Biomedical subjects

K Kashiwagi

Publications and source records attributed to K Kashiwagi.

At least 19 recordsLinked to original sources

PubMed2006

Polyamines in renal failure.

The levels of polyamines (putrescine, spermidine and spermine) and polyamine oxidase in plasma of patients with chronic renal failure were determined. The level of putrescine was increased but the level of spermine was decreased in the plasma of these patients. The patients also had increased plasma polyamine oxidase activity leading to increased degradation of spermine. As acrolein was a major toxic compound produced from spermine by polyamine oxidase, the levels of free and protein-conjugated acrolein in plasma were also measured. Acrolein levels were enhanced in plasma of patients with chronic renal failure. The accumulated acrolein found as protein conjugates was equivalent to 170 microM, which was about 5-fold higher than in plasma of normal subjects. It was found that acrolein is mainly produced by spermine oxidase in plasma. An increase in putrescine, spermine oxidase and acrolein in plasma was observed in all cases such as diabetic nephropathy, chronic glomerulonephritis and nephrosclerosis. After patients with chronic renal failure had undergone hemodialysis, their levels of plasma polyamines, spermine oxidase and acrolein returned towards normal. It is likely that acrolein produced from spermine accumulates in the blood due to decreased excretion into urine and may function as a uremic "toxin".

Acrolein↗

PubMed2006

Finding cases of angle-closure glaucoma in clinic setting using a newly developed instrument.

PURPOSE: To validate the applicability of a newly developed, noncontact scanning peripheral anterior chamber depth analyzer (SPAC) for screening eyes at the risk of angle-closure glaucoma (ACG). SUBJECTS AND METHODS: All glaucoma patients who visited the University of Yamanashi Hospital from February through May 2003 were enrolled, except those with aphakic eye or pseudophakic eye. Of the 552 enrolled patients, 48 with ACG or narrow angles requiring laser iridotomy (LI) were categorized as patients with high-risk ACG eyes, and those with open angle were categorized as patients with control eyes. In all, 20 patients with ACG or narrow angles requiring prophylactic LI, who were followed up by an independent private ophthalmic clinic, were enrolled for threshold analysis. Nonophthalmologists measured anterior chamber depth and the averaged values of three measurements were employed for analysis. Threshold analysis and discriminant analysis were employed for determining the sensitivity and specificity of SPAC for diagnosing eyes with high-risk ACG. RESULTS: SPAC distinguished well the high-risk ACG eyes from the control eyes, and one of the most useful criteria for screening is as follows: any of the four measured points should exceed 95% confidence interval, and sensitivity and specificity should be 97.6 and 83.5%, respectively. CONCLUSION: SPAC is thought to be useful for detecting eyes at the risk of ACG by nonophthalmologists.

Anterior Chamber↗

PubMed2006

Effect of non-steroidal anti-inflammatory ophthalmic solution on intraocular pressure reduction by latanoprost in patients with primary open angle glaucoma or ocular hypertension.

AIM: To investigate the effects of a non-steroidal anti-inflammatory drug (NSAID) ophthalmic solution on latanoprost induced intraocular pressure (IOP) reduction in glaucoma patients. METHODS: Examination was conducted on 16 eyes of 16 glaucoma patients who had been given only latanoprost for at least 6 weeks. The NSAID ophthalmic solution, sodium 2-amino-3-(4-bromobenzoyl) phenylacetate sesquihydrate, was additionally given for 12 weeks into one eye (NSAID group), while sodium hyaluronic acid ophthalmic solution was administered into the other eye (control group) in a double masked fashion. The IOP measurement was performed before the start of additional administration of ophthalmic solutions, 2, 4, 6, 8, 10, and 12 weeks after the start of additional administration, and 2, 4, and 6 weeks after discontinuing additional administration. RESULTS: No significant difference was observed in the IOPs before additional administration of ophthalmic solution between the NSAID group and the control group. Following the additional administration of ophthalmic solution, IOP in the NSAID group was consistently higher than that in the control group, and a maximum difference in IOP between the two groups was 1.08 (SD 1.75) mm Hg (p = 0.03). This trend was observed even after additional administration was discontinued. CONCLUSION: NSAID ophthalmic solution may partly affect IOP reduction by latanoprost.

