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Biomedical subjects

Y Kodama

Publications and source records attributed to Y Kodama.

At least 73 records · Page 4Linked to original sources

Adherence protects the binding sites of Helicobacter pylori urease from acid-induced damage.

Colonization by Helicobacter pylori partly depends on acid-dependent adherence by urease to gastric mucin. To further verify the relevance of urease adherence to colonization, the influence of acidity on the binding sites of H. pylori urease was investigated. When enzyme-based in vitro ligand capture assays were used, the effect of acidity on the binding site of H. pylori urease was determined against a backdrop medium consisting of acidic buffers simulating the luminal side of gastric mucus. A high degree of stability was exhibited by adherent urease, suggesting a pivotal role by the denatured enzyme in the persistence of the bacterium within the acidified compartment of gastric mucus.

Bacterial Adhesion↗

Antepartum evaluation of monochorionic diamniotic (MD) twins; MD-twin score: a new scoring method for perinatal outcome.

OBJECTIVE: Our purpose was to establish a new scoring method to survey monochorionic diamniotic (MD) twins during antepartum periods. STUDY DESIGN: A retrospective study was performed regarding MD twins delivered between January 1992 and July 1996. Maternal and neonatal records were assessed for the following 5 perinatal variables; birth-weight discordance, amniotic-fluid discordance, hydrops fetalis, umbilical-cord insertion, and fetal-heart-rate monitoring. Each variable was coded as normal or abnormal and then assigned an arbitrary weight of 0 if normal and 1 if abnormal, yielding a range of scores from 0 (all normal) to 5 (all abnormal). The relationships between individual variables and their combinations and the outcome of pregnancy was determined. A poor pregnancy outcome consisted of intrauterine death, neonatal death, or neurological sequelae of at least one twin. The 5-variable combination was termed as the MD-twin score. A chi-square test and logistic regression analysis were used to determine statistical significance. RESULTS: There were 59 MD pregnancies, of which 13 pregnancies resulted in a poor outcome. The single variable that most likely contributed to a poor outcome was amniotic-fluid discordance. All 35 pregnancies with an MD-twin score of < or = 2 had a good outcome. There were 14 pregnancies with a score of 3, and 21% of them had a poor outcome. All of the pregnancies with a score of > or = 4 had a poor outcome. When we chose the MD-twin score of 3 as the critical point for a poor outcome, the likelihood ratio statistics became the highest of any single variable or any combination of variables. CONCLUSION: The MD-twin score predicted poor outcomes better than did any single variable or combination of variables.

Amniotic Fluid↗

Enhanced reduction of Helicobacter pylori load in precolonized mice treated with combined famotidine and urease-binding polysaccharides.

The present study investigated the effect of a model urease-binding polysaccharide in combination with a histamine H(2) receptor antagonist on Helicobacter pylori colonization in vivo. Euthymic hairless mice were treated daily with dextran sulfate via drinking water and/or famotidine via intragastric gavage starting at 1 week postchallenge with a CagA(+) VacA(+) (type 1) strain of H. pylori. Treatment of precolonized mice for 2 weeks with dextran sulfate combined with famotidine yielded a group mean bacterial load (per 100 mg of gastric tissue) of log(10) 1.04 CFU, which was significantly lower than those of the famotidine (log(10) 3.35 CFU, P < 0.01) and dextran sulfate (log(10) 2.45 CFU, P < 0.05) monotherapy groups and the infected nontreated group (log(10) 3.64 CFU, P < 0.01). Eradication was achieved after 2 weeks of treatment in 50% or more of the test mice using drug combinations (1 or 2 weeks of famotidine plus 2 weeks of dextran sulfate) versus none in the monotherapy and positive control groups. The enhanced activity of the drug combination may be related to the daily pattern of transient acid suppression by famotidine inducing periodic bacterial convergence to superficial mucus sites penetrated by dextran sulfate from the lumen. Increased urease-dextran sulfate avidity was observed in vitro in the presence of famotidine and may partly account for the enhanced activity. With potential utility in abbreviating treatment time and eradication of antibiotic-resistant strains, the use of urease-targeted polysaccharides concurrently with a gastric acid inhibitor warrants consideration as an additional component of the standard multidrug chemotherapy of H. pylori infection.

