Search PubMed⌕ Search

Biomedical subjects

H Toyoda

Publications and source records attributed to H Toyoda.

At least 37 records · Page 2Linked to original sources
PubMed2001

Analytical method for keratan sulfates by high-performance liquid chromatography/turbo-ionspray tandem mass spectrometry.

We established a highly sensitive LC/MS/MS method for the analysis of the disaccharides produced from keratan sulfates (KS). It was revealed that the disaccharides produced by keratanase II enzymatic digestion of KS could be determined with high sensitivity by the negative-ion mode of multiple reaction monitoring. Furthermore, monosulfated and disulfated disaccharides can be separated using a short column of Capcell Pak NH2 UG80 (35 mm x 2 mm i.d.). The complete analysis of one sample can be performed within 5 min. The assay method was validated and showed satisfactory sensitivity, precision, and accuracy, which enabled quantitation at subpicomole levels. From the results of analyses of KS obtained from cornea, nasal cartilage, and brain, it was found that the degree of sulfation at the C-6 position of the galactose residues differed among those samples in the following order: nasal cartilage > cornea > brain. Our analytical method is very useful for the analyses of KS in various biological materials and for comparison of the degree of sulfation of KS from various biological samples.

Animals↗
PubMed2001

Impact of diabetes mellitus on the prognosis of patients with hepatocellular carcinoma.

BACKGROUND: The majority of patients with hepatocellular carcinoma (HCC) have coexisting cirrhosis or chronic hepatitis, often complicated by diabetes mellitus. In the current study, the authors evaluated the impact of diabetes mellitus on the prognosis of patients with HCC. METHODS: Among 581 patients with HCC who had been diagnosed and treated between 1990 and 1999, survival was compared between those patients with and those patients without diabetes mellitus. The rate of disease recurrence after treatment also was analyzed. RESULTS: Ninety-two patients (15.8%) had diabetes mellitus. There was no significant difference with regard to patient characteristics (i.e., age, gender, or alcohol intake) or liver function between those patients with and those patients without diabetes mellitus. No differences were observed in survival between patients with diabetes mellitus and patients without it. Among the 195 patients with a solitary HCC lesion measuring < or = 3 cm in greatest dimension, the survival of the 32 patients with diabetes mellitus was significantly poorer than that of the 163 patients without diabetes mellitus (P = 0.0273), despite no apparent difference in liver function between the 2 groups. On multivariate analysis, diabetes mellitus was found to be an independent factor predicting lower survival after treatment (P = 0.0077) among patients with a solitary HCC lesion measuring < or = 3 cm in greatest dimension. No difference in the rate of recurrence was observed between the two groups in all the patients and in those patients with a solitary HCC lesion measuring < or = 3 cm in greatest dimension. CONCLUSION: The results of the current study indicated that the presence of diabetes mellitus worsens the prognosis of patients with a solitary HCC lesion measuring < or = 3 cm in greatest dimension; it appears to impact prognosis in patients with HCC when HCC is treatable, based on the size and the number of lesions. However, diabetes mellitus did not appear to affect the prognosis in the general population of patients with HCC. Based on the current study data, diabetes mellitus does not appear to modify the progression of HCC and its recurrence after treatment, but it does appear to worsen the prognosis of patients with HCC by means of a rapid decline in remnant liver function caused by repeated treatment of HCC.

Aged↗
PubMed2001

Analytical method of chondroitin/dermatan sulfates using high performance liquid chromatography/turbo ionspray ionization mass spectrometry: application to analyses of the tumor tissue sections on glass slides.

We established a highly sensitive quantitative analytical method for chondroitin/dermatan sulfates by LC/MS method. By this method, the unsaturated disaccharides produced after the enzymatic digestion of chondroitin/dermatan sulfates can be determined in the amounts as low as 0.5 pmol levels. The use of tetrabutylammonium hydroxide as an ion-pair reagent for LC/MS allowed us to separate unsaturated 4-sulfated disaccharide and unsaturated 6-sulfated disaccharide. Furthermore, the peak areas of unsaturated disaccharides were increased almost 10 times by the postcolumn addition of acetonitrile. We applied this LC/MS method to the analyses of unsaturated disaccharides from chondroitin/dermatan sulfates in the tissues sections on glass slides, which were prepared from MethA tumor-bearing mice. This method brought about considerable reduction in the time distance from sample collection to preparation of analytical results.

