similar strains of HCV in the H district, 16 (80%) had at least one parenteral risk factor associated with medical care. These results indicate an increased transmission of similar strains of HCV in the H district as a result of nosocomial infection.

Base Sequence↗

Efficacy and side effects of intermittent recombinant interferon-alpha 2a in chronic aggressive hepatitis C: with or without initial daily administration.

To investigate the therapeutic effect and incidence of side effects of recombinant interferon-alpha 2a (IFN-alpha) in chronic aggressive hepatitis C under stratification by administration mode, a study was conducted by assigning patients to either group A (daily consecutive administration of 9 million units (MU) IFN-alpha for 2 weeks and, thereafter, 3 MU intermittently 3 times weekly for 22 weeks) or group B (exclusively intermittent administration; 9 MU IFN-alpha twice weekly or 6 MU IFN-alpha thrice weekly for 24 weeks). The 28 patients in group A received IFN-alpha for 24 weeks up to a total dose of 324 MU and the 53 patients in group B received the same for 24 weeks up to a total dose of 432 MU. When recovery was defined as the absence of hepatitis C virus (HCV)-RNA 6 months after the completion of treatment, the rate of recovery for group A was 32.1% and that for group B was 37.7%, the latter being higher but without significance. Side effects in groups A and B consisted of leucopenia occupying 14.3 and 7.5%, respectively, and thrombocytopenia occupying 42.9 and 11.3%, respectively; group B exhibited lower values for both side effects. No difference was detected between these groups in other side effects, including pyrexia, generalized malaise, arthralgia or psilosis. Intermittent administration from the outset permitted shortened duration of hospitalization and earlier rehabilitation. Intermittent administration of INF-alpha is required when treating patients with chronic hepatitis C showing lower leucocyte or platelet counts.

Chronic Disease↗