Adult↗

PubMed2005

Usefulness of peripheral anterior chamber depth assessment in glaucoma screening.

PURPOSE: This study was conducted to determine the usefulness of peripheral anterior chamber depth assessment in angle-closure glaucoma (ACG) screening in Japanese subjects. SUBJECTS AND METHODS: The subjects were 14,779 adults 40 years old or older. Eyes having peripheral anterior chamber depth that is 1/4 the peripheral corneal thickness (van Herick's classification: grade 2) and less than 1/4 the peripheral corneal thickness (van Herick's classification: grade 1) were extracted as narrow angle eyes, and those eyes were further examined. RESULTS: Of 14,779 subjects, 923 eyes of 505 subjects were diagnosed as narrow angle eyes (3.4%). Narrow angle eyes were observed in 4.9% of female subjects and 1.9% of male subjects, indicating a significantly higher frequency in women. The percentage of narrow angle eyes increased with age. Among the narrow angle eyes, 61 eyes of 32 subjects were diagnosed with ACG suspect (6.5%). In contrast to the frequency of ACG suspect in eyes classified as grade 1, according to van Herick's classification, being 17.9%, that in eyes classified as grade 2 was significantly lower at 5.6%. CONCLUSION: Since the incidence of ACG suspect increases as the peripheral anterior chamber depth decreases, caution for the peripheral anterior chamber depth is required for the ACG screening.

Adult↗

PubMed2004

A newly developed peripheral anterior chamber depth analysis system: principle, accuracy, and reproducibility.

AIM: To develop a new, non-contact system for measuring anterior chamber depth (ACD) quantitatively, and to investigate its accuracy as well as interobserver and intraobserver reproducibility. METHODS: The system scanned the ACD from the optical axis to the limbus in approximately 0.5 second and took 21 consecutive slit lamp images at 0.4 mm intervals. A computer installed program automatically evaluated the ACD, central corneal thickness (CT), and corneal radius of curvature (CRC) instantly. A dummy eye was used for investigating measurement accuracy. The effects of CT and CRC on the measurement results were examined using a computer simulation model to minimise measurement errors. Three examiners measured the ACD in 10 normal eyes, and interobserver and intraobserver reproducibility was analysed. RESULTS: The ACD values measured by this system were very similar to theoretical values. Increase of CRC and decrease in CT decreased ACD and vice versa. Data calibration using evaluated CT and CRC successfully reduced measurement errors. Intraobserver and interobserver variations were small. Their coefficient variation values were 7.4% (SD 2.3%) and 6.7% (0.7%), and these values tended to increase along the distance from the optical axis. CONCLUSION: The current system can measure ACD with high accuracy as well as high intraobserver and interobserver reproducibility. It has potential use in measuring ACD quantitatively and screening subjects with narrow angle.

Adult↗

PubMed2004

Quantitative evaluation of changes in anterior segment biometry by peripheral laser iridotomy using newly developed scanning peripheral anterior chamber depth analyser.

AIM: Using the newly developed scanning peripheral anterior chamber depth analyser (SPAC), the effects of peripheral laser iridotomy (PLI) on peripheral anterior chamber depth (PACD) were determined quantitatively as was the association between PACD and chronic elevation of intraocular pressure (IOP) after PLI. METHODS: 16 eyes of 15 patients with acute primary angle closure glaucoma (PACG) attack, 14 eyes of 14 patients with narrow angle and PACG attack in their fellow eyes, and 13 eyes of seven patients with chronic angle closure glaucoma (CACG) were enrolled. The SPAC scanned the anterior ocular segment from the optical axis to the limbus and took 21 consecutive slit lamp images at 0.4 mm intervals. A computer installed program automatically evaluated the PACD and the averaged values of three measurements were employed for analysis. RESULTS: PLI significantly increased PACD and changed the iris contour from convex to flat or concave in all the enrolled eyes. The extent of the PLI induced PACD increase was enhanced with increasing distance from the optical axis. Comparing PACDs after PLI, eyes that received prophylactic PLI showed the greatest extent of PLI induced PACD increase, followed by eyes with CACG and eyes with PACG attack. The PACD of eyes with PACG attack was almost the same as that of the fellow eyes of PACG attack before prophylactic PLI. Eyes with PACG attack showed poorer IOP control after PLI than eyes with narrow angle and CACG with PLI. CONCLUSIONS: PLI significantly increases PACD and the small PLI induced opening of PACD may contribute to chronic IOP elevation after PLI.