Chondroitin Sulfates↗
PubMed2001

Analysis of clonal relationship using single-cell polymerase chain reaction in a patient with concomitant mantle cell lymphoma and multiple myeloma.

We report a case of concomitant mantle cell lymphoma (MCL) and multiple myeloma (MM) in which we investigated the possibility of a clonal relationship. A 76-year-old man was diagnosed with MCL [immunoglobulin (Ig)M,D-kappa; stage IVB] and MM (IgG-kappa; stage I). Ig heavy chain (IgH) gene complementarity-determining region 3 in DNA from both the MCL tumor and from single MM cells from bone marrow smears was amplified to investigate whether there was a clonal relationship between MCL and MM. Sequence analysis revealed no clonal relationship between MCL and MM in our patient.

Aged↗
PubMed2001

Double-injection FDG method to measure cerebral glucose metabolism twice in a single procedure.

UNLABELLED: [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) may be used to examine changes in cerebral glucose metabolism in two physiological conditions. We proposed and evaluated a double injection-single session FDG method with biological constraints for this purpose. METHODS: Simulated brain time-radioactivity curves (TACs) generated by using a plasma TAC from an actual study and physiological combinations of input values in a kinetic model were analyzed to evaluate the accuracy of the proposed method. The reproducibility of the estimated values obtained by this method was tested in five normal volunteers who were studied with a dynamic PET scan and two injections of FDG in a single session while fasting. RESULTS: The simulation study showed that the estimated values obtained by the proposed method agreed well with the input values. In the human study, plasma glucose levels were 5.3 +/- 0.2 and 5.0 +/- 0.2 mM in the first and second measurements, respectively. The difference between the plasma glucose measurements was small but statistically significant (p < 0.05). Although no systematic deviations were noted in K*1 or rCMRglc, there were small deviations in K* (less than 10%) and LC (less than 5%) with a statistical significance (p < 0.01). CONCLUSION: The deviation between the measurements in K* and LC seemed to relate to the difference in the plasma glucose level. The double-injection FDG method with biological constraints can be used to estimate rCMRglc and LC sequentially in a single PET scanning session.

Blood Glucose↗
PubMed2001

Assessment of cerebral hemodynamics before and after revascularization in patients with occlusive cerebrovascular disease by means of quantitative IMP-SPECT with double-injection protocol.

UNLABELLED: The purpose of this study was to validate a double-injection (DI) method with N-isopropyl-[123I]p-iodoamphetamine (IMP) to measure regional cerebral blood flow (rCBF) twice in a single session of dynamic SPECT and to elucidate a possible role of this method to identify patients with occlusive disease of major cerebral arteries, who might benefit from cerebral revascularization procedures (CR). MATERIALS AND METHODS: Fourteen patients with occlusion or severe stenosis of the internal carotid or middle cerebral artery were studied before and after CR to assess hemodynamic changes after revascularization treatment. We quantitatively measured rCBF before and after acetazolamide (ACZ) challenge along with cerebrovascular reserve capacity (CVR) with two injections of IMP in a single session of dynamic SPECT scans (DI method). The reliability and reproducibility of the DI method were validated by means of a simulation study and in eight patients who were examined without ACZ challenge to measure baseline rCBF twice. RESULTS: The analysis of simulated noisy data with realistic noise levels showed that the errors of the estimates for the first and the second rCBF and for the increase in rCBF were 2.6%, 8.1% and 10.4%, respectively. In the 8 patients examined by the DI method to measure baseline rCBF twice, the mean and the SD of percentage differences between the two consecutive measurements in rCBF were -1.3% and 5.5%, respectively. Eight out of 14 patients with occlusive disease had at least one region with a CVR less than 10%. They showed a significant increase in resting rCBF after CR, not only in the ipsilateral hemisphere (from 26.1 +/- 6.4 to 33.4 +/- 4.7) but also in the contralateral one (from 28.3 +/- 7.0 to 34.7 +/- 4.7) with a recovery of the ipsilateral CVR from 9.3 +/- 17.2 to 41.2 +/- 20.1%. The remaining six patients with good-moderate CVR did not show an increase in rCBF after CR (from 28.0 +/- 2.7 to 28.3 +/- 3.4). The three of them with a moderate CVR (10-25%) before CR showed normalization of CVR after CR. CONCLUSION: Patients with decreased rCBF and reduced CVR benefited from CR in terms of an increase in rCBF and recovery of CVR. The quantitative double-injection IMP-SPECT has the ability to identify those patients who may benefit from CR.

