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Biomedical subjects

T Nakamoto

Publications and source records attributed to T Nakamoto.

At least 73 records · Page 4Linked to original sources

[Effect of percutaneous transluminal mitral commissurotomy on pulmonary function and on the pulmonary vasculature].

We evaluated the therapeutic effect of percutaneous transluminal mitral commissurotomy (PTMC) on pulmonary function, and the damage caused to pulmonary vasculature by transient occlusion of the mitral valve during PTMC in patients with mild mitral stenosis. Pulmonary function tests were done and serum thrombomodulin was measured in 6 patients before and after PTMC. The mean pulmonary arterial pressure and mean pulmonary arterial wedge pressure decreased significantly from the control values, and the decreases were proportional to the increase in the area of the mitral valve. VC, %VC, and DLco were in the normal range before and after PTMC but PEFR, FEV1%, FEV1, V50, V25, and V50/V25 were significantly higher after PTMC. Change in the area of the mitral valve correlated with the changes in FEV1% (r = 0.841), in V50 (r = 0.624), and in V25 (r = 0.697). The serum thrombomodulin levels before and after PTMC did not differ. We conclude that pulmonary dysfunction in patients with mild mitral stenosis MS is mainly due to an obstructive ventilatory defect, and that PTMC can correct this dysfunction without damaging the pulmonary vasculature.

Aged↗

Effect of phenobarbital on the pharmacokinetics of lidocaine, monoethylglycinexylidide and 3-hydroxylidocaine in the rat: correlation with P450 isoform levels.

To elucidate the effect of cytochrome P450 levels in hepatic microsomes on the metabolism of lidocaine in vivo, we investigated the metabolism of lidocaine in untreated (UT group) and phenobarbital-treated rats (PB group) in vivo and compared the results with those obtained by immunoblotting of rat hepatic microsomes. There were no differences in pharmacokinetic parameters for lidocaine between the UT and PB groups. The plasma concentrations of the N-deethylated metabolite of lidocaine, monoethyl-glycinexylidide (MEGX), in the PB group were significantly higher than those in the UT group. On the other hand, the plasma concentrations of the aromatic ring hydroxylated metabolite of lidocaine, 3-hydroxylidocaine (3-OH LID), were significantly lower in the PB group than in the UT group. When lidocaine metabolism was studied with hepatic microsomes prepared from rats in the UT and PB groups, the rates of formation of MEGX were higher in the microsomes of the PB group than in those of the UT group. The contents of CYP2B1 and 3A2 in rat hepatic microsomes of the BP group measured by immunoblotting were significantly higher than those of the UT group. Strong correlations were found between the area under the plasma concentration vs. time curve for MEGX and specific contents of CYP2B1 and 3A2. These findings suggest that formation of MEGX in vivo is dependent on the levels of CYP2B1 or 3A2 in rat liver.

Anesthetics, Local↗

Src kinase plays an essential role in integrin-mediated tyrosine phosphorylation of Crk-associated substrate p130Cas.

A novel signaling molecule p130Cas has been shown to undergo tyrosine phosphorylation in response to integrin-mediated cell adhesion. In this study, we have attempted to identify kinases that mediate Cas phosphorylation in integrin signaling by examining various mutant cell lines that do not express either p125FAK, c-Scr, c-Fyn or c-Abl. We found that deficiency of c-Src but not of other kinases completely abrogated integrin-mediated Cas phosphorylation. Importantly, paxillin phosphorylation was not compromised in each mutant cell line examined. These results suggest that c-Src primarily mediates adhesion-dependent Cas phosphorylation. As for paxillin phosphorylation, there may exist substantial redundancy amongst multiple kinases. Finally, adhesion-induced Cas phosphorylation resulted in its association with c-Crk adapter protein via the Crk-SH2 domain. Thus, Cas plays a role in the transmission of integrin-initiated signals through tyrosine phosphorylation and subsequent binding to c-Crk.

3T3 Cells↗

Direct binding of C-terminal region of p130Cas to SH2 and SH3 domains of Src kinase.

p130Cas is a major tyrosine-phosphorylated protein that tightly binds v-Crk in v-crk-transformed cells and v-Src in v-src-transformed cells. The "substrate domain" of p130Cas contains 15 possible Src homology (SH) 2-binding motifs, most of which conform to the binding motif for the Crk SH2 domain. Another region near its C terminus contains possible binding motifs for the Src SH2 domain and proline-rich sequences that are candidates for SH3-binding sites. Using GST fusion proteins, we revealed that both SH2 and SH3 domains of Src bind p130Cas, whereas v-Crk binds p130Cas through its SH2 domain. We located the binding site of p130Cas for the Src SH3 domain at the sequence RPLPSPP in the region near its C terminus. Mutations within this sequence or at Tyr762 of p130Cas caused a significant reduction in the association of p130Cas with Src, and no association was detected when both of them were deleted. The kinase activity in v-Crk-transformed cells was also associated with p130Cas through this region. On the other hand, the deletion of the substrate domain abolished the binding with v-Crk. The association through the C-terminal region of p130Cas with Src kinase may facilitate effective hyperphosphorylation of tyrosine residues in the substrate domain of p130Cas, resulting in the binding of SH2-containing molecules to p130Cas.

