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Biomedical subjects

M Saito

Publications and source records attributed to M Saito.

At least 19 recordsLinked to original sources

Hypercalcemia in childhood acute lymphoblastic leukemia: frequent implication of parathyroid hormone-related peptide and E2A-HLF from translocation 17;19.

Hypercalcemia is relatively rare but clinically important complication in childhood leukemic patients. To clarify the clinical characteristics, mechanisms of hypercalcemia, response to management for hypercalcemia, incidence of t(17;19) and final outcome of childhood acute lymphoblastic leukemia (ALL) accompanied by hypercalcemia, clinical data of 22 cases of childhood ALL accompanied by hypercalcemia (>12 mg/dl) reported in Japan from 1990 to 2005 were retrospectively analyzed. Eleven patients were 10 years and older. Twenty patients had low white blood cell count (<20 x 10(9)/l), 15 showed hemoglobin> or =8 g/dl and 14 showed platelet count > or =100 x 10(9)/l. Parathyroid hormone-related peptide (PTHrP)-mediated hypercalcemia was confirmed in 11 of the 16 patients in whom elevated-serum level or positive immunohistochemistry of PTHrP was observed. Hypercalcemia and accompanying renal insufficiency resolved quickly, particularly in patients treated with bisphosphonate. t(17;19) or add(19)(p13) was detected in five patients among 17 patients in whom karyotypic data were available, and the presence of E2A-HLF was confirmed in these five patients. All five patients with t(17;19)-ALL relapsed very early. Excluding the t(17;19)-ALL patients, the final outcome of ALL accompanied by hypercalcemia was similar to that of all childhood ALL patients, indicating that the development of hypercalcemia itself is not a poor prognostic factor.

Adolescent↗

Beta3-adrenoceptor agonist AJ-9677 reduces body fat in obese beagles.

A selective beta3-adrenoceptor agonist, AJ-9677, was reported to ameliorate obesity and insulin resistance in KK-Ay mice. We examined the acute and chronic effects of AJ-9677 on obese dogs. Oral administration of AJ-9677 (0.01 or 0.1 mg/kg) to overnight fasted obese beagles produced a dose-dependent rise in the plasma levels of non-esterified fatty acids and insulin in 1h, followed by a gradual drop of the plasma glucose level. It produced no apparent abnormal behaviors, but easily detectable cutaneous flushing. Daily treatment of AJ-9677 at a lower dose (0.01 mg/kg) for three weeks produced no notable change in body weight, but at a higher dose (0.1 mg/kg) it reduced the body weight compared to a placebo treatment after seven weeks. Computed tomographic examinations revealed a remarkable reduction of body fat after the AJ treatment, being consistent with the histological observations that the adipose tissue of AJ-9677-treated dogs consisted of smaller and some multilocular adipocytes. The plasma levels of leptin and adiponectin were decreased and increased, respectively, after the AJ treatment, reflecting the reduction of adiposity. It was concluded that AJ-9677 is useful for the treatment of obesity in the dog.

Acetates↗

Purification of branched-chain amino acid aminotransferase from Helicobacter pylori NCTC 11637.

Branched-chain amino acid aminotransferase was purified by several column chromatographies from Helicobacter pylori NCTC 11637, and the N-terminal amino acid sequence was analyzed. The enzyme gene was sequenced based on a putative branched-chain amino acid aminotransferase gene, ilvE of H. pylori 26695, and the whole amino acid sequence was deduced from the nucleotide sequence. The enzyme existed in a homodimer with a calculated subunit molecular weight (MW) of 37,539 and an isoelectric point (pI) of 6.47. The enzyme showed high affinity to 2-oxoglutarate (K (m) = 0.085 mM) and L-isoleucine (K (m) = 0.34 mM), and V (max) was 27.3 micromol/min/mg. The best substrate was found to be L-isoleucine followed by L-leucine and L-valine. No activity was shown toward the D-enantiomers of these amino acids. The optimal pH and temperature were pH 8.0 and 37 degrees C, respectively.

Amino Acid Sequence↗

Fine mapping of the clubroot resistance gene, Crr3, in Brassica rapa.

