Biomedical subjects

A Sakai

Publications and source records attributed to A Sakai.

At least 109 records · Page 6Linked to original sources

PubMed1998

Bone marrow cell development and trabecular bone dynamics after ovariectomy in ddy mice.

To clarify the relationship between the sequential changes of trabecular bone turnover and bone marrow cell development in ovariectomized (ovx) mice, bilateral tibiae of 8-week-old ddy mice were obtained. Histomorphometric analyses of the trabecular bone of the proximal tibia of ovx mice revealed increases in the bone formation rate and the osteoclast surface for the first 28 days postovariectomy. The trabecular bone volume showed a rapid decrease for the first 28 days and a steady state for the subsequent 14 days. In bone marrow cell culture experiments, the numbers of total and nonadherent bone marrow cells per tibia obtained from the ovx mice increased. The formation of osteogenic nodules and osteoclast-like multinucleated cells in the marrow cultures obtained from ovx limbs showed a significant increase on days 14 and 28 and returned to the sham-operated level by day 42. The numbers of colony forming units (fibroblastic) and colony forming units (granulocytes and macrophages) that developed from the marrow cells did not differ between the ovx and sham limbs at any time during the study period. Fluorescence-activated cell-sorter analysis revealed no population changes in the cell development of macrophages. These results demonstrate that there are two stages in the development of osteopenia after ovx. During the first 28 days after ovx, the ovariectomy enhances the developmental process from bone marrow stromal cells to osteoblasts and the terminal differentiation from osteoclast precursors to mature osteoclasts. The trabecular bone turnover also increases. In the subsequent 14 days, the changes in the osteogenic and osteoclastogenic potentials of the bone marrow cells are alleviated and the trabecular bone dynamics are in a steady state. The changes in bone marrow cell development are closely associated with those at the trabecular bone surface.

Animals↗

PubMed1998

Dhh1p, a putative RNA helicase, associates with the general transcription factors Pop2p and Ccr4p from Saccharomyces cerevisiae.

The POP2 (Caf1) protein in Saccharomyces cerevisiae affects a variety of transcriptional processes and is a component of the Ccr4p complex. We have isolated five multicopy suppressor genes of a pop2 deletion mutation: CCR4, DHH1 (a putative RNA helicase), PKC1, STM1, and MPT5 (multicopy suppressor of pop two). Overexpression of either the CCR4 or DHH1 genes effectively suppressed phenotypes associated with pop2 mutant cells; overexpression of PKC1, STM1, or MPT5 genes produced only partial suppression. Disruption of the CCR4 or DHH1 genes resulted in phenotypes similar to those observed for pop2 cells. In addition, overexpression of the DHH1 gene also suppressed the ccr4 mutation, suggesting a close relationship between the POP2, CCR4, and DHH1 genes. Two-hybrid analysis and coimmunoprecipitation experiments revealed that Pop2p and Dhh1p interact physically, and these and other data suggest that Dhh1p is also a component of the Ccr4p complex. Finally, we investigated the genetic interaction between factors associated with POP2 and the PKC1 pathway. The temperature-sensitive growth defect of dhh1 or mpt5 cells was suppressed by overexpression of PKC1, and the defect of mpk1 cells was suppressed by overexpression of MPT5. These results and phenotypic analysis of double mutants from the POP2 and PKC1 pathways suggested that the POP2 and the PKC1 pathways are independent but have some overlapping functions.

Bacterial Proteins↗

PubMed1998

Transcriptional activities of the chloroplast-nuclei and proplastid-nuclei isolated from tobacco exhibit different sensitivities to tagetitoxin: implication of the presence of distinct RNA polymerases.

