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Biomedical subjects

K Hoshi

Publications and source records attributed to K Hoshi.

At least 145 records · Page 8Linked to original sources
PubMed1996

Local production of the p40 subunit of interleukin 12 suppresses T-helper 1-mediated immune responses and prevents allogeneic myoblast rejection.

The p40 subunit of interleukin 12 (IL-12p40) has been known to act as an IL-12 antagonist in vitro. We here describe the immunosuppressive effect of IL-12p40 in vivo. A murine myoblast cell line, C2C12, was transduced with retro-virus vectors carrying the lacZ gene as a marker and the IL-12p40 gene. IL-12p40 secreted from the transfectant inhibited the IL-12-induced interferon gamma (IFN-gamma) production by splenocytes in vitro. Survival of C2C12 transplanted into allogeneic recipients was substantially prolonged when transduced with IL-12p40. Cytokine (IL-2 and IFN-gamma) production and cytotoxic T lymphocyte induction against allogeneic C2C12 were impaired in the recipients transplanted with the IL-12p40 transfectant. Delayed-type hypersensitivity response against C2C12 was also diminished in the IL-12p40 recipients. Furthermore, serum antibodies against beta-galactosidase of the T-helper 1-dependent isotypes (IgG2 and IgG3) were decreased in the IL-12p40 recipients. These results indicate that locally produced IL-12p40 exerts a potent immunosuppressive effect on T-helper 1-mediated immune responses that lead to allograft rejection. Therefore, IL-12p40 gene transduction would be useful for preventing the rejection of allografts and genetically modified own cells that are transduced with potentially antigenic molecules in gene therapy.

Animals↗
PubMed1996

Vitamin K2 promotes 1alpha,25(OH)2 vitamin D3-induced mineralization in human periosteal osteoblasts.

The effect of vitamin K on mineralization by human periosteal osteoblasts was investigated in the absence and presence of 1alpha, 25 dihydroxyvitamin D3 (1,25(OH)2D3). Vitamin K1 and K2, but not vitamin K3, at 2.5 microM enhanced in vitro mineralization when cells were cultured with vitamin K for 20 days after reaching confluence in vitro. Vitamin K2 (2-methyl-3-all-trans-tetraphenyl-1, 4-naphthoquinone : menatetrenone) was the most potent of these vitamin K analogs; it slightly inhibited alkaline phosphatase (ALP) activity. Human osteoblasts were mineralized and showed the enhanced ALP activity on treatment with 10(-9) M of 1,25(OH)2D3 for 20 or 25 days after confluence. Vitamin K2 promoted the 1,25(OH)2D3-induced mineralization, but slightly inhibited the 1,25(OH)2D3-induced ALP activity. Moreover, vitamin K2 enhanced the 1,25(OH)2D3-induced osteocalcin accumulation in the cells and the extracellular matrix (cell layer), but inhibited the osteocalcin content in the medium produced by the 1,25(OH)2D3 treatment. However, vitamin K2 alone did not induce osteocalcin production in the human osteoblasts. On Northern blot analysis, osteocalcin mRNA expression on 1, 25(OH)2D3-treated cells was enhanced by vitamin K2 treatment, but vitamin K2 alone did not induce osteocalcin mRNA expression. Warfarin blocked both the 1,25(OH)2D3-induced osteocalcin production and the accumulation in the cell layer, and also blocked the 1, 25(OH)2D3 plus vitamin K2-induced osteocalcin production and the accumulation in the cell layer. The 1,25(OH)2D3-induced mineralization promoted by vitamin K2 was probably due to the enhanced accumulation of osteocalcin induced by vitamin K2 in the cell layer. However, we concluded that the mineralization induced by vitamin K2 alone was due to the accumulation of osteocalcin in bovine serum on the cell layer, since osteocalcin extracted from the cell layer was not identified by specific antiserum against human osteocalcin, which does not cross-react with bovine osteocalcin. These results suggest that the mechanism underlying the mineralization induced by vitamin K2 in the presence of 1,25(OH)2D3 was different from that of vitamin K2 alone, and that osteocalcin plays an important role in mineralization by osteoblasts in vitro.

Adult↗
PubMed1996

The relationship between acridine orange fluorescence of sperm nuclei and the fertilizing ability of human sperm.