A linkage map of Chinese cabbage (Brassica rapa) was constructed to localize the clubroot resistance (CR) gene, Crr3. Quantitative trait loci analysis using an F(3) population revealed a sharp peak in the logarithm of odds score around the sequence-tagged site (STS) marker, OPC11-2S. Therefore, this region contained Crr3. Nucleotide sequences of OPC11-2S and its proximal markers showed homology to sequences in the top arm of Arabidopsis chromosome 3, suggesting a synteny between the two species. For fine mapping of Crr3, a number of STS markers were developed based on genomic information from Arabidopsis. We obtained polymorphisms in 23 Arabidopsis-derived STS markers, 11 of which were closely linked to Crr3. The precise position of Crr3 was determined using a population of 888 F(2) plants. Eighty plants showing recombination around Crr3 locus were selected and used for the mapping. A fine map of 4.74 cM was obtained, in which two markers (BrSTS-41 and BrSTS-44) and three markers (OPC11-2S, BrSTS-54 and BrSTS-61) were cosegregated. Marker genotypes of the 21 selected F(2) families and CR tests of their progenies strongly suggested that the Crr3 gene is located in a 0.35 cM segment between the two markers, BrSTS-33 and BrSTS-78.

Arabidopsis↗

Role of spin-orbit coupling and hybridization effects in the electronic structure of ultrathin Bi films.

The electronic structure of Bi(001) ultrathin films (thickness > or =7 bilayers) on Si(111)-7x7 was studied by angle-resolved photoemission spectroscopy and first-principles calculations. In contrast with the semimetallic nature of bulk Bi, both the experiment and theory demonstrate the metallic character of the films with the Fermi surface formed by spin-orbit-split surface states (SSs) showing little thickness dependence. Below the Fermi level, we clearly detected quantum well states (QWSs) at the M point, which were surprisingly found to be non-spin-orbit split; the films are "electronically symmetric" despite the obvious structural nonequivalence of the top and bottom interfaces. We found that the SSs hybridize with the QWSs near M and lose their spin-orbit-split character.

Journal Article↗

Establishment of immortalized dental follicle cells for generating periodontal ligament in vivo.

The dental follicle is a mesenchymal tissue that surrounds the developing tooth germ. During tooth root formation, periodontal components, viz., cementum, periodontal ligament (PDL), and alveolar bone, are created by dental follicle progenitors. Here, we report the presence of PDL progenitors in mouse dental follicle (MDF) cells. MDF cells were obtained from mouse incisor tooth germs and immortalized by the expression of a mutant human papilloma virus type 16 E6 gene lacking the PDZ-domain-binding motif. MDF cells expressing the mutant E6 gene (MDF( E6-EGFP ) cells) had an extended life span, beyond 150 population doublings (PD). In contrast, normal MDF cells failed to proliferate beyond 10 PD. MDF( E6-EGFP ) cells expressed tendon/ligament phenotype-related genes such as Scleraxis (Scx), growth and differentiation factor-5, EphA4, Six-1, and type I collagen. In addition, the expression of periostin was observed. To elucidate the differentiation capacity of MDF( E6-EGFP ) cells in vivo, the cells were transplanted into severe combined immunodeficiency mice. At 4 weeks, MDF( E6-EGFP ) cell transplants had the capacity to generate a PDL-like tissue that expressed periostin, Scx, and type XII collagen and the fibrillar assembly of type I collagen. Our findings suggest that MDF( E6-EGFP ) cells can act as PDL progenitors, and that these cells may be a useful research tool for studying PDL formation and for developing regeneration therapies.

Alkaline Phosphatase↗

Giant combined microdissected thin thigh perforator flap.

Despite recent advances in reconstructive surgery, extremely wide and thin flap coverage has rarely been reported. Recently, the authors developed a technique for transferring a very wide and thin flap from the thigh area using microdissection. In this procedure, both perforators of the anterolateral thigh flap and the tensor fasciae latae perforator flap were microdissected simultaneously and these two perforator flaps were elevated in combination based on the common pedicle of the vessels. In this report, the detailed technique of the procedure is described along with a discussion of the safety of this giant flap in consideration of 60 clinical experiences of microdissected thin tensor fasciae latae perforator and anterolateral thigh flaps.

Adolescent↗

Plasma leptin concentration in dogs: effects of body condition score, age, gender and breeds.