Aged↗

PubMed2003

Acrolein produced from polyamines as one of the uraemic toxins.

It is well known that the addition of spermine or spermidine to culture medium containing ruminant serum inhibits cellular proliferation. This effect is caused by the products of oxidation of polyamines that are generated by serum amine oxidase. Among the products, we found that acrolein is a major toxic compound produced from spermine and spermidine by amine oxidase. We then analysed the level of polyamines (putrescine, spermidine and spermine) and amine oxidase activity in plasma of patients with chronic renal failure. It was found that the levels of putrescine and the amine oxidase activity were increased, whereas spermidine and spermine were decreased in plasma of patients with chronic renal failure. The levels of free and protein-conjugated acrolein were also increased in plasma of patients with chronic renal failure. An increase in putrescine, amine oxidase and acrolein in plasma was observed in all cases such as diabetic nephropathy, chronic glomerulonephritis and nephrosclerosis. These results suggest that acrolein is produced during the early stage of nephritis through kidney damage and also during uraemia through accumulation of polyamines in blood due to the decrease in their excretion into urine.

Acrolein↗

PubMed2003

Effect of non-steroidal anti-inflammatory ophthalmic solution on intraocular pressure reduction by latanoprost.

AIM: To investigate the effects of a non-steroidal anti-inflammatory drug (NSAID) ophthalmic solution on latanoprost induced intraocular pressure (IOP) reduction using normal volunteers. METHODS: This study was conducted as a prospective and observer masked clinical trial. 13 normal volunteers were enrolled. After measurement of basal IOP and ophthalmic examination, latanoprost ophthalmic solution was initially administered to both eyes once daily. Four weeks later, an NSAID ophthalmic solution, sodium 2-amino-3-(4-bromobenzoyl) phenylacetate sesquihydrate (refer to bromfenac sodium hydrate), was co-administered to one randomly selected eye (NSAID group) twice daily for 2 weeks. The other eye was employed as a control (non-NSAID group). After withdrawal of the NSAID ophthalmic solution, latanoprost ophthalmic solution was continuously administered for another 2 weeks and was then withdrawn. After a 4 week washout, only bromfenac sodium hydrate ophthalmic solution was administered to the eyes of the NSAID group for 2 weeks. During the study period, ophthalmic examination, including IOP measurement was performed in an observer masked fashion. RESULTS: Before initiation of bromfenac sodium hydrate, baseline IOPs of the non-NSAID group and the NSAID group were 15.73 (SD 1.97) mm Hg and 15.86 (2.06) mm Hg, respectively (p=0.88). Although latanoprost ophthalmic solution significantly reduced IOP in both groups, co-administration of bromfenac sodium hydrate significantly inhibited latanoprost induced IOP reduction compared with the non-NSAID group. The IOPs of the non-NSAID and NSAID groups were 10.18 (1.17) mm Hg and 11.63 (1.35) mm Hg with a 2 week co-administration, respectively (p <0.01). Withdrawal of bromfenac sodium hydrate ophthalmic solution diminished the difference between the two groups. Re-administration of bromfenac sodium ophthalmic solution only did not affect IOP. CONCLUSION: These results indicate that NSAID ophthalmic solution may interfere with IOP reduction by latanoprost ophthalmic solution in normal volunteers and that we should take this into account when treating patients with glaucoma using latanoprost ophthalmic solution.

Adult↗

PubMed2003

Agreement between frequency doubling perimetry and static perimetry in eyes with high tension glaucoma and normal tension glaucoma.