Aged↗
PubMed2001

Comparison of myocardial blood flow during dobutamine-atropine infusion with that after dipyridamole administration in normal men.

OBJECTIVES: The present study was designed to compare the absolute myocardial blood flow (MBF) after intravenous dipyridamole infusion with that during dobutamine-atropine administration in normal healthy male volunteers. BACKGROUND: Both safety and usefulness of dobutamine-atropine stress in myocardial perfusion imaging have been reported. However, no information exists on whether the magnitude ofhyperemia achieved with dipyridamole and dobutamine-atropine is comparable. METHODS: Myocardial blood flow was measured with positron emission tomography and 15O-labeled water in 20 healthy young men (23 +/- 3 years) 1) at baseline, 2) after dipyridamole infusion (0.56 mg/kg over 4 min), and 3) during dobutamine (40 microg/kg/min) and atropine (0.25 to 1.0 mg) infusion. RESULTS: The MBF was significantly increased during dipyridamole infusion and during dobutamine-atropine stress compared with at rest (4.33 +/- 1.23 and 5.89 +/- 1.58 vs. 0.67 +/- 0.16 ml/min/g, respectively, p < 0.0001). Moreover, dobutamine-atropine infusion produced greater MBF compared with dipyridamole (p = 0.0011), while coronary vascular resistance did not differ significantly after dipyridamole administration and during dobutamine-atropine infusion (17.6 +/- 7.9 vs. 18.6 +/- 5.6 mm Hg/[ml/min/g], respectively). CONCLUSIONS: Near maximal coronary vasodilatation caused by dipyridamole is attainable using dobutamine and atropine in young healthy volunteers. Dobutamine in conjunction with atropine is no less effective than dipyridamole in producing myocardial hyperemia.

Adult↗
PubMed2001

Congestion of superior mesenteric veins and small bowel mucosal injury after endoscopic treatment of esophageal varices in patients with portal hypertension.

We investigated treatment-induced changes in venous return from the small bowel and small bowel intestinal mucosal injury induced by the treatment of esophageal varices in patients with portal hypertension. A total of 14 patients (age 59.8+/-9.5 years, five women and 9 men) who received prophylactic treatment of esophageal varices between December 1998 and March 1999 were investigated. Diamine oxidase (DAO) activity was measured before and after treatment. Changes in blood flow of the portal and superior mesenteric veins were investigated by Doppler ultrasonography in six patients. A significant decrease in DAO activity was observed three days after treatment (11.5+/-1.6 units/liter prior to treatment versus 8.6+/-1.6 units/liter three days after treatment; P < 0.001). Decreases in superior mesenteric and portal venous flow velocity were observed in four and three patients, respectively. In two patients with an increase in the cross-sectional area of the superior mesenteric vein with delayed venous return, a marked decrease in DAO activity was observed three days after treatment. In patients with portal hypertension, rapid reduction of pooling of portal flow caused by the treatment of esophageal varices can induce transient congestion of the mesenteric venous system which can produce some small bowel mucosal injury.

Amine Oxidase (Copper-Containing)↗
PubMed2001

Comparison of oligosaccharides derived from salivary mucin of Japanese secretor and non-secretor individuals of blood group type-A.

Comparison of oligosaccharide components derived from salivary mucin was performed between secretor and non-secretor individuals. Salivary mucin was collected from four secretors and three non-secretors having blood group type-A. Compositional analysis showed that the contents of galactose and N-acetylglucosamine in the non-secretor were higher than those in the secretor. The O-linked oligosaccharides obtained by treatment with alkaline borohydride were separated by gel filtration using Sephadex G-50. The results indicated that the size of the type-A active oligosaccharides from the secretor was similar to or smaller than that of the non-secretor. Ion-exchange chromatography showed that the secretors had strong type-A activities in both the neutral and acidic fractions but the non-secretors showed type-A activity mainly in the neutral fraction. These results suggest that compositional differences in blood group substances exist between secretors and non-secretors.

ABO Blood-Group System↗
PubMed2001

UDP-sugar transporter implicated in glycosylation and processing of Notch.

Glycosylation modifies protein activities in various biological processes. Here, we report the functions of a novel UDP-sugar transporter (UST74C, an alternative name for Fringe connection (Frc)) localized to the Golgi apparatus in cellular signalling of Drosophila. Mutants in the frc gene exhibit phenotypes resembling wingless and Notch mutants. Both Fringe-dependent and Fringe-independent Notch pathways are affected, and both glycosylation and proteolytic maturation of Notch are defective in mutant larvae. The results suggest that changes in nucleotide-sugar levels can differently affect Wingless and two distinct aspects of Notch signalling.

