Search PubMed⌕ Search

Biomedical subjects

Y Kodama

Publications and source records attributed to Y Kodama.

At least 55 records · Page 3Linked to original sources

Stable chromosome aberrations in atomic bomb survivors: results from 25 years of investigation.

Frequencies of stable chromosome aberrations from more than 3,000 atomic bomb survivors were used to examine the nature of the radiation dose response. The end point was the proportion of cells with at least one translocation or inversion detected in Giemsa-stained cultures of approximately 100 lymphocytes per person. The statistical methods allow for both imprecision of individual dose estimates and extra-binomial variation. A highly significant and nonlinear dose response was seen. The shape of the dose response was concave upward for doses below 1.5 Sv but exhibited some leveling off at higher doses. This curvature was similar for the two cities, with a crossover dose (i.e. the ratio of the linear coefficient to the quadratic coefficient) of 1.7 Sv (95% CI 0.9, 4). The low-dose slopes for the two cities differed significantly: 6.6% per Sv (95% CI 5.5, 8.4) in Hiroshima and 3.7% (95% CI 2.6, 4.9) in Nagasaki. This difference was reduced considerably, but not eliminated, when the comparison was limited to people who were exposed in houses or tenements. Nagasaki survivors exposed in factories, as well as people in either city who were outside with little or no shielding, had a lower dose response than those exposed in houses. This suggests that doses for Nagasaki factory worker survivors may be overestimated by the DS86, apparently by about 60%. Even though factory workers constitute about 20% of Nagasaki survivors with dose estimates in the range of 0.5 to 2 Sv, calculations indicate that the dosimetry problems for these people have little impact on cancer risk estimates for Nagasaki.

Adolescent↗

Persistent behavioural changes in rats following inescapable shock stress: a potential model of posttraumatic stress disorder.

Behavioural changes in rats two weeks after inescapable shock stress were studied using a shuttle-box task (active avoidance/escape). Rats exposed to inescapable shock stress two weeks beforehand showed more frequent avoidance responses and greater within-group variation in both avoidance response and general activity during the test than rats in a control group. General activity during an unstressful period (before starting the test) did not differ significantly between groups. This relatively prolonged increase in responsiveness to external stimuli in the stressful context may be a useful experimental model of posttraumatic stress disorder, especially in relation to hypervigilance.

Adaptation, Psychological↗

Expression of multidrug resistance protein and messenger RNA correlate with (99m)Tc-MIBI imaging in patients with lung cancer.

UNLABELLED: In vitro studies have shown that (99m)Tc-sestamibi (MIBI) is a transport substrate for the P-glycoprotein (Pgp) pump and the multidrug resistance-associated protein (MRP) pump. However, whether MRP and lung resistance protein (LRP) affect tumor accumulation and efflux of (99m)Tc-MIBI in lung cancer is not known. In this study, we explored whether Pgp and the other pumps, MRP and LRP, affect tumor accumulation and efflux of (99m)Tc-MIBI in lung cancer. METHODS: Thirty-four lung cancer patients who underwent surgery were examined. Before surgery, (99m)Tc-MIBI SPECT was performed 15 min and 180 min after injection, and early uptake, delayed uptake (L/Nd), and washout rate (L/Nwr) of (99m)Tc-MIBI were obtained. Pgp, MRP, and LRP expression were investigated by immunohistochemistry. The messenger RNA (mRNA) level of Pgp, MRP, and LRP was determined by real-time reverse-transcription polymerase chain reaction. The lung cancer (99m)Tc-MIBI images were correlated with protein and mRNA expression. RESULTS: The mean L/Nd of the Pgp (-) group was significantly higher than that of the Pgp (++) group (P = 0.0324). The Pgp (++) group had a higher L/Nwr than did the Pgp (-) group (P = 0.0269). The mean L/Nd of the Pgp mRNA low-expression group was significantly higher than that of the Pgp mRNA high-expression group (P = 0.0127). The Pgp mRNA high-expression group had a higher L/Nwr than did the Pgp mRNA low-expression group (P = 0.0825). No appreciable correlation was found between the lung cancer (99m)Tc-MIBI images and the expression of MRP or LRP on the level of protein or mRNA. CONCLUSION: These data suggest that an increased level of Pgp expression correlates with a low accumulation on delayed scans and a high L/Nwr of (99m)Tc-MIBI in lung cancer. Neither MRP nor LRP expression on the level of either protein or mRNA correlated significantly with tumor accumulation or efflux of (99m)Tc-MIBI in lung cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Evaluation of spontaneous pneumothorax in patients with pulmonary lymphangioleiomyomatosis].

