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Biomedical subjects

Y Kawaguchi

Publications and source records attributed to Y Kawaguchi.

At least 91 records · Page 5Linked to original sources

Age-related association of MHC class I chain-related gene A (MICA) with type 1 (insulin-dependent) diabetes mellitus.

To assess the contribution of the HLA class I region to susceptibility to and heterogeneity of type 1 diabetes, we investigated the association of polymorphism of MHC class I chain-related gene A (MICA) with age-at-onset as well as susceptibility to type 1 diabetes. One hundred one Japanese patients and 110 healthy control subjects were studied. The frequency of A4 allele was significantly higher and that of A6 allele was significantly lower in patients than in control subjects. The frequency of A5.1 allele was highest in early-onset patients (23.0%), intermediate in intermediate-onset patients (9.2%) and lowest in late-onset patients (7.7%) (trend chi-squared test, p = 0.0098). A5. 1 allele was strongly associated with HLA-B7 and Cw7, suggesting that MICA*A5.1-B7-Cw7 haplotype contains a gene responsible for age-at-onset. A4 allele was associated with a susceptible haplotype, DR4-DQB1*0401, and A6 allele was associated with a protective haplotype, DR2-DQB1*0601, suggesting that the association of MICA with type 1 diabetes susceptibility may be due to linkage disequilibrium with class II haplotypes. These data suggest that MICA gene is associated with age-at-onset and that a gene (or genes) responsible for age-at-onset of type 1 diabetes is located in the HLA class I region, probably near the region of MICA-B-C.

Adolescent↗

Gender difference in the mean age at the induction of hemodialysis in patients with autosomal dominant polycystic kidney disease.

Male patients with autosomal dominant polycystic kidney disease (ADPKD) begin hemodialysis earlier than female patients. The rate of progression of many other renal diseases is also faster in men than women. In this study, gender difference in ADPKD was compared with that in other diseases, such as chronic glomerulonephritis, diabetic nephropathy, and nephrosclerosis, using the data obtained from an annual statistical survey of the Japanese Society for Dialysis Therapy. The male-female ratio in ADPKD (n = 8,176) was 1.17:1 and closer to 1.0:1 than the other diseases. Men with ADPKD started hemodialysis therapy 1.3 years earlier than women (male age, 55.9 +/- 12.4 years versus female age, 57.2 +/- 11.5 years), and the age difference was less than that in other diseases. These results suggest that the prognosis in women with ADPKD is relatively worse than that in men with ADPKD or that women are not well protected against the progression of this disease compared with other renal diseases. In conclusion, men with ADPKD are introduced to hemodialysis therapy earlier than women; however, the age difference was small compared with other common renal diseases.

Adolescent↗

Presence of sonographically detectable parathyroid glands can predict resistance to oral pulsed-dose calcitriol treatment of secondary hyperparathyroidism.

Oral pulsed-dose calcitriol administration has been shown to be effective therapy for patients with secondary hyperparathyroidism. However, this effect is not consistently observed in the clinical setting. This study was undertaken to examine whether enlarged parathyroid glands can serve as a clinical marker that predicts the suppressive effect of calcitriol. Thirty-five patients undergoing chronic hemodialysis (HD) were examined (age, 51.9 +/- 14.9 years; duration of HD, 72.0 +/- 56.0 months). Based on the volume of parathyroid glands measured using an ultrasonographic scanner, patients were divided into two groups: 15 patients with undetectable parathyroid glands (ND group) and 20 patients with detectable parathyroid glands (D group; mean volume of parathyroid glands, 261. 9 +/- 347.5 mm(3)). No significant differences were found in serum ionized calcium (Ca(++)) or parathyroid hormone (PTH) levels before calcitriol administration between the two groups. For each patient, 8 microg of calcitriol was administered orally at the end of the HD session, and the changes in serum PTH levels were determined 44 hours after dosing. No significant differences were found between the two groups in serum Ca(++) levels. However, a significant decrease in serum PTH levels was observed in the ND group, whereas no significant changes were found in the D group. The results of the study show that the suppressive effect on PTH through calcitriol therapy was reduced in patients with detectable enlarged parathyroid glands. This may indicate that the size of parathyroid glands is one factor determining the therapeutic potential of pulsed-dose calcitriol administration for secondary hyperparathyroidism.