Animals↗

Molecular characterization of bacterial populations in petroleum-contaminated groundwater discharged from underground crude oil storage cavities.

Petroleum-contaminated groundwater discharged from underground crude oil storage cavities (cavity groundwater) harbored more than 10(6) microorganisms ml(-1), a density 100 times higher than the densities in groundwater around the cavities (control groundwater). To characterize bacterial populations growing in the cavity groundwater, 46 PCR-amplified almost full-length 16S ribosomal DNA (rDNA) fragments were cloned and sequenced, and 28 different sequences were obtained. All of the sequences were affiliated with the Proteobacteria; 25 sequences (43 clones) were affiliated with the epsilon subclass, 2 were affiliated with the beta subclass, and 1 was affiliated with the delta subclass. Two major clusters (designated clusters 1 and 2) were found for the epsilon subclass proteobacterial clones; cluster 1 (25 clones) was most closely related to Thiomicrospira denitrificans (88% identical in nucleotide sequence), while cluster 2 (11 clones) was closely related to Arcobacter spp. Denaturing gradient gel electrophoresis (DGGE) of PCR-amplified partial 16S rDNA fragments showed that one band was detected most strongly in cavity groundwater profiles independent of storage oil type and season. The sequence of this major band was identical to the sequences of most of the cluster 1 clones. Fluorescence in situ hybridization (FISH) indicated that the cluster 1 population accounted for 12 to 24% of the total bacterial population. This phylotype was not detected in the control groundwater by DGGE and FISH analyses. These results indicate that the novel members of the epsilon subclass of the Proteobacteria grow as major populations in the petroleum-contaminated cavity groundwater.

Cloning, Molecular↗

Efficient production of N-terminally truncated biologically active human interleukin-6 by Bacillus brevis.

cDNAs encoding human interleukin 6 (hIL-6) and its variants lacking the N-terminal Pro and Pro-Val-Pro-Pro, respectively, were expressed in Bacillus brevis by using the signal peptide fusion approach. The presence of Pro at the N-terminus of the mature protein hindered the action of the Bacillus brevis signal peptidase. hIL-6 lacking the N-terminal Pro-Val-Pro-Pro was most efficiently secreted in a biologically active form and accumulated in the culture medium to a level of 200 mg per liter, which is the highest level reported for the bacterial secretion of hIL-6.

Amino Acid Sequence↗

Clinical trials and the new good clinical practice guideline in Japan. An economic perspective.

Japanese clinical trials have been drastically changing in response to the implementation of the International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) guideline in 1997. The most important aim of the new guideline is to standardise the quality of clinical trials in the US, European Union and Japan, but it inevitably imposes substantial costs on investigators, sponsors and even patients in Japan. The study environment in Japan differs from that in the US in several ways: (i) historical lack of a formal requirement for informed consent; (ii) patients' attitudes to clinical trials in terms of expectation of positive outcomes; (iii) the implications of universal health insurance for trial participation; (iv) the historical absence of on-site monitoring by the sponsor, with the attendant effects on study quality; and (v) the lack of adequate financial and personnel support for the conduct of trials. Implementation of the new GCP guideline will improve the ethical and scientific quality of trials conducted in Japan. It may also lead to an improved relationship between medical professionals and patients if the requirement for explicit informed consent in clinical trials leads to the provision of a similar level of patient information in routine care and changes the traditional paternalistic attitude of physicians to patients. The initial response of the Japanese 'market' for clinical trials to the implementation of the ICH-GCP guideline has been clinical trial price increases and a decrease in the number of study contracts. These changes can be explained by applying a simple demand-supply scheme. Whether clinical trials undertaken in Japan become more or less attractive to the industry in the long term will depend on other factors such as international regulations on the acceptability of foreign clinical trials and the reform of domestic healthcare policies.

Clinical Trials as Topic↗

In vivo binding characteristics of phenytoin to serum proteins in monotherapy pediatric patients with epilepsy.

