Search PubMed⌕ Search

Biomedical subjects

Y Kawaguchi

Publications and source records attributed to Y Kawaguchi.

At least 55 records · Page 3Linked to original sources
PubMed2001

Change of muscle motor-evoked potentials after motor cortex stimulation caused by acute spinal cord injury in cats.

The validity of the evoked compound muscle action potential (ECMAP) as an index of spinal cord injury has not been established in neurophysiologic monitoring of motor function, although evoked spinal cord potential (ESCP) has been. In the current study, nine cats were used. After craniotomy, electric stimuli were applied to the motor area. Four cats were given stimulation of various numbers and frequencies, and the other five cats underwent graded compression of the spinal cord, and then ECMAPs and ESCPs were recorded. Three cats were awakened and their motor functions were assessed 3 weeks later. The amplitude of the ESCP never decreased to 60% or less of the control value, even when ECMAPs disappeared. No motor dysfunction was present 3 weeks after the experiment. ECMAP is clinically useful, providing information on impairments of the spinal cord that otherwise would remain undetected.

Action Potentials↗
PubMed2001

Minimum 10-year follow-up study of anterior lumbar interbody fusion for isthmic spondylolisthesis.

The aims of the current study were to evaluate the long-term clinical and radiologic results of anterior lumbar interbody fusion (ALIF) for isthmic spondylolisthesis. Between 1981 and 1988, a total of 35 patients underwent ALIF for isthmic spondylolisthesis. Of these, 23 patients were followed clinically and radiographically for more than 10 years (average, 13.3 years). The Japanese Orthopaedic Association low-back pain score was used to evaluate the outcome of subjective symptoms and clinical signs. The preoperative and postoperative percentage of slip, preoperative and postoperative intervertebral disk height, interbody graft union, and pars defect union were evaluated by serial radiographs. The adjacent disk degeneration was also evaluated by radiographs and magnetic resonance imaging. Although the low-back pain score worsened after 5 years, ALIF provides satisfactory overall long-term clinical results. The preoperative percentage of slip and the disk height were corrected after surgery, but at the time of interbody graft union, slip and disk height recurred as a result of grafted bone collapse. The rate of union in the grafted area was 83%. In the nonunion cases, the scores gradually deteriorated with time, but the overall results were not different from those of union cases. Radiographs showed adjacent disk degeneration in 52% of cases in the upper adjacent level and in 70% of cases in the lower adjacent level, but these changes were not correlated with clinical outcomes.

Adolescent↗
PubMed2001

Serial changes of herniated intervertebral discs after posterior lumbar discectomy: the relation between magnetic resonance imaging of the postoperative intervertebral discs and clinical outcome.

To evaluate the relation between the morphologic changes of postoperative intervertebral discs and the clinical outcome after posterior lumbar discectomy, the size of the bulging disc was analyzed prospectively on serial follow-up magnetic resonance images in 26 randomly selected patients. The bulging of postoperative intervertebral discs involved three patterns of reduction: early reduction (n = 15), gradual reduction (n = 6), and late reduction (n = 5). There was a significant difference in the serial changes of subjective symptoms and neurologic function among the three patterns. A late reduction of postoperative disc bulging could cause late recovery of subjective symptoms and neurologic disturbance.

Adolescent↗
PubMed2001

Clinical symptoms and surgical outcome in lumbar spinal stenosis patients with neuropathic bladder.

We evaluated the clinical and radiologic features of patients with lumbar spinal stenosis with neuropathic bladder. Based on cystometrogram analysis, the patients were divided into two groups--the neuropathic bladder (NB) group: the NB+ group (23 patients), and the nonneuropathic bladder group: the NB- group (14 patients). The symptom of incontinence was characteristic in patients in the NB+ group. Patients in the NB+ group had a more severe neurologic disturbance, compared with those in the NB- group. The more severe neurologic disturbance was caused by the more striking finding of degenerative spinal stenosis associated with developmental narrowing of the spinal canal. Decompressive surgery had a beneficial effect on the recovery of the neurologic symptoms in both groups. Residual urine volume was reduced after surgery. Postoperative cystometrogram was carried out in nine patients in the NB+ group. It showed a normal pattern in six patients; however, three patients remained in an underactive pattern. Furthermore, four patients still required clear intermittent self-catheterization after surgery.