Administration, Oral↗

Multicenter cross-sectional study for dialysis dose and physician's subjective judgment in Japanese peritoneal dialysis patients. Group for the Water and Electrocyte Balance Study in CAPD.

The purpose of this study was to investigate the state of dialysis and nutrition among Japanese peritoneal dialysis (PD) patients. Two hundred thirty-nine Japanese PD patients from 21 centers, 79 female and 160 male, were evaluated to determine their status of dialysis and nutrition. Mean age of the patients was 50 years; mean duration on PD, 4.2 years; mean body weight, 58 kg; and body surface area (BSA), 1.61 m(2). Sixty-three percent of the patients had no residual renal function. Mean daily delivered volume was 6.9 L for female continuous ambulatory peritoneal dialysis (CAPD), 8.1 L for male CAPD, 10.5 L for female automated peritoneal dialysis (APD), and 10.7 L for male APD. Total (dialysis and kidney) mean weekly values for creatinine clearance (Ccr), Kt/V, and beta2 microglobulin (beta2MG) clearance were 56 L/1.75 m(2), 1.80, and 11 L/1.73 m(2), respectively. Fifty percent of the patients who had no residual renal function (RRF) and 17% of the patients with RRF did not achieve 50 L/wk/1.73 m(2) of Ccr. With regard to nutritional parameters, mean values for plasma total protein, serum albumin, and normalized protein catabolic rate (nPCR) were 6.5 g/dL, 3.6 g/dL, and 0.97 g/kg BW/d. Mean daily protein loss was 5.8 g. Although a significant number of patients did not achieve 50 or 60 L/wk/1.73 m(2) of Ccr, the physicians determined that 72% of the patients received adequate dialysis and 71% were well nourished according to clinical and laboratory features. In conclusion, the daily prescribed volume and the delivered dialysis dose were lower than expected. The discrepancy between the actual delivered dialysis dose and the physicians' evaluation should be explored in the future.

Adult↗

Differential expression of human spasmolytic polypeptide (trefoil factor family-2) in pancreatic carcinomas, ampullary carcinomas, and mucin-producing tumors of the pancreas.

Human spasmolytic polypeptide (hSP) is a member of the trefoil peptide group, thought to be involved in mucin production and cell growth. It has been reported that hSP protein is expressed in digestive cancers but not in normal pancreas. The expression of hSP in pancreatic neoplasms has not been investigated in detail. The immunohistochemical expression of hSP protein was investigated in pancreatic carcinomas, ampullary carcinomas, mucin-producing tumors, serous cystadenomas and islet cell tumors of the pancreas. hSP was expressed in 23% of pancreatic duct cell carcinomas, and hSP protein was more frequently detected in cases of early-stage or histologically low-grade duct cell carcinomas than in cases of late-stage or histologically high-grade carcinomas. Patients with hSP protein expression showed a better prognosis than did those with negative hSP expression. hSP expression was detected in 92% of mucin-producing tumors, but was not detected in serous cystadenoma or islet cell tumors. Immunohistochemical hSP expression is related to differentiation and a better prognosis in pancreatic duct cell carcinomas. Furthermore, hSP protein is related to the pathogenesis and clinical characteristics of mucin-producing tumors of the pancreas.

Adenoma, Islet Cell↗

Isolation of replicational cue elements from a library of bent DNAs of Aspergillus oryzae.

Two fragments that could function as replicational cue elements were isolated from a genomic DNA digest of Aspergillus oryzae on the basis of abnormal behavior in polyacrylamide gel electrophoresis. The vector used in this study contained a scaffold-associated region of the Drosophila melanogaster ftz gene to provide nuclear retention. Neither fragment contained a yeast ARS consensus sequence or an eukaryotic topoisomerase II binding sequence. One of the fragments showed sequence homology with the mitochondrial replication origin of Candida utilis and a portion of mitochondrial DNA of Aspergillus nidulans. This plasmid carrying the cue fragment could also replicate in HeLa and NIH3T3 cells.