We retrospectively evaluated the development of spontaneous pneumothorax in patients with pulmonary lymphangioleiomyomatosis (LAM). Fifteen patients with LAM, whose diagnosis was confirmed histopathologically, were enrolled. All were women, and had a mean age at diagnosis of 31.6 +/- 7.3 years. They were divided into two groups according to the presence or absence of pneumothorax at the time of onset, Group A consisting of nine patients with pneumothorax, and Group B, of six without pneumothorax. Spontaneous pneumothorax developed in 15 out of a total of 18 hemithoraces in Group A patients in whom 13 hemithoraces were surgically treated for pneumothorax (eight open thoracotomies and five video-assisted thoracoscopic surgeries). Bullectomy with either parietal pleurectomy, pleural abrasion, or instillation of chemical irritants to prevent the recurrence of pneumothorax offered better outcomes than bullectomy alone in terms of the postoperative recurrence rate of pneumothorax (p < 0.05). On the other hand, three of the five Group B cases developed pneumothorax during the course of LAM, but none was operated because of severely impaired lung function. The other patient in Group B was not only free of pneumothorax at onset, but also did not develop pneumothorax or suffer from impaired lung function. There were no deaths due to pneumothorax recorded among Group A patients, but two patients in group B died. A better survival rate was noted in Group A than in Group B by Kaplan-Meier analysis, suggesting that these two groups may represent the broad clinical spectrum of LAM.

Adult↗

[Effect of ATP-sensitive K+ channel blocker (quinine) on the dopamine decrease induced by selective D3 agonist (7-OH-DPAT) in the rat striatum].

In vivo brain microdialysis was used to investigate the role of D3 receptors relating to dopamine auto-regulated systems in the rat. A local infusion of the dopamine D3 selective agonist, 7-OH-DPAT (100 nM), into the striatum through the dialysis membrane produced a significant decrease in extracellular concentrations of dopamine. A local application of ATP-sensitive K+ (KATP) channel blocker, quinine (10 microM, 100 microM, 1 mM), produced dose-dependent increases in extracellular concentrations of dopamine. Quinine (100 microM, 1 mM) significantly blocked a 7-OH-DPAT-induced decrease in the striatal dopamine levels in the dose-dependent manner. Because of many previous reports, the autoregulated functions of dopamine release by D3 receptors in the striatum can be regarded mainly as nerve terminal autoreceptors and/or a short-loop negative feedback system. Therefore these results suggest that KATP channels may be present in nigrostriatal dopaminergic terminals and that in the striatum, presynaptic dopamine D3 autoreceptors and/or a post-synaptic D3 related short-loop negative feedback system inhibit dopamine release tonically by the activation of KATP channels.

Adenosine Triphosphate↗

Lack of oxidative DNA damage or initiation of carcinogenesis in the kidneys of male F344 rats given subchronic exposure to p-dichlorobenzene (pDCB) at a carcinogenic dose.

