Biomedical subjects

Hiroyuki Yokoyama

Publications and source records attributed to Hiroyuki Yokoyama.

At least 19 recordsLinked to original sources

PubMed2006

A preliminary analysis of trace elements in the scalp hair of patients with severe motor disabilities receiving enteral nutrition.

The concentrations of essential trace elements (copper, zinc, selenium, manganese, chromium, molybdenum, cobalt, and iodine) in the scalp hair of 21 patients with severe motor disabilities receiving enteral nutrition were measured using inductively coupled plasma-mass spectrometry. Preliminary results show that copper, selenium, and molybdenum concentrations in the patients' hair were significantly lower than those in an age-matched control group (p<0.01). This suggests that intake of these elements may be reduced in patients receiving restricted enteral nutrition, although the clinical significance of these results should be discussed.

Adolescent↗

PubMed2006

Successful treatment of a 2-year-old girl with intractable myasthenia gravis using tacrolimus.

We used tacrolimus to successfully treat a patient with childhood-onset oropharyngeal myasthenia gravis (MG). A girl (2 years, 5 months old) with oropharyngeal MG responded partially to treatment including pyridostigmine bromide, intravenous immunoglobulin, and prednisolone (2 mg/kg/day) for 7 weeks, but this resulted in worsening of her eye symptoms. By contrast, tacrolimus at 2 mg/day resulted in complete remission of the MG, which made it possible to reduce the dose of prednisolone. This is a rare report of the use of tacrolimus as an effective treatment for patients with intractable childhood-onset MG.

Child, Preschool↗

PubMed2006

A case of Fukuyama-type congenital muscular dystrophy with a very mild mental deficit.

A boy had the clinical features of congenital muscular dystrophy with a very mild mental deficit. A muscle biopsy at one year of age showed the typical findings of Fukuyama-type congenital muscular dystrophy, including selective loss of immunoreactions for alpha dystroglycan. Magnetic resonance imaging showed no findings suggestive of migration disorders. The diagnosis of Fukuyama-type congenital muscular dystrophy was confirmed by a molecular assay at 8 years of age, and his haplotype analysis was heterozygous. At 9 years of age, his FIQ on the Wechsler Scale for Children revealed 69, while his IQ on the Tanaka Binnet scale of intelligence was 97. In this report the relationship between mild clinical condition of the studied case and its genotype is discussed.

Biopsy↗

PubMed2006

Naproxen-induced oxidative stress in the isolated perfused rat liver.

We previously showed that naproxen induced the oxidative stress in the liver microsomes and the isolated hepatocytes of rats. In this study, the in situ effect of naproxen on the rat liver tissue was investigated, using the isolated perfused liver from the view-point of the naproxen-induced hepatotoxicity. The leakage of glutamic-oxaloacetic transaminase (GOT) from the perfused liver and appearance of thiobarbituric acid reactive substances (TBARS) in the perfusate increased with the progress of perfusion after a lag time of about 1h. The naproxen-perfusion of the liver decreased the biliary excretion of glutathione (GSH) and oxidized glutathione, glutathione disulfide (GSSG) prior to TBARS production and GOT leakage. GSSG content in the naproxen-perfused liver was significantly higher than in the control. TBARS appeared in the perfusate of the naproxen-perfused liver for 30 min, but not in the control. The biliary excretion clearance (CL(bile)) of indocyanine green (ICG), a reagent for testing the liver function, in the liver perfused with naproxen decreased to a half of that in the liver perfused without naproxen. Thus, the naproxen-induced oxidative stress in the liver was shown to affect the physiological function of liver through the impairment of biliary excretion, which is recognized as a detoxification system.

Animals↗

PubMed2006

Biological significance of isolated tumor cells and micrometastasis in lymph nodes evaluated using a green fluorescent protein-tagged human gastric cancer cell line.

