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Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 127 records · Page 7Linked to original sources
PubMed1999

In vivo adenovirus-mediated gene transfer and expression in ischemic rabbit spinal cord.

PURPOSE: In an attempt to study whether ischemic spinal cord expresses a foreign gene in vivo, a replication-defective adenoviral vector containing the Escherichia coli lacZ gene was directly injected into the ischemic spinal cord of rabbits, and temporal and spatial profiles of the exogenous gene expression were compared with that of the control spinal cord. METHODS: Thirty-nine Japanese domesticated white rabbits weighing 2 to 3 kg were used in this study and were divided into two subgroups, a 15-minute ischemia group and a sham control group. The adenoviral vector was directly injected into lumbar spinal cord by a needle from dorsal spine just after the infrarenal aortic occlusion in the case of ischemia. Animals were allowed to recover at ambient temperature and were killed at 1, 2, 4, and 7 days after reperfusion (n = 3 at each time point). RESULTS: In the control rabbit, adenoviral vector was transferred into the spinal cord, and the lacZ gene was expressed at dorsal astroglia and anterior motor neurons at 1 to 7 days of reperfusion. After 15 minutes of ischemia, the lacZ gene was expressed at 2 and 4 days of reperfusion in dorsal astroglia and anterior motor neurons, which were positive for Fas antigen. CONCLUSION: This result suggests that it is possible to transfer and express the lacZ gene in ischemic motor neurons, which eventually show apoptotic change with induction of Fas antigen, and also suggests a great potential of gene therapy for paraplegic patients in the future.

Adenoviridae↗
PubMed1999

A randomised dose-comparison trial of granisetron in preventing emesis in children with leukaemia receiving emetogenic chemotherapy.

This randomised study was performed to assess the anti-emetic efficacy and tolerability of two-dose regimens of granisetron in children with leukaemia. 49 children with leukaemia were treated with three consecutive courses of high-dose methotrexate or cytarabine regimen. During the first course, patients were evaluated regarding the emetogenicity of each regimen. They were randomised in a crossover manner to receive 20 or 40 micrograms/kg of granisetron before the second and third course of chemotherapy. Neither emesis nor severe appetite loss were observed in over 80% of patients within the first 24 h in all treatment groups. There was no significant difference in the anti-emetic efficacy between the two-dose regimens of granisetron. However, complete protection was achieved less frequently on days 2 and 3. Older children and girls appeared to be less well protected. No adverse events attributable to granisetron were observed. Granisetron dose regimens of 20 and 40 micrograms/kg are, comparably, well tolerated and effective in controlling chemotherapy-induced emesis in the first 24 h, though this protection fails thereafter, particularly in older patients and girls.

Adolescent↗
PubMed1999

Synthesis and antibacterial activity of novel 4-pyrrolidinylthio carbapenems. Part III: Novel 2-alkyl substituents containing cationic heteroaromatics linked via a C-N bond.

The synthesis and biological activity of a novel series of 2-alkyl-4-pyrrolidinylthio-beta-methylcarbapenems containing a variety of cationic heteroaromatic substituents is described. As a result of these studies, we uncovered a relationship between in vitro antibacterial activity and the length of the alkyl spacer part, and discovered FR20950 (1c), containing a two methylene spacer moiety and an imidazolio group, which possesses a balanced spectrum of antibacterial activity, including Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, FR20950 exhibited excellent urinary recovery, and comparable stability against renal dehydropeptidase-I (DHP-I) to Biapenem. DHP-I stability could be improved by introduction of a substituent on to the imidazole ring.

Animals↗
PubMed1999

Chromosome abnormalities and MLL rearrangements in acute myeloid leukemia of infants.