p-Dichlorobenzene (pDCB) is a male rat kidney carcinogen believed to act through alpha2u-globulin nephropathy. Recent data on metabolism, however, suggest a potential for generating oxidative stress. To examine possible mechanisms of kidney carcinogenesis, pDCB was studied for ability to produce 8-oxodeoxyguanosine (8-oxodG) in kidney nuclear DNA and for initiating activity in a two-stage renal carcinogenesis model. F344 male rats were given pDCB by intragastric instillation, 5 days/week for 13 weeks at 300 mg/kg per day, which is a carcinogenic dose with chronic administration. To assess initiation after exposure, trisodium nitrilotriacetic acid (NTA), a kidney tumor promoter was given in the drinking water at 1,000 ppm for 39 weeks. At the end of the exposure segment, pDCB did not produce an increase of 8-oxodG levels in the kidney nuclear DNA in contrast to potassium bromate (KBrO3). Following NTA promotion, no neoplastic lesions occurred in rats given pDCB, although diethylnitrosamine carcinogenesis was enhanced. Thus, pDCB did not produce oxidative DNA damage in the rat kidney or effect initiation of kidney carcinogenesis. These data suggest that oxidative stress is not involved in pDCB-induced renal carcinogenesis. The alpha2u-globulin-mediated chronic nephropathy probably acts as a promoter, not an initiation of renal carcinogenesis. Accordingly, pDCB is assessed to have no cancer hazard to humans who are not susceptible to the alpha2u-globulin nephropathy.

8-Hydroxy-2'-Deoxyguanosine↗

Exercise and mechanical loading increase periosteal bone formation and whole bone strength in C57BL/6J mice but not in C3H/Hej mice.

To identify the genes, and the mechanisms that account for the 53% higher peak bone density in C3H/HeJ (C3H) mice compared with C57BL/6J (B6) mice, we are performing quantitative trait locus and phenotypic analyses. The phenotypic studies revealed differences in bone formation and resorption, and showed that hindlimb immobilization (by sciatic neurectomy) caused a greater increase in endosteal resorption in the tibiae of B6 compared with C3H mice. The current studies were intended to examine the hypothesis that the bones of C3H mice are less sensitive to mechanical loading than the bones of B6 mice. To increase mechanical loading, 9-week-old female B6 and C3H mice (n = 10-13 mice/group) were subjected to a jumping exercise (20 jumps/day, 5 days/week, to heights of 20-30 cm) for a total of 4 weeks. Control mice did not jump. Osteocalcin, alkaline phosphatase (ALP) activity, and IGF-I were measured in serum. The left tibiae were used for histomorphometry (ground cross-sections prepared at the tibiofibular junction) and the right tibiae and femora were used for determinations of bone breaking strength (3-point bending). The results of these studies revealed (1) significant effects of both mouse strain (B6 and C3H) and the jumping exercise on tibial strength; (2) an exercise-dependent increase in serum IGF-I in C3H, but not B6 mice; and (3) no effects on serum ALP or osteocalcin. The histomorphometric analyses showed no effect of exercise on C3H tibiae, but significant exercise-dependent increases in total bone area, periosteal perimeter, periosteal mineral apposition rate (MAR), and periosteal bone formation (P < 0.02 for each) in B6 tibiae. There were no effects of exercise on periosteal resorption or any endosteal measurement in either C3H or B6 mice. Since the jumping exercise was designed to cause a two-three fold increase in muscular-skeletal loading at the tibio-fibular junction, and the calculated stress (g/mm2) at this sampling site was only 16% greater for B6 compared with C3H mice, we had anticipated that both strains of mice would show exercise-dependent increases in periosteal bone formation, with a greater response in the B6 mice. The lack of a response in the C3H tibiae demonstrates that the bones of C3H mice are less sensitive to mechanical loading (and unloading) than the bones of B6 mice.

Alkaline Phosphatase↗

A type 2 diabetic patient with liver dysfunction due to human insulin.

A 45-year-old man had been complaining of thirst and polydypsia for the last 3 months and was diagnosed as having type 2 diabetes mellitus because his fasting blood glucose showed 221 mg/dl with positive urinary ketone. He was hospitalized to a private hospital and Penfil 30R was started. However, serum gamma-GTP and aminotransferases began to elevate after insulin treatment and exceeded 1000 IU/l. Insulin was discontinued and serum gamma-GTP and aminotransferases returned close to the normal range. Since his glycemic control became poor again, Penfil 30R was restarted and serum gamma-GTP and aminotransferases elevated again. Therefore, insulin was discontinued and the patient was referred to the Third Department of Internal Medicine, Yamanashi Medical University Hospital because of liver dysfunction. His plasma glucose decreased by diet therapy, and improved further by the administration of glibenclamide. After obtaining informed consent, Humalin R was challenged. Seven days after insulin injection, serum aminotransferases began to elevate again. Lymphocyte stimulation test was negative against three preparations (Penfil R, Penfil N and Humalin R). The present case suggests that human insulin itself can cause liver dysfunction and we need to pay more attention to liver function tests when we start insulin treatment.

