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Biomedical subjects

T Kuroda

Publications and source records attributed to T Kuroda.

At least 55 records · Page 3Linked to original sources

A family affected by branchio-oto syndrome with EYA1 mutations.

Branchio-oto (BO) syndrome is complicated with congenital preauricular fistulae, branchial fistulae (cysts), and hearing loss (sensorineural, conductive or mixed). As well as branchio-oto-renal (BOR) syndrome. it is known to be an autosomal dominant hereditary disorder. Since mutations in the EYA1 gene have been identified in both BO and BOR syndromes, mutation screening of this gene has been drawing attention as a genetic test to diagnose BOR/BO syndromes. In this study, we genetically investigated the presence of EYA1 mutations in a BO syndrome family in which we observed congenital preauricular fistulae, branchial fistulae (cysts) and hearing loss in four generations. Whereas there was a variety of phenotype expressions in this family, all subjects tested had a nonsense mutation (R264X) in exon 8 of the EYA1 gene. The present report adds further examples to support the usefulness of molecular genetic testing for the diagnosis of patients with BO syndrome.

Branchio-Oto-Renal Syndrome↗

Apoptosis of periodontal ligament cells induced by mechanical stress during tooth movement.

The mechanical force generated during tooth movement creates compressed and cell-free areas in the periodontal membrane. The way in which periodontal ligament cells disappear at the compressed area during tooth movement remains unclear. In the present study we examined whether periodontal ligament cells undergo apoptosis by mechanical stress during tooth movement using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end-labelling method (TUNEL). TUNEL-positive stainings of periodontal ligament cells began to appear at the compressed areas 12 h after tooth movement, and the number of those cells reached maximum at 24 h after tooth movement. Thereafter TUNEL-positive cells disappeared at 48 h, and direct and undermining bone resorption began at the same area 72 h after tooth movement. These results showed that compressed periodontal ligament cells were eliminated by apoptosis in the early phase of tooth movement.

Alveolar Bone Loss↗

Effects of S-2474, a novel nonsteroidal anti-inflammatory drug, on amyloid beta protein-induced neuronal cell death.

1. The accumulation of amyloid beta protein (Abeta) in the brain is a characteristic feature of Alzheimer's disease (AD). Clinical trials of AD patients with nonsteroidal anti-inflammatory drugs (NSAIDs) indicate a clinical benefit. NSAIDs are presumed to act by suppressing inhibiting chronic inflammation in the brain of AD patients. 2. In the present study, we investigated effects of S-2474 on Abeta-induced cell death in primary cultures of rat cortical neurons. 3. S-2474 is a novel NSAID, which inhibits cyclo-oxygenase-2 (COX-2) and contains the di-tert-butylphenol antioxidant moiety. S-2474 significantly prevented neurons from Abeta(25 - 35)- and Abeta(1 - 40)-induced cell death. S-2474 ameliorated Abeta-induced apoptotic features such as the condensation of chromatin and the fragmentation of DNA completely. 4. Prior to cell death, Abeta(25 - 35) generated prostaglandin D(2) (PGD(2)) and free radicals from neurons. PGD(2) is a product of cyclo-oxygenase (COX), and caused neuronal cell death. 5. S-2474 significantly inhibited the Abeta(25 - 35)-induced generation of PGD(2) and free radicals. 6. The present cortical cultures contained little non-neuronal cells, indicating that S-2474 affected neuronal survival directly, but not indirectly via non-neuronal cells. Both an inhibitory effect of COX-2 and an antioxidant effect might contribute to the neuroprotective effects of S-2474. 7. In conclusion, S-2474 exhibits protective effects against neurotoxicity of Abeta. Furthermore, the present study suggests that S-2474 may possess therapeutic potential for AD via ameliorating degeneration in neurons as well as suppressing chronic inflammation in non-neuronal cells.

Amyloid beta-Peptides↗

Modulation of the stretch reflex of jaw-closing muscles in different modes and phases of respiration.

The objective of this study was to investigate whether and how changes in the mode of respiration affect the electromyographic activity of human jaw-closing muscles. Fifteen men were examined in this study. A pair of surface electrodes was attached bilaterally to the masseter and anterior and posterior temporalis muscles for electromyographic recording. Respiratory movements of the chest wall and nasal airflow were recorded simultaneously. Recordings were performed with subjects in the sitting position during quiet nasal and oral respiration. The stretch reflex of jaw-closing muscles was elicited by randomly tapping the chin with an impulse hammer. In 11 subjects, we measured nasal resistance with a rhinomanometer. The amplitude of electromyographic activities of the masseter and anterior temporalis muscles during oral respiration was significantly less than that during nasal respiration, whereas that of the posterior temporalis muscle showed no significant difference between the different modes of respiration. Furthermore, the reduction in the amplitude of the electromyographic activity was more evident in the inspiratory phase during oral respiration. There was a significant positive correlation between the ratio of the reflex amplitude during inspiration in the 2 respiratory modes and nasal resistance for the masseter muscle, but not for the anterior temporalis muscle. These results suggest that the reflexive electromyographic activity of some human jaw-closing muscles is modulated during oral respiration.