We examined the effects of tagetitoxin, a potent inhibitor of RNA polymerases from chloroplasts and Escherichia coli, on the transcriptional activities of chloroplast- and proplastid-nuclei (nucleoids) isolated from mature tobacco (Nicotiana tabacum L.) leaves and cultured tobacco cells (line BY-2), respectively. Transcription by the isolated chloroplast-nuclei was effectively inhibited by tagetitoxin (95-99% reduction at 10 microM tagetitoxin), but transcription by the isolated proplastid-nuclei was only partially inhibited (40-50% reduction) by this compound. Southern hybridization experiments revealed that the transcription of various plastid genes (psbA, atpA, rpoB, psaA/B, atpB, rbcL, petB, rpl16, and rrn23) was sensitive to tagetitoxin in the isolated chloroplast-nuclei, whereas the transcription of the same genes was relatively resistant to this compound in the isolated proplastid-nuclei. These results suggest that; (i) distinct RNA polymerase activities with different sensitivities to tagetitoxin are present in plastids, (ii) a tagetitoxin-sensitive RNA polymerase is the major RNA polymerase in chloroplasts whereas a tagetitoxin-insensitive enzyme is major in proplastids, and (iii) both RNA polymerases can transcribe various plastid genes.

Aurintricarboxylic Acid↗

PubMed1998

Preparation and characterization of echogenic liposome as an ultrasound contrast agent: size-dependency and stabilizing effect of cholesterol on the echogenicity of gas-entrapping liposome.

The liposome entrapping CO2 gas inside the vesicle, which is called the echogenic liposome, has been made and characterized in vitro as an ultrasound contrast agent. The small unilamellar vesicle (SUV), large unilamellar vesicle (LUV) and multilamellar vesicle (MLV) as echogenic liposomes were compared in their echogenic efficiency and stability, and the effect of size and acoustic property was tested. The acoustic reflectivity increased with the increase in size of the vesicle, largest for the gas filled MLV among the three liposome suspensions. The acoustic reflectivity obtained with the echogenic MLV was larger than that of the gas bubbles enclosed within a surfactant mixture. A half-lifetime of 39 min was observed for the MLV prepared from egg-yolk phosphatidylcholine liposomes. The duration of reflectivity was prolonged drastically to a half-lifetime of 866 min by incorporating cholesterol into the MLV, although the echogenicity was decreased by such incorporation. The stabilizing effect of cholesterol for the ordinary liposomal membrane was thus ascertained in the present case of the gas-entrapping liposome. Our findings encourage the future development of improved gas-entrapping liposomes for the clinical trials of ultrasound contrast agents.

Chemical Phenomena↗

PubMed1998

Rearing of Plateau pika (Ochotona daurica) captured in Mongolia.

We attempted to rear and breed Plateau pikas (Ochotona daurica) captured in Mongolia in 1994 and 1995. In rearing indoors, though coitus was observed, none of the females became pregnant. In rearing outdoors, males began to make high-pitched, continuous cries and the first offspring (3 newborns) were obtained in June, 1997. The body weight averaged 8.4 g at birth, and 75.8 g at 4 weeks of age. They were weaned at 4 weeks of age. In August the testes, which had descended into the scrotum, atrophied. In September, the atrophied testes returned to the abdominal cavity. These results indicate that breeding of plateau pikas is possible when they are reared outdoors, and they have a specific reproductive season.

Animals↗

PubMed1998

Can recovered protein from the CAPD patient's own dialysis effluent substitute for dextrose?

Albumin has been evaluated as an osmotic agent for peritoneal dialysis as being physiologically safe and having modest colloidal osmotic pressure. However its extremely high cost inhibits clinical applications, and hypoalbuminemia is often seen in continuous ambulatory peritoneal dialysis (CAPD) patients, especially those with high peritoneal equilibration test (PET) values and who lose a large quantity of albumin everyday. This study aims at recovering protein from CAPD effluent and reusing it safely at reasonable cost as a substitute for dextrose. The dialysis effluent was collected and concentrated with a semipermeable membrane. Uremic toxins and low-molecular-weight solutes were removed by repeated filtration and water dilution. The concentrate was acidified with hydrochloric acid down to pH 2, thence de-acidified with water dialysis up to pH 5. At this point, the isoelectric point of albumin, at which precipitate was deposited, the precipitate was separated from the supernatant and re-dissolved into electrolyte solution. The acidified concentrate exhaled an unpleasant odor, like that of decayed food. The precipitate solution, however, did not smell at all. The initial ultrafiltration rate of the recovered protein solution was measured and compared with that of dextrose and dextran by using a high-sensitivity differential manometer, one end of which was connected with the test solution cell, and the other with the serum cell. The ends were separated by a semipermeable membrane. The recovered protein solution at 20 g/dL concentration was almost equivalent in initial ultrafiltration rate to the 2.0 g/dL dextrose solution and to 20 g/dL dextran (MW: 75,000 dalton) solution.