AIM: The aim of the present study was to determine the binding characteristics of phenytoin (PHT) to serum proteins in the pediatric population. Binding parameters of PHT to serum proteins in our study were conducted to compare with in vivo or in vitro binding parameters of PHT to serum proteins in adult subjects reported by other investigators. SUBJECTS AND MATERIALS: Serum samples in the study were obtained from 40 pediatric patients (16 male, 24 female) receiving PHT monotherapy. Their age ranged from 1 to 15 years (9.2 +/- 3.6 years, mean +/- SD). The in vivo population binding parameters of PHT to serum proteins and theoretical minimal unbound serum PHT fraction (fu) were determined using an equation derived from the Scatchard equation. RESULTS: The association constant (Ka) was 0.014 l/micromol, while the total concentration of binding sites (n(Pt)) was 747 micromol/l. The number of binding sites per albumin molecule (n) was 1.13, while binding ability (n x Ka) was 0.0161/micromol. The fu was 0.087. The n x Ka is approximately 1.2 times higher in PHT monotherapy adult patients of Pospisil et al. [1992] (i.e. 0.0191 l/micromol) than in all our patients. The association constant is approximately 1.3 times higher in the in vitro study of Monks et al. [1978] (i.e. 0.0186 l/micromol) than in our study, while n is similar between the two studies. The fu in our pediatric patients is similar to the unbound serum PHT fraction in adult patients receiving PHT therapy reported by Richens [1979] (i.e. 0.1). CONCLUSION: Our results suggest that there may be small differences in the binding characteristics of PHT to serum proteins between Japanese pediatric and non-Japanese adult subjects. The unbound serum fraction of PHT in pediatric patients with epilepsy can be assumed to be relatively constant in the therapeutic concentration range of PHT.

Adolescent↗

[Nontuberculous mycobacterial infection followed for 12 years].

A 67-year-old woman presented in September 1985 with productive cough, bloody sputum, and dyspnea on exertion. Productive cough and bloody sputum had developed when the patient was 55 years old. Sputum culture and radiologic findings yielded a diagnosis of nontuberculous mycobacteriosis (NTM). Antituberculous therapy with INH, RFP, and EB was initiated in November 1987 because of the development of a cavity in the right upper lobe, and led to resolution of the lesion and clinical symptoms. Despite progression of bronchiectatic changes in both lungs and a relapse of her clinical symptoms during the following 10 years, the patient retained enough pulmonary function to be able to maintain an active daily life until she died of advanced gastric cancer at the age of 79. Autopsy revealed cystic bronchiectasis accompanied by bronchial wall thickening in both lungs, with some granuloma and acid-fast-bacteria observed in lung tissue. In this report, we concluded that patients with NTM usually experience a gradual progression of symptoms and radiographic changes during their clinical course, and that their pulmonary function may be conserved well enough to maintain an active daily life.

Aged↗

Psychological changes of Japan Self-Defense Forces personnel during selection and training for the peacekeeping mission in the Golan Heights.

We sought to determine whether a selection process for deployment had a measurable effect on psychological symptoms by comparing scores on the Yatabe-Guilford Personality Index, the Manifest Anxiety Scale, and the 30-item version of the General Health Questionnaire between deployed and nondeployed mission candidates from the Japan Self-Defense Forces. The studies were undertaken in Japan during education and training for the United Nations peacekeeping mission in the Golan Heights. The participants included 80 candidates for deployment. Personnel who were not deployed had significantly higher measures of manifest anxiety and general psychological distress than deployed personnel, whereas deployed personnel showed more symptoms suggesting somatization. The selection process and training for deployment appear to have been stressful for all personnel, whether deployed or not.

Anxiety↗

[A case of chorea-acanthocytosis with dilated cardiomyopathy and myopathy].