Amino Acid Sequence↗
PubMed2001

Successful unrelated BMT in a patient with Kostmann syndrome complicated by pre-transplant pulmonary 'bacterial' abscesses.

Kostmann syndrome, severe congenital neutropenia, is often associated with life-threatening bacterial infections. A 5-year-old girl with Kostmann syndrome developed pulmonary abscesses. She was refractory to granulocyte colony-stimulating factor and antibiotics. She underwent unrelated HLA-matched BMT. Myeloablative conditioning consisted of 12-Gy TBI with lung shielding, antithymocyte globulin, etoposide, and cyclophosphamide. After successful engraftment, the pulmonary abscesses resolved by day 75 post-transplant. Although the option of transplantation is not established in the setting of unrelated HLA-matched BMT in Kostmann syndrome, this case may provide useful information. Furthermore, pre-transplant pulmonary bacterial abscesses may not be a contraindication for BMT in some patients with Kostmann syndrome.

Bone Marrow Transplantation↗
PubMed2001

Safety and complications of interventional radiology for hepatocellular carcinoma in patients with haemophilia and cirrhosis.

Many patients with haemophilia have been chronically infected with hepatitis virus owing to multiple transfusions and the prevalence of hepatocellular carcinoma will probably increase in this population. We evaluated the safety and complications of radiological intervention for hepatocellular carcinoma in eight patients with haemophilia and cirrhosis. Radiological interventions can be performed safely in all patients with haemophilia. Unexpectedly, the most common complication was bleeding from the gastrointestinal tract. Attention should be paid to this potential problem in order to take appropriate steps to minimize its occurrence.

Adult↗
PubMed2001

Effects of HAART on hepatitis C, hepatitis G, and TT virus in multiply coinfected HIV-positive patients with haemophilia.

In multiply coinfected human immunodeficiency virus (HIV)-positive patients, we investigated the effects of high-activity antiretroviral therapy (HAART) using HIV protease inhibitors on three other viruses: hepatitis C virus (HCV), hepatitis G virus (HGV), and TT virus (TTV). Viral concentrations were measured serially by polymerase chain reaction methods in five patients with quadruple infection (HIV, HCV, HGV, and TTV) and in two patients with triple infection (HIV, HCV, and HGV) before and during HAART. In addition, CD4+ cell counts and serum alanine aminotransferase (ALT) levels were measured serially. Generally we observed no difference in serum HCV RNA, HGV RNA, or TTV DNA concentrations between samples obtained before and after initiation of HAART, whereas HIV RNA concentration decreased and CD4 counts increased in most patients. However, two patients had markedly decreased concentrations of HCV RNA and HGV RNA, respectively, more than 12 months after beginning HAART. Normalization of serum ALT levels was observed in a patient with decline of HCV RNA concentrations. No interactions were observed among these four viruses. HAART had no apparent direct effects on HCV, HGV, or TTV. Further studies will be required to elucidate whether the restoration of immune status through suppression of HIV replication by HAART may affect HCV or HGV RNA concentrations.

AIDS-Related Opportunistic Infections↗
PubMed2001

Analysis of hepatocellular carcinoma tumor growth detected in sustained responders to interferon in patients with chronic hepatitis C.

BACKGROUND: By analyzing a tumor growth of hepatocellular carcinoma (HCC) detected in sustained responders (SR) to interferon (IFN) therapy for chronic hepatitis C, we sought to determine the duration of follow up in SR that would be sufficient to detect HCC. In addition, we sought to elucidate the presence of HCC, which truly developed after the eradication of hepatitis C virus (de novo HCC development). METHODS: Tumor volume doubling time (DT) was calculated in a total of 46 cases of HCC detected in SR after IFN therapy. Based on DT, the annual growth rate was estimated for each tumor. Survival was compared between patients with HCC < or = 30 mm and patients with HCC > 30 mm in diameter. RESULTS: Doubling time in SR was similar to the previously reported DT of HCC irrespective of IFN therapy. However, extensive DT was observed in three HCCs despite relatively poor differentiation, which may represent de novo HCC development. In the analysis of tumor growth, all HCCs grew to exceed 20 mm in estimated diameter between 6 months and 7 years after the end of IFN therapy. Better survival was observed in patients with HCC < or = 30 mm in diameter compared with patients with HCC > 30 mm (P = 0.0107). In surviving patients, recurrences of HCC were very infrequent. CONCLUSIONS: We may be able to detect most HCC in SR between 6 months and 7 years after IFN therapy. However, we cannot neglect the presence of de novo HCC development after the eradication of HCV, which makes it difficult to determine completely sufficient follow-up duration after IFN therapy in this population.