3T3 Cells↗

Effects of caffeine on bone cells and bone development in fast-growing rats.

BACKGROUND AND METHODS: Caffeine exerts harmful effects on fetal and suckling rats. To elucidate the effects of caffeine on bone in growing rats further, dams were fed normal laboratory chow until delivery. At birth, the litters were combined and eight pups were randomly assigned to each dam. Dams with the combined litters were divided into two groups. Dams of group 1 received a 20% protein diet as a control, and dams of group 2 received the 20% protein diet supplemented with caffeine (4 mg/100 g b.w.). Pups from both groups were killed on days 11, 15, 22, and 50. Parameters studied were ultrastructure of femoral osteoblasts, osteocytes, and osteoclasts; the number of osteocytes per area of bone in femoral histological cross sections; structural remodeling and shape of the lateral tibial metaphysis as revealed by scanning electron microscopy; and plasma Cu and Zn concentrations. RESULTS: Rats in the caffeine groups had significantly fewer osteocytes per area of femoral cross section, retarded structural remodeling of the lateral tibial metaphysis, osteoblasts and osteocytes with disrupted swollen mitochondria, and decreased plasma Cu and Zn levels when compared with controls. CONCLUSIONS: These results indicate that if young, rapidly growing rats are exposed to caffeine, disruption of osteoblasts and retarded bone development occur, which could be related to the decreased plasma Cu level in the young animals.

Animals↗

The configuration of the seminal roots of Triticum aestivum L. (Poaceae).

The seminal root system of wheat (Triticum aestivum L.) is composed of the primary seminal root, the first pair of seminal roots, and the second pair of seminal roots, which are known to grow in different directions. The direction of root growth, which can be expressed by theta (the angle between the root and the plumb line) and phi (the angle between the root and a vertical plane including the primary seminal root), was studied with special attention to the latter. It was measured on seedlings grown in a small hemispherical soil-filled mesh basket. There were varietal differences in the phi of the first pair of roots (phi f) and in the phi of the second pair of roots (phi s). phi f and phi s were significantly correlated. The mean distance (MD), a measure to evaluate the efficiency of root spacing, was correlated with the difference between phi f and phi s. Neither experimentally applied low soil water potential nor the excision of the primary seminal root affected phi. When the grain was sown vertically with the tip of the embryo pointing downwards, it was found that the growth movement into a direction different from the plumb line and phi s was greatly modified. It is suggested that certain internal mechanisms, possibly involving gravitropic reactions, are operating to control the direction of root growth. The significance of root growth direction at the seedling stage is discussed.

Gravitropism↗

Combined effects of caffeine and alcohol during pregnancy on bones in newborn rats.

The combined effects of caffeine and alcohol on mineral contents of fetal mandibles and femurs were studied. Pregnant rats were divided into four groups: group 1, control; group 2, caffeine; group 3, alcohol; and group 4, caffeine-plus-alcohol. Alcohol (1.0 g ethanol/kg body weight) was intubated twice daily, beginning at day 9 of gestation. Caffeine (2 mg/100 g body weight) was given as a dietary supplement. Groups 1 and 2 were intubated with isocaloric sucrose solution. At birth, randomly selected pups were killed and the mandible and femur were removed and dried. Ca, P, Mg, Zn and hydroxyproline in these bones were measured. Notwithstanding the dams' intake of caffeine and alcohol administered separately, the present results suggest that the combination of caffeine and alcohol exhibited the most detrimental effects.

Animals↗

Fibroepithelial polyp in the renal pelvis.

Benign tumors in the renal pelvis are unique and rarely reported. We report a case of a benign polyp in the renal pelvis. A 68-year-old woman presented with a mass in the right renal sinus and underwent right nephrectomy. Histological investigations of the tumor revealed a polypoid angiofibromatous lesion of the renal pelvis which was benign in nature. Final pathological diagnosis was a benign fibroepithelial polyp.

Aged↗

Early diagnosis and estimation of pulmonary congestion and edema in patients with left-sided heart diseases from histogram of pulmonary CT number.