Adult↗

Influence of age and comedication on steady-state clonazepam serum level-dose ratios in Japanese epileptic patients.

BACKGROUND: In antiepileptic drugs, the marked inter- and intrapatient variability of the level-dose ratio makes it difficult to predict serum concentrations from the administered per kg dose. It is therefore important to identify factors, such as age and comedication, that could contribute to this observed variability. OBJECTIVE: To investigate the effect of age and comedication on clonazepam (CZP) level-dose (L/D) ratios. METHOD: A retrospective evaluation of data from 137 epileptic patients who had received clonazepam. RESULTS: The CZP L/D ratio increased slowly with age up to 15 years in patients on monotherapy. Associated antiepileptic therapy affected the CZP L/D ratio, which was significantly reduced in patients on polytherapy as compared to patients on monotherapy. CONCLUSION: The study therefore suggests that routine monitoring of CZP serum levels is extremely useful, especially in the paediatric age group, and in patients who require associated antiepileptic medication.

Adolescent↗

Changes in mandibular position and upper airway dimension by wearing cervical headgear during sleep.

We previously reported that the wearing of cervical headgear induced forward displacement of the mandible in awake subjects. However, it was unclear whether such mandibular displacement also occurred during sleep. The purpose of this study was to examine changes in mandibular position and oropharyngeal structures that were induced by the wearing of cervical headgear during sleep. Ten healthy adults (7 male and 3 female) who gave their informed consent were included in this study. A pair of lateral cephalograms was taken with the patient in the supine position with and without cervical headgear at end-expiration during stage 1 to 2 non-rapid-eye-movement sleep. The Wilcoxon signed-rank test was used for a statistical analysis. The amount of jaw opening was significantly decreased by the wearing of the cervical headgear (P <.05), although no significant anteroposterior mandibular displacement was induced. The sagittal dimension of the upper airway was significantly reduced (P <.05); however, no significant changes were observed in the vertical length of the upper airway. Although the hyoid bone and the third cervical vertebra moved significantly forward by the wearing of the cervical headgear (P <.05), the relationship among the mandibular symphysis, the hyoid bone, and the third cervical vertebra did not change. These results suggest that cervical headgear significantly reduced the sagittal dimension of the upper airway during sleep, although there was no significant anteroposterior displacement of the mandible.

Adult↗

nhaG Na(+)/H(+) antiporter gene of Bacillus subtilis ATCC9372, which is missing in the complete genome sequence of strain 168, and properties of the antiporter.

We cloned a gene which enabled Escherichia coli mutant host cells lacking all of the major Na(+)/H(+) antiporters to grow in the presence of 0.2 M NaCl from chromosomal DNA of Bacillus subtilis ATCC9372. An Na(+)/H(+) antiport activity was observed with membrane vesicles prepared from E. coli cells possessing the cloned gene, but not with vesicles from the host cells. Lithium ion was also a substrate for the antiporter. We sequenced the cloned DNA and found one open reading frame (designated nhaG) preceded by a promoter-like sequence and a Shine-Dalgarno sequence, and followed by a terminator-like sequence. The deduced amino acid sequence of NhaG suggested that it consisted of 524 residues and that the calculated molecular mass was 58.1 kDa. None of the bacterial Na(+)/H(+) antiporters so far reported, except NhaP of Pseudomonas aeruginosa and SynNhaP (NhaS1) of Synechocystis sp., showed significant sequence similarity with the NhaG. However, the NhaP, the SynNhaP, animal NHEs (Na(+)/H(+) exchangers), and some hypothetical Na(+)/H(+) antiporters of several organisms showed significant sequence similarities with the NhaG. Interestingly, the entire DNA region corresponding to the nhaG gene is missing in the reported complete genome sequence of B. subtilis strain 168. We detected a band that hybridized with the nhaG DNA in chromosomal DNA from B. subtilis ATCC9372 but not with that from strain 168. The missing DNA region (1,774 base pairs) is sandwiched by two identical sequences, TTTTCTT.

Animals↗

Gender- and age-related differences in corneal topography.

