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Biomedical subjects

T Hara

Publications and source records attributed to T Hara.

At least 1,333 records · Page 74Linked to original sources
PubMedDate not supplied

Preparation and disposition of asialofetuin-labelled liposome.

A liposome labelled with asialofetuin(AF-liposome) was prepared by the detergent dialysis method. Asialofetuin in the amount of 34-68 micrograms were imposed among the 1 microM of phospholipids constituting the outer surface of liposome. The AF-liposome containing [14C]-cholesterol in the lipid layer and [3H]-sucrose in the aqueous layer was intravenously administered to rats. Both radioactivities were biphasically cleared from systemic circulation at rates faster than that of the fetuin-labelled liposome. These radioactivities were recovered in the liver by about 90 per cent within 60 min, and per gram of tissue, were highest in this organ. In an in vitro experiment using isolated rat hepatocytes, the high affinity of the AF-liposome toward hepatocytes was observed from scanning electron micrographs. Based on these findings, the AF-liposome may possibly be stable in circulation and function as a carrier of encapsulated drugs to hepatocytes.

Animals↗
PubMedDate not supplied

Specific incorporation of asialofetuin-labeled liposomes into hepatocytes through the action of galactose-binding protein.

Asialofetuin-labelled liposomes (AF-liposomes) having mean diameters of 0.13 micron ([S]) and 0.35 micron ([L]) were obtained by the subsequent extrusion method in combination with dialysis. Intravenously administered AF-liposomes [S] were rapidly cleared from the systemic circulation. By pre- and post-treatment of the rats with free asialofetuin (AF), the rate of elimination decreased to that of non-labelled liposomes (N-liposomes) [S]. The liver uptake of AF-liposomes [S] (60 per cent of dose in 30 min) was about twice that of N-liposomes [S]. Forty-seven per cent of the AF-liposomes [S] incorporated into the liver were found in the parenchymal cell fraction as against 20 per cent in the non-parenchymal cell fraction. In contrast, N-liposomes [S] were taken up primarily by non-parenchymal cells as was also the case for AF- or N-liposomes [L]. Both the lipid and aqueous markers of AF-liposomes [S] were detected in subcellular fractions of the liver, but their distribution was noted to change differently with the lapse of time. Intravenously administered AF-liposomes [S] were specifically recognized by galactose-binding protein and underwent disruption in the cell after being taken up by hepatocytes. AF-liposomes [S] may possibly be utilized to deliver drugs into hepatocytes.

Animals↗
PubMedDate not supplied

Asthma-like attacks resulting from the isolated congenital left pulmonary artery agenesis with right main bronchus stenosis.

A 5-year-old girl with isolated congenital left pulmonary artery agenesis suffered from recurrent attacks of dyspnea and right-sided pneumonia due to the stenosis of the right main bronchus. The division of ligamentum of the ductus arteriosus and suspension of the right pulmonary artery resulted in the disappearance of symptoms. It is notable that the compression of contralateral bronchus by the remaining pulmonary artery can cause respiratory symptoms in patients with isolated unilateral pulmonary artery agenesis.

Asthma↗
PubMedDate not supplied

Sensorineural deafness in siblings with adenosine deaminase deficiency.

Two siblings with adenosine deaminase deficiency were successfully treated with allogeneic bone marrow transplantation without conditioning. Although the patients were free from infections after immunologic reconstitution, both showed sensorineural deafness at 1 year of age. Because there were no structural abnormalities in the inner and middle ears, no evidence of prenatal infections of rubella, cytomegalovirus or toxoplasma, and no postnatal infection of mumps in the siblings, sensorineural deafness might be one of the neurologic problems associated with adenosine deaminase deficiency.

Adenosine Deaminase↗
PubMedDate not supplied

Mechanical properties of osteopenic vertebral bodies monitored by acoustic emission.

A microdamage event, either bone microfracture or microcrack propagation, releases energy. Some of this energy is in the form of acoustic waves. We measured acoustic emission (AE) in normal and osteopenic vertebral bodies during compression loading to confirm the microdamage accumulation. The 2nd to 4th lumbar vertebrae taken from the embalmed cadavers of a 37-year-old male and a 75-year-old female were used. Bone mineral densities (BMDs) were measured by dual energy X-ray absorptiometer (DEXA). The male vertebrae had normal BMDs, while the female vertebrae had lower BMDs than the normal range and were graded osteopenic. Mechanical parameters (maximum load, maximum stress, stiffness, strain at maximum load, and apparent elastic modulus) and AE event count rates in the load-deformation curve were measured during quasi-static compression loading (deformation rate 0.1 mm/min). For all mechanical parameters, the normal vertebrae had higher values than the osteopenic vertebrae. Cumulative AE event counts until maximum load of the osteopenic vertebrae were much greater than that of normal vertebrae. The vertebrae which were well compressed to the plastic range in the load-deformation curve displayed dome-shaped fracture lines just above the end plates. These results are consistent with the hypotheses that microcracks of osteopenic vertebral bodies are generated and accumulate at lower strains than those of normal vertebrae at a specific site.