Albumins↗

PubMed1998

Floating density of hepatitis C virus particles and response to interferon treatment.

Hepatitis C virus (HCV) particles can be classified into two major fractions according to their floating density in serum. However, the genomic heterogeneity of each fraction and the relationship between this viral characteristic and interferon (IFN) response in patients with chronic hepatitis are not known. In this study, floating density and single strand conformation polymorphism (SSCP) of the hypervariable region 1 (HVR1) of HCV were examined in 16 patients with chronic hepatitis prior to IFN treatment. The ratio of HCV RNA titers in the top (T) and bottom (B) fractions, or T:B ratio, was 10:1 in 4 patients, 1:1 in 7, and 1:10 in 5. Three of the 4 patients with a 10:1 ratio showed a sustained response to IFN, while none of the 5 patients with a 1:10 ratio demonstrated a sustained response (P < 0.05). All 4 patients with a 10:1 ratio had 1 or 2 SSCP bands, and 4 of the 5 patients with a 1:10 ratio had 4 or 5 bands (P < 0.01). Furthermore, the number of SSCP bands in the top fraction from 6 sustained responders (1.8 +/- 0.3) was significantly smaller than from 10 non sustained responders (4.1 +/- 0.8) (P < 0.05). Thus, patients with a high T:B ratio and low heterogeneity in HVR1 demonstrated sustained responses to IFN, while those with low T:B ratios and high heterogeneity did not.

Adult↗

PubMed1998

[Effect of diltiazem on jugular bulb oxygen saturation (SjO2)].

We investigated the effect of diltiazem on jugular bulb oxygen saturation (SjO2) in patients undergoing superficial temporal artery-middle cerebral artery anastomosis. In the presence of stable vital signs, diltiazem was administered by continuous infusion (2 micrograms.kg-1.min-1). There was no significant change in blood pressure, heart rate, SjO2 in response to diltiazem administration. The arterial plasma concentration of diltiazem reached 75 +/- 14.2 ng.ml-1 after 180 min. The difference of areas under the curve between the arterial and jugular venous diltiazem concentrations from start of infusion to the end was significant. We conclude that this dose of diltiazem produced effective concentration and uptake in the brain tissue, but produced no significant effect on jugular bulb oxygen saturation (SjO2).

Aged↗

PubMed1998

[Criteria and classification for diagnosis of osteoporosis in Japan].

Osteoporosis has become one of the most serious medical and social problems in Japan, as the number of elderly people is increasing. Osteoporosis should be diagnosed early and treated properly to maintain the patients' quality of life before associated fractures occur. The Japanese society for bone and mineral research prepared the criteria for diagnosis of osteoporosis in 1995 and modified them in 1996. Here, we explained the 1996's modified criteria and described the actual way to diagnose osteoporosis. Low bone mass is evaluated by radiographic osteopenia or bone mineral density in lumbar body. We have to exclude the other disorders showing low bone mass.

Aged↗

PubMed1998

[Clinical efficacy and reduction effect on prostatic volume of chlormadinone acetate combined with tamsulosin hydrochloride in benign prostatic hyperplasia patients insufficiently treated with tamsulosin hydrochloride only].