PURPOSE: To investigate gender- and age-related differences in the corneal topography of a normal population. METHODS: One hundred thirty-two topographic examinations were collected from 100 patients ranging in age from 23 to 83 years (average, 57.35+/-17.38 years). Data were segregated by gender and further divided into younger (less than 50 years) and older (50 years or more) age groups. The topographic indices of Surface Regularity Index, Surface Asymmetry Index, Irregular Astigmatism Index, Standard Deviation of Corneal Power, Corneal Eccentricity Index, Coefficient of Variation of Corneal Power, Simulated Keratometry 1 and 2, and Average Corneal Power were examined. The astigmatism pattern and corneal irregularity were determined and compared with respect to gender and age. RESULTS: The corneas of older men were flatter than those of older women (p < 0.001). The vertical corneal meridian, but not the horizontal meridian, showed statistically significant gender-related changes with aging (p < 0.001). Older men had a significantly higher potential for against-the-rule astigmatism than women (p < 0.001). Corneal irregularity (measured in terms of the Surface Regularity Index and Irregular Astigmatism Index) increased with age (p < 0.001 and p < 0.001, respectively), although there was no gender-related difference. In the younger group, no gender-related differences in corneal curvature or astigmatism pattern were found. CONCLUSION: Aging influences changes in patterns of astigmatism differently in men and women. Decreases in levels of sex hormones may play a role in gender-related changes in corneal structure with age.

Adult↗

Pharmacoepidemiologic investigation of a clonazepam-carbamazepine interaction by mixed effect modeling using routine clinical pharmacokinetic data in Japanese patients.

Nonlinear mixed effects modeling was used to estimate the effects of clonazepam-carbamazepine interaction on clearance values using 359 serum levels gathered from 183 pediatric and adult epileptic patients (age range, 0.3-26.8 years) during their clinical routine care. Patients received the administration of clonazepam and/or carbamazepine. The final model describing clonazepam clearance was CL = 179.0 x TBW(-0.231) x 1.22(CBZ), where CL is total body clearance (mL/kg/h) and TBW is total body weight (kg); CBZ = 1 for concomitant administration of carbamazepine and CBZ = zero otherwise. The final model describing carbamazepine clearance was CL = 92.7 x TBW(-0.394) x DOSE(0-397) x 0.795(CZP), where DOSE is the daily dose of carbamazepine (mg/kg/day); CZP = 1 for concomitant administration of clonazepam and CZP = zero otherwise. Concomitant administration of clonazepam and carbamazepine resulted in a 22% increase in clonazepam clearance and a 20.5% decrease in carbamazepine clearance.

Adolescent↗

Detection of myocardial viability using rest-redistribution thallium-201 imaging in a stress 99Tcm-tetrofosmin/rest thallium-201 dual-isotope protocol.

This study investigated the utility of optional thallium-201 (201Tl) imaging for detecting myocardial viability in the stress 99Tcm-tetrofosmin/rest 201Tl dual-isotope protocol. Seventy-nine patients with old myocardial infarction and 25 patients with acute myocardial infarction underwent acquisition of three consecutive 201Tl images (early, intermediate and delayed) using the dual-isotope protocol. A polar map was created and defect scores (extent and severity) were determined by comparison with normal control data. Fluorodeoxyglucose positron emission tomography was also performed in 16 patients with old myocardial infarction. In patients with old infarction, the severity score decreased significantly from the early to the intermediate images, and decreased further on the delayed images. In patients with acute infarction, the score increased from the early to the intermediate images, but not on the delayed images. Regional uptake on the delayed images showed a better correlation with the fluorodeoxyglucose images than that on the early images. Redistribution on the delayed images was exclusively observed in the myocardial segments with less uptake than that estimated by fluorodeoxyglucose. In conclusion, addition of delayed 201Tl imaging to the dual-isotope protocol could improve the sensitivity for detecting myocardial viability.

Aged↗

Common regulation of growth arrest and differentiation of osteoblasts by helix-loop-helix factors.