PURPOSE: The biological significance of isolated tumor cells and micrometastasis in lymph node defined by the International Union against Cancer remains essentially unknown because of the lack of appropriate animal models. In the present study, we developed a lymph node micrometastasis model featuring a human gastric cancer cell line tagged with green fluorescent protein gene (GCIY-EGFP), which allows visualization of even isolated tumor cells in the development of metastasis without histologic procedure. Using this model, we investigated the effect of surgery and chemotherapy on the growth of early-phase metastasis formation in the lymph nodes. EXPERIMENTAL DESIGN: The time course of spontaneous inguinal lymph node metastasis after s.c. inoculation of GCIY-EGFP cells into nude mice was examined with fluorescence dissecting microscopy. Then, the effects of surgical removal of the primary tumor with or without anti-asialo GM1 treatment or postoperative chemotherapy on the growth of isolated tumor cells and micrometastasis in the lymph nodes were examined. RESULTS: GCIY-EGFP cells were found to metastasize spontaneously to the inguinal lymph nodes to form isolated tumor cells, micrometastasis, and, finally, develop macroscopic metastasis at 1 to 2, 3 to 5, and 5 weeks postinjection, respectively. When the primary tumors were removed within 2 weeks of inoculation, isolated tumor cells, but not micrometastasis, in the lymph nodes regressed by 4 weeks after surgery in all the mice examined (five of five). This spontaneous regression of isolated tumor cells was completely reversed by anti-asialo GM1 treatment, which could deplete natural killer cells effectively in nude mice. Chemotherapy following resection of the primary tumor at an early stage partially eliminated the remaining micrometastasis in the lymph nodes. CONCLUSIONS: These results suggest that isolated tumor cells in the regional lymph nodes regressed by removal of the primary tumor mainly via natural killer cell-mediated antitumor activity and that micrometastasis in the lymph nodes could be effectively eliminated by the postoperative chemotherapy.

Animals↗

PubMed2006

Novel mutations in the guanosine triphosphate cyclohydrolase 1 gene associated with DYT5 dystonia.

OBJECTIVES: To better understand the relationship between mutation of the guanosine triphosphate cyclohydrolase I (GCH1) gene and the etiology of DYT5 dystonia and to accumulate data on the mutation in the Japanese population for genetic diagnosis of the disease. SETTING: Japanese population. Patients Eight Japanese patients with suspected DYT5 dystonia were analyzed. Intervention Direct genomic sequencing of 6 exons of GCH1 was performed. MAIN OUTCOME MEASURES: For patients who did not exhibit any abnormality in the sequence analysis, the possibility of exon deletions was examined. In cases for which cerebrospinal fluid was available, the concentrations of neopterin and biopterin were measured as an index of GCH1 enzyme activity. RESULTS: In 2 patients, we found a new T106I mutation in exon 1 of GCH1, a position involved in the helix-turn-helix structure of the enzyme. In the third patient, we found a new mutation (a 15-base pair nucleotide deletion) in exon 5 that may cause a frameshift involving the active site. In the fourth patient, we detected a known nucleotide G>A substitution in the splice site of intron 5, which has been reported to produce exon 5-skipped messenger RNA. The concentrations of both neopterin and biopterin in the cerebrospinal fluid of the third and fourth patients were markedly lower than the normal range, indicating that the GCH1 enzyme was functionally abnormal in these mutations. Gene dosage analysis showed that the fifth patient had a deletion of both exon 3 and exon 4, whereas the sixth patient had a deletion of exon 3. CONCLUSIONS: We found several novel, as well as known, GCH1 mutations in Japanese patients with DYT5 dystonia. In some of them, the GCH1 enzyme activity was proved to be impaired.

Adolescent↗

PubMed2006

Impact of histological plaque characteristics on intravascular ultrasound parameters at culprit lesions in coronary artery disease.

Prior intravascular ultrasound (IVUS) studies have demonstrated that a positive remodeling pattern of a culprit lesion is observed more frequently in acute coronary syndrome (ACS) than stable angina (SA). However, the relationship between the plaque morphology detected by IVUS and the histological type of atherosclerotic plaque has not been well defined. This is a prospective study on 37 consecutive patients who underwent directional coronary atherectomy. The 37 patients were divided into 2 groups; 21 patients with SA and 16 with ACS. Vessel and plaque cross sectional area were measured at the culprit lesion and the remodeling index (RI) was calculated by IVUS. The plaque tissue was assessed for the presence of inflammatory cells and lipids, and the presence of each was scored as 0 (absent), 1 (sparse), 2 (dense), or 3 (predominant). The RI of the patients with ACS was higher than that of SA. Inflammatory cells were present to a greater extent in patients with ACS. Inflammatory cells and lipids were significantly correlated with the RI (Inflammatory cell score grade > or = 2 patients; 1.14 +/- 0.13 versus grade 0 patients; 0.87 +/- 0.24, and grade 1 patients; 0.93 +/- 0.17, P < 0.01 and lipid score grade > or = 2 patients; 1.13 +/- 0.17 versus grade 0 patients; 0.85 +/- 0.18, P < 0.001 and grade 1 patients; 0.95 +/- 0.19, P < 0.05). The results clearly indicate that the evaluation of vessel morphology by vascular imaging is an important indicator of plaque instability.