Alanine Transaminase↗

Effects of dietary calcium depletion and repletion on dynamic determinants of tibial bone volume in two inbred strains of mice.

As an adjunct to our efforts to identify the genes that determine peak bone density, we examined phenotypic differences between two inbred strains of mice, C3H/HeJ (C3H) and C57BL/6J (B6), which are of similar size but differ with respect to peak bone density (e.g., C3H mice have 53% higher femoral bone density than B6 mice). The current studies were intended to compare the skeletal responses of C3H and B6 mice to 2 weeks of dietary calcium (Ca) depletion, followed by 2 weeks of Ca repletion. Initial studies showed that: (a) femur dry weight decreased during Ca depletion in both C3H and B6 mice (by 25% and 19%, respectively, p < 0.001) and most of this loss was recovered during Ca repletion; and (b) serum alkaline phosphatase (ALP) activity increased during Ca depletion, in both strains of mice (p < 0.001), and returned to normal after Ca repletion. Histological analyses of ground cross sections prepared at the tibiofibular junction showed that Ca-depletion increased medullary area in both C3H and B6 mice (indicating endosteal bone loss, p < 0.01), with reversal during Ca repletion. There were no effects of Ca depletion or repletion on periosteal bone growth. Endosteal bone forming surface and endosteal mineral apposition decreased during Ca depletion and increased during repletion in both C3H and B6 mice (p < 0.05). Net bone formation decreased during Ca depletion in C3H mice, but not B6 mice (p < 0.01), and was normal during Ca repletion in both strains. Endosteal bone resorbing surface and net bone resorption increased during Ca depletion and decreased during repletion in both strains (p < 0.01). A supplemental study (of Ca depletion without repletion) confirmed the effects of Ca depletion on femoral dry weight and serum ALP activity (p < 0.001 for each). This supplemental study also showed that Ca deficiency increased serum parathyroid hormone (PTH) (p < 0.05) and decreased (tibial) cortical bone area and cortical mineral content (p < 0.05 to p < 0.001) in both strains of mice. Together, these data demonstrate that the skeletal responses to Ca depletion and repletion are, qualitatively, similar in C3H and B6 mice.

Alkaline Phosphatase↗

Comparison of bone formation responses to parathyroid hormone(1-34), (1-31), and (2-34) in mice.

In this study we used a mouse model system to compare the in vivo effects of parathyroid hormone(1-34) [PTH(1-34)] with that of PTH(1-31) or PTH(2-34) analogs. Daily subcutaneous administration of PTH(1-34) for 15 days caused a dose-dependent increase in the serum osteocalcin level and bone extract alkaline phosphatase activity, markers of bone formation. PTH(2-34) was much less potent, whereas PTH(1-31) was equipotent in stimulating bone formation parameters in mice. PTH(1-34) caused significant increases in serum calcium (after 4 h) and tartrate-resistant acid phosphatase activity in bone extract (after 4 h), whereas PTH(2-34) and PTH(1-31) were less potent. Because PTH(1-31) caused a smaller increase in bone resorption parameters compared to PTH(1-34), despite similar effects on bone formation parameters, we evaluated the long-term anabolic effects of PTH(1-31) and PTH(1-34) in mice. Weekly evaluations of serum osteocalcin levels demonstrated that daily injections of PTH(1-34) and PTH(1-31) at 80 microg/kg body weight increased serum osteocalcin levels within 1 week of the start of treatment, which were maintained during the entire 22 week treatment. Assessment of bone density at the end of the treatment period with peripheral quantitated computed tomography (pQCT) revealed that PTH(1-34) caused a significantly greater increase in femoral bone density compared to PTH(1-31) at the middiaphysis (18% vs. 9% over vehicle control; p < 0.001). Both PTH(1-34) and PTH(1-31) increased periosteal circumference compared to vehicle (p < 0.01) without a significant difference between the two treatments. In contrast, PTH(1-34) caused a significantly greater reduction in endosteal circumference than PTH(1-31) (p < 0.001). Both analogs significantly increased maximum load and area of moment of inertia over the vehicle group. In conclusion, our findings suggest that PTH(1-34) and PTH(1-31) may exhibit different anabolic effects at the periosteum vs. endosteum in the long bones of mice.