OBJECTIVE: To determine whether the outcome of IVF can be predicted by acridine orange (AO) nuclear fluorescence of sperm. DESIGN: Based on the fact that AO nuclear fluorescence color after acid treatment reflects maturity (green fluorescence) or immaturity (yellow to red fluorescence) of spermatozoa, the relationships between sperm maturity and the outcome of IVF, subzonal insemination, or intracytoplasmic sperm injection (ICSI) were investigated. SETTING: The IVF program at the Obstetrics and Gynecology Hospital, Fukushima Medical College. PATIENTS: Sixty-eight patients undergoing 68 IVF treatment cycles. MAIN OUTCOME MEASURES: Acridine orange fluorescence of sperm nuclei and successful oocyte fertilization. RESULTS: conventional semen parameters (sperm concentration and percentages of motile or morphologically normal spermatozoa in semen) did not correlate with the incidence of spermatozoa with green AO fluorescent (mature) nuclei. When > or = 50% of spermatozoa in semen samples exhibited green AO nuclear fluorescence, IVF was always successful. When green AO nuclear fluorescence was < 50%, only 39% of IVF treatment cycles (13/33) were successful. Only green AO fluorescent spermatozoa were able to bind efficiently human zona pellucida. When the incidence of green AO fluorescent spermatozoa was < 50%, no pregnancy resulted even though an average of 26% of the oocytes could be fertilized by ICSI. CONCLUSIONS: The spermatozoa which fertilized oocytes in vivo and in IVF were limited to those whose nuclei exhibited green AO fluorescence. Intracytoplasmic sperm injection may be the method of choice when the incidence of green AO nuclear fluorescence is low regardless of the results of semen analysis.

Acridine Orange↗
PubMed1996

Expansive cervical laminoplasties--observations on comparative changes in spinous process lengths following longitudinal laminal divisions using autogenous bone or hydroxyapatite spacers.

Expansive laminoplasty is devised to preserve the posterior structures, including the original length of the spinous process which anchors the nucheal muscles, in order to prevent the postoperative development of instability and cervical kyphosis due to structural loss and poor tone of the nucheal muscles, which can result in late neurological regression after laminectomy for cervical myelopathy. We retrospectively compared the length of the spinous process at the time of follow-up with that within 3 months postoperatively using CT images. The shortening was observed in 80% of 60 spinous processes in 13 patients, where a hydroxyapatite (HA) block was used as a spacer placed between the two sides of the split spinous process. The incidence was 9% of 22 spinous processes in six patients where auto bone graft (ABG) was used as a spacer, and the difference was significant (P < 0.01, Chi-square test). Although the usage of HA has the advantage of being less invasive than ABG, it may jeopardize the biomechanical function of nucheal muscles due to reduction in the original length of the spinous process.

Adult↗
PubMed1996

Fertilization and development of mouse oocytes injected with isolated sperm heads.

To determine whether spermatozoa must be structurally intact before microsurgical injection into oocytes for normal fertilization, intact spermatozoa, as well as sperm heads separated from tails by sonication, were individually injected into oocytes. When whole spermatozoa were injected immediately after their immobilization, the majority of the oocytes were fertilized and developed normally. Sonication in the presence or absence of Triton X-100 decapitated more than 95% of spermatozoa. Although all decapitated spermatozoa were diagnosed as "dead" by live/dead sperm staining, separated sperm heads (nuclei) could participate in normal embryo development when injected into the oocytes. The ability of isolated sperm heads (nuclei) to participate in normal embryo development was maintained under cryopreservation conditions that were not suitable for the survival of plasma membrane-intact spermatozoa. These results indicate that 1) spermatozoa do not need to be structurally intact for intracytoplasmic injection, 2) the plasma and acrosomal membranes and all tail components are not essential for normal embryo development, at least in the mouse, and 3) the cryopreservation conditions required for maintenance of the genetic integrity of sperm nuclei are less stringent than those necessary for keeping plasma membrane-intact spermatozoa alive.

Animals↗
PubMed1996

Evaluation with MIB1 antibody of proliferative activity in ovarian clear cell adenocarcinoma.