Absorptiometry, Photon↗
PubMedDate not supplied

Ocular tissue concentrations of mitomycin C with variable dose and duration of application time in rabbits.

We measured mitomycin C (MMC) concentrations in ocular tissues in rabbits with variable dose (0.1, 0.2, or 0.4 mg) and duration of application time (1, 3, or 5 minutes) of MMC using high-performance liquid chromatography. Mitomycin C concentrations at the administered site after single subconjunctival application of MMC and after irrigation showed significant correlation with dose and duration of time of application. By multiple regression analysis, MMC concentrations (microg/g) at the conjunctiva were described as -6.73 + 67.4 x Dose (mg) + 1.66 x Time (minutes) (R2 0.65); at the sclera, -1.85 + 38.2 x Dose + 0.927 x Time (R2 0.63); at the cornea, -0.727 + 8.44 x Dose (R2 0.46). With a 0.2-mg MMC dose, in all three application times (1, 3, or 5 minutes), MMC concentrations in the conjunctiva at the administered quadrant were three times higher than in the neighboring quadrants and 6 to 7 times higher than in the opposite quadrant. In the sclera, MMC concentrations were 3.5 times higher than in the neighboring sites and over 8 to 9 times higher than in the opposite site. In the cornea, MMC concentrations were 2 to 3 times higher than in the neighboring sites and opposite site. In the iris-ciliary body, MMC concentrations were 0.61 microg/g at the administered site with 0.2 mg for 3-minute application, 2 times higher than in neighboring sites, and 2 times higher than in opposite sites.

Animals↗
PubMedDate not supplied

Homologous complement activation on drug-induced apoptotic cells from a human lung adenocarcinoma cell line.

Activation of the alternative pathway of homologous complement (C) was observed in a human lung adenocarcinoma cell line, CADO 43, after the cells had become apoptotic following treatment in vitro with vincristine and predonisolone. Deposition of C3b and C3bi on the serum-treated apoptotic cells was revealed by flow cytometry with anti-C3b and -C3bi-specific antibodies and immunoblotting with anti-C3 antibody immunoprecipitates extracted from solubilized fractions of serum-treated apoptotic cells. Two molecular mechanisms were found to be responsible for this post-apoptotic C-activation. Firstly, all C regulators, decay accelerating factor (DAF), membrane cofactor protein (MCP) and C3b/C4b receptor (CR1), were diminished on the cell surface concomitantly with the apoptotic process. Secondly, unidentified molecules which potentially activate homologous C and accept C3b/C3bi fragments became expressed on the cell surface during the apoptotic process. These findings may explain the mechanism whereby tumor cells are efficiently eliminated through chemotherapy.

Adenocarcinoma↗
PubMedDate not supplied

Hematopoietic cells in cultures of the murine embryonic aorta-gonad-mesonephros region are induced by c-Myb.

Definitive hematopoiesis begins in the para-aortic, splanchnopleural (P-Sp) and aorta-gonad-mesonephros (AGM) regions of mouse embryos and then switches to the fetal liver [1] [2] [3]. Gene-targeted mice lacking the c-Myb transcription factor have severe hematopoietic defects in the fetal liver [4]. The role of c-Myb, if any, in P-Sp/AGM hematopoiesis has not been examined, however. Recently, we reported that oncostatin M can effectively expand both hematopoietic and endothelial-like cells from in vitro cultures of the AGM region [5]. Using this cell culture system, we examined the involvement of c-Myb in definitive hematopoiesis in the P-Sp and AGM regions. When primary cultures from the P-Sp or AGM regions of wild-type mouse embryos were probed with an anti-c-Myb antibody, hematopoietic cells but not endothelial-like cells showed positive staining. In contrast, in the P-Sp/AGM culture from c-myb(-/-) embryos, no hematopoietic cells were generated and endothelial-like cells predominated, indicating that the impairment of hematopoiesis in the liver of c-myb(-/-) embryos is actually preceded by a defect in P-Sp/AGM hematopoiesis. Hematogenic precursor cells were, however, still present in an inert but competent form among the endothelial-like, adherent cell population of c-myb(-/-) P-Sp/AGM cultures. When infected with a retrovirus carrying c-myb cDNA, these cultures gave rise to a significant number of hematopoietic cells. The rescued cells, unlike wild-type hematopoietic cells, were negative for c-Kit (a marker of hematopoietic progenitors), but did express other hematopoietic cell surface markers such as Mac-1, Gr-1 (myeloid markers), CD19, B220, Thy-1.2 (Iymphoid markers), and Ter119 (an erythroid marker). Thus, c-Myb plays a role in the generation of hematopoietic cells in the embryonic P-Sp and AGM regions.

