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Biomedical subjects

S Takeda

Publications and source records attributed to S Takeda.

At least 19 recordsLinked to original sources

ED-71, a novel vitamin D analog, promotes bone formation and angiogenesis and inhibits bone resorption after bone marrow ablation.

ED-71, a novel analog of 1alpha,25-(OH)2 D3, increases bone mass to a greater extent than alfacalcidol, an 1alpha,25-(OH)2 D3 prodrug. In this study, we used a murine bone marrow ablation model to compare the effect of ED-71 on bone formation and resorption in vivo with that of 1alpha,25-(OH)2 D3. We discovered that bone matrix remodeling occurring within the first week after bone marrow ablation was enhanced by a single injection of ED-71, but not by 1alpha,25-(OH)2 D3. This enhancement was associated with an increase in bone surface. Trabecular bone resorption occurring from 1 to 2 weeks after the procedure was suppressed by a single injection of ED-71, but not 1alpha,25-(OH)2 D3, with treated mice exhibiting a reduction in osteoclast numbers, despite increases in osteoblast surface. As seen with the single injection, daily administration of ED-71 also enhanced bone modeling. Bone marrow osteoblast differentiation was also augmented by ED-71 pretreatment. Furthermore, ED-71 treatment immediately after bone marrow ablation enhanced angiogenesis within the bone marrow cavity via enhancement of VEGF(120) expression. In this paper, we clearly demonstrate that ED-71 is an orally administered small molecular weight compound with an anabolic effect on bone metabolism.

Animals↗

Effect of arachnoid plasty using fibrin glue membrane after clipping of ruptured aneurysm on the occurrence of complications and outcome in the elderly patients.

BACKGROUND: In elderly patients with aneurysmal subarachnoid hemorrhage (SAH), complications including vasosopasm, subdural effusion, and late hydrocephalus, are liable to occur even after aneurysmal surgery. We examined prospectively the efficacy of arachnoid plasty using fibrin glue membrane during surgery of ruptured aneurysms in the elderly patients for preventing complications. The effects on the modified Rankin scale (mRS) and the Glasgow outcome scale (GOS) 3 months after SAH were noted. METHODS: Total of 31 patients aged more than 70 years selected from a consecutive series of patients with aneurysmal SAH, were divided into two groups alternately, a group with arachnoid plasty (n = 16) and a control group without arachnoid plasty (n = 15). Statistical analyses were performed to assess relationships among various clinical and neuroradiological variables, especially between arachnoid plasty and occurrence of symptomatic vasospasm, subdural effusion, late hydrocephalus, or outcome such as mRS and GOS 3 months after onset. FINDINGS: Statistical analyses revealed that arachnoid plasty were associated with late hydrocephalus and subdural effusion negatively, but with better mRS at 3 months after SAH. A tendency to be associated with less frequent symptomatic vasospasm was also noted. CONCLUSION: Arachnoid plasty using fibrin glue is suggested to be effective in preventing complications associated with SAH and aneurysmal surgery. A better outcome in the elderly patients can be achieved.

Age Factors↗

Correlation between copy number of mitochondrial DNA and clinico-pathologic parameters of hepatocellular carcinoma.

AIMS: In the current study, we investigated possible correlations of the mtDNA copy number in hepatocellular carcinoma (HCC) with the pathological findings and prognosis. METHODS: We studied 31 HCC specimens using quantitative real-time polymerase chain reaction analysis, and the correlation between the mtDNA copy number and the clinicopathologic parameters and mutations in the D-loop region of the mitochondrial genome. RESULTS: The mtDNA copy number was reduced in HCCs compared with the corresponding non-cancerous liver tissues (p=0.002), and significantly correlated with tumour size (p=0.014) and cirrhosis (p=0.048). Patients with a low mtDNA copy number tended to show shorter 5-year survival rates than patients with a high mtDNA copy number when assessed by Kaplan-Meier curves, but not a significant (overall survival rate, 63 vs 83%; p=0.19). The copy number of HCC with mtDNA D-loop mutation or deletion was lower, but not significantly so (p=0.656, p=0.590, respectively). CONCLUSIONS: Our results indicated that a reduced copy number of mtDNA is correlated with HCC and associated with malignant potential.

Adult↗

Clinical impact of interstitial pneumonia following surgery for lung cancer.