The purpose of this study was to determine whether proliferative activity is a prognostic factor in ovarian clear cell adenocarcinoma. The paraffin-embedded sections from eight cases of ovarian clear cell adenocarcinoma were immunostained with monoclonal antibody MIB1 using microwave oven heating for antigen retrieval. The difference in survival (Kaplan-Meier) between patients with high and low MIB1 expression was estimated with the generalized Wilcoxon test. MIB1 positivity ranged from 1.80 to 27.12% with a mean of 11.43%. A cutoff point of 10% dichotomized patients into two groups. The survival of high (> or = 10%) expressing tumors was worse than that of low (< 10%) expressing tumors (p < 0.05). MIB1 immunostaining may have useful prognostic value in ovarian clear cell adenocarcinoma.

Adenocarcinoma, Clear Cell↗
PubMed1996

Effects of adenine nucleotide analogues on myocardial dysfunction during reperfusion after ischemia in dogs.

We examined effects of adenine nucleotide on ischemic myocardial stunning in dogs. Pentobarbitalanesthetized open-chest dogs were subjected to 20-min ligation of the left anterior descending coronary artery (LAD), followed by reperfusion for 30 min. Either saline, 5 mM 8-bromo-5'-AMP (tributyryl-AMP), or 30 mM N6, 2', 3'-tributyryl-5'-AMP (tributyryl-AMP), 5 mM 5-amino-4-imidazole carboxamide riboside (AICAr) as a positive reference, was infused at 0.1 ml/kg/min in the left femoral vein throughout the experiment. The myocardial contractile function was measured by ultrasonometry. The tissue levels of high-energy phosphates in the reperfused heart were determined. Myocardial contractile function assessed by % segment shortening (%SS) in the saline-infused group decreased during ischemia and returned toward the preischemic level during reperfusion but incompletely. A significant improvement in the %SS during reperfusion was observed in the 8-bromo-AMP- and AICAr-infused groups but not in the tributyryl-AMP-infused group. The magnitude of the protective effect of the drugs on myocardial contractility during reperfusion was 8-bromo-AMP > AICAr > tributyryl-AMP = saline. Only in the 8-bromo-AMP-infused group were the levels of ATP, ADP, and total adenine nucleotides in the reperfused heart significantly higher than those in the saline-infused group. The present result indicates that 8-bromo-AMP improves the ability of the heart to recover from ischemia and reperfusion associated with a significant restoration of ATP.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Early detection of platelet activation after coronary angioplasty.

BACKGROUND: Although platelet activation has been considered an important reaction after percutaneous transluminal coronary angioplasty (PTCA), it is still difficult to detect the activated platelets in vivo directly. METHODS: To detect platelets activated at an early stage after PTCA, blood samples were take from the coronary sinus and the aorta in 22 patients with coronary artery disease, who underwent PTCA for a lesion of the left anterior descending artery. Ten patients with coronary artery disease, who underwent diagnostic coronary angiography only, were compared with them. The expression of activation-dependent granular protein, CD62P (P-selectin) and CD63, on the platelet membrane surface was analysed using flow cytometry. The plasma thrombomodulin level was also measured. RESULTS: The percentage of platelets positive for CD62P (0.53 +/- 0.04 to 0.80 +/- 0.11%, P < 0.01) and CD63 (16.0 +/- 1.4 to 19.8 +/- 2.0%, P < 0.05) increased after PTCA in the coronary sinus, although it did not change in the aorta. The plasma thrombomodulin level also increased after PTCA in the coronary sinus (16.7 +/- 1.0 to 20.4 +/- 2.0 mu/ml, P < 0.05). However, these parameters did not change after coronary angiography only. After PTCA, the plasma thrombomodulin level was correlated with the percentage of platelets positive for CD62P (r = 0.88, P < 0.001) and with that for CD63 (r = 0.69, P < 0.001) in the coronary sinus. CONCLUSIONS: PTCA produced activation of circulatory platelets, which might have been caused by balloon-induced vascular endothelial injury. One should take care to avoid needless vascular injury during the PTCA procedure to inhibit the platelet activation.

Angioplasty, Balloon, Coronary↗
PubMed1996

Effects of BIBR-277, an angiotensin II type 1 receptor antagonist, on stunned myocardium in dogs.