Aged↗
PubMed2001

Identification of major phosphorylation sites of Epstein-Barr virus nuclear antigen leader protein (EBNA-LP): ability of EBNA-LP to induce latent membrane protein 1 cooperatively with EBNA-2 is regulated by phosphorylation.

Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) is a phosphoprotein suggested to play important roles in EBV-induced immortalization of B cells. One of the potential functions of EBNA-LP is a cooperative induction with EBNA-2 of viral and cellular gene expression, including that of the genes for viral latent membrane protein 1 (LMP-1) and cellular cyclin D2. We report here that the phosphorylation of EBNA-LP by cellular kinase(s) is critical to its ability to cooperate with EBNA-2 in up-regulating the expression of LMP-1 in a B-lymphoma cell line. Our conclusion is based on the following observations. (i) Mass-spectrometric analysis of purified EBNA-LP and mutational analyses of EBNA-LP revealed that the serine residue at position 35 in the W2 repeat domain is the major phosphorylation site of EBNA-LP in vivo. (ii) Substitutions of this site in each W2 repeat domain with alanine markedly reduced the ability of the protein to induce LMP-1 expression in combination with EBNA-2 in Akata cells. (iii) Replacement at the major phosphorylation sites with glutamic acids restored the wild-type phenotype. It is well established that this substitution mimics constitutive phosphorylation. These results indicated that the coactivator function of EBNA-LP is regulated by phosphorylation.

Alanine↗
PubMed2001

Vitamin D receptor gene polymorphism detected by digestion with Apa I influences the parathyroid response to extracellular calcium in Japanese chronic dialysis patients.

BACKGROUND: To play its physiological role, 1,25(OH)2D3 must bind to a specific vitamin D receptor (VDR) in the nucleus. We have previously reported that VDR gene polymorphism influences the parathyroid function in patients with end-stage renal disease (ESRD). In the present study, we have investigated the relationship between the parathyroid responsiveness and VDR gene polymorphism, as detected by the Apa I restriction enzyme, by changing the concentration of Ca2+ in the dialysate. METHODS: 58 Japanese ESRD patients undergoing renal replacement therapy in our institution were evaluated. Genomic DNA was extracted from peripheral leukocytes and digested at the intron between exon 8 and exon 9 of the VDR gene using Apa I enzyme. Then alleles were classified into genotype A (undigested allele) and genotype a (digested allele). Extracellular ionized calcium ([Ca2+]e), serum phosphate, and intact parathyroid hormone (PTH) were measured before and after each hemodialysis (HD) session with dialysates having different concentrations of Ca2+ (1.5 or 1.25 mmol/l). The significance of differences in statistical analyses was defined within confidence limits of 5.0%. RESULTS: The AA, Aa, and aa genotypes were observed in 7/58 patients (12.1%), 23/58 patients (39.6%), and 28/58 patients (48.3%), respectively. The PTH reduction after HD with the 1.5-mmol/l Ca dialysate did not differ significantly between group AA+Aa and group aa. On the other hand, the PTH increase was significantly higher in group aa than in group AA+Aa after HD with the 1.25-mmol/l Ca dialysate (p = 0.0107), despite a similar PTH level before HD. Similarly, the percent increase of PTH after HD with the 1.25-mmol/l Ca dialysate was significantly higher (p = 0.0112) in group aa (50.2 +/- 9.4%) than in group AA+Aa (19.7 +/- 7.2%). There were no significant differences between the two groups in [Ca2+]e nor in serum phosphorus (Pi) before and after HD with either dialysate. Group AA+Aa and group aa did not show statistically significant differences in age, female/male ratio, ratio of diabetic nephropathy, or dialysis period. CONCLUSIONS: The study results showed that the patients in group aa were more sensitive to changes in [Ca2+]e than those in group AA+Aa. Moreover, they suggested that the VDR gene polymorphism may affect parathyroid responsiveness to changes in [Ca2+]e, which in turn may influence onset and progression of hyperparathyroidism in ESRD patients.

Alleles↗
PubMed2001

Sequence analysis of candidate genes for common susceptibility to type 1 and type 2 diabetes in mice.