AIMS: To investigate the agreement in results between frequency doubling technology (FDT) and the conventional automated static perimeter in eyes with normal tension glaucoma (NTG) and high tension glaucoma (HTG). METHODS: 72 eyes of 36 patients, who had two or more experiences with the Humphrey field analyser (HFA) program C30-2, were examined with the screening C-20-1 program of FDT. The result of FDT at each of the 17 stimulus points was graded as one of four categories. 58 out of 76 test points of HFA were assigned to one of the 17 clusters corresponding to FDT test points. Each cluster was represented as the lowest (scotoma of HFA) or the highest (threshold of HFA) probability symbol of total deviation (TD) of the HFA test points included in the cluster. The agreement between scotoma/threshold of HFA and FDT results was evaluated for NTG and HTG. RESULTS: In a total of 65 eyes, the Spearman coefficients between the FDT and HFA (threshold/scotoma of HFA) were 0.599 and 0.515 (p<0.0001), respectively. In the HFA mean deviation matched 20 HTG eyes and 20 NTG eyes, the number of points with abnormal FDT results were 102 and 62 in eyes with HTG and NTG, respectively. The eyes with HTG had more abnormal FDT results than NTG eyes (p=0.0014, Mann-Whitney U test). The kappa coefficient between FDT and threshold of HFA in eyes with HTG and NTG was 0.288 and 0.520, respectively, and the agreement between FDT and scotoma of HFA was 0.480 and 0.439, respectively. CONCLUSIONS: The best agreement of the results of FDT and HFA was observed in eyes with NTG using threshold of HFA. The eyes with HTG showed lower agreement with more abnormal points in FDT results, which suggests enough sensitivity of FDT in eyes with NTG, and higher sensitivity of FDT in eyes with HTG.

Adult↗

PubMed2003

Comparison of iridial pigmentation between latanoprost and isopropyl unoprostone: a long term prospective comparative study.

AIM: To compare incidence of iridial pigmentation prospectively induced by long term treatment with latanoprost and isopropyl unoprostone (hereafter, unoprostone) in Japanese patients with glaucoma. METHODS: Patients with glaucoma treated with prostaglandin (PG) related ophthalmic solutions were sequentially enrolled. Patients treated for more than 30 months with PG related ophthalmic solutions were subjected to analysis. The entry criteria were no history of intraocular surgery, laser iridotomy, and/or laser trabeculoplasty within 12 months before and after the enrolment; and no history of uveitis; no changes in antiglaucoma drugs within 6 months before and after the enrolment. Photographs of the irides were taken under the same conditions and three glaucoma specialists evaluated the iridial pigmentation with masking of patient information. The correlation of iridial pigmentation with the background factors and the reduction of intraocular pressure (IOP) before and after the treatment were investigated. RESULTS: 48 eyes in 48 patients satisfied the enrolment criteria (25 eyes in the latanoprost group, 23 eyes in the unoprostone group). At the end of the follow up period, iridial pigmentation was present in 15 patients (60.0%) in the latanoprost group and seven patients (30.4%) in the unoprostone group. The correlation between development of iridial pigmentation and age, sex, concurrent use of other ophthalmic solutions, and IOP reduction was not significant. CONCLUSIONS: The incidence of iridial pigmentation induced by latanoprost or unoprostone is high in the case of long term treatment. Iridial pigmentation did not affect PG related ophthalmic solution induced IOP reduction.

Adult↗

PubMed2001

Human T lymphotropic virus type 1 infection influences hepatitis C virus clearance.

To explore the effect of human T lymphotropic virus type 1 (HTLV-1) infection on hepatitis C virus (HCV) infection, a survey for these viral infections was conducted that involved 2280 residents in an area in which HTLV-1 and HCV are endemic. The response of patients with HCV and HTLV-1 to interferon (IFN)-alpha treatment was also assessed. Antibody to HCV was detected in 13.8% of the residents tested, and antibody to HTLV-1 was detected in 15.4%. The prevalence of HCV RNA was significantly higher among residents who had antibodies to both HCV and HTLV-1 than in those who had antibodies to HCV only (P<.05). Sustained elimination of HCV RNA by IFN was significantly more frequent among patients with HCV alone than among those with HCV and HTLV-1. By logistic regression analysis, HTLV-1 infection was associated with nonresponse to IFN treatment. Thus, HTLV-1 infection affects the clearance, both natural and in association with IFN treatment, of HCV.

Adult↗

PubMed2001

Expression of thyroid hormone receptor betaA gene assayed by transgenic Xenopus laevis carrying its promoter sequences.