Animals↗

Educating overseas students: just another responsibility or a chance to grow for faculty?

With a gradual decrease of the university-entering young population, Japanese universities face more and more competition for survival. It is up to each university's efforts to be distinctive and competitive to flourish toward the 21st century. At Tokyo Medical and Dental University, the Faculty of Medicine and the Faculty of Dentistry will be reorganised in April 2000 as a graduate-school-centred university, where faculty will face increased demands in research activities while maintaining or even improving undergraduate education. On the other hand, our university has a 20-year history of accepting overseas students mainly from Asia, and ranks first among Japanese national universities in terms of the number of overseas students studying health sciences. Do our faculty regard teaching overseas students as just another responsibility to be fulfilled or as a unique opportunity to grow as a university faculty? In October 1998, a questionnaire was conducted to discover the faculty attitude towards education of overseas students. Out of 211 dental faculty members, 164 responded to the questionnaire. The results indicated that about 90% of the respondents were interested in teaching overseas students and that those who had already served as a supervisor or a tutor found the experience very meaningful. The results also indicated that they encountered problems deriving from language and culture. It was suggested that our university should redefine overseas student education as an important part of our mission by establishing a more comprehensive system for accepting and teaching overseas students.

Attitude of Health Personnel↗

Intraarticular osteoid osteoma associated with synovitis: a possible role of cyclooxygenase-2 expression by osteoblasts in the nidus.

To clarify the condition of development of synovitis associated with intraarticular osteoid osteoma (OO), expressions of cyclooxygenase-2 (COX-2) protein and its messenger ribonucleic acid were investigated both in the nidus and the synovial tissue using immunohistochemical and reverse transcription-polymerase chain reaction analyses. Diffuse and strong COX-2 immunoreactivity was found in osteoblast-like tumor cells in the nidus of all six cases of OO (three of six cases were intraarticular OO associated with synovitis) and one case of osteoblastoma associated with synovitis. Expression of COX-2 messenger ribonucleic acid was demonstrated in one case of OO associated with synovitis, and was higher in the nidus than that in the inflamed synovial tissue. However, there were no significant difference between the nidus and synovium in the expression of cytosolic phospholipase A2, one of the enzymes involved in arachidonic acid metabolism, and inflammatory cytokines such as interleukin-1beta and tumor necrosis factor alpha. Finally, as there was only one case in which the examinations of gene expression were performed, no definitive overall conclusions could be reached; rather it is suggested that COX-2 expressed primarily by osteoblasts in the nidus of intraarticular OO may play a role in activating the pathway of arachidonic acid metabolism, resulting in synovitis of the involved joint.

Adolescent↗

Gradual tilting of crystallographic orientation and configuration of dislocations in GaN selectively grown by vapour phase epitaxy methods

Cross-sectional transmission electron microscope (TEM) observation was performed for selectively grown gallium nitride (GaN) in order to examine the dependence of GaN microstructure on the growth conditions. The GaN films were grown by hydride vapour phase epitaxy (HVPE) or metalorganic vapour phase epitaxy (MOVPE) on GaN covered with a patterned mask. Thin foil specimens for TEM observation were prepared with focused ion beam (FIB) machining apparatus. It was demonstrated that the c-axis of GaN grown over the terrace of the mask tilts towards the centre of the terrace when the GaN is grown in a carrier gas of N2. The wider terrace results in a larger tilting angle if other growth conditions are identical. The tilting is attributed to 'horizontal dislocations' (HDs) generated during the overgrowth of GaN on the mask terrace. The HDs in HVPE-GaN have a semi-loop shape and are tangled with one another, while those in MOVPE-GaN are straight and lined up to form low-angle grain boundaries.

Journal Article↗

Interaction of Epstein-Barr virus nuclear antigen leader protein (EBNA-LP) with HS1-associated protein X-1: implication of cytoplasmic function of EBNA-LP.

Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) consists of W1W2 repeats and a unique C-terminal Y1Y2 domain and has been suggested to play an important role in EBV-induced transformation. To identify the cellular factors interacting with EBNA-LP, we performed a yeast two-hybrid screen, using EBNA-LP cDNA containing four W1W2 repeats as bait and an EBV-transformed human peripheral blood lymphocyte cDNA library as the source of cellular genes. Our results were as follows. (i) All three cDNAs in positive yeast colonies were found to encode the same cellular protein, HS1-associated protein X-1 (HAX-1), which is localized mainly in the cytoplasm and has been suggested to be involved in the regulation of B-cell signal transduction and apoptosis. (ii) Mutational analysis of EBNA-LP revealed that the association with HAX-1 is mediated by the W1W2 repeat domain. (iii) A purified chimeric protein consisting of glutathione S-transferase fused to EBNA-LP specifically formed complexes with HAX-1 transiently expressed in COS-7 cells. (iv) When EBNA-LP and HAX-1 were coexpressed in COS-7 cells, EBNA-LP was specifically coimmunoprecipitated with HAX-1. (v) Careful cell fractionation experiments of an EBV-infected lymphoblastoid cell line revealed that EBNA-LP is localized in the cytoplasm as well as in the nucleus. (vi) When EBNA-LP containing four W1W2 repeats was expressed in COS-7 cells, EBNA-LP was detected mainly in the nucleus by immunofluorescence assay. Interestingly, when EBNA-LP containing a single W1W2 repeat was expressed in COS-7 cells, EBNA-LP was localized predominantly in the cytoplasm and was colocalized with HAX-1. These results indicate that EBNA-LP is in fact present and may have a significant function in the cytoplasm, possibly by interacting with and affecting the function of HAX-1.

Adaptor Proteins, Signal Transducing↗

Development of an effective polyvalent vaccine against both Marek's and Newcastle diseases based on recombinant Marek's disease virus type 1 in commercial chickens with maternal antibodies.

An earlier report (M. Sakaguchi et al., Vaccine 16:472-479, 1998) showed that recombinant Marek's disease virus type 1 (rMDV1) expressing the fusion (F) protein of Newcastle disease virus (NDV-F) under the control of the simian virus 40 late promoter [rMDV1-US10L(F)] protected specific pathogen-free chickens from NDV challenge, but not commercial chickens with maternal antibodies against NDV and MDV1. In the present study, we constructed an improved polyvalent vaccine based on MDV1 against MDV and NDV in commercial chickens with maternal antibodies. The study can be summarized as follows. (i) We constructed rMDV1 expressing NDV-F under the control of the MDV1 glycoprotein B (gB) promoter [rMDV1-US10P(F)]. (ii) Much less NDV-F protein was expressed in cells infected with rMDV1-US10P(F) than in those infected with rMDV1-US10L(F). (iii) The antibody response against NDV-F and MDV1 antigens of commercial chickens vaccinated with rMDV1-US10P(F) was much stronger and faster than with rMDV1-US10L(F), and a high level of antibody against NDV-F persisted for over 80 weeks postvaccination. (iv) rMDV1-US10P(F) was readily reisolated from the vaccinated chickens, and the recovered viruses were found to express NDV-F. (v) Vaccination of commercial chickens having maternal antibodies to rMDV1-US10P(F) completely protected them from NDV challenge. (vi) rMDV1-US10P(F) offered the same degree of protection against very virulent MDV1 as the parental MDV1 and commercial vaccines. These results indicate that rMDV1-US10P(F) is an effective and stable polyvalent vaccine against both Marek's and Newcastle diseases even in the presence of maternal antibodies.

Animals↗

An intron 4 gene polymorphism in endothelial cell nitric oxide synthase might modulate volume-dependent hypertension in patients on hemodialysis.