Antiviral Agents↗
PubMed2001

TT virus genotype changes frequently in multiply transfused patients with hemophilia but rarely in patients with chronic hepatitis C and in healthy subjects.

BACKGROUND: TT virus (TTV), a novel DNA virus, was originally thought to be transmitted by transfusion. However, nonparenteral transmission is recently suspected to be a major mode of transmission. To investigate the possibility of reinfection with TTV in multiply transfused patients and to evaluate the significance of transfusion transmission of TTV in patients with hemophilia, serial changes in TTV genotype were investigated in three groups. STUDY DESIGN AND METHODS: Serial changes in TTV genotype were investigated in 16 multiply transfused patients with hemophilia, 16 age-matched patients with chronic hepatitis C, and 16 age-matched healthy subjects. RESULTS: Mixed infection with multiple TTV genotypes was common in all groups. However, changes in TTV genotype were frequent in patients with hemophilia (15/16; 93.8%) but rare in patients with chronic hepatitis C and in healthy subjects (each group: 1/16; 6.3%). CONCLUSION: Changes in TTV genotype were frequently observed in multiply transfused patients with hemophilia but not in patients with chronic hepatitis or in healthy subjects without risk of transfusion transmission. This difference may suggest that exposure to TTV or even reinfection occurs frequently in patients with hemophilia, which could be evidence of transfusion transmission of TTV in this population.

Adolescent↗
PubMed2001

Infection of hepatitis A virus in Japanese haemophiliacs.

OBJECTIVES: Outbreaks of hepatitis A virus (HAV) infection in haemophiliacs have been reported from many countries. The aim of this study was to determine the prevalence of hepatitis A virus antibody (HAVAb) in Japanese haemophiliacs. METHODS: Sixty-seven male haemophiliacs were recruited for this study of HAV infection. We also compared the rate of HAV infection with that of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis G virus (HGV). RESULTS: Fifteen of 67 haemophiliacs (22.4%) were positive for HAVAb. Prevalence of HAVAb was significantly higher in haemophiliacs than in Japanese normal subjects previously reported (P= 0.0001). Age, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin and prevalence of HIV, HCV, and HGV were not statistically different between HAVAb positive and HAVAb negative haemophiliacs. We suggest that the use of clotting factor concentrates is closely associated with HAV infection, but HAV infection does not have an effect on clinical course. CONCLUSIONS: Administration of clotting factor concentrates may increase risk of HAV infection in haemophiliacs.

Adolescent↗
PubMed2001

Preparation and inhibitory activity on hyaluronidase of fully O-sulfated hyaluro-oligosaccharides.

Hyaluronan was partially depolymerized on a large-scale quantity using bacterial hyaluronidase (E.C. 4.2.2.1) for preparation of chemically fully O-sulfated oligosaccharides. The hyaluro-oligosaccharide (HAoligo) mixture obtained by partial digestion was repeatedly applied to low pressure gel permeation chromatographic separation to purify the size-unified oligosaccharide ranged from 4- to 20-mer. The purity and size of each HAoligo was confirmed by using proton nuclear magnetic resonance ((1)H NMR) spectroscopy, capillary electrophoresis (CE) on normal polarity mode, and a newly established separation method by normal phase chromatography with Amide-80 column. The purified HAoligos ranged 4- to 20-mer were applied to chemically fully O-sulfation. Characterization of chemically fully O-sulfated HAoligos was performed by both chemical compositional analyses after hydrolysis and (1)H NMR spectroscopy. While the anti-factor IIa activity of 4- to 20-mer O-sulfated HAoligos was less than 3.1 units/mg, the inhibitory action for hyaluronidase (bovine testicular hyaluronidase (E.C.3.2.1.35)) of the oligosaccharides ranged 16- to 20-mer were corresponding to 79% of that shown by fully O-sulfated hyaluronan (MW 100 kDa) through both competitive and noncompetitive effects.

Chromatography, High Pressure Liquid↗