Aged↗

PubMed2006

Effective treatment with levodopa and carbidopa for hypomyelination with atrophy of the basal ganglia and cerebellum.

Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare leukoencephalopathy presenting in the infantile period and characterized by diffuse cerebral hypomyelination, and atrophy of the basal ganglia and cerebellum. As patients with H-ABC lack remarkable laboratory findings, the diagnosis is based on brain magnetic resonance imaging findings alone. Only eight cases have been reported in the literature, and thus the natural course and treatment of this disease are not fully understood. We report a 35-month-old boy with H-ABC who had hemidystonia, hypomyelination, and cerebellar ataxia. We diagnosed H-ABC after considering a thorough differential diagnosis, excluding other diseases involving hemidystonia, hypomyelination, and cerebellar ataxia. Furthermore, technetium-99m ethyl cysteinate dimmer-single-photon emission computerized tomography (Tc-ECD-SPECT) and positron emission tomography with fluorodeoxyglucose (18)F (FDG-PET) revealed decreased blood flow and glucose metabolism in the bilateral lenticular nucleus, thalamus, and cerebellum. A peroral levodopa preparation containing carbidopa (levodopa-carbidopa) was effective at ameliorating and stopping the progression of the patient's dystonia (final effective doses: levodopa, 200 mg/day and carbidopa, 20 mg/day). This is the first case report of a Japanese patient with H-ABC and treatment for this disease. Levodopa-carbidopa may be an effective treatment for H-ABC.

Administration, Oral↗

PubMed2006

Reduced exposure to mercury in patients receiving enteral nutrition.

The exposure to mercury (Hg) of various groups of people with different dietary backgrounds has been assessed because of its hazardous effects, but little is known about that in patients receiving enteral nutrition. Therefore, we studied the Hg exposure in 25 patients with severe motor disabilities, who received liquid enteral feedings for more than one year, by determining total mercury (T-Hg) in their hair samples with inductively coupled plasma-mass spectrometry. The geometric mean of the T-Hg level in hair from the patients was 88 ng/g hair (+/- 1 geometric standard deviation [GSD], 34 - 228 ng/g), whereas that for the control group on a normal diet was 1,900 ng/g (+/- 1 GSD, 1,022 - 3,531 ng/g). The T-Hg levels in the patients' hair were far lower than those in the controls (p < 0.001). The T-Hg levels in the enteral feedings used were below the detection limit of cold-vapor atomic absorption spectrophotometry (< 10 ng/g). The present study has shown that Hg exposure is low in patients receiving enteral nutrition, indicating that food is a primary source of Hg exposure.

Adolescent↗

PubMed2005

Surface-emitted terahertz-wave difference-frequency generation in two-dimensional periodically poled lithium niobate.

We report on the demonstration of surface-emitted terahertz- (THz-) wave difference-frequency generation from two-dimensional (2D) periodically poled lithium niobate (PPLN). The two orthogonal periodic structures individually compensate for both the phase mismatch of the launched lasers and the generated THz wave. Tunable 1.5-1.8 THz wave generation with a bandwidth of 10-GHz was obtained by use of two 2D PPLN crystals. We also confirmed that THz waves were simultaneously generated into two opposite directions, which suggests the possibility of higher THz-wave output power.

Journal Article↗

PubMed2005

In vitro metabolism of the calmodulin antagonist DY-9760e (3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate) by human liver microsomes: involvement of cytochromes p450 in atypical kinetics and potential drug interactions.

Human cytochrome P450 (P450) isozyme(s) responsible for metabolism of the calmodulin antagonist 3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate (DY-9760e) and kinetic profiles for formation of its six primary metabolites [M3, M5, M6, M7, M8, and DY-9836 (3-[2-[4-(3-chloro-2-methylphenyl)piperazinyl]ethyl]-5,6-dimethoxyindazole)] were identified using human liver microsomes and recombinant P450 enzymes. In vitro experiments, including an immunoinhibition study, correlation analysis, and reactions with recombinant P450 enzymes, revealed that CYP3A4 is the primary P450 isozyme responsible for the formation of the DY-9760e metabolites, except for M5, which is metabolized by CYP2C9. Additionally, at clinically relevant concentrations, CYP2C8 and 2C19 make some contribution to the formation of M3 and M5, respectively. The formation rates of DY-9760e metabolites except for M8 by human liver microsomes are not consistent with a Michaelis-Menten kinetics model, but are better described by a substrate inhibition model. In contrast, the enzyme kinetics for all metabolites formed by recombinant CYP3A4 can be described by an autoactivation model or a mixed model of autoactivation and biphasic kinetics. Inhibition of human P450 enzymes by DY-9760e in human liver microsomes was also investigated. DY-9760e is a very potent competitive inhibitor of CYP2C8, 2C9 and 2D6 (Ki 0.25-1.7 microM), a mixed competitive and noncompetitive inhibitor of CYP2C19 (Ki 2.4 microM) and a moderate inhibitor of CYP1A2 and 3A4 (Ki 11.4-20.1 microM), suggesting a high possibility for human drug-drug interaction.