To establish an early diagnosis and have a quantitative estimation of congestion or edema, pulmonary CT scans were performed to detect the increase of regional lung water volume of patients with congestive heart failure. CT scanning of the upper, middle, and lower lung fields at maximum inspiration and hemodynamic analysis to ensure a hemodynamically chronic stable condition after the heart failure therapy for 5 weeks by cardiac catheterization within 2 weeks before CT scanning were performed in 10 normal subjects and 25 patients with left-sided heart failure. Patients were divided into two groups according to the presence or absence of pulmonary congestion or edema on chest radiographs, and the mean pulmonary wedge pressure (mPWP). The pulmonary congestion group (14 patients) had pulmonary congestion or edema, and mPWP was greater than 13 mm Hg despite the heart failure therapy. The nonpulmonary congestion group (11 patients) had no pulmonary congestion or edema, and mPWP was lower than 10 mm Hg. Histograms of pulmonary CT numbers were graphed to a set region of interest (ROI) on transverse CT images in all subjects; then changes of pulmonary CT numbers when pulmonary congestion or edema occurred were estimated from those histograms. We found that when severe pulmonary congestion or edema occurred in 6 patients with severe left heart failure, the pulmonary CT numbers within the ROI rapidly increased from -650 to -750 Hounsfield units (HU). We defined the amount ratio between the pixels (pixel counts between -650 and -750 HU within these R0Is) and the pixels (pixel counts between -300 and -950 HU) of the CT number (which were all pixels composing these R0Is) x100(%) as "%PXL." %PXL showed a linear correlation with mPWP. Compared with the %PXL in the normal group, the %PXL in the pulmonary congestion group was significantly higher than that in the normal group (p<0.05, p<0.01, p<0.001) in all lung fields. Similarly, compared with the %PXL in the normal group, %PXL in the nonpulmonary congestion group was significantly higher than that in the normal group in the middle and lower lung fields (p<0.05, p<0.01) in the posterior field. From these results, we concluded that %PXL was a good index to identify abnormal water content usually not recognizable by routine chest radiograph in the lungs.

Adult↗

[Usefulness of bladder auto-augmentation in neurogenic bladder: a case report].

A 41-year-old male with myelomenigocele underwent a bladder auto-augmentation and endoscopic collagen injections. He has been performing self intermittent catheterization for 10 years but urinary incontinence remained unchanged. Furthermore, he suffered from recurrent pyelonephritis due to the left vesicoureteral reflux. A preoperative fluoroscopic urodynamic study showed a poorly compliant bladder with the maximal bladder capacity of 200 ml at 60 cmH2O. The left vesicoureteral reflux was observed at 10 cmH2O. The low compliant bladder was treated with the bladder autoaugmentation and the left vesicoureteral reflux was treated with the endoscopic subureteral injection of collagen 5 months after the previous operation. A fluoroscopic urodynamic study 6 months postoperatively showed the increase of the maximal bladder capacity of 300 ml at 18 cmH2O and the reflux disappeared completely. The endoscopic periurethral injections of collagen improved his persisting urinary incontinence. In patient with neurogenic bladder having a lot of clinical problems, bladder auto-augmentation is less invasive and offers many advantages over enterocystoplasy.

Adult↗

[Pulmonary typical carcinoid with metastases to pulmonary hilar, and mediastinal lymph nodes].

A 50-year-old woman was admitted to our hospital complaining of recurrent bloody sputum and hemoptysis. Chest X-ray films showed an infiltrative shadow in the left lower lung field. Chest computed tomograms showed a nodular tumor shadow near the left B8 and this tumor shadow was found between A8 and A9 by pulmonary arteriography. Bronchoscopic examination revealed a red coagulum in the left B8 and cytologic examination of broncho alveolar lavage fluid revealed atypical squamous cells. With a clinical diagnosis of squamous cell carcinoma of the lung, a left lower lobectomy with hilar and mediastinal lymph node dissection was done. A milk-white tumor was found in the lower lobe of the resected lung. The pathological diagnosis of the resected tissue specimen was carcinoid, accompanied by pulmonary, hilar, and mediastinal lymph node metastases. Reduced immunofluorescence by Chromogranin A and serotonin staining were further evidence that the tumor was atypical. This case is very interesting in that the tumor metastasized to the lung and lymph nodes, even-though it was pathologically typical.

Carcinoid Tumor↗

[Cesarean section under spinal anesthesia for a patient with chronic renal failure].