Of 29 infants with acute myeloid leukemia (AML), 14 (48%) had various 11q23 translocations. MLL rearrangements were examined in 21 of the 29 patients, and 11 (52%) showed the rearrangements. 11q23 translocations and/or MLL rearrangements were found in 17 (58%) of the 29 patients. While all but one of the 17 patients with 11q23/MLL rearrangements had M4 or M5 type of the FAB classification, the 12 patients without such rearrangements had various FAB types, including M2, M4, M4EO, M6 and M7. Of the 12 patients with other chromosome abnormalities or normal karyotypes, two had inv(16) ort(16;16), one had t(1;22)(p13;q13), and two had a novel translocation, t(7;12)(q32;p13). The breakpoint on 12p of the t(7;12) was assigned to intron 1 or the region just upstream of exon 1 of the TEL/ETV6 gene by fluorescence in situ hybridization. The event-free survival at 5 years for the 17 patients with 11q23/MLL rearrangements was 42.2%, and that for the 12 patients without such rearrangements was 31.3% (P = 0.5544). 11q231MLL rearrangements have been frequently reported and a poor prognosis in infant acute lymphoblastic leukemia implied. Our study showed that while 11q23/MLL rearrangements were also common in infant AML, AML infants with such rearrangements had a clinical outcome similar to that of AML infants without such rearrangements.

Acute Disease↗
PubMed1999

Human dendritic cells express the thrombopoietin receptor, c-Mpl.

Human thrombopoietin (TPO) is a haemopoietic growth factor that is essential for the growth and development of megakaryocytes. However, c-Mpl, the TPO receptor, has been detected in human leukaemic cell lines with a myelomonocytic phenotype. These results raise the possibility that dendritic cells (DC), a putative myeloid lineage cell, may also express c-Mpl and respond to TPO. In haemopoietic stem cell transplantation, DC could induce graft-versus-host disease by its strong antigen-presenting capacity. In this study we have examined the effect of TPO on differentiation and the antigen-presenting capacity of DC. To differentiate DC, cord blood CD34+ cells were cultured in the presence of a cytokine cocktail either in serum-free medium or RPMI1640 containing 10% fetal bovine serum. Flow cytometric analysis and immunocytochemical staining demonstrated that c-Mpl was expressed on DC. Furthermore, the expression of c-Mpl mRNA was detected in DC by RNase protection assay. However, when TPO was added to the culture system there were no significant changes in the differentiation and mixed leucocyte-stimulating capacity of DC. These findings suggest that TPO may be administered following cord blood transplantation without significant augmentation of antigen presentation mediated by DC.

Cell Division↗
PubMed1999

Expression of angiogenic factors in rabbit spinal cord after transient ischaemia.

It is known that angiogenic factors are induced in brain by ischaemia, and new vessel formation is correlated with better prognosis in patients of stroke. However, the role of angiogenesis and expression of angiogenic factors in spinal cord ischaemia is uncertain. We here investigated expression of three highly potent angiogenic peptides, i.e. basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) in the rabbit spinal cord after transient ischaemia, by Western blot and immunohistochemical analysis. Western blot analysis revealed that bFGF was induced at 8 h after transient ischaemia and decreased thereafter. Immunoreactive VEGF was also induced at 8 h, and it disappeared thereafter. HGF was not detected in the spinal cord with sham-operation or ischaemic injury. By immunohistochemical analysis, bFGF was weakly expressed in only a few small interneurons in sham-operated spinal cords. However, it was induced to a marked degree in motor neurons and interneurons of the anterior horn at 8 h after reperfusion. It was also induced in small neurons of the posterior horn. The expression in the anterior horn decayed thereafter though it lasted until 7 d in the posterior horn. VEGF was not expressed in sham-operated spinal cords, but the expression was induced in large motor neurons and interneurons at 8 h with marked reduction at 1 d. In contrast, HGF was not expressed in the spinal cord with sham-operation or ischaemic injury. These factors are known to play pivotal roles in angiogenesis, regulation of blood flow, and protection of endothelial cells. Through induction of these angiogenic peptides, protection of vascular endothelial cells and improvement of regional blood flow might be occurring in the spinal cord after ischaemia.

Acute Disease↗
PubMed1999

DNA fragmentation precedes aberrant expression of cell cycle-related protein in rat brain after MCA occlusion.