Alpha adrenergic blocker has become the first choice in the medical treatment of benign prostatic hyperplasia (BPH). The efficacy of alpha adrenergic blocker has been suggested to be related to the prostatic tissue components, and to be ineffective in treating the clinical symptoms caused by BPH in some cases. The efficacy and prostate reduction of an anti-androgenic agent, chlormadinone acetate, combined with alpha adrenergic blocker, tamsulosin hydrochloride, were evaluated using 40-BPH patients insufficiently treated with tamsulosin hydrochloride alone. Fifty mg of chlormadinone acetate and 0.2 mg of tamsulosin hydrochloride were administered orally once a day for 16 weeks to patients with a prostate subjective symptoms score, I-PSS, of greater than 13 or a peak flow rate of less than 12 ml/s, even after the treatment with 0.2 mg of tamsulosin hydrochloride alone for more than four weeks. Total I-PSS decreased significantly after four weeks. The total irritative symptom score did not change for 16 weeks, but the total obstructive symptom score decreased significantly, as did the total I-PSS. In objective data, the estimated volume of both total prostate and the transition zone on transrectal ultrasonogram decreased significantly at the end of the treatment, and the peak flow rate decreased significantly after 12 weeks. These findings suggest that the addition of chlormadinone acetate may be a reasonable alternative in the treatment of BPH patients responding insufficiently to tamsulosin hydrochloride alone, and that combination therapy using chlormadinone acetate and tamsulosin hydrochloride may be useful for BPH patients with serious obstructive symptoms.

Adrenergic alpha-Antagonists↗

PubMed1997

Promoting activity of 3-tert-butyl-4-hydroxyanisole (BHA) in BALB/3T3 cell transformation.

3-Tert-butyl-4-hydroxyanisole (BHA), a synthetic antioxidant, is an initiator in the transformation of BALB/3T3 mouse embryo cells, when cells are treated first with the chemical and then with a tumor promoter, 12-O-tetradecanoylphorbol-13-acetate. In the present study, BHA was examined for its promoting activity in BALB/3T3 cell transformation. BHA in a range of 5-20 microg/ml enhanced transformation induced by a subthreshold dose of 3-methylcholanthrene (MCA, 0.1 microg/ml) in a dose-dependent manner. Statistically significant increases were noted in the proportion of dishes with transformed foci in the cultures treated with 10 and 20 microg/ml BHA following MCA as compared to the cultures treated with MCA alone. When BHA was applied to the cultures both on initiating and promoting stages in the absence of another initiator or promoter, however, BHA did not increase the transformation frequency, suggesting that the transforming activities of BHA are too weak and require combination with a potent initiator or promoter to attain complete transformation in this assay system. BHA did not increase postconfluent cell density nor induce DNA synthesis in density-arrested cells, suggesting that cell proliferation is excluded from the causal events of transformation enhancement by BHA in BALB/3T3 cells.

3T3 Cells↗

PubMed1997

Induction of endothelial platelet-derived growth factor-B-chain and intercellular adhesion molecule-1 by lysophosphatidylcholine.

Lysophosphatidylcholine (lyso-PC) is a major phospholipid component of atherogenic lipoproteins. Lyso-PC has been shown to differentially upregulate the adhesion molecules, such as VCAM-1 and ICAM-1, as well as smooth muscle growth factors, such as PDGF-A, B chains and HB-EGF gene expression in various cultured endothelial cells. In this paper, we demonstrate increased expression of cell- and matrix-associated forms of PDGF-B protein elicited by lyso-PC and further characterized potential signal transduction mechanisms responsible for lyso-PC-induced human umbilical vein endothelial cell. Cycloheximide inhibited PDGF-B but not ICAM-1 mRNA induction by lyso-PC, suggesting the dependence on de novo protein synthesis for PDGF-B, but not ICAM-1. A protein kinase C (PKC) inhibitor did not block lyso-PC-induced increases in PDGF-B or ICAM-1 mRNA. The elevated level of cAMP blocked both PDGF-B and ICAM-1 upregulation by lyso-PC. However cAMP-elevating agents did not suppress ICAM-1 upregulation by PMA. Taken together, PDGF-B and ICAM-1 gene induction by lyso-PC may involve different signaling mechanisms; however, both appear to be independent of PMA-regulatable PKC activation but are suppressed by increased levels of intracellular cAMP.

Blotting, Northern↗

PubMed1997

[The effect of brain-derived neurotrophic factor on elongation of axons after transection with suture-morphometric evaluation].