Leptin is a cytokine produced by adipocytes, and plays a key role in the regulation of energy balance. In the present study, we measured plasma leptin concentrations of 166 normal and obese dogs visiting veterinary practices, and clarified the influence of age, gender and breed on plasma leptin levels in dogs. Leptin levels were higher in the dogs with higher body condition scores. There was no noticeable influence of age, gender and breed, but those in optimal puppies and obese Miniature Dachshund tended to be lower than those in corresponding groups. We conclude that plasma leptin is a reliable marker of adiposity in dogs regardless of age, gender and breed variations, and thereby useful as a blood biochemistry test for health examinations and treatment of obesity.

Aging↗

Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN/Kob rats.

INTRODUCTION: Diabetes is associated with an increased risk of fracture, although type 2 diabetes is often characterized by normal bone mineral density (BMD). Enzymatic and glycation-induced non-enzymatic cross-links play important roles in the expression of bone strength. The serum vitamin B6 concentration is lower in patients with diabetes than in healthy controls. The aim our study was to see if spontaneously diabetic WBN/Kob rats in the pre- and post-onset of diabetes would serve as a suitable model for studying the pathogenesis of the susceptibility to fracture in diabetes without the reduction of bone mineral density. Seventy male WBN/Kob rats were obtained at the ages of 1 to 18 months. METHODS: Seventy normal male Wistar rats were used as the non-diabetic, age-matched control. The contents of enzymatic cross-links (dihydroxylysinonorleucine, hydroxylysinonorleucine, lysinonorleucine, pyridinoline and deoxypyridinoline) and non-enzymatic cross-links (pentosidine) were determined in femoral bone. We also analyzed the serum concentration of vitamin B6 (pyridoxal and pyridoxamine), femoral BMD and a three-point bending test of the femur. RESULTS: A low level of serum vitamin B6 was associated with a decrease in enzymatic crosslinking in bone during the subclinical diabetes stage. After the onset of diabetes, there was a steady decrease in enzymatic cross-links and a steep increase in pentosidine. Furthermore, impaired bone mechanical properties in the WBN/Kob rats despite the lack of reduction in BMD coincided with impaired enzymatic cross-link formation and increases in glycation-induced pentosidine. CONCLUSIONS: These results indicate that the alteration of enzymatic and non-enzymatic crosslinking in bone could be important for explaining the variation of fracture susceptibility in diabetes.

Animals↗

The Bax pore in liposomes, Biophysics.

The protein BAX of the Bcl-2-family is felt to be one of the two Bcl-2-family proteins that directly participate in the mitochondrial cytochrome c-translocating pore. We have studied the kinetics, stoichiometry and size of the pore formed by BAX in planar lipid bilayers and synthetic liposomes. Our data indicate that a cytochrome c-competent pore can be formed by in-membrane association of BAX monomers.

Animals↗

Biomechanical testing of the fractured distal radius treated with a new bone cement--is it strong enough?

This study evaluates the in vitro ability of CAP, a bone graft substitute with osteointegration and osteoconductive properties, to restore the anatomy and strength of fractured distal radii. Ten pairs of cadaveric radii were imaged and tested to failure, simulating a fracture. The radii were reconstructed using CAP and were re-fractured and sequentially imaged. The deformities of the bones were determined through computerised evaluation of the radiographs. Radiographic analysis showed that CAP is capable of restoring the anatomy of the distal radius. The load and work required to fracture intact radii were compared to those required to fracture the reconstructed radii. The load to fracture was similar in the two situations. The work to fracture, however, was higher with reconstructed radii, suggesting that these are stronger than the original bones. Our study supports the hypothesis that CAP is capable of restoring the original anatomy and dimensions of the distal radius and re-establishing its mechanical strength.

Biomechanical Phenomena↗

Functional roles of 5-hydroxytryptamine 3/4 receptors in neurons of rat dorsal motor nucleus of the vagus.