Although type 1 and type 2 diabetes are regarded as clinically distinct diseases, several lines of evidence have suggested common genetic factors between the two types of diabetes. The non-obese diabetic (NOD) mouse, an animal model of type 1 diabetes, and the Nagoya-Shibata-Yasuda (NSY) mouse, a model of type 2 diabetes, are derived from the same outbred colony, Jcl:HCR, suggesting a shared susceptibility between the two types of diabetes in mice. Genetic as well as functional studies have supported the possibility that Tcf2, which encodes the transcription factor, hepatocyte nuclear factor 1beta (HNF-1beta), is a candidate gene for the common susceptibility between NSY and NOD mice. Txn, encoding thioredoxin which is a redox (reduction/oxidation)-active protein, is also a positional and functional candidate for a common susceptibility gene. To investigate whether either of these two genes is a common susceptibility gene, the coding nucleotide sequences of these two genes were compared among the NSY, NOD and control C3H strains. The coding sequence of Tcf2 of the NOD mouse was identical to that of the C3H mouse, but was different from that of the NSY mouse. The coding sequence of Txn was identical in the three strains. These data suggest that neither of the two genes is a common susceptiblity gene between type 1 and type 2 diabetes in mice.

Animals↗
PubMed2001

Progression of ossification of the posterior longitudinal ligament following en bloc cervical laminoplasty.

BACKGROUND: Ossification of the posterior longitudinal ligament often causes compressive myelopathy. Ossification is a progressive disease, and it has been reported that the area of ossification increases after decompressive surgery. However, it is uncertain how the progression of ossification affects the long-term outcome after cervical laminoplasty. This study was performed to clarify the relationship between the progression of ossification of the posterior longitudinal ligament and the clinical results following en bloc cervical laminoplasty. METHODS: Forty-five patients who were followed for more than ten years after laminoplasty participated in this study. Radiographs and tomograms of the cervical spine of each patient were made before and after the operation and at the time of the latest follow-up. The extent of ossification in the longitudinal and sagittal axes was evaluated. Neurological function was graded with use of the Japanese Orthopaedic Association scoring system. The relationship between the progression of ossification and the score-based rate of recovery was analyzed. RESULTS: Thirty-three (73%) of the patients had progression of ossification of the posterior longitudinal ligament after laminoplasty. Progression was frequent in patients with the mixed type of ossification and in those with the continuous type, whereas it was rare in patients with the segmental type. The patients with progression of the ossification were significantly younger than those without progression (p = 0.018). The Japanese Orthopaedic Association score improved rapidly within one year and continued to improve up to five years after surgery. The score tended to decrease thereafter. For thirteen patients, the score had worsened at the time of the latest follow-up. Three patients had neurological deterioration following an increase in the thickness of the ossification. CONCLUSIONS: Progression of ossification of the posterior longitudinal ligament was often observed during the long-term follow-up period after laminoplasty. Young patients with mixed and continuous types of ossification had the greatest risk for progression. Preventive measures, such as the use of a wider laminar opening during the laminoplasty, should be considered for patients who are at risk for progression of ossification.

Adult↗
PubMed2001

Progressive interstitial renal fibrosis due to Chinese herbs in a patient with calcinosis Raynaud esophageal sclerodactyly telangiectasia (CREST) syndrome.

A 58-year-old woman with calcinosis Raynaud esophageal sclerodactyly telangiectasia (CREST) syndrome presented with slowly progressive renal dysfunction. She was normotensive with normal plasma renin activity and lacking symptoms of vasculitis. Mild proteinuria was of tubular origin, but serological tests and an absence of sicca symptoms excluded the possibility of Sjögren's syndrome. Light microscopic study of renal biopsy showed interstitial fibrosis with ectasia and degeneration of proximal tubule and lymphocyte infiltration. There were no remarkable changes in the glomeruli. Chromatographic analysis of the Chinese herbs regimen that she had been taking for several years demonstrated aristolochic acid. She was diagnosed as Chinese herbs nephropathy. Therapy with oral prednisolone was markedly effective in improving renal function and anemia. To our knowledge, this is the first report of Chinese herbs nephropathy complicating connective tissue disease. It is important to consider the possibility of Chinese herbs nephropathy when patients treated with Chinese herbs develop renal dysfunction.

Aristolochic Acids↗
PubMed2001

The Pro12 -->Ala substitution in PPAR-gamma is associated with resistance to development of diabetes in the general population: possible involvement in impairment of insulin secretion in individuals with type 2 diabetes.