The responsiveness of thyroid hormone responsive element (TRE)-containing promoter sequence to thyroid hormone (TH) was studied utilizing Xenopus laevis carrying a transgene containing 5'-upstream region of TRbetaA1 gene and green fluorescent protein (EGFP) gene. EGFP-expression was seen first in neurulae, which continued to stage 45, then became weak, and again started to increase at the prometamorphic stage, culminating at the metamorphic climax stage. Immunohistochemistry identified eyes, viscera, and muscles as the EGFP-expressing larval tissues. The treatment of premetamorphic tadpoles with TH induced the precocious EGFP-expression. We also showed that the transgenic Xenopus adults were responsive to exogenous TH, a high responsiveness being seen in brain, small intestine, kidney, and bone. TRbeta-expression in the embryo, larva, and adult was verified by Western blotting. Thus, TH not only regulates the metamorphosis, but also might play some biological role(s) in embryos and adults.

Animals↗

PubMed2001

Polyamine cytotoxicity in the presence of bovine serum amine oxidase.

The toxicity of extracellular spermine, determined in the presence of fetal calf serum, was studied using three cell lines: FM3A, L1210, and NIH3T3 cells. Amine oxidase in fetal calf serum produces aminodialdehyde generating acrolein spontaneously, H(2)O(2), and ammonia from spermine. Spermine toxicity was prevented by aldehyde dehydrogenase, but not by catalase. Similar concentrations of spermine and acrolein were needed to produce toxicity. Other aldehydes (formaldehyde, acetaldehyde, and propionaldehyde) and hydrogen peroxide were less toxic than acrolein. Spermidine and 3-aminopropanal, which produces acrolein, also exhibited severe cytotoxicity. The degree of cytotoxicity of spermine, spermidine, and 3-aminopropanal was nearly parallel with the amount of acrolein produced from each compound. Thus, it was deduced that acrolein is a major toxic compound produced from polyamines (spermine and spermidine) by amine oxidase.

3T3 Cells↗

PubMed2001

Multiple polyamine transport systems on the vacuolar membrane in yeast.

We recently identified a gene (TPO1, YLL028w) that encodes a polyamine transport protein on the vacuolar membrane in yeast [Tomitori, Kashiwagi, Sakata, Kakinuma and Igarashi (1999) J. Biol. Chem. 274, 3265-3267]. Because the existence of one or more other genes for a polyamine transport protein on the vacuolar membrane was expected, we searched sequence databases for homologues of the protein encoded by TPO1. Membrane proteins encoded by the open reading frames YGR138c (TPO2), YPR156c (TPO3) and YOR273c (TPO4) were postulated to be polyamine transporters and, indeed, were subsequently shown to be polyamine transport proteins on the vacuolar membrane. Cells overexpressing these genes were resistant to polyamine toxicity and showed an increase in polyamine uptake activity and polyamine content in vacuoles. Furthermore, cells in which these genes were disrupted showed an increased sensitivity to polyamine toxicity and a decrease in polyamine uptake activity and polyamine content in vacuoles. Resistance to polyamine toxicity in cells overexpressing the genes was overcome by bafilomycin A(1), an inhibitor of the vacuolar H(+)-ATPase. Among the four polyamine transporters, those encoded by TPO2 and TPO3 were specific for spermine, whereas those encoded by TPO1 and TPO4 recognized spermidine and spermine. These results suggest that polyamine content in the cytoplasm of yeast is elaborately regulated by several polyamine transport systems in vacuoles. Furthermore, it was shown that Glu-207, Glu-324 (or Glu-323) and Glu-574 of TPO1 protein were important for the transport activity.

Amino Acid Sequence↗

PubMed2001

Polyamine enhancement of the synthesis of adenylate cyclase at the translational level and the consequential stimulation of the synthesis of the RNA polymerase sigma 28 subunit.

The effects of polyamines on the synthesis of various final sigma subunits of RNA polymerase were studied using Western blot analysis. Synthesis of final sigma(28) was stimulated 4.0-fold and that of final sigma(38) was stimulated 2.3-fold by polyamines, whereas synthesis of other final sigma subunits was not influenced by polyamines. Stimulation of final sigma(28) synthesis was due to an increase in the level of cAMP, which occurred through polyamine stimulation of the synthesis of adenylate cyclase at the level of translation. Polyamines were found to increase the translation of adenylate cyclase mRNA by facilitating the UUG codon-dependent initiation. Analysis of RNA secondary structure suggests that exposure of the Shine-Dalgarno sequence of mRNA is a prerequisite for polyamine stimulation of the UUG codon-dependent initiation.

Adenylyl Cyclases↗

PubMed2001

A sequence change (Arg158Gln) in the leucine zipper-like motif region of the MYOC/TIGR protein.