We report a patient of chorea-acanthocytosis (CA), presenting with dilated cardiomyopathy and myopathy. The patient, 40-year-old male, was seen in our clinic because of progressive gait disturbance. Neurologically, he had chorea, tic, dystonia, diminished tendon reflexes and mild muscular atrophy and weakness. Serum creatine kinase level was elevated to 5.514 IU/l, MRI study showed atrophy of the putamen and caudate nucleus. Peripheral nerve involvement was confirmed pathologically and electrophysiologically. Acanthocytosis was found after repeated blood examinations. Furthermore, he had dilated cardiomyopathy on echocardiogram and cardiac muscle biopsy, and his muscle biopsy taken from gastrocnemius indicated myopathic changes with fiber necrosis. From these clinical and laboratory data, he was suspected to have McLeod syndrome (McS). However, he had normal expression of Kell antigens, and direct sequence of XK gene from genomic DNA sample showed no mutations. Accordingly, he was diagnosed as having CA. As CA shares the similar clinical and laboratory features with McS except Kell antigens, the evaluation of Kell blood system is crucial for differential diagnosis. As seen in our patient, blood sampling should be repeated for identification of acanthocytosis, because the finding is not always clearly present.

Adult↗

[A case of multiple intracranial cavernous angiomas presented with dementia and parkinsonism--clinical and MRI study for 10 years].

We report a case of multiple intracranial cavernous angiomas with serial clinical examination and with MRI imaging for 10 years. The patient, 72 years old woman, had slowly progressive postural tremor and Parkinsonism followed by dementia. Pathological confirmation of cavernous angioma was obtained. At the age of 62, brain MRI study demonstrated hydrocephalus, multiple small hypointensity dots in cerebellum and cerebral white matter, and reticulated cores predominantly adjacent to the ventricles on T2-weighted images. Serial MRI imaging shows that the number of small dots has markedly increased and that hypointense lesions surrounding reticulated core, corresponding to hemosidern deposit, have extended. This case indicates that probably due to chronic compression and continuous hemorrhage' multiple and long-standing intracranial lesions could cause dementia and Parkinsonism, which are uncommon symptoms of cavernous angioma.

Aged↗

Susceptibility to urethane carcinogenesis of transgenic mice carrying a human prototype c-Ha-ras gene (rasH2 mice) and its modification by butylhydroxytoluene.

The susceptibility of rasH2 mice to urethane lung carcinogenesis and the modifying effects of butylhydroxytoluene (BHT) on development of pulmonary lesions were examined. Single i.p. injections of urethane at 250 mg/kg in males or 500 mg/kg in females induced alveolar/bronchiolar adenomas within 6 weeks. At 4 weeks after the injection with a dose of 1000 mg/kg, adenomas occurred in both sexes. BHT administration increased the multiplicity of hyperplasias observed 3 weeks after the urethane injection and additionally caused adenomas which did not occur in the urethane alone-treated animals. The overall data suggest the possibility of rapid assays for lung carcinogens using rasH2 mice.

Adenoma↗

Auditory brainstem responses in patients with autonomic failure with Parkinson's disease and multiple system atrophy.

Auditory brainstem responses (ABRs) were examined in six patients with autonomic failure with Parkinson's disease (AF with PD) and 10 patients with autonomic failure with multiple system atrophy (AF with MSA), all of which showed marked parkinsonian features as a principal sign. We designated the central abnormalities of ABRs as prolongation of latencies (wave III or V) and interpeak latencies (IPLs; I-III, I-V, and III-V IPL) or decreased amplitude ratios of wave III or V to those of wave I (less than 1.0). None of the patients with AF with PD showed abnormalities in ABRs. In contrast, in those with AF with MSA, the peak latencies or IPLs were prolonged in two of the 10 patients, and the amplitude ratios of wave III or V to those of wave I were decreased in other two of these patients. Moreover, both prolongation of latencies and a decreased ratio were observed in other one. Overall, five of the 10 patients with AF with MSA showed central abnormalities in ABRs. It is clinically difficult to differentiate AF with PD from AF with MSA, particularly when no cerebellar signs are apparent in AF with MSA patients. When central abnormalities of ABRs are observed in AF patients, AF with MSA should be suspected rather than AF with PD. In conclusion, ABRs provide useful information for the differential diagnosis of AF with PD and AF with MSA.

Aged↗

Is a proton pump inhibitor necessary for the treatment of lower-grade reflux esophagitis?