The allele frequencies for a Pro12-->Ala substitution in peroxisome proliferator-activated receptor-gamma differ among ethnic groups, and its relationship with diabetes and associated diseases is controversial. The prevalence of this polymorphism and its effects on clinical characteristics have now been evaluated with a large number of Japanese individuals with type 2 diabetes (n = 2,201) and normal control subjects (n = 1,212) recruited by 10 institutions located in seven different cities in Japan. The allele frequency for the Ala12 variant was significantly lower in the type 2 diabetic group than in the control group (2.39 vs. 4.13%, P = 0.000054). However, compared with subjects without the Ala12 variant, the diabetic subjects with this variant exhibited a significantly higher serum concentration of total cholesterol (P = 0.001), manifested a reduced capacity for insulin secretion as evaluated by homeostasis model assessment (P = 0.007), and tended to possess a higher level of HbA1c. These data suggest that the Ala12 variant is associated with a reduced risk for the development of diabetes in the general population, but that it may be also a risk factor for insulin deficiency and disease severity in individuals with type 2 diabetes.

Adult↗
PubMed2001

[Dental treatment in the north area of Ishigaki Island in Okinawa].

Dental treatment and oral health care were performed on inhabitants in the north area of Ishigaki Island in Okinawa. There are no dentists in the area at present. One hundred sixty-six patients received treatment taking 528 man-days, during the period from November 9 to December 8, 2000. The area has 2 primary schools and 1 junior high school. The average DMFT of the children in the primary schools was 1.31, and in the junior high school it was 4.98. Compared with Japanese national survey data, the children in the area had a higher DMFT. Among the treatment procedures, the rate of conservative treatment was 62%, most of which was composite resin filling. Preventive measures for dental disease were offered to the inhabitants by means of topical fluoride application or oral health education. The period of this promotion was too short to perform complete dental treatment and to prevent caries and periodontal disease. It seems that primary prevention and higher dental hygiene education are needed for inhabitants in no-dentist areas, because the inhabitants do not have access to dental service easily.

Community Dentistry↗
PubMed2001

[Statistical analysis of a dental care program for homebound elderly patients in Shinjuku-ku].

A dental care service program for homebound elderly patients has been operating since 1988 in Shinjuku-ku, Tokyo. The purpose of this study was to clarify the characteristics of patients who received this dental care service. Based on a survey questionnaire and treatment card from April 1995 to March 1999, we analyzed the characteristics of patients. The following conclusions were obtained. 1. We studied 301 patients (males, 124; females, 177). The average age of the patients was 81.2 +/- 9.0 years. Eighty-four percent of the patients had a medical history. 2. Oral hygiene was practiced by 68% of the subjects: 78% by themselves, and 22% by caregivers. Half of the patients (53%) brushed their teeth every day, and one-third (32%) did not. 3. The mean number of DMF teeth was 25.4 (DT, 1.6; MT, 20.5; FT, 3.3). 4. About eighty percent (79%) of the patients had removable dentures, and one-third of them were upper and lower complete dentures. 5. The chief complaint of homebound elderly was the denture problem (73%). Therefore, the care provided at the bedside was mainly denture-related treatments. 6. Average times for visiting were 5.1. 7. Sixty-eight percent of the patients requested home dentist's visitation for dental care service, and 80% of the requested dentists performed such treatment. 8. Seventy-eight percent of the elderly patients were satisfied with the service program. This dental care program for homebound elderly patients seemed to work well. However, to meet needs for the expanding number of aged persons and to make it coincide with the new health and welfare scheme, reform of the program might be necessary.

Aged↗
PubMed2001

Decreases in phenytoin hydroxylation activities catalyzed by liver microsomal cytochrome P450 enzymes in phenytoin-treated rats.

Phenytoin, 5,5-diphenylhydantoin, is a widely used anticonvulsant agent with a variety of toxicities, including drug interactions. The formation of four oxidative metabolites, 4'-hydroxylated (4'-HPPH), 3'-hydroxylated (3'-HPPH), a catechol (3',4'-diHPPH), and the 3',4'-dihydrodiol form of phenytoin was examined in rat liver microsomes. In 11 cDNA-expressed rat P450 enzymes tested, CYP2C6 had the highest activities in 4'- and 3'-HPPH formation from phenytoin, followed only by CYP2C11. In contrast, CYP2C11 had high activity for 3',4'-diHPPH formation from 4'-HPPH, followed by CYP2C6. The rates of 4'-HPPH and 3',4'-diHPPH formation from phenytoin in liver microsomes in the presence of NADPH were significantly decreased by oral administration of phenytoin (300 mg/kg for 20 days) to rats, despite the increase in P450 contents. However, the cumene hydroperoxide-supported formation of 3',4'-dihydrodiol and 4'-HPPH from phenytoin was induced by phenytoin administration. Hydrogen peroxide formation in reaction mixtures with NADPH was induced by the administration of phenytoin; however, the coupling ratio of phenytoin oxidation was decreased in phenytoin-induced liver microsomal P450 systems. These results suggested that phenytoin could not stimulate its own apparent oxidative metabolism by liver P450s induced with phenytoin administration. The increase of unmetabolized phenytoin and byproducts of oxygen generated in the phenytoin-induced liver microsomal P450 system may be involved in phenytoin-related drug toxicity.