Nitric oxide (NO) has some relevance to the pathophysiology of hypertension. We examined the distribution of endothelial nitric oxide synthase (ecNOS4) gene polymorphism in patients with essential hypertension (n = 107) in comparison with healthy subjects (n = 362), and then studied the possibility that ecNOS4 gene polymorphism affects changes in blood pressure (BP) due to water load in hemodialysis patients. Though the NO metabolite (NOx) level in subjects with the a allele (31.2 +/- 1.76 micromol/l) was significantly lower than in those without the a allele (35.6 +/- 0.90 micromol/l) (p = 0.0263), we found no association between this gene polymorphism and essential hypertension. However, there still remains the possibility that the NO response to elevation of BP might be suppressed in patients with hypertension. In order to examine the association between ecNOS4 gene polymorphism and volume-dependent hypertension, 181 hemodialysis patients with complete anuria were recruited. Depending on the increase in mean BP (mm Hg) divided by percent increase in body weight (deltaBP/deltaBW), patients were divided into high responders (High-R: deltaBP/deltaBW >2.0 mm Hg; n = 90) and low responders (Low-R: deltaBP/deltaBW <2.0 mm Hg; n = 91). In the High-R group, the frequencies of a/a, b/a and b/b genotypes were 1.1, 32.1 and 66.8%, respectively, and in the Low-R group, these frequencies were 1.1, 9.4 and 89.5%, respectively. The relative risk for those in the High-R group conferred by the ecNOS4 a allele (b/a + a/a) was 3.64 (95% confidence intervals: 1.60-8.24, p = 0.0089). This study did not show a strong involvement of ecNOS4 gene polymorphism, at least in the basal NO production in patients with essential hypertension, however, it indicated that ecNOS4 gene polymorphism might modulate changes in BP due to water load in patients on hemodialysis, thus indicating that these polymorphisms may be involved in the pathophysiology of volume-dependent hypertension.

Alleles↗

Pharmacokinetic interactions between HIV-1 protease inhibitors in rats: study on combinations of two kinds of HIV-1 protease inhibitors.

The drug interactions between four human immune deficiency virus (HIV-1) protease inhibitors have been characterized by in-vitro metabolic studies using rat liver microsomal fractions and in-vivo oral administration. In this study, a new HPLC analytical method developed by us was used for the simultaneous determination of saquinavir and nelfinavir in rat plasma and microsomes. The metabolic clearance rates (Vmax/Km) of saquinavir, nelfinavir, and indinavir were 170.9 +/- 10.9, 126.1 +/- 4-4, and 73.0 +/- 2.0 microL min(-1) (mg protein)(-1), respectively. Ritonavir was the strongest inhibitor with inhibition constants (Ki) of 1.64 microM for saquinavir, 0.95 microM for indinavir, and 1.01 microM for nelfinavir. Nelfinavir was the second strongest inhibitor with Ki's of 2.35 microM for saquinavir and 2.14 microM for indinavir. Indinavir was the third strongest inhibitor with Ki's of 2.76 microM for nelfinavir and 3.55 microM for saquinavir. Saquinavir was the weakest inhibitor for the other three HIV- 1 protease inhibitors. After oral co-administration in combination with another HIV-1 protease inhibitor, the AUCs of saquinavir, indinavir, and nelfinavir were significantly increased compared with mono-treatment. The AUCs of saquinavir were increased about 10.1-, 3.1- and 45.9-fold in the presence of indinavir, nelfinavir and ritonavir, respectively. The AUCs of indinavir were increased about 6.8-, 5.9- and 9.4-fold in the presence of nelfinavir, saquinavir and ritonavir, respectively. The AUCs of nelfinavir were increased about 2.2-, 6.6- and 8.5-fold in the presence of indinavir, saquinavir and ritonavir, respectively. The in-vivo effects observed after co-administration of two kinds of HIV-1 protease inhibitor were not always expected from in-vitro data, suggesting the presence of other interaction processes besides metabolism in the liver. These results provide useful information for the treatment of AIDS patients receiving combination therapy with two HIV-1 protease inhibitors.

Animals↗

Neurophysiological tests of respiratory function by compound muscle action potentials from the diaphragm. Detection of lesions in the higher cervical cord.