The efficacy of histamine H2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) therapies in healing reflux esophagitis was compared in a prospective randomized case-control comparative study. A total of 71 patients with grade A to D esophagitis (Los Angeles classification) were given either famotidine 20 mg twice a day (Fam; n = 35) or omeprazole 20 mg once daily (Ome; n = 36) for 8 weeks. Endoscopy was performed to assess healing in 57 patients. Healed patients were followed-up without H2RA or PPI therapy for 3 months. At the end of follow-up, endoscopy was able to be performed in 33 patients. Healing rates for patients in the Fam and Ome groups were 58.6% (17/OFF and 97.4% (27/28), respectively (P < 0.001), and when limited to grade A to B, healing rates were 60.9% (14/23) and 100% (25/25), respectively (P < 0.001). Concerning Helicobacter pylori infection, healing rates for the Fam and Ome groups in H. pylori (+) patients were 90.0% (9/10) and 90.9% (10/11), respectively (P = 1.00). Remission rates in the Fam and Ome groups were 45.0% (91/2)) and 33.3% (6/18), respectively (P > 0.4). In regard to alcohol drinking, remission rates of daily and social drinkers were 7.7% and 42.4%, respectively (P < 0.03). Thus, PPI should be the drug of choice even for healing lower-grade reflux esophagitis, especially in H. pylori (-) patients. Treatment with H2RA may be an alternative choice in H. pylori (+) patients. After healing, most patients cannot sustain remission without maintenance therapy.

Alcohol Drinking↗

Temperature effect on serum protein binding kinetics of phenytoin in monotherapy patients with epilepsy.

The effects of temperature on the binding kinetics of phenytoin (PHT) to serum proteins were determined in patients with epilepsy. Serum samples examined in the study were obtained from 59 patients (31 male, 28 female) with epilepsy on PHT monotherapy. Their age ranged from 3 to 64 years (mean (SD), 23.3 (16.3) years). Protein binding of PHT was evaluated by ultrafiltration under current routine laboratory conditions (25 +/- 3 degrees C) or at a temperature of 37 degrees C. The in vivo binding parameters of PHT to serum proteins were determined using a binding equation derived from the Scatchard equation for a one-site binding model. Significant differences were observed in serum concentrations of unbound PHT between paired data (P < 0.05). The mean association constant (K) of PHT to serum proteins is 0.011 microM-1 at 25 +/- 3 degrees C and 0.006 microM-1 at 37 degrees C, while mean total concentration of binding sites (n(Pt)) is 1002 microM for 25 +/- 3 degrees C and 1112 microM for 37 degrees C. Significant differences were observed in the binding kinetics of PHT to serum proteins for the different temperature conditions of ultrafiltration (P < 0.05). Our study confirms that binding affinity for PHT-serum protein interaction is approximately 45% lower at 37 degrees C than at 25 +/- 3 degrees C and consequently, binding potential (K.n(Pt)) is approximately 39% lower at 37 degrees C than at 25 +/- 3 degrees C.

Adolescent↗

Cortical tibial bone volume in two strains of mice: effects of sciatic neurectomy and genetic regulation of bone response to mechanical loading.

Although C3H/HeJ (C3H) and C57BL/6J (B6) mice are similar in body size (and adult weight), and have bones of similar external size, C3H mice have higher peak bone densities than B6 mice (e.g., 53% higher peak bone density in the femora). The current studies were intended to assess the role of mechanical loading/unloading as a possible determinant of the bone density difference between these inbred strains of mice and, specifically, to assess the effect of sciatic neurectomy on histomorphometric indices of bone formation and resorption in the tibiae of female C3H and B6 mice. Groups of 10 mice of each strain were subjected to left-side sciatic neurectomy (left hindlimb immobilization) or a sham procedure. The contralateral (right) legs of each mouse were used as controls. Four weeks of immobilization produced no systemic changes in bone formation indices in either strain of mice (i.e., no change in serum alkaline phosphatase or serum osteocalcin). However, histomorphometric assessments at the tibiofibular junction showed that 4 weeks of immobilization caused a time-dependent decrease in the length of the endosteal bone forming perimeter (e.g., 14% of control single-labeled, noneroded surface at 4 weeks, p < 0.005) with a concomitant increase in the length of the endosteal bone resorbing perimeter (i.e., 424% of control eroded surface at 4 weeks, p < 0.005), in the B6 mice. These effects were associated with an increase in medullary area (132% of control, p < 0.05) at this site, in the B6 mice. The pattern of response was different in the tibiae of the C3 mice-a much smaller decrease in bone forming perimeter (88% of control at 4 weeks, p < 0.05), with no associated increase in bone resorbing perimeter, and no change in medullary area. Similar effects were seen at a second cross-sectional sampling site, in the proximal tibia. Together, these findings indicate that B6 mice are more sensitive to endosteal bone loss from hindlimb immobilization than C3H mice.