3T3 Cells↗
PubMedDate not supplied

High expression but no internal tandem duplication of FLT3 in normal hematopoietic cells.

The FLT3 gene encodes a tyrosine kinase receptor that regulates proliferation and differentiation of hematopoietic cells. Recently, the internal duplication of FLT3 has been observed in hematological malignancies, suggesting the involvement of these mutations in leukemogenesis. The authors analyzed the expression of FLT3 mRNA and the incidence of its internal tandem duplication in normal hematopoietic and blood samples by reverse transcription-polymerase chain reaction (RT-PCR). Mononuclear cells (MNCs) in cord blood and bone marrow highly expressed FLT3 mRNA, whereas MNCs and polymorphonuclear cells (PMNs) in peripheral blood showed low or undetectable levels of FLT3. When the ratio of FLT3/beta-actin PCR products was calculated, the level of FLT3 mRNA expression was significantly higher in cord blood MNCs (n = 42) than that in peripheral MNCs (n = 14) or PMNs (n = 10). Although several PCR bands with different sizes were observed, no internal tandem duplication of FLT3 was detected in these normal blood samples. These findings indicate that the expression of FLT3 is lineage specific and consistently decreases during hematopoietic differentiation. The internal duplication of FLT3 is restricted in hematological malignancies and may occur at a specific stage in leukemogenesis.

Bone Marrow Cells↗
PubMedDate not supplied

Treatment of standard-risk acute lymphoblastic leukemia in children: the results of protocol AL841 from the Kyushu-Yamaguchi Children's Cancer Study Group in Japan.

A total of 62 patients with standard-risk acute lymphoblastic leukemia received three-drug induction consisting of vincristine, prednisolone, and L-asparaginase (l-Asp) followed by consolidation therapy with intermediate-dose methotrexate (MTX), intrathecal MTX, and 18 Gy of cranial irradiation. Maintenance therapy consisting of 6 drugs including daunorubicin (DNR, 450 mg/m2 in total) was continued for 3 years. Patients were randomized and half of them received weekly l-Asp during maintenance therapy as a late intensification. Complete remission (CR) was achieved in 61/62 (98.4%), and 11 of 61 patients relapsed. At 10 years, the event-free survival (EFS) was 80.6 +/- 5.0% and overall survival was 88.7 +/- 4.0%; median follow-up time was 9.3 years. The 10-year EFS of patients with additional l-Asp (84.8 +/- 6.2%) was superior to that without l-Asp (75.9 +/- 7.9%), although it was not statistically significant. No patients who received a full dose of DNR and maintained CR developed heart failure, although the shortening fraction decreased from 41.0% at diagnosis to 35.2% (median). The protocol AL841 provided good long-term disease control without severe late cardiac dysfunction.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Deficiency of a parathyroid hormone fragment containing the midportion and 1,25-dihydroxyvitamin D in serum of patients with slipped capital femoral epiphysis.

The endocrine abnormality that causes slipped capital femoral epiphysis (SCFE) has not been revealed. Recent studies have shown that parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25-(OH)2D] are involved in growth-plate chondrogenesis and matrix mineralization. Thus we examined in 13 patients with SCFE the serum levels of three immunoreactive forms of PTH (iPTH): the whole peptide [(1-84)PTH], the fragment containing the COOH-terminal portion (C-PTH), and the midportion (M-PTH). Additionally, serum levels of 25-hydroxyvitamin D [25-(OH)D] and 1,25-(OH)2D were measured. We found that the levels of M-PTH were significantly lower than those of controls, whereas levels of C-PTH and (1-84)PTH were not significantly different from those of controls. Similarly, levels of 1,25-(OH)2D were also significantly lower than control levels. In patients with initially low levels of M-PTH and 1,25-(OH)2D in whom the levels were monitored over a period, all levels returned to normal within a year after the onset of disease. The deficiency of M-PTH or 1,25-(OH)2D during the growth spurt could result in SCFE, although in this study, we cannot deny the possibility that the slippage may cause the deficiency.

Adolescent↗
PubMedDate not supplied

Interferon-alpha therapy for chronic active Epstein-Barr virus infection: potential effect on the development of T-lymphoproliferative disease.