Animals↗

The distribution of serotonergic nerves in microencephalic rats treated prenatally with methylazoxymethanol.

Prenatal exposure of pregnant rats to methylazoxymethanol acetate (MAM) induces microencephaly in the offspring. In the present study of these microencephalic rats (MAM rats) we used quantitative autoradiography to investigate [3H] paroxetine binding sites, which are a selective marker of serotonin (5-HT) transporters (5-HTT). The binding in the accumbens, cortex, hippocampus, and dorsolateral thalamus was significantly increased in MAM rats, compared to the control rats, while there was a significant decrease in the dorsal raphe nucleus of the MAM rats. The levels of 5-HTT mRNA in the dorsal raphe nuclei were analyzed by in situ hybridization, which revealed a significant decrease in 5-HTT mRNA-positive neurons in the MAM rats compared to the control rats. The results imply serotonergic hyperinnervation in the cerebral hemispheres of MAM rats, while a target-dependent secondary degeneration of 5-HT neurons might be induced in the dorsal raphe nuclei of MAM rats.

Animals↗

Acid-dependent adherence of Helicobacter pylori urease to diverse polysaccharides.

BACKGROUND & AIMS: The significance of acid-primed recognition of ligands by Helicobacter pylori urease is unknown. This study aimed to further characterize the specificity of urease adherence in vitro and verify whether specific inhibition will translate into in vivo suppression of colonization. METHODS: A highly sensitive competitive enzyme-linked ligand capture assay was used to quantify the capacity of each test inhibitor to compete with labeled mucin for binding sites on immobilized native urease. A model polymer that strongly bound urease was used in an in vivo trial using euthymic hairless mice as an infection model. RESULTS: The blockage of urease-gastric mucin interaction by certain inhibitors revealed an acid-functional lectin-like activity by urease, specifically recognizing bacterial lipopolysaccharides and certain species of polysaccharides, nonbacterial glycolipids, and glycoproteins. Dextran sulfate significantly (P < 0.01) suppressed colonization of mice by H. pylori when given before and/or after challenge. CONCLUSIONS: The acid-driven high-affinity adherence of H. pylori urease to mucin and lipopolysaccharides contributes to gastric mucosal colonization by the bacterium based on in vivo targeting experiments using specific polysaccharides in a mouse model with acute infection. Acid-functional urease-homing polysaccharides that can interfere with urease-mucin or H. pylori whole cell-mucin interaction in vitro can significantly interfere with colonization by the bacterium in vivo.

Acids↗

Pena-shokeir type I syndrome with thymic and systemic lymphoid hyperplasia: report of an autopsy case.

We report a case of Pena-Shokeir type I syndrome in a female neonate who died of respiratory failure shortly after the birth at 32 weeks of gestation. In general appearance, she had apparent ocural hypertelorism, a depressed tip of the nose, low-set malformed ears, and microglossia in the head. There were severe contractures at the ankle, hand, fingers, and toes, and moderate contractures at the hip, shoulder, knee, and elbow. An autopsy analysis showed severe pulmonary hypoplasia and group atrophy of the skeletal muscle tissues. In addition to these findings which are well known characteristics of the infant with this syndrome, the thymus was markedly hyperplastic and lymph nodes were systemically swollen, especially the mesenteric ones which were visible and measured 2-5 mm in diameter. Histologically, the lymph nodes showed massive paracortical hyperplasia without apparent follicular structures, although no atypical lymphocytes were observed in both the thymus and lymph nodes. Immunohistochemically, proliferating lymphocytes seemed to be immature CD4+/CD8+ T cells, suggesting the insufficiency of T-cell negative selection in the thymus. This report is the first case of Pena-Shokeir type I syndrome with T-lymphocytic disorder.