Alkaline Phosphatase↗

S values are not a signature for a significant contribution of neutrons to the radiation dose received by atomic-bomb survivors.

PURPOSE: It has been proposed previously that the ratio of complete to incomplete translocations as seen by fluorescence in situ hybridization (FISH), the S value, can be a cytogenetic fingerprint of exposure to radiation of different qualities. Results from a previous study suggested that the S value is approximately 10 for sparsely ionizing radiations such as X- and gamma-rays, and 2 for densely ionizing radiations. Based on FISH data of atomic-bomb (A-bomb) survivors, which showed an S value of 3.25, a significant neutron component to A-bomb radiation was suggested. To examine the possibility, the present in vitro study was conducted using X-rays. MATERIALS AND METHODS: Human blood lymphocytes were exposed to X-rays and first metaphases were examined with FISH using DNA probes for chromosomes 1, 2 and 4. RESULTS: The S value was 3.16 for X-rays, which differs from approximately 10 as reported previously, and not larger than the 3.25 obtained from the blood lymphocytes of A-bomb survivors. CONCLUSIONS: S values seem to vary among laboratories even after exposure of cells to sparsely ionizing radiations. Data from this study show that S values are not a signature for a significant contribution of neutrons to the radiation dose received by A-bomb survivors in Hiroshima.

Chromosome Breakage↗

No effect of gender or age on binding characteristics of valproic acid to serum proteins in pediatric patients with epilepsy.

The gender- and age-related binding characteristics of valproic acid to serum proteins were determined in the pediatric population. Serum samples examined in the study were obtained from 61 pediatric patients (28 males, 33 females) with epilepsy on valproic acid monotherapy. Their ages ranged from 1 to 15 years (mean age with [SD]: 7.8 [3.9] years; < 10 years, n = 41; > or = 10 years, n = 20). The in vivo population binding parameters of valproic acid to serum proteins and theoretical minimal unbound serum fraction (fu) of valproic acid were determined in (1) all, (2) male and female subgroups, and (3) prepubescent (< 10 years) and pubescent (> or = 10 years) subgroups. The association constant (K) was approximately 1.4 times higher in male (0.018 L/mumol) than in female (0.013 L/mumol) patients, while the total concentration of binding sites (n(Pt)) was 1.2 times greater in female (1235 mumol/L) than in male (997 mumol/L) patients. The fu was 0.053 and 0.059 for male and female patients, respectively. The value of K was approximately 1.6 times higher in the pubescent (0.019 L/mumol) than in the prepubescent (0.012 L/mumol) patients, while the n(Pt) was 1.2 times higher in the prepubescent (1244 mumol/L) than in the pubescent (1057 mumol/L) patients. The fu was 0.063 for the prepubescent and 0.047 for the pubescent patients. No significant differences were observed in binding characteristics of valproic acid to serum proteins between male and female or younger and older patients. However, the differences in valproic acid binding to serum proteins appear to be relatively larger in binding affinity than in binding capacity between the two groups. Because no significant differences were observed in serum concentrations of total and unbound valproic acid, albumin, or free fatty acids between any subgroups (male and female, younger and older), the results suggest that gender or age may not be factors for the determination of the binding characteristics of valproic acid to serum proteins in pediatric patients.

Adolescent↗