Aryl Hydrocarbon Hydroxylases↗

PubMed2005

Laparoscopy-assisted distal gastrectomy with systemic lymph node dissection: a phase II study following the learning curve.

BACKGROUND AND OBJECTIVES: A preliminary study on the use of laparoscopy-assisted approach to treat gastric carcinoma resulted in higher morbidity. STUDY DESIGN: A prospective phase II study of laparoscopy-assisted distal gastrectomy (LADG) was performed for patients with preoperative diagnosis of T1 N0 stage cancer located in the lower or middle-third stomach. Bleeding amount, operating time, mortality, morbidity, and the number of lymph node retrieval were recorded and compared with the preliminary series reported previously by the same authors. RESULTS: Between 2000 and 2002, 47 patients were accrued. The mean blood loss and postoperative hospital stay were significantly decreased compared with the previous series, whereas the operating time was not. There were no in-hospital deaths, with the incidence of anastomotic leakage significantly decreased. All patients remain disease-free to date. CONCLUSIONS: LADG can be performed safely and morbidity, no longer, is a drawback by experienced hands that have reached plateau of the learning curve, although it remains a time-consuming procedure. Its application to gastric cancer surgery is feasible for early stage cancer, and its applicability to the treatment of T2 stage cancer will be the next issue to be explored.

Adult↗

PubMed2005

Linewidth and relative intensity noise measurements of longitudinal modes in ultrahigh-speed mode-locked laser diodes.

The longitudinal linewidth and corresponding relative intensity noise (RIN) of 10- and 40-GHz mode-locked laser diodes are measured for the first time to our knowledge. It is shown that the cavity Q value is a dominant parameter of the linewidth. It is also shown that the linewidth of the individual modes is almost constant. This means that the phase noise of each mode is almost the same in the mode-locked condition. The RIN value is larger for modes that are distant from the center longitudinal mode. This mode dependence is a consequence of the mode partition noise.

Journal Article↗

PubMed2005

Establishment and characterization of three novel human gastric cancer cell lines with differentiated intestinal phenotype derived from liver metastasis.

Gastric cancers with liver metastasis are fatal diseases with rapid progression and poor patient outcome. To date, however, the molecular basis of their growth and metastasis remains essentially unknown, largely because of the presence of few available gastric cancer cell lines established from liver metastasis. In the present study, we developed two novel cultured cell lines (designated GLM-1 and GLM-2) and one transplantable line in nude mice (designated GLM-3) derived from liver metastasis of gastric cancer patients. These GLM cell lines share unique biological features such as differentiation, growth and metastasis. They form moderately differentiated tumors with CD10 positive and MUC2 negative intestinal absorptive phenotype when injected into nude mice. Their growth is stimulated by EGF and TGF-alpha in vitro like other gastric cancer cell lines. However, GLM cells differ from conventional gastric cancer cell lines in their high apoptotic rate, even in the absence of apoptosis inducing stimuli as revealed by Caspase3/7 assay and the TUNEL method. This apoptosis is further enhanced by phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002), but not by MEK1/2 inhibitor (U0126), indicating the strong dependency of their survival on PI3K/Akt pathway rather than MAPK pathway, the major downstream signaling pathways of EGFR. GLM-1 cells can metastasize to the liver after intrasplenic injection, and GLM-3 cells have spontaneous lung metastatic potential after subcutaneous transplantation, respectively. These results indicate that the GLM series are the first cell lines reflecting the intestinal-type differentiated adenocarcinoma, a major subtype of gastric cancer with liver metastasis. Therefore, they would be excellent models for understanding the mechanism of metastatic growth and the development of a new molecular targeting therapy for gastric cancer with liver metastasis.

Adenocarcinoma↗

PubMed2005

The effects of copper-histidine therapy on brain metabolism in a patient with Menkes disease: a proton magnetic resonance spectroscopic study.