PURPOSE: A patient with aggressive chronic active Epstein-Barr virus (CAEBV) infection is described whose disease activity subsided after interferon (IFN)-alpha therapy. PATIENT AND METHODS: The patient had intermittent fever, cytopenia, liver dysfunction, hepatosplenomegaly, abnormal titers of EBV-associated antibodies, and positive EBV genomes. RESULTS: Despite repeated trials of the antiviral agents prednisolone and gamma-globulin, his condition deteriorated. The administration of IFN-alpha (1 x 10(5) U/kg subcutaneously 3 times per week) led to a dramatic clinical improvement. During the IFN-alpha therapy, the rearrangement bands of T-cell antigen receptor genes disappeared assessed by Southern blotting with a decrease in the number of activated T cells, although the EBV-genome remained evident. CONCLUSIONS: These observations suggest that IFN-alpha is useful in managing CAEBV, possibly restraining the clonal development of T-lymphoproliferative disease (LPD) and EBV-associated B-LPD, although it does not eradicate the proliferation of EBV.

Antiviral Agents↗
PubMedDate not supplied

Analysis of nucleotide sequences of hepatitis C virus isolates from husband-wife pairs.

To identify the route of hepatitis C virus (HCV) transmission, we investigated the sexual transmission of HCV by examining HCV markers among spouses of patients with chronic liver disease (CLD) due to HCV. Of 83 spouses, 14 (16.9%) had elevated serum aspartate aminotransferase or alanine aminotransferase, 20 (24.1%) had detectable anti-HCV antibodies, and 17 (20.5%) had measurable HCV-RNA in serum. However, the seropositivity rate of anti-HCV antibodies (24.1%) of patients' spouses was not significantly higher than that (15.4-27.5%) of an unselected population in the same district. Ten patient-spouse pairs underwent nucleotide sequence analysis of the HCV core and envelope genes. Overall the sequence homology of 10 couples (91.1%) was not significantly higher than that of 10 randomly chosen unrelated pairs (88.2%). As reported earlier, in an age and sex matched case-control study of HCV transmission, a history of surgery is a prominent HCV risk factor. These results suggest that sexual transmission of HCV is rare.

Adult↗
PubMedDate not supplied

Recurrent parotid swelling in children: clinical features useful for differential diagnosis of Sjögren's syndrome.

Immunological evaluations were performed in 59 children with at least five episodes of parotid swelling. Autoantibody(ies) was transiently or persistently detected in 12 (20%) of 59 patients with recurrent parotitis. Three of the 12 children with autoantibodies were diagnosed as having Sjögren's syndrome. The mean age at onset of parotid swelling in Sjögren's syndrome was significantly higher than that of recurrent parotitis of unknown etiology. The present study and the review of the literature suggest that patients with the onset of parotid swelling at age five years or over deserve screening for underlying systemic immune disorders.

Adolescent↗
PubMedDate not supplied

Preventive effect of argatroban on ellagic acid-induced cerebral thromboembolism in rats.

The preventive effect of argatroban, a synthetic thrombin inhibitor, on cerebral infarction was evaluated with ellagic acid (EA)-induced cerebral thromboembolism in rats. Platelet-rich thrombi containing fibrin and EA crystal were formed in the microarteries in the affected hemisphere by the injection of EA suspension into the cerebral arteries. The mortality in saline control was over 80% 6 h after the EA injection. Argatroban decreased the mortality to 0% at a dose of 3 mg/kg/h, and significantly reduced the ischemic area in the affected cerebral hemisphere. Heparin also decreased the mortality to 30% at a dose of 600 U/kg/h, but marked bleeding was observed at the incised wound. These findings suggest that argatroban is a more effective and safer anticoagulant than heparin for the prevention of ischemic damage on cerebral thrombosis.

Animals↗
PubMedDate not supplied

Evaluation of transverse colon interposition following total gastrectomy in patients with gastric carcinoma.

In order to improve the quality of life of patients who received total gastrectomy for treatment of gastric carcinoma, transverse colon interposition (TCI) was performed on 133 patients since June, 1986. To evaluate TCI, post-operative follow-up studies were conducted. Group I patients received TCI (N=40). Group II patients received Roux en Y anastomosis (R-Y anastomosis) (N=20). These groups were compared in a five-year post-operative study. Alkaline reflux esophagitis was significantly lower among patients who received TCI compared to patients who received R-Y anastomosis (p<0. 05). There was no significant difference between groups I and II with respect to food consumption. In the period from four months to five years following surgery, the average weight loss (% body weight) was significantly lower (p<0.01) in patients who received TCI compared to patients who received R-Y anastomosis. During OGTT, group I patients had significantly higher postprandial pancreatic glucagon response than group II patients. The plasma glucose tolerance in group I was significantly better than that of group II (p<0.05). The average postprandial plasma gastrin level, 30 through 120 min following glucose loading, was significantly higher in group I (p<0.05).

Anastomosis, Roux-en-Y↗