Recent experiments suggest that apoptotic mechanisms are involved in neuronal cell death after ischemic injury. Although the exact mechanism that triggers activation of apoptotic machinery remains uncertain, in vitro studies revealed that forced expression of cell cycle-related proteins induced apoptosis. Thus, aberrant expression of such proteins might be related to ischemic neuronal death. In the present experiment, we investigated expression of cell cycle-related proteins, i.e., cyclin B1, cyclin D1, cdk4, and PCNA, in rat brain after transient MCA occlusion, and compared the temporal profile of the results with that of TUNEL study, which detects double strand breaks in DNA. There were no immunoreactivities for cyclin B1, cyclin D1, and PCNA in the brain with and without ischemia. As for cdk4, however, it became present at 1 and 3 days of reperfusion after 2 h of ischemia. On the other hand, TUNEL positive cells appeared as early as 3 h of reperfusion, which peaked at 1 and 3 days. These results indicate that aberrant expression of cdk4, but not cyclin B1, cyclin D1 or PCNA, actually takes place in the brain after MCA occlusion, but this is not the causative mechanism of apoptotic cell death in the brain with ischemia.

Animals↗
PubMed1999

Epitopes and functional responses defined by a panel of anti-Fas (CD95) monoclonal antibodies.

Fas (CD95) is a cell surface glycoprotein that mediates apoptotic cell death when cross-linked with agonistic anti-Fas monoclonal antibodies (MAbs) or the endogenous Fas ligand. In this study, we investigated the in vitro biological properties of a panel of anti-human Fas MAbs. We found that five anti-Fas MAbs of IgG1 subclass (B.E28, B.G30, B.L25, DX2, and B.G34) induced marked apoptotic cell death in Fas-expressing leukemia cells, although this killing was delayed when compared to the cytolytic effect mediated by the prototypic anti-Fas MAb of IgM subclass (clone CH-11). On the other hand, four clones (ZB4, B.G27, B.D29, and B.K14) efficiently blocked apoptotic cell death induced by the CH-11 MAb or Fas ligand. The ability of these MAbs to inhibit cell death appeared to correlate with their relative affinity for the Fas molecule. Furthermore, different clones recognized the same epitope and elicited different effects (induction or inhibition of cell killing); conversely, different clones elicited the same effect but recognized different epitopes. These results suggest that the different biological effects of anti-Fas MAbs would not be mediated in an epitope-restricted manner. The relative binding affinity might correlate to some extent with the biological properties of the MAb.

Animals↗
PubMed1999

Lambert-Eaton myasthenic syndrome associated with idiopathic thrombocytopenic purpura and diffuse panbronchiolitis: long-term remission after a course of intravenous immunoglobulin combined with low-dose prednisolone.

We report a case of Lambert-Eaton myasthenic syndrome (LEMS) associated with idiopathic thrombocytopenic purpura (ITP) and diffuse panbronchiolitis (DPB). An extensive search for malignancy yielded negative results. Interestingly, ITP and DPB developed simultaneously when the patient suffered from myasthenic symptoms. This is the first report in the Japanese or English literature of an association of LEMS, ITP, and DPB. The use of cholinesterase blocker alone did not improve the myasthenic symptoms, and the symptoms and signs relapsed with the tapering of prednisolone (PSL) dosage. However, after administration of immunoglobulin (IVIG) (0.4 g/kg/day x 5 days), low-dose PSL (20 mg/day) alleviated the LEMS and ITP, and the diseases have remained in remission for 8 months without additional IVIG. We suspect that there is a synergistic relationship between IVIG and PSL.

Anti-Inflammatory Agents↗
PubMed1999

Effect of hydrostatic pressure on unfolding of alpha-lactalbumin: volumetric equivalence of the molten globule and unfolded state.

The effect of pressure on the unfolding of bovine alpha-lactalbumin was investigated by ultraviolet absorption methods. The change of molar volume associated with unfolding, deltaV, was measured in the presence or absence of guanidine hydrochloride at pH 7. The deltaV was estimated to be -63 cm3/mol in the absence of a chemical denaturant. While in the presence of guanidine hydrochloride (GuHCl), it was found that deltaV was -66 cm3/mol at 25 degrees C and was independent of the concentration of GuHCl, despite the fact that the molten globule fraction in the total unfolding product decreased with the increase of GuHCl concentration. The results indicate that the volume of alpha-lactalbumin only changes at the transition from a native to a molten globule state, and almost no volume change has been found during the transition from a molten globule to the unfolded state.

Animals↗
PubMed1999

Mast cell chymase in pulmonary hypertension.