We report on metabolic changes in the brain of a boy with Menkes disease. He was treated with parenteral copper (Cu)-histidine supplementation, from 5 months of age, and assessed with proton magnetic resonance spectroscopy ((1)H-MRS). The single-voxel (1)H-MRS before treatment revealed an accumulation of lactate and a reduced N-acetyl aspartate (NAA)/total creatine (tCr) ratio with a z-score of -3.0. During treatment, the lactate signal faded away, whereas the NAA signal gradually increased to a z-score of -1.5 at 120 days of treatment. The choline/tCr ratio did not deviate much initially (z-score +0.5), but the ratio increased markedly during treatment (z-score +4.8). Consequently, the Cu-histidine therapy initiated after the critical period still improved the neuronal metabolism, suggesting that some Cu was delivered to neurons. Nevertheless, the brain atrophy, impaired myelination, and severe neurological symptoms were not ameliorated.

Brain↗

PubMed2005

Rationale and design of a randomized trial to assess the effects of beta-blocker in diastolic heart failure; Japanese Diastolic Heart Failure Study (J-DHF).

BACKGROUND: Heart failure consists of two phenotypes: systolic heart failure and diastolic heart failure (DHF). A growing body of evidence demonstrated benefits of beta-blocker, angiotensin-converting enzyme inhibitor, and angiotensin II receptor blocker in systolic heart failure; however, evidence leading to therapeutic strategy of DHF is lacking. METHODS AND RESULTS: The Japanese Diastolic Heart Failure Study (J-DHF) is a multicenter, prospective, randomized trial designed to assess effects of beta-blocker in patients with DHF. A total of 800 patients (400 patients in each group) will be enrolled. The primary outcome is a composite of cardiovascular death and unplanned admission to hospital for congestive heart failure. Other outcomes include all-cause mortality, worsening of the symptoms of heart failure, or a need for modification of the treatment for heart failure. Serial assessment of echocardiographic and neurohumoral parameters and cost analysis of the treatment regimen will be conducted. The follow-up period is a minimum of 2 years. CONCLUSION: This study will provide important evidences for the treatment of DHF.

Adrenergic beta-Antagonists↗

PubMed2005

Efficacy of intraperitoneal chemotherapy with paclitaxel targeting peritoneal micrometastasis as revealed by GFP-tagged human gastric cancer cell lines in nude mice.

To explore the effect of chemotherapy against peritoneal micrometastases, we used in vivo models of peritoneal micrometastasis featuring three human gastric cancer cell lines tagged with the green fluorescence protein gene. With a highly metastatic cell line, GCIY-EGFP, the survival rate of mice treated with weekly intraperitoneal paclitaxel starting one day following inoculation was significantly higher than those of control mice or mice given the same treatment starting on day eight. Intravenous paclitaxel exhibited no significant survival benefit regardless of the treatment schedule. Pharmacokinetic analysis revealed that the concentration of paclitaxel in the metastatic nodules treated with intraperitoneal administration was 2-3-fold higher than those treated with intravenous paclitaxel, provided the treatment was given on day one. Even greater responses were observed with less aggressive MKN28-EGFP and MKN45-EGFP cell lines, whose peritoneal metastases resolved completely due to early intraperitoneal treatment in 13 of the 14 mice tested. These results indicate that intraperitoneal paclitaxel is effective against peritoneal metastasis in early phase.

Animals↗

PubMed2004

Theophylline impairs memory/learning in developing mice.

We studied the relationship between theophylline and memory/learning using an elevated plus-maze test and measuring spontaneous locomotor activity in developing mice. There were no significant differences in transfer latency (TL) in 21-, 30- and 42-day-old mice in the acquisition trial, but theophylline significantly prolonged TL in comparison with the control group in 21- and 30-day-old mice in the retention trial (n = 20; 21-day-old mice, P = 0.0009; 30-day-old mice, P = 0.03). The dose-dependent stimulant effects of theophylline were shown in spontaneous locomotor activity (n = 16; 21-day-old mice, P = 0.0005; 30-day-old mice, P = 0.0007; 42-day-old mice, P = 0.0003) in all groups and in rearing in 21-day-old mice (P = 0.02) 1 h after drug administration, but there were no significant effects 24 h after drug administration in all groups. Our study showed that even a therapeutic dose of theophylline impaired memory/learning only in developing mice, and theophylline increased locomotor activity both in developing and adolescent mice. These observations are consistent with several clinical studies, which reported the relationships between theophylline use and memory/learning and learning-related behaviors in children, such as difficulty in studying and hyperactivity. Theophylline possibly induces memory/learning disabilities and hyperactivity in infants and young children.

Age Factors↗