Cellular differentiation entails the coordination of cell cycle arrest and tissue-specific gene expression. We investigated the involvement of basic helix-loop-helix (bHLH) factors in differentiation of osteoblasts using the human osteoblastic cell line MG63. Serum starvation induced growth arrest at G1 phase, accompanied by expression of cyclin-dependent kinase inhibitor p21(WAF1/Cip1). Reporter assays with the p21 gene promoter demonstrated that the combination of E2A (E12 or E47) and coactivator CBP was responsible for p21 induction independent of p53. Twist inhibited E2A-CBP-dependent activation of the exogenous and endogenous p21 promoters. Ids similarly inhibited the exogenously transfected p21 promoter; however less antagonistic effect on the endogenous p21 promoter was observed. Twist was predominantly present in nuclei in MG63 cells growing in complete medium, while it localized mainly in the cytoplasm after serum starvation. The fibroblast growth factor receptor 3 gene (FGFR3), which generates signals leading to differentiation of osteoblasts, was found to be controlled by the same transcriptional regulation as the p21 gene. E2A and Twist influenced alkaline phosphatase expression, a consensus marker of osteoblast differentiation. Expression of E2A and FGFR3 was seen at the location of osteoblast differentiation in the calvaria of mouse embryos, implicating bHLH molecules in physiological osteoblast differentiation. These results demonstrate that a common regulatory system is involved in at least two distinct steps in osteoblastic differentiation. Our results also provide the molecular basis of Saethre-Chotzen syndrome, caused by mutations of the TWIST and FGFR3 genes.

Alkaline Phosphatase↗

Parathyroid hormone-related protein is required for normal intramembranous bone development.

It is well established that parathyroid hormone-related protein (PTHrP) regulates chondrocytic differentiation and endochondral bone formation. Besides its effect on cartilage, PTHrP and its major receptor (type I PTH/PTHrP receptor) have been found in osteoblasts, suggesting an important role of PTHrP during the process of intramembranous bone formation. To clarify this issue, we examined intramembranous ossification in homozygous PTHrP-knockout mice histologically. We also analyzed phenotypic markers of osteoblasts and osteoclasts in vitro and in vivo. A well-organized branching and anastomosing pattern was seen in the wild-type mice. In contrast, marked disorganization of the branching pattern of bone trabeculae and irregularly aligned osteoblasts were recognized in the mandible and in the bone collar of the femur of neonatal homozygous mutant mice. In situ hybridization showed that most of the osteoblasts along the bone surfaces of the wild-type mice and some of the irregularly aligned osteoblastic cells in the homozygous mice expressed osteocalcin. Alkaline phosphatase (ALP) activity and expression of osteopontin messenger RNA (mRNA) in primary osteoblastic cells did not show significant differences between cultures derived from the mixture of heterozygous mutant and wild-type mice (+/? mice) and those from homozygous mutant mice. However, both mRNA and protein levels of osteocalcin in the osteoblastic cells of homozygous mutant mice were lower than those of +/? mice, and exogenous PTHrP treatment corrected this suppression. Immunohistochemical localization of characteristic markers of osteoclasts and ruffled border formation did not differ between genotypes. Cocultures of calvarial osteoblastic cells and spleen cells of homozygous mutant mice generated an equivalent number of tartrate-resistant acid phosphatase-positive (TRAP+) mononuclear and multinucleated cells and of pit formation to that of +/? mice, suggesting that osteoclast differentiation is not impaired in the homozygous mutant mice. These results suggest that PTHrP is required not only for the regulation of cartilage formation but also for the normal intramembranous bone development.

Adenosine Triphosphatases↗

Primary pulmonary hypertension with severe systemic hypertension, Raynaud's phenomenon and relative polycythemia.

A 32-year-old Japanese man was hospitalized for evaluation of unconsciousness. He was diagnosed as having primary pulmonary hypertension (PPH) with severe systemic hypertension, Raynaud's phenomenon and relative polycythemia. Hemostatic studies revealed increased coagulation and decreased fibrinolysis, similar to findings of chronic disseminated intravascular coagulation (DIC). Although activation of coagulation and systemic hypertension were improved after treatment with phlebotomy and administration of nifedipine, enerapril and warfarin, pulmonary hypertension was unchanged, suggesting that irreversible change had already occurred in the pulmonary arteries. Those complications could modify the process of pulmonary hypertension by inducing a hyperviscosity state.

Adult↗

[Utility of OAE screener (GSI 70) for the evaluation of distortion product otoacoustic emissions].