BACKGROUND: Operative morbidity in patients with lung cancer associated with perioperative interstitial pneumonia (IP) has emerged as a serious problem. PATIENTS AND METHODS: We studied the clinical impact of perioperative related IP in 11 patients (IP group: 7 preoperative known, 4 acute onset) of 473 lung cancer patients who received a pulmonary resection. The IP group was compared to the remaining 462 patients (non-IP group). Demographic data, clinical presentation, and serum KL-6 levels were compared. RESULTS: There were no differences in age, gender, type of surgery, and pulmonary function except for % DLco between the non-IP and IP groups. The IP group showed a higher in-hospital mortality (n=2: 18.3%) than that of the non-IP group (n=3: 0.6%) (P<0.005). Seven patients with underlying IP with high KL-6 levels showed an uneventful recovery. Two patients with postoperative onset of acute IP had a fatal course associated with elevation of serum KL-6 levels. CONCLUSIONS: Postoperative development IP is a serious complication with high mortality, and serial measurement of KL-6 levels is useful to assess the activity of IP.

Adolescent↗

Midazolam depresses carotid body chemoreceptor activity.

BACKGROUND: Although the contribution of the gamma-aminobutyric acid (GABA) receptor system in peripheral chemosensation is unclear, immunohistochemistry has demonstrated the presence of GABA-ergic receptors in mammalian carotid bodies. We hypothesized that an activation of the carotid body GABA receptors would counteract the depolarizing effect of hypoxia. METHODS: The carotid body with arterial supply and the carotid sinus nerve was removed en bloc from New Zealand White rabbits and placed in a perfusion chamber. The carotid body preparation was perfused via the cut common carotid artery with a modified Tyrode's solution at a rate of 3.5-4.5 ml/min with a constant pressure of 45 cmH2O. The carotid sinus nerve firing frequency (Hz) was recorded at two different oxygen tension levels during perfusion with midazolam of 1, 10 and 100 microg/l. RESULTS: The frequency was decreased by midazolam in a dose-dependent manner (n = 8). Firing frequencies (mean +/- SEM) at the low oxygen tension level decreased from 643.13 +/- 67.2 Hz in the control to 554.5 +/- 67.7 Hz (P = 0.054 vs. control), 509.01 +/- 100.5 Hz (P < 0.012 vs. control) and 422.6 +/- 77.3 Hz (P < 0.001 vs. control) during perfusion with midazolam of 1, 10 and 100 microg/l, respectively. CONCLUSION: Midazolam depresses carotid body chemoreceptor activity in a dose-dependent manner.

Action Potentials↗

[Rapidly enlarging giant left ventricular pseudo-false aneurysm after myocardial infarction; report of a case].

A 71-year-old man was admitted to our hospital with acute myocardial infarction and cardiac tamponade. After pericardial drainage, his hemodynamics was improved. Because more than 3 days had been passed after the onset of myocardial infarction and he had severe renal dysfunction, emergent coronary angiography (CAG) was not performed. After improvement of his general status, coronary angiography and percutaneous catheter intervention was carried out, and his course was uneventful. But transthoracic echocardiography before discharge revealed a giant posterior psudoaneurysm. Patch closure and coronary artery bypass grafting was carried out under cardiopulmonary bypass, and postoperative course was uneventful. Postoperative left ventriculogram revealed disappearance of pseudoaneurysm, but relatively large akinetic area of posterior-inferior wall was left around a patch. Pseudo-false aneurysm was diagnosed by histological examination.

Aged↗

Effects of lithium on endolymph homeostasis and experimentally induced endolymphatic hydrops.

There is evidence to suggest that water homeostasis in the inner ear is regulated via the vasopressin (VP)-aquaporin 2 (AQP2) system in the same fashion as in the kidney. The VP-AQP2 system in the kidney is well known to be inhibited by lithium, resulting in polyuria due to a decrease in reabsorption of water in the collecting duct of the kidney. Therefore, lithium is also likely to inhibit the VP-AQP2 system in the inner ear, and consequently exert some influence on inner ear fluid homeostasis. In this study, we investigated the effects of lithium on AQP2 expression in the rat inner ear, and on the cochlear fluid volume in hydropic ears of guinea pigs. A quantitative PCR study revealed that lithium reduced AQP2 mRNA expression in the cochlea and endolymphatic sac. Lithium application also decreased the immunoreactivity of AQP2 in the cochlea and endolymphatic sac. In a morphological study, lithium intake significantly reduced endolymphatic hydrops dose-dependently. These results indicate that lithium acts on the VP-AQP2 system in the inner ear, consequently producing a dehydratic effect on the endolymphatic compartment.

Animals↗

Relationship between the pharyngeal airway space and craniofacial morphology, taking into account head posture.

This study assessed the relationship between craniofacial characteristics and the size of the pharyngeal airway space (PAS), taking into account head posture. Sixty dental students 25-30 years of age (30 men and 30 women) were examined by lateral cephalometry. The data were corrected with the use of appropriate regression equations for the PAS. The PAS significantly correlated with hyoid position, maxillary and mandibular size, maxillary and mandibular prognathism, and mandibular inclination. A large, anteriorly positioned mandible was associated with a large PAS-TP (the most proximal distance between the posterior pharyngeal wall and the tongue base). Uvula length and PNS-Ba (the distance between the most posterior point of the hard palate and the most inferior point of the anterior foramen magnum) correlated with PAS-UP (the most proximal distance between the posterior pharyngeal wall and uvula). Our results suggest that the anteroposterior dimension of the PAS is substantially affected by the size of the enclosure surrounding the PAS, including the maxilla, mandible and soft palate.