Animals↗
PubMed2001

Involvement of microsomal cytochrome P450 and cytosolic thymidine phosphorylase in 5-fluorouracil formation from tegafur in human liver.

Recently, we have reported that tegafur, an anticancer agent, is biotransformed into active drug 5-fluorouracil (5-FU) by cytochromes P450 1A2, 2A6, and 2C8 in human liver microsomes (T. Komatsu et al., Drug Metab. Dispos, 28: 1457-1463, 2000). Because the conversion of tegafur into 5-FU has also been reported to be catalyzed by cytosolic thymidine phosphorylase (dThdPase), the involvement of human liver microsomes and cytosol and individual differences in 5-FU formation from tegafur were investigated. In 14 human samples, the mean rates of 5-FU formation in liver microsomes were 5-fold and 2-fold higher than those in liver cytosol at substrate concentrations of 100 microM and 1 mM tegafur, respectively. In the presence of 5-chloro-2,4-dihydroxypyridine, a dihydropyrimidine dehydrogenase inhibitor, the rates of 5-FU formation by the combination of liver microsomes and cytosol showed 5- and 3-fold interindividual differences at 100 microM and 1 mM tegafur, respectively. Kinetic analysis of human liver cytosolic 5-FU formation indicated an apparent higher Km value (16 +/- 4 mM) than that of liver microsomes (1.8 +/- 0.3 mM) with similar Vmax values. Human liver cytosolic 5-FU formation was confirmed to be catalyzed by dThdPase with correlation and chemical inhibition studies. These results suggested that 5-FU formation from tegafur in human liver was mainly catalyzed by microsomal P450 at low concentrations of tegafur, but the contribution of cytosolic 5-FU formation by dThdPase would be important at high concentrations.

Antimetabolites, Antineoplastic↗
PubMed2001

Effects of 5-fluorouracil on the drug-metabolizing enzymes of the small intestine and the consequent drug interaction with nifedipine in rats.

5-Fluorouracil (5-FU) is a widely used antineoplastic agent. 5-FU therapy often causes gastrointestinal toxicity, which is suppressed by concomitant administration of potassium oxonate (Oxo). Here, we investigated the effect of 5-FU on the small-intestinal drug-metabolizing enzymes, which play important roles in the first-pass metabolism of drugs, in rats, by enzyme measurements and immunoblot analyses. During repeated administration of a combination of 1-(2-tetrahydrofuryl)-5-fluorouracil, an oral 5-FU-derivative drug, and 5-chloro-2,4-dihydroxypyridine (FCD), an inhibitor of 5-FU degradation, the activities of 7-ethoxyresorufin-O-deethylase, testosterone 6beta-hydroxylase, 4-methylumbelliferone UDP-glucuronyltransferase, and 1-chloro-2,4-dinitrobenzene glutathione S-transferase decreased significantly on day 4, and the activity of NADPH-cytochrome P450 (CYP) reductase decreased significantly on day 7. These effects were found to be attributable to a reduction in the enzyme protein contents in the small-intestinal mucosa. The enzymatic alterations significantly increased the plasma concentrations of orally administered nifedipine, which was prevented by concomitant administration of Oxo with FCD. However, consecutive administration of FCD for 4 days did not cause any alterations in the activity of the hepatic CYP isozyme-supported testosterone hydroxylase. These results suggest that continuous exposure to 5-FU leads to a decrease in the activities of drug-metabolizing enzymes in the intestinal mucosa by decreasing their enzyme protein contents, and increases the plasma concentrations of orally administered nifedipine, and that the sensitivity of these enzymes to the drug is greater than that of the enzymes of the liver. These effects were prevented by concomitant administration of Oxo.

Administration, Oral↗