We recorded compound muscle action potentials (CMAPs) from the diaphragm in 15 normal volunteers, nine patients with lesions of the lower cervical cord (C5 to C8), one completely quadriplegic patient (C6) and seven patients with lesions at a higher cervical level (C1 to C4). Transcranial magnetic stimulation and electrical stimulation of the phrenic nerve were carried out. When the centre of the coil was placed on the interauricular line at a point 3 cm lateral to the vertex on the scalp, the CMAPs from the diaphragm had the largest amplitude and the shortest latency. There was no difference in the mean latency of the CMAPs recorded by transcranial magnetic stimulation in the normal volunteers and in the patients with lesions of the lower cervical cord. In the quadriplegic patient, the latency of the CMAPs was not delayed, but was prolonged in the patients with lesions at a higher level. Those evoked by electrical stimulation of the phrenic nerve were not prolonged in the patients with higher lesions. Our findings suggest that the prolongation of the latency by transcranial magnetic stimulation reflects dysfunction of the higher cervical cord. The combination of transcranial magnetic stimulation and electrical stimulation of the phrenic nerve can detect the precise level of the lesion in the motor tract to the diaphragm.

Action Potentials↗

Lotka's law and productivity index of authors in a scientific journal.

Lotka's law of scientific productivity is a bibliometric example: the number of authors against the number of contributions made by the authors was plotted on a logarithmic scale. The points were closely scattered around a straight line having a slope of -2. The purpose of this study was to apply information technology to real-world data and to quantify the extent of the bibliometric regularity that exists in the literature of dental science. We have analyzed the productivity index of authors (PI) in a scientific journal (Journal of American Dental Association). Details of a total of 4,088 papers published between 1966 and 1995 were extracted electronically from MEDLINE. The total number of authors was 5,589, responsible for 8,569 authorships. Only 0.8% of the authors presented a PI > = 1 (large producers), and 78.1% a PI = 0 (occasional authors). The number of authors publishing N papers was 1/N2.64 of those publishing one paper. The result suggested that repeated publications in the Journal were more difficult than those predicted by Lotka (1/N2).

Algorithms↗

[Questionnaire on "having a family dentist" and the status of oral health].

In 1999, we gave a Questionnaire on "having a family dentist" to 414 workers (300 males, 114 females) at a government office. Oral health examination was also provided to the same subjects. The following results were obtained: 1. Female workers (43%) had a family dentist more often than male workers (29%), and the difference was significant (p < 0.01). 2. About 45% of the subjects received regular dental checkups at least once a year; however, half of them did not have a family dentist. 3. Convenience, comfort, and communication factors were the main reasons for choosing a particular dentist, while continuity, comprehensiveness, and specialty factors were not taken into consideration in choosing a dentist. 4. The persons who had family dentists had more FT and DMFT, and fewer total numbers of teeth than those without family dentists. From these results, it was suggested that people visited dentists with dental problems and received treatment repeatedly, and then they came to have family dentists. The habit of visiting a dentist regularly seeking checkups and prevention is not yet popular among Japanese adults. To improve oral health consciousness and to promote oral health, it should be recommended to receive regular checkups and oral health education by a family dentist. However, the present condition does not allow this system. Therefore in Japan, it should be encouraged to provide oral health examination and oral health education regularly at work sites, to improve the oral health of the adult population.

Adult↗

[Regulation of alphaherpesvirus gene expression].

Human alphaherpesviruses are common human pathogens associated with a variety of diseases. The striking characteristics of the viruses are to establish a latent infection in neurons after lytic infection at the periphery. The alphaherpesvirus genes have been shown to fall into several major groups (designated alpha, beta, and gamma) whose expression is coodinately regulated and sequentially ordered in a cascade fashion during the lytic cycle of alphaherpesvirus infection. Recently, cellular proteins which interact with alphaherpesvirus regulatory proteins have been identified and the studies have revealed that the regulatory proteins interact with and modulate a plethora of cellular components and functions including transcription, cell cycle, protein degradation pathway, and translation. These findings suggest that they are multifunctional protein and the functions of the regulatory proteins result from the sum of these interactions.

Alphaherpesvirinae↗