Adult↗

Pharyngeal narrowing as a common feature in pycnodysostosis--a cephalometric study.

We report on pycnodysostosis presenting as severe snoring caused by pharyngeal narrowing in two siblings. Cephalograms showed pharyngeal narrowing at the level of the soft palate and the base of the tongue caused by the long soft palate and mandibular hypoplasia. From the literature review and our results, we suggest that respiratory insufficiency such as snoring or obstructed sleep apnea are common and under-appreciated symptoms of pycnodysostosis.

Aged↗

Chronic exercise accelerates the degeneration-regeneration cycle and downregulates insulin-like growth factor-1 in muscle of mdx mice.

The aim of this study was to examine the effects of chronic running exercise on degenerative-regenerative processes in the hindlimb muscles of dystrophin-deficient mdx mice. The number of large-sized degenerative-regenerative groups (DRGs) was markedly decreased, whereas that of small-sized DRGs was unchanged by exercise. Expression of insulin-like growth factor-1 (Igf1), as well as a myogenic factor MyoD (Myod1), was downregulated in mdx muscles by exercise. The downregulation of Igf1 may well correlate with the decrease in the population of early regenerating fibers, which existed predominantly in DRGs, because IGF-1 was mainly localized in these fibers. Our data indicate that chronic exercise may accelerate the active cycle of degeneration-regeneration in mdx skeletal muscles. This means that mdx skeletal muscles can temporarily cope with work-induced injury by enhancing muscle regeneration and repair, but we speculate that an early decline of IGF-1 will accelerate age-dependent muscle wasting and weakness in the later stage of life in mdx mice.

Adaptation, Physiological↗

Computed tomographic analysis of the position and course of the mandibular canal: relevance to the sagittal split ramus osteotomy.

The aim of this study was to investigate the position and course of the mandibular canal through the mandibular ramus using computed tomographic (CT) imaging and to relate the findings to performing sagittal split ramus osteotomies. The mandibles of 35 patients with skeletal Class III prognathism with symmetry (12 males and 23 females) were observed on transaxial computed tomograms acquired with a slice thickness of 2 mm. The position and course of the mandibular canal from the mandibular foramen to the mandibular body at the level of the second molar were measured at four specific locations in the same plane. Among the 70 rami examined, lack of a bone marrow space on the buccal side, including a fusion type anatomy with no buccal side cortical bone of the mandibular canal, were observed at the CT location between the mandibular foramen and mandibular angle. Our results suggest that special care must be taken when sagittal splitting is performed, and the safest location for the buccal corticotomy is anterior to the mandibular angle.

Adolescent↗

Fukutin and alpha-dystroglycanopathies.

Fukuyama-type congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), and muscle-eye-brain (MEB) disease are clinically similar autosomal recessive disorders characterized by congenital muscular dystrophy, lissencephaly, and eye anomalies. We identified the gene for FCMD and MEB, which encodes the fukutin protein and the protein O-linked mannose beta1, 2-N-acetylglucosaminyltransferase (POMGnT1), respectively. Recent studies have revealed that posttranslational modification of alpha-dystroglycan is associated with these congenital muscular dystrophies with brain malformations. All are characterized by hypoglycosylated alpha-dystroglycan. Fukutin's function and the relation with other alpha-dystroglycanopathies are discussed.

Animals↗

Serum leptin level is a regulator of bone mass.

Leptin is a powerful inhibitor of bone formation in vivo. This antiosteogenic function involves leptin binding to its receptors on ventromedial hypothalamic neurons, the autonomous nervous system and beta-adrenergic receptors on osteoblasts. However, the mechanisms whereby leptin controls the function of ventromedial hypothalamic antiosteogenic neurons remain unclear. In this study, we compared the ability of leptin to regulate body weight and bone mass and show that leptin antiosteogenic and anorexigenic functions are affected by similar amounts of leptin. Using a knock-in of LacZ in the leptin locus, we failed to detect any leptin synthesis in the central nervous system. However, increasing serum leptin level, even dramatically, reduced bone mass. Conversely, reducing serum-free leptin level by overexpressing a soluble receptor for leptin increased bone mass. Congruent with these results, the high bone mass of lipodystrophic mice could be corrected by restoring serum leptin level, suggesting that leptin is an adipocyte product both necessary and sufficient to control bone mass. Consistent with the high bone mass phenotype of lipodystrophic mice, we observed an advanced bone age, an indirect reflection of premature bone formation, in lipodystrophic patients. Taken together, these results indicate that adipocyte-derived circulating leptin is a determinant of bone formation and suggests that leptin antiosteogenic function is conserved in vertebrates.