The purpose of this study was to investigate the ability of the OAE screener GSI 70 to evaluate of cochlea function in neonates, infants and adults. Distortion product otoacoustic emissions (DPOAEs) were measured using the GSI 70 DPOAE Analyzer and evaluated in 123 human ears between December 1999 and June 2000. We performed the following four general clinical tests to determine the reliability of the GSI 70: 1) comparison of DPOAE levels measured using the ILO 92 and the GSI 70 in 55 adult ears, 2) comparison of DPOAE levels measured using the GSI 70 and hearing levels in 55 adult ears, 3) comparison of DPOAE levels measured using the GSI 70 and ABR levels in 45 neonate and infant ears, and 4) evaluation of the utility of DPOAE measurements obtained using the GSI 70 in functional deafness cases. The following results were obtained: 1) DPOAE levels measured with the ILO 92 and the GSI 70 were closely correlated (correlation coefficient, 0.773 at 2 kHz and 0.813 at 4 kHz). 2) The sensitivity of the GSI 70 in adult ears confirmed to have normal hearing was 80% at 2 kHz and 100% at 4 kHz; the specificity of hearing-impaired ears was 94% at 2 kHz and 94% at 4 kHz. 3) The sensitivity of the GSI 70 in normal neonate and infant ears with normal hearing was 100% at 2 kHz and 100% at 4 kHz; the specificity of hearing-impaired neonate and infant ears was 97% at 2 kHz and 94% at 4 kHz. 4) All of the functionally deaf ears showed excellent DPOAE responses. Examinations using the GSI 70 DPOAE analyzer were very easy and fast. Also, the results were highly reliable, with the exception of one adult who was classified as having normal hearing in an out-of-scale hearing level at 2 kHz. We suggest that specific criteria be established for the clinical usage of the GSI 70 in performing objective hearing evaluations.

Adolescent↗

[Effectiveness of a new toothbrush with irrigation and suctioning capabilities (ty e-Brush) for removing supragingival plaque].

Patients with dysphagia typically have poor oral health. Because of improper swallowing, they cannot easily and safely clean their mouths. As a solution for such a problem, a manual toothbrush with both irrigation and suctioning functions has been developed, called the "e-Brush". The purpose of this study was to evaluate the cleaning effectiveness of the new e-Brush (9 mm and 11 mm in bristle length) for removing supragingival plaque, compared with a conventional toothbrush, GUM # 211 by Butler. In this study, 12 subjects (12 female of average age 20.6) were selected, and plaque control record (PCR) and scrubbing method were used. The following results were obtained: 1. Significant differences (p < 0.05) were recognized between e-Brush/9 mm (55.54 +/- 18.27%) and the others (e-Brush/11 mm: 30.88 +/- 8.14%, GUM # 211: 35.42 +/- 9.32%). 2. Bristles 9 mm in length were more effective than 11 mm bristles (p < 0.05). 3. Irrigation/suctioning function is more effective than the conventional tooth-brushing method. 4. The irrigation function of e-Brush was meritorious in making almost all users comfortable. These results suggest that this new oral hygiene device, "e-Brush/9 mm", is effective for improving oral care management for patients with dysphagia.

Adult↗

Clinical study of strangulation obstruction of the small bowel.

Early diagnosis of strangulation obstruction is very important for surgeons because delayed diagnosis often leads to severe complications. Thirty patients underwent an operation because of small bowel obstruction between April, 1993 and December, 1999. In the present study, we examined the differences in clinical findings between simple obstruction and strangulation obstruction. In addition, we examined the manifestation of systemic inflammatory response syndrome (SIRS) and whether it is useful for early diagnosis of strangulation obstruction, and whether it is correlated with the severity of ischemia due to strangulation. Tenderness was examined in all patients and signs such as abdominal irritation were detected more often in patients with strangulation obstruction than in the patients with simple obstruction. According to SIRS, the large number of the patients with strangulation obstruction showed SIRS before operation and the manifestation of SIRS correlated well with the length of the necrosis in the strangulated small bowel. We recognized the importance of anamnesis and clinical findings in examinations of small bowel obstruction, furthermore, it was suggested that SIRS should be the warning sign for strangulation obstruction.

Abdomen↗

[Quantitative determination of lipoprotein by agarose gel electrophoresis and enzymatic staining of cholesterol and triglyceride: effects of age and gender].

290 normal duplicate samples (152 males and 138 females), were subjected to lipoprotein analysis by agarose gel electrophoresis to yield HDL, VLDL and LDL fractions which were respectively stained with Cholesterol and Triglyceride reagents. HDL-Cholesterol were significantly higher in female than male, and VLDL-TG were significantly higher in male than female. Assay C.V.'s varied from 0.96 to 5.75 for cholesterol fractions and 2.00 to 4.34 for triglyceride fractions. Comparison of electrophoretic HDL-Cholesterol and LDL-Cholesterol concentrations with the results of a direct method (HDL-EX and LDL-EX, Denka Seiken) gave correlation coefficients of 0.967 and 0.952 respectively. This method is simple, rapid and can provide the simultaneous assessment of the cholesterol and triglyceride component in each Lipoprotein fraction. Additionally, the method is useful for evaluating lipoprotein assays.

Adult↗