In neurons of dorsal motor nucleus of the vagus that is involved in the gastric motility and possibly emesis, application of 5-hydroxytryptamine produces membrane depolarization, and suppresses spike-repolarization and spike-afterhyperpolarization, suggesting divergent effects of 5-hydroxytryptamine through activating multiple subtypes of 5-hydroxytryptamine receptors. However, only the role of 5-hydroxytryptamine 2A receptors has been established to be responsible for the depolarization, and the mechanisms underlying the modulation of spikes remain unknown although a role of 5-hydroxytryptamine 4 receptors was implicated in modulations of spikes. There is now increasing evidence for the role of 5-hydroxytryptamine receptors in neurons involved in generating emesis following administration of anticancer drug. Since antagonists of 5-hydroxytryptamine 3/4 receptors are widely used as anti-emetic drugs, we have reevaluated the functional roles of 5-hydroxytryptamine 3/4 receptors of dorsal motor nucleus of the vagus neurons, especially in modulating transient outward currents that are presumed to be involved in spike-repolarization and spike-afterhyperpolarization. Whole-cell patch-clamp recordings were made from the dorsal motor nucleus of the vagus neurons, which were identified by a retrograde tracing method with dextran-tetramethylrhodamine-lysine injected into a bundle of abdominal vagus nerves. Under a voltage-clamp condition, dorsal motor nucleus of the vagus neurons expressed a prominent A-like current. The activation of 5-hydroxytryptamine 3 receptors reversibly increased the resting membrane conductance while the activation of 5-hydroxytryptamine 4 receptors led to an almost irreversible decrease in the A-like current. A long-lasting suppression of A-like current by transient activation of 5-hydroxytryptamine 4 receptors would result in a long-lasting increase in the excitability of dorsal motor nucleus of the vagus neurons, which might be involved in generation of the long-lasting facilitation of gastric motility or in generation of the long-lasting gastric relaxation through the activation of enteric non-adrenergic non-cholinergic neurons as implicated in the delayed emesis induced by anticancer drugs.

4-Aminobenzoic Acid↗

Electric-field effect on the angle-dependent magnetotransport properties of quasi-one-dimensional conductors.

We report a novel electric field effect on angular dependent magnetotransport in quasi-one-dimensional layered conductors with a pair of sheetlike Fermi surfaces. Under tilted magnetic fields and additional interlayer electric fields, semiclassical electron orbits on two Fermi sheets become periodic at different magnetic field orientations. This causes double splitting of the Lebed's commensurability resonance in interlayer transport, and the amount of splitting allows us to estimate the Fermi velocity directly. We have successfully demonstrated this effect in the organic conductor alpha-(BEDT-TTF)2KHg(SCN)4.

Journal Article↗

Reductions in degree of mineralization and enzymatic collagen cross-links and increases in glycation-induced pentosidine in the femoral neck cortex in cases of femoral neck fracture.

INTRODUCTION: Enzymatic and glycation-induced nonenzymatic cross-links play important roles in the expression of bone strength. The cross-link pattern is affected by tissue maturation and senescence. The aim of our study was to understand the distinctive posttranslational modifications of collagen in areas with different degrees of mineralization with and without hip fracture. METHODS: Sixteen female cases of intracapsular hip fracture (78+/-6 years) and 16 age- and gender-matched postmortem controls (76+/-6 years) were included in this study. A sample of each femoral neck cortex was fractionated into low (1.7 to 2.0 g/ml) and high (>2.0 g/ml) density portions. The contents of enzymatic cross-links (dihydroxylysinonorleucine, hydroxylysinonorleucine, lysinonorleucine, pyridinoline, and deoxypyridinoline) and nonenzymatic cross-links (pentosidine) and the extent of lysine (Lys) hydroxylation were determined in each fraction. RESULTS: In the controls, there was no significant difference in the contents of enzymatic cross-links between low- and high-mineralized bone fractions whereas pentosidine content was significantly higher in high-mineralized bone compared with low-mineralized bone (p=0.0014). When comparing enzymatic cross-link contents between controls and fracture cases, a trend toward lower (p=0.0961) cross-link content in low-mineralized bone and a significant reduction (p<0.0001) in high-mineralized bone were observed. Pentosidine content of low-mineralized bone was significantly higher in fracture cases than in controls (p<0.0001). The extent of Lys hydroxylation was significantly higher in fracture cases than in controls (p<0.001). The higher hydroxylation of Lys in collagen from fracture cases relative to controls was associated with significantly higher values of hydroxylysine-derived cross-link such that the enzymatic cross-link patterns correlated with the extent of Lys hydroxylation in the collagen molecules. CONCLUSIONS: These results suggest that reductions in the degree of mineralization and enzymatic cross-links and excessive formation of pentosidine may play an important role in explaining poor bone quality in osteoporosis.

Aged↗

Novel roles of osteopontin and CXC chemokine ligand 7 in the defence against mycobacterial infection.

Granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced human monocyte-derived macrophage (GM-Mphi) or macrophage CSF (M-CSF)-induced human monocyte-derived Mphi (M-Mphi) are distinct in terms of the resistance to Mycobacterium tuberculosis. To elucidate the role of molecules involved in the functional differences between these Mphis, we investigated the gene expression profiles using microarray. After culture of CD14+ monocytes with CSFs, Mphis were cultured with or without bacillus Calmette-Guérin (BCG) (GM-Mphi-BCG and M-Mphi-BCG). The gene expression profiles from these cells were compared. Chemokines highly expressed in M-Mphis were selected and evaluated for anti-mycobacterial activity and superoxide production. FN1 and FCGR2B were the most up-regulated genes in GM-Mphi and M-Mphi, respectively. After stimulation with BCG, three chemokine genes (Osteopontin (SPP1), CXC chemokine ligand 7 (CXCL7) and CC chemokine ligand 11 (CCL11)) were highly expressed in M-Mphi-BCG when compared to those in GM-Mphi-BCG. A significantly increased resistance to M. tuberculosis H37Ra was observed after the stimulation of GM-Mphi with SPP1 or CXCL7. Superoxide production levels of SPP1- or CXCL7-stimulated GM-Mphis were higher than those of GM-Mphis without stimulation. These results indicate that both SPP1 and CXCL7 might have a role in the resistance against mycobacteria, at least in part, through augmenting reactive oxygen intermediate production in Mphis.

BCG Vaccine↗

Carvedilol accelerate elevation of serum potassium in chronic heart failure patients administered spironolactone plus furosemide and either enalapril maleate or candesartan cilexetil.

OBJECTIVE: To retrospectively investigate the effect of carvedilol and spironolactone plus furosemide, administered concomitantly with an angiotensin II converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB) to patients with chronic heart failure (CHF). METHODS: Patients with CHF, who visited Departments of Cardiovascular Internal Medicine at the National Hospital Organization Osaka Medical Center, were enrolled for this study. Serum potassium, blood urea nitrogen (BUN), serum creatinine (Scr) and serum sodium were measured in every patient at the time of start of treatment and after 3 and 12 months of treatment. Data from patients in groups A (20 mg/day carvedilol + 25 mg/day spironolactone + 40 mg/day furosemide + an ACE-I) and B (20 mg/day carvedilol + 25 mg/day spironolactone + 40 mg/day furosemide + ARB) were compared. RESULTS: When 20 mg/day carvedilol plus 25 mg/day spironolactone plus 5 mg/day enalapril maleate (enalapril, group A) or 8 mg/day candesartan cilexetil (candesartan, group B) plus 40 mg/day furosemide were used concomitantly, the mean serum potassium increased significantly in both groups of patients. Seven of 59 (11.9%) patients had hyperkalemia (>5.5 mEq/L) during 12 months of treatment whereas 8.5% of patients (five of 59) had hypokalemia (< or =3.5 mEq/L). CONCLUSION: When carvedilol is used concomitantly with spironolactone, furosemide and enalapril or candesartan, it is necessary to monitor serum potassium concentration, even if spironolactone is administered at a low dose of 25 mg/day.

Adult↗

Effect of ovariectomy and ad libitum feeding on body composition, thyroid status, ghrelin and leptin plasma concentrations in female dogs.

The objective of this study was to evaluate the effects of ovariectomy (i) and ad libitum feeding (ii) on energy intake, body weight (BW), body composition, thyroid status, leptin and ghrelin plasma concentrations. Four young adult female Beagle dogs were fed a maintenance diet for 6 weeks prior to ovariectomy, then 6 months after. Food allowance was adjusted in order to maintain optimal BW. Then, a diet slightly higher in energy concentration was fed ad libitum for 4 months. The maintenance diet was then fed ad libitum for one additional month. The maintenance of optimal BW after ovariectomy required a significant decrease in energy allowance. No increase in fat mass was observed. Ghrelin concentration remained unchanged. During the first month of ad libitum feeding, plasma ghrelin concentration and energy intake increased, then they decreased. Mean BW, plasma leptin, thyrotropin (TSH), total triiodothyronine (TT3) and total thyroxine (TT4) concentrations significantly increased over the study. The BW increase was exclusively due to an increase in body fat. In conclusion, energy allowance should be strictly controlled in spayed female dogs. The results suggest that in dogs, thyroid hormones, leptin and ghrelin concentrations change in response to a positive energy balance in an attempt to limit weight gain. However, the significant weight gain shows that this goal was not achieved.

Adipose Tissue↗