The myocilin/trabecular meshwork-inducible glucocorticoid response (MYOC/TIGR) gene was identified as a gene that caused open angle glaucoma (OAG). Single-strand conformation polymorphism analysis and subsequent sequence analysis were performed for the MYOC/TIGR gene in 120 unrelated Japanese OAG patients with increased intraocular pressure (IOP), 116 unrelated OAG patients without increased IOP, and 106 unrelated control subjects without glaucoma. An Arg158Gln sequence change in the leucine zipper-like motif (LZM) region in the myosin-homology domain was found in 2 OAG patients with or without increased IOP, and in a 56-year-old control subject without glaucoma. This is the first report of missense sequence change in the LZM region of the MYOC/TIGR protein in subjects showing various phenotypes, including a control subject. These findings suggest that Arg158Gln in the LZM region is probably a rare nondisease-causing polymorphism, despite its important role in this region, because it was found in a control subject, although Arg158Gln was previously reported as a probable disease-causing mutation.

Adult↗

PubMed2001

Analysis of myocilin gene mutations in Japanese patients with normal tension glaucoma and primary open-angle glaucoma.

The myocilin gene was identified as a gene (MYOC) that caused primary open-angle glaucoma (POAG). Although a normal tension glaucoma (NTG) patient with the myocilin gene mutation was previously reported, no study using large numbers of patients with NTG has been reported. Single-strand conformation polymorphism analysis and subsequent sequence analysis were performed for genotyping the myocilin gene in 114 unrelated Japanese patients with NTG. One hundred and nineteen patients with POAG and 100 control subjects without glaucoma were studied as reference subjects. Five amino acid sequence changes of the myocilin were identified: Arg46Stop (one NTG), Arg76Lys (four NTG, 10 POAG, seven control), Arg158Gln (one NTG, one POAG, one control) found in only Japanese, Asp208Glu (four NTG, three POAG, one control), Pro481Ser (one control). Pro481Ser was novel. Arg76Lys always occurred with 1-83 from G to A in the promoter as it was reported in Chinese. Although some Japanese patients with NTG had sequence changes of the myocilin gene, there were no apparent specific mutations in patients with NTG.

Adolescent↗

PubMed2001

Efficacy of treatment with chimeric monoclonal antibody (Infliximab) to tumor necrosis factor-alpha for Crohn's disease in Japan: evaluation by rapid turnover proteins, and radiologic and endoscopic findings.

BACKGROUND: Several studies have reported that the chimeric monoclonal antibody to tumor necrosis factor (TNF)-alpha (Infliximab) is extremely valuable in the treatment of Crohn's disease. The aim of this study was to clarify the efficacy of this treatment in Japanese patients with Crohn's disease. METHODS: A 12-week multicenter, open trial of Infliximab was carried out and involved 25 patients with moderate to severe Crohn's disease who were resistant to conventional treatment. Patients received a single 2-h intravenous infusion of Infliximab at a dose of 1, 3, 5 or 10 mg/kg bodyweight. Clinical evaluation of this treatment response was defined as a reduction in the index of the inflammatory bowel disease (IOIBD) and of the Crohn's disease activity index scores (CDAI), and in serum levels of C-reactive protein (CRP) at 2, 4, 8 and 12 weeks, and as an increase in serum levels of rapid turnover proteins as well as improvement of radiologic and endoscopic findings at 4 weeks. RESULTS: The IOIBD score was reduced after 4 weeks in 66.7% of the group receiving 1 mg/kg Infliximab, 71.4% in the group receiving 3 mg/kg, 80.0% in the group receiving 5 mg/kg, and 85.7% in the group receiving 10 mg/kg. Improvement was better maintained over 12 weeks in the 5 and 10 mg/kg groups compared with the 1 and 3 mg/kg groups. Similar results were obtained for the CDAI scores. Serum levels of rapid turnover proteins significantly increased to within the normal ranges after infusion in all groups. Seven of the 11 (63.6%) patients evaluated showed improvement of radiologic and endoscopic findings. CONCLUSIONS: A single infusion of Infliximab was effective for the treatment of Japanese patients with Crohn's disease. Serum rapid turnover proteins reflected the clinical response to antibody for TNF-alpha well.

Adult↗