Brain-derived neurotrophic factor (BDNF) is considered to play an important role in survival, maintenance, development and repair of the peripheral neuron. In this study, the effect of human recombinant BDNF on sprouting and elongation of axons, the early phase of regeneration of nerve fibers, was morphometrically evaluated 7 days following the sciatic nerve transection and juxtaposition of proximal and distal stumps with suture in Sprague-Dawley rats. In the experimental group (test), 20 mg/kg of BDNF was injected subcutaneously every day for seven days in eight rats, starting 30 minutes after the transection. In the control group (control), phosphate buffered-saline alone was injected in nine rats as in the experimental group. The various morphometric parameters were evaluated in the sciatic nerve of each rat of the control and test, 3 mm distal to the site of the transection on light and electron microscopy of Epon-embedded sections. On both light and electron microscopy only a few myelinated fibers with a very thin myelin sheath were found only in one nerve in each of the control and test. However, significant numbers of unmyelinated axons were found in each nerve of the control and test. There were no statistically significant differences in the total fascicular area per nerve, the numbers of myelinated and unmyelinated axons per mm2 of fascicular area and per nerve, their maximum and median diameters and their size distribution histograms between control and test. In addition, there were no statistically significant differences in the numbers of myelin ovoids per mm2 of the fascicular area and per nerve, their maximum and median diameters and their size distribution histograms between control and test. Therefore, we concluded that there was no definite evidence that BDNF promoted the sprouting and elongation of axons, the early phase of the regeneration of nerve fibers, at least under this experimental conditions.

Animals↗

PubMed1997

Congenital extension contracture of metacarpophalangeal joints.

We report a case of congenital extension contracture of the fifth metacarpophalangeal joints in a 15-year-old boy who had no associated anomalies and was successfully treated by surgery. Congenital extension contracture of bilateral metacarpophalangeal joints has not been reported previously, and the entity can be considered to be a new subgroup of distal arthrogryposis with congenital distal limb contracture.

Adolescent↗

PubMed1997

Study on the mechanism of immunopotentiating antitumor effect of 6-MPG, a water-soluble derivative of 6-mercaptopurine.

We investigated possible mechanisms of the antitumor action of gamma-(9H-purine-6-yl) thiomethyl L-glutamate (6-MPG), a water-soluble derivative of 6-MP. In the double grafted tumor system, BALB/c mice were inoculated intradermally with 10(6) cells of MethA fibrosarcoma at the right inguinal region on day 0 (the primary tumor) and later with 3 x 10(6) cells at the left on day 10 (the secondary tumor). Intraperitoneal administration of 6-MPG at a dose of 100 mg/kg/day from day 3 through 7 completely prevented growth of the secondary tumor. 6-MPG showed no effect on growth of colon 26 adenocarcinoma cells inoculated in place of the secondary MethA cells (antigen specificity). 6-MPG did not inhibit the secondary MethA growth in the BALB/c (nu/nu) mouse. The inhibitory effect of 6-MPG on the secondary tumor growth was diminished by prior treatment of the primed animals with cyclosporin A and anti-Thy antibody. Spleen cells from the tumor-bearing mice treated with 6-MPG showed a tumor-neutralizing activity (Winn assay). Treatment of the spleen cells with anti-CD8 antibody plus complement diminished the tumor-neutralizing effect but that with anti-CD4 antibody plus complement did not, indicating that CD8-positive cells are responsible for potentiation of the tumor immunity. These results suggest that the antitumor effect of 6-MPG against the secondary tumor is elicited by augmenting tumor specific T-cell production.

Adenocarcinoma↗

PubMed1997

Different mechanisms of ischemic adaptation to repeated coronary occlusion in patients with and without recruitable collateral circulation.