Mast cells are known to be involved in various types of tissue remodelling but their role in pulmonary hypertension is still poorly understood. Two subtypes of mast cells have recently been identified by demonstrating one protease, chymase. This enzyme might be implicated in vascular remodelling. The changes in mast cells in lung tissue from three patients with primary or secondary pulmonary hypertension were therefore investigated. Compared with tissue from four control subjects the number of mast cells in the three patients was markedly increased, which suggests that chymase containing mast cells are involved in tissue remodelling accompanied by fibrotic changes in primary and secondary pulmonary hypertension.

Adult↗
PubMed1999

A nucleoside-sensitive organic cation transporter in opossum kidney cells.

Renal secretion of organic cations and anions are pleiotropic, active processes in mammals. Some nucleosides such as deoxyadenosine (dAdo), 2-chlorodeoxyadenosine, and azidothymidine are secreted by human and rodent kidneys. Previous work (J. A. Nelson, J. F. Kuttesch, Jr., and B. H. Herbert. Biochemical Pharmacology 32: 2323-2327, 1983) indicated a role for the classic organic cation transporter (OCT) in the secretion of the dAdo analog, 2'-deoxytubercidin, by mouse kidney. Using [14C]tetraethylammonium bromide ([14C]TEA) as a substrate, we tested several renal cell lines for a nucleoside-sensitive OCT. American opossum kidney proximal tubule cells (OK) express a cimetidine-sensitive and metabolic-dependent ability to efflux TEA. Other classic OCT inhibitors and several nucleosides also inhibit TEA efflux by these cells in a manner reflecting structural specificity for the carrier. Inhibition of OCT by nucleosides is not a universal feature of OCTs, since TEA transport mediated by cloned rat kidney OCT2 in the Xenopus laevis oocyte system was not inhibited by the same nucleosides. In conclusion, OK cells appear to possess an OCT that may also transport some nucleosides by a novel carrier.

Animals↗
PubMed1999

Exercise training does not alter acetylcholine-induced responses in isolated pulmonary artery from rat.

In chronic exercise-trained animals, acetylcholine (ACh)-stimulated endothelial nitric oxide (NO) release is enhanced in the systemic circulation. The purpose of the present study was to determine whether chronic exercise training also enhances NO-mediated relaxation in rat pulmonary artery. Sprague-Dawley rats were randomly divided into groups of exercise-trained and sedentary control rats. The exercise-trained rats ran on a motor-driven treadmill at 30 m x min(-1) up a 15 degree incline 10-60 min x day(-1), 5 days per week for 10 weeks, and had less body weight, lower serum total cholesterol and triglyceride levels than sedentary rats. Contraction induced by potassium chloride and prostaglandin (PG)F2alpha were similar between isolated conduit pulmonary arterial rings from sedentary and exercise-trained rats. There were no differences between PGF2alpha-precontracted rings from sedentary and exercise trained rats in both ACh and sodium nitroprusside-induced relaxations. The NO synthase inhibitor, nitro-L-arginine, suppressed ACh-induced relaxation in both sedentary and exercise-trained rats. These results suggested chronic exercise training did not alter the acetylcholine-induced endothelial NO production and release and the sensitivity of vascular smooth muscle cell to NO in isolated conduit pulmonary artery of rat.

Acetylcholine↗
PubMed1999

Differentiation of donor primordial germ cells into functional gametes in the gonads of mixed-sex germline chimaeric chickens produced by transfer of primordial germ cells isolated from embryonic blood.

This study was carried out to elucidate whether primordial germ cells, obtained from embryonic blood and transferred into partially sterilized male and female recipient embryos, could differentiate into functional gametes and give rise to viable offspring. Manipulated embryos were cultured until hatching and the chicks were raised until maturity, when they were mated. When the sex of the donor primordial germ cells and the recipient embryo was the same, 15 out of 22 male chimaeric chickens (68.2%) and 10 out of 16 female chimaeric chickens (62.5%) produced donor-derived offspring. When the sex of the donor primordial germ cells and the recipient embryo was different, 4 out of 18 male chimaeric chickens (22.2%) and 2 out of 18 female chimaeric chickens (11.1%) produced donor-derived offspring. The rates of donor-derived offspring from the chimaeric chickens were 0.6-40.0% in male donor and male recipient and 0.4-34.9% in female donor and female recipient. However, the rates of donor-derived offspring from the chimaeric chickens were 0.4-0.9% in male donor and female recipient and 0.1-0.3% in female donor and male recipient. The presence of W chromosome-specific repeating sequences was detected in the sperm samples of male chimaeric chickens produced by transfer of female primordial germ cells. These results indicate that primordial germ cells isolated from embryonic blood can differentiate into functional gametes giving rise to viable offspring in the gonads of opposite-sex recipient embryos and chickens, although the efficiency was very low.