A 37-year-old primipara was scheduled for cesarean section under spinal anesthesia in the 38th gestational week because of cephalo-pelvic disproportion. She had suffered from chronic renal failure since 27 years of age, and had been undergoing hemodialysis three times per week. The frequency of hemodialysis was increased to 4-6 times per week during pregnancy to maintain blood urea nitrogen and serum creatinine concentration below 60 mg.dl-1 and 6.0 mg.dl-1, respectively. Since she had no bleeding tendency, spinal anesthesia with 8 mg of tetracaine was successfully performed after hemodialysis eliminating only solute but not water in the morning of surgery and after infusion of 500 ml of acetated Ringer solution. Blood pressure and heart rate were stable during surgery. Monitoring of central venous pressure was useful for fluid management. A baby weighing 2,575 g with an Apgar Score of 8 at one minute and 9 at five minutes was delivered five minutes after the beginning the surgery. The mother recovered uneventfully and returned to regular hemodialysis on the first postoperative day. These findings suggest that with careful fluid management, spinal anesthesia can be safely performed for cesarean section, for patients undergoing hemodialysis.

Adult↗

Intraoperative continuous epidural lidocaine for early postoperative analgesia.

We determined the early postoperative analgesia using intraoperative continuous epidural infusion of lidocaine during general anesthesia in patients undergoing upper abdominal surgery in a prospective double-blind manner. After insertion of an epidural catheter at the T10-T11 interspace, general anesthesia was induced. Thirty patients were randomly allocated to receive continuous epidural infusion of either 0.5% (n = 15) or 1% (n = 15) plain lidocaine at 10 ml/hr. The infusion was continued from 10 to 15 minutes before surgery until the end of surgery. Visual analog pain scale (0-10) within 30 minutes after the end of surgery was significantly lower in the 1% lidocaine group (5.6 +/- 0.9, mean +/-SE) than in the 0.5% lidocaine group (8.2 +/- 0.8), however, it was unsatisfactory in both groups. Plasma concentrations of lidocaine and its principal metabolite, monoethylglycinexylidide, gradually increased through epidural infusion, but remained below the toxic range in both groups. We conclude that continuous epidural lidocaine during general anesthesia offered limited analgesia in the early postoperative period.

Aged↗

Tyrosine phosphorylation of p130Cas in cell adhesion and transformation.

Integrins comprise the major class of receptors used by cells to interact with the extracellular matrix. Integrin/matrix interactions play a critical role in a variety of biological processes, including embryonic development, wound healing, tumor metastasis, cell growth and differentiation. It is now evident that integrins can transduce biochemical signals across the plasma membrane to the cell interior. Protein tyrosine phosphorylation has attracted much attention as an important regulator for integrin-mediated signal transduction. Recently, we have identified a novel signaling molecule, p130Cas, which participates in integrin-mediated signal transduction. p130Cas was originally identified as a protein hyperphosphorylated in cells expressing transforming gene products p47v-crk (v-Crk) and p60v-crk (v-Src). In this brief review, we will discuss about a role of p130Cas in signal transduction triggered by cell adhesion and transformation.

Cell Adhesion↗

Sandwich immunoassay specific for the N-terminal sequence of osteocalcin.

A monoclonal antibody (10B) against the N-terminal sequence of human osteocalcin was selected to characterize its epitope and species specificity. The cross-reactivity of 10B with human and rat osteocalcin demonstrated that the reactivities of 10B with both human and rat osteocalcins were very similar. The pin technology method was used to determine the epitope and clearly demonstrated that the epitope recognized by 10B was localized to residues 12-16, the sequence of which is identical in rat and human osteocalcin molecules. This monoclonal antibody was found to be useful for designing region-specific sandwich immunoassay systems for human and rat N-terminal osteocalcin (N-OC) molecules using rabbit anti-hN20 and anti-rN20 polyclonal antibodies, respectively. The osteocalcin levels in serum determined by this N-OC method were stable during prolonged storage at 25 degrees C and the method could be usefully applied in the development of immunoassay systems for many osteocalcin molecules from many other species.

Amino Acid Sequence↗

Tau in cerebrospinal fluids: establishment of the sandwich ELISA with antibody specific to the repeat sequence in tau.

Clinical diagnosis for Alzheimer's disease (AD) is provided by the criteria of DSMIV and clinical progress in addition to imaging analysis with MRI after negative screening. The final exclusive diagnosis is confirmed by the neuropathological findings of neurofibrillary tangles and senile plaques in autopsy brains. We developed a new ELISA system to measure the amount of tau in cerebrospinal fluids (CSF) using phosphorylation-independent and sequence-specific antibodies. The present ELISA was sensitive enough to detect tau in CSF of normal subjects. The amount of tau was significantly elevated in CSF of AD subjects compared with those of normal subjects and subjects with dementia of cerebrovascular disease, suggesting that tau in CSF reflects the massive and continuous neuronal cell death in the AD brain. In conclusion, we established an ELISA system which enabled us to detect tau in CSF and demonstrated that tau was significantly and specifically elevated in CSF of AD subjects. This assay system can provide us with a potent diagnostic tool for clinical AD.

Alzheimer Disease↗