OBJECTIVES: The aim of this study was to investigate the interaction between ischemic preconditioning (IP) and collateral recruitment (CR) during ischemic adaptation in patients. BACKGROUND: The mechanism of ischemic adaptation still remains controversial in humans. METHODS: The clinical, electrocardiographic, hemodynamic and echocardiographic responses to three 150-s occlusions of the left anterior descending coronary artery were assessed in relation to CR in 18 patients with effort angina undergoing elective percutaneous transluminal coronary angioplasty. RESULTS: During the first occlusion, recruitable collateral circulation (RCC) to the occluded myocardium was detected by myocardial contrast echocardiography in 6 patients (Group C) and was not seen in 12 (Group N). In Group N, all patients manifested signs of severe ischemia during each inflation. However, their symptoms and ST segment shift significantly decreased from the first to the third occlusions, suggesting the occurrence of IP. The elevation of mean pulmonary artery pressure and deterioration of anterior wall motion were comparable between the first and the third occlusions in Group N. In contrast, myocardial ischemia was significantly less marked during occlusion in Group C than in Group N, and no preconditioning effect was observed. The extent of RCC did not differ between the first and the third occlusions in each group. CONCLUSIONS: Both IP and CR may play independent roles in ischemic adaptation in humans. With RCC, myocardial ischemia was greatly reduced. Without RCC, preconditioning clinically and electrocardiographically lessened myocardial ischemia but failed to preserve left ventricular function.

Angina Pectoris↗

PubMed1997

The cGMP pathway is not responsible for the blunted hypoxic vasoconstriction in rat lungs after altitude exposure.

To examine the contribution of the cyclic guanosine monophosphate (cGMP) pathway in changes in pulmonary vasoconstriction during the initial days of altitude exposure, we tested the effects of LY83583 (an inhibitor of guanylate cyclase activation) and those of N(G)-monomethyl-L-arginine (an inhibitor of nitric oxide synthesis) on airway hypoxia- (3% O2) and angiotensin II- (AII, 0.2 microg) induced vasoconstrictions in lungs from the rats exposed to either moderate altitude (MA, 570 torr) or high altitude (HA, 430 torr) At 2 days' exposure, hypoxic response was significantly blunted compared with the response in low-altitude (LA, 710 torr) lungs in an altitude-dependent manner. At 7 days' exposure, the response was recovered fully in MA lungs but partially in HA lungs. AII response was not significantly blunted at 2 days' exposure, but was significantly augmented in an altitude-dependent manner at 7 days' exposure. LY83583 (10 micromol L(-1)) potentiated both responses in LA lungs but did not significantly potentiate either response in any altitude-exposed lungs. N(G)-monomethyl-L-arginine (10 micromol L(-1)) potentiated both responses in LA lungs but did not significantly potentiate either response in HA lungs at 2 days' and 7 days' exposure. Thus the cGMP pathway is not responsible for either the change in hypoxic vasoconstriction or the change in AII vasoconstriction in rat lungs during the initial 7 days of altitude exposure.

Altitude↗

PubMed1997

Novel isoforms of rat brain fructose 6-phosphate 2-kinase/fructose 2,6-bisphosphatase are generated by tissue-specific alternative splicing.

Fructose 6-phosphate 2-kinase/fructose 2,6-bisphosphatase catalyzes the synthesis and degradation of fructose 2,6-bisphosphate, which is the most potent activator of glycolysis. We have shown previously the occurrence of a partial cDNA (RB7) encoding the catalytic core domain of a novel brain-type isozyme. To elucidate the full-length sequence of RB7 cDNA, we have carried out cDNA cloning using the 3'- and 5'-rapid amplification cDNA ends method and have isolated eight isoforms from rat brain. The cDNA sequences encoding the 5'-untranslated region, the amino-terminal domain, and the catalytic core domain were identical among all the isoforms. However, heterogeneity of the carboxyl-terminus was found by sequence analysis. This heterogeneity was shown not to have resulted from transcription of multiple genes, as Southern blot and genomic sequence analysis revealed that the gene was a single copy in the rat genome. It is likely that these transcripts represent splice variants of the gene. High-level expression of the gene was also observed by northern blot analysis in skeletal muscle. However, the pattern of alternative splicing was different from that of brain, and only four isoforms were detected in skeletal muscle.

Alternative Splicing↗