BACKGROUND: Angiotensin converting enzyme inhibitors can protect the myocardium from ischaemic damage. We examined the effect of BIBR-277, an angiotensin II receptor type 1 antagonist, on myocardial stunning in dogs. METHODS: Pentobarbital-anaesthetized open-chest dogs were subjected to 20 min ligation of the left anterior descending coronary artery, followed by reperfusion for 60 min. Saline or 0.3, 1 or 3 mg/kg body weight BIBR-277 was injected intravenously 10 min before coronary ligation. The myocardial contractile function was measured by ultrasonometry. The tissue levels of energy metabolites in the 60 min reperfused heart were determined. RESULTS: Myocardial contractile function assessed in terms of percentage segment-shortening in the saline-treated group decreased during ischaemia and returned towards the pre-ischaemic level during reperfusion but incompletely (myocardial stunning). A significant and dose-dependent improvement in the percentage segment-shortening during reperfusion was observed in the BIBR-277-treated groups. The levels of ATP, ADP and AMP in the reperfused heart were not modified by BIBR-277 treatment compared with those in the saline-treated group. CONCLUSION: BIBR-277 ameliorates the myocardial contractile dysfunction during reperfusion after ischaemia, although it did not bring about any improvement in the high-energy phosphate levels in the reperfused heart.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

A method of measuring dipalmitoylphosphatidylcholine (DPPC) by high-performance liquid chromatography (HPLC): effect of dexamethasone on DPPC secretion in fetal rat alveolar type II cell culture.

OBJECTIVE: To establish a method by which to measure dipalmitoylphosphatidylcholine (DPPC), which is the most prevalent phospholipid in lung surfactant, by high-performance liquid chromatography (HPLC), and to measure DPPC secretion in type-II alveolar cell culture to determine whether glucocorticoid has a direct accerelating effect. METHOD: Type-II alveolar cell suspensions were made with fetal rat lungs and then cultured. Dexamethasone, (10(-9), 10(-8) M) was added to some of the culture dishes. DPPC was extracted from the culture medium, purified, and measured by high-performance liquid chromatography (HPLC). RESULTS: In the measurements of DPPC, the specificity of isolation and measurement parity were excellent [coefficient of variation: intraassay; 5.66% (0.005 mg/ml), 25.37% (0.05 mg/ml): interassay; 8.35% (0.005 mg/ml), 0.08% (0.05 mg/ml)]. The DPPC concentration in the culture dishes of the dexamethasone was not significantly different than that of the control dishes (Student's t-test). CONCLUSION: The above results prove that dexamethasone does not directly stimulate lung alveolar type-II cells.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

Programmed cell death of chondrocytes and aberrant chondrogenesis in mice homozygous for parathyroid hormone-related peptide gene deletion.

In previous work we showed that the chondrodysplastic phenotype of mice homozygous for a null mutation of the PTH-related peptide (PTHrP) gene was due in part to reduced proliferation and aberrant differentiation of growth plate chondrocytes. In the present study we have extended those observations by examining chondrocytes for evidence of PTH/PTHrP receptor expression, proliferation, and programmed cell death. Receptor messenger RNA and protein were expressed in chondrocytes in the resting and proliferative zones of both wild-type and mutant mice. In normal animals, expression was abundant in the area of transition between proliferative and hypertrophic chondrocytes and absent from cells in the lower hypertrophic region. On the other hand, the hypertrophic zone in mutant mice contained nonhypertrophic chondrocytes, which exhibited characteristics of proliferating cells, including PTH/PTHrP receptor expression, [3H]thymidine incorporation, and expression of proliferating cell nuclear antigen. In contrast to the situation in normal animals, some cells adjacent to the zone of vascular invasion in mutant growth plates showed biochemical and morphological evidence of programmed cell death. In addition to these alterations in the maturation of growth plate chondrocytes, homozygous mutants demonstrated signs of aberrant differentiation of periosteal precursor cells. In some specimens, clusters of chondrocytes embedded in a cartilaginous matrix were observed between the layers of periosteal osteoblasts and the bony collar in the sterna and tibiae of mice homozygous for a null mutation of the PTHrP gene. Taken together, these observations indicate that PTHrP plays a pivotal role in the orderly progression of chondrocytes through stages of proliferation, differentiation, and programmed cell death in the epiphyseal growth plate and may also facilitate the commitment of precursors to cells of the chondrocytic or osteoblastic lineages.