Abnormalities, Multiple↗

Effect of temperature on binding characteristics of phenytoin to serum proteins in monotherapy adult patients with epilepsy.

The effects of temperature on binding characteristics of phenytoin (PHT) to serum proteins were determined in adult patients with epilepsy. Serum samples examined in the study were obtained from 47 adult patients (29 men, 18 women) with epilepsy on PHT monotherapy. Ages ranged from 18 to 64 years (mean [SD], 36.8 [12.1] years). Protein binding of PHT was evaluated by ultrafiltration under current laboratory routine 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 <.05). The mean association constants (K) of PHT to serum proteins are 0.009 L micromol(-1) at 25 +/- 3 degrees C and 0.003 L micromol(-1) at 37 degrees C, whereas mean total concentrations of binding sites [n(Pt)] are 1215 micromol L(-1) for 25 +/- 3 degrees C and 2263 micromol L(-1) for 37 degrees C. Significant differences were observed in binding characteristics of PHT to serum proteins between the data determined in different conditions of ultrafiltration (P <.05). Our study confirms that binding affinity for PHT-serum protein interaction is approximately 67% lower at 37 degrees C than at 25 +/- 3 degrees C, and, consequently, binding potential [K.n(Pt)] is approximately 38% lower at 37 degrees C than at 25 +/- 3 degrees C.

Adolescent↗

No gender effect on binding characteristics of phenytoin to serum proteins in monotherapy for adult patients with epilepsy.

The aim of the present study was to determine the gender-related binding characteristics of phenytoin (PHT) to serum proteins in adult patients with epilepsy. Serum samples examined in the study were obtained from 80 adult patients (40 men and 40 women) with epilepsy on PHT monotherapy. Their age ranged from 16 to 64 years (mean [SD], 36.0 [11.7] years). Protein binding of PHT was evaluated by ultrafiltration under current laboratory routine conditions (25 +/- 3 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. No significant differences were observed in age and serum concentrations of albumin between male and female patients (p > 0.05), but significant differences were observed in serum concentrations of total and unbound PHT between the two groups (p < 0.05). The mean association constant of PHT to serum proteins is the same value of 0.008 L micromol(-1) between male and female patients, whereas total concentration of binding sites seems to be similar between the two groups (1389 micromol L(-1) for men and 1345 micromol L(-1) for women). No significant differences were observed in binding characteristics of PHT to serum proteins between male and female patients (p > 0.05). Our results show that gender does not have a significant effect on the binding characteristics of PHT to serum proteins in adult patients receiving monotherapy under normal pathophysiologic conditions.

Adolescent↗

In vivo binding characteristics of phenytoin to serum proteins in monotherapy for adults with epilepsy.

The aim of the present study was to determine the binding characteristics of phenytoin (PHT) to serum proteins in the adults. Binding parameters of PHT to serum proteins in our study were compared with in vivo or in vitro binding parameters of PHT to serum proteins reported by other investigators. Serum samples in the study were obtained from 36 adult patients (17 men, 19 women) receiving PHT monotherapy. A total of 43 steady-state concentrations were analyzed in the study. Patients' age ranged from 16 to 73 years (mean [SD], 42.9 [14.7] years). 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. The association constant (K) was 0.014 L x micromol(-1), whereas the total concentration of binding sites (n(Pt)) was 754 micromol x L(-1). The number of binding sites per albumin molecule (n) was 1.16, whereas binding ability (n.K) was 0.016 L x micromol(-1). The fu was 0.087. The n.K is approximately 1.2 times higher in PHT monotherapy patients of Pospísil and Perlík (ie, 0.0191 L x micromol(-1)) than in all our patients. The association constant is approximately 1.3 times higher in the in vitro study of Monks et al (ie, 0.0186 L x micromol(-1)) than in our study, whereas n is similar between the two studies. The fu in our patients is similar to the unbound serum PHT fraction in patients receiving PHT therapy reported by Richens (ie, 0.1). Our results suggest that there may be small differences in the binding affinity of PHT to serum proteins between in vivo and in vitro studies. The unbound serum fraction of PHT in epileptic patients can be assumed to be relatively constant in the therapeutic concentration range of PHT.

Adolescent↗