Animals↗

Critical progressive small-graft injury caused by intrasinusoidal pressure elevation following living donor liver transplantation.

In adult-to-adult living liver transplantation, small-for-size graft syndrome sometimes occurs. The relationship between the hemodynamic changes and histologic findings has not been studied in patients with failure of small-for-size grafts. We analyzed the relationship between the postoperative hemodynamic changes and pathologic findings in patients with small-for-size grafts that ended in graft failure. From March 1999 to December 2002, adult-to-adult living-donor liver transplantation with small-size grafts (graft volume/standard liver volume less than 40%) was performed in eight patients. Three patients died from graft failure caused by overperfusion, which was diagnosed from pathologic findings. We analyzed the relation between hepatic hemodynamic parameters, such as portal venous blood velocity or splenic arterial pulsatility index, and histologic changes in patients with graft failure. Severe portal hyperperfusion (90 cm/sec at the umbilical portion) was observed on postoperative day 1. Among patients with graft failure, critical hemodynamic changes, such as sudden onset of extremely deteriorated portal venous blood flow, occurred during the early postoperative period (postoperative day 5, 3, 6, respectively). Histologic examination revealed vacuolar changes in the cytoplasm of hepatocytes, and submassive necrosis indicated intrasinusoidal pressure elevation. These changes were not observed in the biopsy obtained soon after reperfusion. In conclusion, critically decreased vascular beds may cause intrasinusoidal pressure elevation and sinusoidal circulatory disturbances.

Adult↗

Pulse dye densitometry using indigo carmine is useful for cardiac output measurement, but not for circulating blood volume measurement.

BACKGROUND AND OBJECTIVE: We evaluated the validity of a newly developed pulse dye densitometer for indigo carmine for measuring cardiac output and circulating blood volume. METHODS: Measurements of cardiac output and circulating blood volume were performed with the indigo carmine densitometer during normovolaemia, hypovolaemia and hypervolaemia in nine mongrel dogs under general anaesthesia. The validity was evaluated by comparison of the values of cardiac output and circulating blood volume obtained by the thermodilution technique and the 51Cr-labelled red blood cell method, respectively. We also examined indigo carmine removal by continuous veno-venous haemofiltration after indigo carmine injection. RESULTS: There was good agreement between dye densitometer- and thermodilution-derived cardiac output (r = 0.885, P < 0.001). The bias and limits of agreement of these values were 0.09 and+/-1.07 L min(-1) (2 SD, n 22), respectively. The dye-densitometer-derived circulating blood volume was greater than that of the 51Cr-labelled red blood cell method, and both values showed weak agreement (r = 0.587, P < 0.027). The sieving coefficient of indigo carmine through continuous veno-venous haemofiltration was 0.34+/-0.06. CONCLUSIONS: These data indicate that indigo carmine densitometry is a reliable method for cardiac output determination, but it overestimates circulating blood volume, probably due to the transition of indigo carmine into the extravascular space in the systemic circulation.

Algorithms↗

Recombination repair pathway in the maintenance of chromosomal integrity against DNA interstrand crosslinks.

DNA interstrand crosslinks (ICL) present a major threat to cell viability and genome integrity. In eukaryotic cells, the ICLs have been suggested to be repaired by a complex process involving Xpf/Ercc1-mediated endonucleolytic incision and homologous recombination (HR). However, the entire feature of the ICL tolerating mechanism is still poorly understood. Here we studied chromosome aberrations (CA) and sister chromatid exchanges (SCE) by the use of the crosslinking agent mitomycin C (MMC), in chicken DT40 cells with the HR genes disrupted by targeted replacement. The disruption of the Rad54, Rad51B, Rad51C, Rad51D, Xrcc2 and Xrcc3 genes resulted in a dramatic reduction of spontaneous and MMC-induced SCEs. Interestingly, while HR-deficient cells were hypersensitive to cell killing by MMC, MMC-induced CAs were also suppressed in the HR-deficient cells except for Rad51D-, Xrcc2- and Xrcc3-deficient cells. These observations indicate that DNA double strand breaks (DSB) at stalled replication forks and those arising as repair intermediates present strong signals to cell death but can be tolerated by the HR repair pathway, where Rad54, Rad51B and Rad51C have an initiative role and repair can be completed by their paralogs Rad51D, Xrcc2 and Xrcc3. The impairment of the HR pathway, which otherwise leads to cell death, may be somewhat substituted by an alternative mechanism such as the Mre11/Rad50/Nbs1 pathway, resulting in reduced frequencies of SCEs and CAs.

Animals↗