Animals↗
PubMed1996

Ovarian epithelial borderline tumor and carcinoma in young women.

To clarify the influence of age on clinical and histologic features, young women with ovarian epithelial borderline tumors and carcinomas were analyzed. A retrospective review of 93 patients with ovarian common epithelial borderline tumors and carcinomas was performed. Twenty-one of 93 patients (22.6%) were under age 40. Predominant symptoms in young patients were abdominal pain or abdominal distention, but 4 (19%) patients had no symptom. Eleven (11/21; 52.4%) patients were nulliparous and six patients received conservative surgery to preserve fertility. The rate of histologic type and stage did not significantly differ between the young and older groups. Although overall survival between young and older patients did not significantly differ, the survival of young patients with advanced disease (stage III and IV) was significantly worse than in older patients with advanced disease. (p < 0.05).

Adolescent↗
PubMed1996

Relationship of thallium-201 clearance on exercise stress myocardial scintigraphy to coronary flow reserve in patients with coronary artery disease.

OBJECTIVE: We evaluated thallium-201 (201Th) clearance measurement during exercise myocardial scintigraphy in patients with coronary artery disease, for the assessment of coronary circulatory function and diagnosis. DESIGN: The clearance rate of 201Th was compared with the coronary flow reserve measured by Doppler coronary flow velocimetry. METHODS: We selected 20 patients who had chronic stable angina with single-vessel coronary artery disease of the left anterior descending artery (LAD) and underwent percutaneous transluminal coronary angioplasty (PTCA). Ten control patients had atypical chest pain but no detectable heart disease. Regional net clearance of 201Th was measured from the early and delayed bull's-eye images of 201Th exercise stress single photon emission tomography (SPECT). Using a Doppler catheter, we also measured coronary flow reserve of the LAD, which was obtained by the intracoronary administration of papaverine. RESULTS: The net 201Th clearance in the anterior wall myocardium in the patients with coronary artery disease before PTCA was significantly less than that in the controls. At follow-up angiography after successful PTCA, it increased. The coronary flow reserve before PTCA was also lower than that in the controls. It was increased immediately after PTCA, and was more markedly increased at the follow-up angiography. Before PTCA, regional net clearance in the anterior myocardium was correlated with the coronary flow reserve of the LAD. The ratio for the net clearance of the anterior myocardium at follow-up angiography to that before PTCA was also correlated with the ratio for coronary flow reserve. CONCLUSIONS: In patients with coronary artery disease, the regional 201Th clearance in the ischaemic area measured by exercise 201Th SPECT is correlated with the coronary flow reserve of the affected artery. Moreover, the increase in the clearance rate after PTCA is also correlated with that in the coronary flow reserve. Thus the measurement of regional 201Th clearance might be a useful non-invasive method of estimating of the coronary flow reserve.

Analysis of Variance↗
PubMed1996

[Effect of vitamin D receptor gene polymorphism on vitamin D therapy for postmenopausal bone loss].

In order to assess the effect of vitamin D receptor (VDR) gene polymorphisms on vitamin D3 therapy for postmenopausal bone loss. Thirty-four Japanese postmenopausal women, administered vitamin D3 (Alfarol 1.0 microgram/day) and Ca (2.0 g/day) for 18 months, were analyzed by RFLP. Bone mineral density (BMD) at the lumbar spine (L2-4) and Os-calcis were measured every 6 months by dual energy X-ray absorptiometry (DXA) and single energy X-ray absorptiometry (SXA). VDR gene allelic polymorphisms were assessed by Bsm 1 endonuclease restriction after specific PCR amplification. Genotypic polymorphism was defined as BB, bb and Bb. The genotypes were BB in 1 (3.1%), Bb in 13 (40.6%), and bb in 18 (56.3%). The women in these two major VDR genotype groups (Bb and bb) were similar in their backgrounds (in terms of age, body mass index, and BMD in premedication), but the VDR genotype was associated with the percent of change in BMD after treatment. In Group-Bb, the mean percent increases in L2-4 BMD were 3.2%, 4.9% and 4.1% at 6, 12 and 18 months. In contrast, in Group-bb they were 0.8%, 1.8% and 1.2% at the same points. Analysis of VDR alleles may prove useful in selecting the vitamin D therapy for osteopenia before treatment.

Aged↗