Animals↗
PubMed1999

Restoration of shoulder movement in quadriplegic and hemiplegic patients by functional electrical stimulation using percutaneous multiple electrodes.

The purpose of this study is to restore the motion of the paralyzed shoulder caused by upper motor neuron disorders using functional electrical stimulation (FES). Percutaneous wire electrodes were implanted into twelve muscles of the shoulder in six patients with stroke or cervical spinal cord injury. The motion of the paralyzed shoulder was controlled by a portable FES computer system, with the three standard stimulation patterns for restoring motion of 90 degrees flexion to 90 degrees horizontal abduction, 90 degrees flexion to 20 degrees horizontal adduction, and 90 degrees abduction to 90 degrees horizontal adduction. Shoulder movements were repeatedly controlled according to the created stimulation patterns in five of the patients. The two dimensional motion analyzer also confirmed shoulder control over a satisfactorily broad range of excursion. One hemiplegic patient, who was a signboard painter, had his paretic left upper extremity improved by FES, and he drew a large picture on a board with his normal right hand and, with his affected left arm against the wall, to support his trunk. This may be a world first case of producing shoulder motion through FES.

Adult↗
PubMed1999

Electromyographic study relating to shoulder motion: control of shoulder joint by functional electrical stimulation.

The purpose of this study is to create the standard stimulation patterns of shoulder motion from electromyographic (EMG) data in 13 healthy human volunteers in order to control the movement of the paralyzed shoulder in quadriplegic and hemiplegic patients by functional electrical stimulation (FES). Simultaneous EMG measurement was made at 24 points of 17 major muscles relating to shoulder motion. Since the number of the output channels in the portable FES apparatus is limited, 12 major muscles were selected from statistically processing these EMG data and stimulation patterns were created based on the EMG data of these muscles. Thus three standard stimulation patterns were created to move the shoulder, i.e., (i) 90 degrees flexion to 90 degrees horizontal abduction, (ii) 90 degrees flexion to 20 degrees horizontal adduction, and (iii) 90 degrees abduction to 90 degrees horizontal adduction. With the created stimulation patterns, the restoration of the shoulder motion in plegic patients was successful and it will be reported in the next paper.

Adolescent↗
PubMed1999

Correlation between findings on chest radiography and survival in neonates with congenital diaphragmatic hernia.

OBJECTIVE: Predictors of survival are helpful when deciding on aggressiveness of care of neonates with congenital diaphragmatic hernia and respiratory failure. We evaluated findings on chest radiography as potential predictors of survival in these patients. MATERIALS AND METHODS: Findings on chest radiographs of neonates less than 24 hr old with congenital diaphragmatic hernia were evaluated. Radiographic findings analyzed included percentage of aerated ipsilateral lung, percentage of aerated contralateral lung, mediastinal shift, and hernia contents. Each finding was compared with survival (equated with hospital discharge) using a Mantel-Haenszel chi-square test. Survival was also determined using the total number of poor prognostic findings present in any one patient. RESULTS: In the 73 neonates with congenital diaphragmatic hernia in our study, the overall survival rate was 55%. There were statistically significant relationships between survival rate and percentage of ipsilateral aeration (p = 0.001), percentage of contralateral aeration (p = 0.016), and mediastinal shift (p = 0.026). The survival rate for multiple poor prognostic factors was 0% with four of four factors and 20% with three of four factors (p = 0.001). Survival rate was not influenced by prematurity (p = 0.102), sex (p = 0.104), or side of hernia (p = 0.895). CONCLUSION: Findings on initial chest radiography are helpful in predicting survival in neonates with congenital diaphragmatic hernia.

Female↗