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Biomedical subjects

Y Kobayashi

Publications and source records attributed to Y Kobayashi.

At least 55 records · Page 3Linked to original sources

Effects of 5'-uridylic acid feeding on postprandial plasma concentrations of GH, insulin and metabolites in young calves.

Postprandial changes in plasma concentrations of GH, insulin, IGF-I, leptin and metabolites were compared between young Holstein bull calves fed with milk alone (control group) and with milk+5'-uridylic acid (UMP) (UMP group). UMP (2 g/day) was given with milk at 0830 h and 1530 h for 11 days from the 4th to the 14th day after birth. The perirenal fat weight was significantly lower in the UMP group than in the control group, but there was no significant difference in the weights of the liver, spleen and heart between the groups. Basal GH concentrations in the UMP group were slightly higher, but the postprandial increase in plasma insulin level and the area under the curve for insulin in the UMP group were significantly lower than those in the control group. There was no significant difference in IGF-I levels between the groups. In addition, the postprandial glucose concentrations were lower in the UMP group as reflected by the insulin level, and nonesterified fatty acid concentrations were not different. In the muscle (M. longissimus thoracis) sampled at 14 days of age, the triacylglycerol (TAG) content was significantly greater but glycogen content was significantly lower in the UMP group than in the control group. From these results, we have concluded that feeding 5'-UMP at 2 g/day for 11 days significantly alters TAG accumulation in the body and plasma concentrations of GH and insulin in young bull calves.

Animals↗

Responses induced by arginine-vasopressin injection in the plasma concentrations of adrenocorticotropic hormone, cortisol, growth hormone and metabolites around weaning time in goats.

In order to assess the biological significance of weaning and water deprivation on the control of plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH) and metabolites in response to stimulation with arginine-vasopressin (AVP) and corticotropin-releasing hormone (CRH), we carried out three experiments in which male goats before and after weaning were intravenously injected with AVP or CRH alone, or in combination with each other. In experiment 1, 17-week-old (post-weaning) goats were intravenously injected with AVP or CRH alone at the doses of 0.1, 0.3 and 1.0 nmol/kg body weight (BW). The AVP injection significantly and dose dependently increased plasma levels of ACTH, cortisol, GH and metabolites, whereas the injection with CRH did not cause significant increases in the levels of these parameters. In experiment 2, 4-week-old (pre-weaning) and 13-week-old (post-weaning) goats were injected with either AVP or CRH alone, followed by a combined injection of both secretagogues at a dose of 0.3 nmol/kg BW. Although the basal levels of the hormones and metabolites, with the exception of glucose, were greater in the 4-week-old goats, the hormone responses induced by stimulation with AVP were weaker than those induced in 13-week-old goats. Additionally, there were no responses in any hormone patterns to CRH stimulation in 4-week-old goats. In experiment 3, 13-week-old goats were injected with CRH alone followed by injection with AVP for two consecutive days of water deprivation. The animals were subjected to withdrawal of up to 20% of the total blood volume and water deprivation for up to 28 h. However, no significant differences in plasma ACTH, cortisol or GH levels were observed between days 1 and 2. Based on these results, we concluded that: (1) AVP is a more potent stimulant than CRH in terms of its ability to induce increases in plasma levels of ACTH, cortisol and GH; (2) the role of AVP as a secretagogue of hypothalamus-pituitary-adrenal hormones is strengthened, whereas the ineffective role of CRH remains unaltered, by weaning; (3) acute stress such as massive withdrawal of blood volume and subjection to water deprivation may not be sufficient burdens to alter stress-related hormone levels in young goats.

Adrenocorticotropic Hormone↗

Initial, continuous and intermittent bolus cardioplegia administration: efficacy of potassium-chloride and magnesium-sulfate as minimal additives for minimally-diluted blood cardioplegia.

AIM: The most effective delivery of blood cardioplegia (BCP) remains controversial, and a combination of initial continuous and intermittent bolus BCP seems to compensate each demerit. However, a large amount of crystalloid solution is infused into the myocardium in this method, which may nullify the advantages of BCP. We examined the hypothesis that minimally-diluted BCP resolves this issue and provides superior myocardial protective effects. METHODS: Seventy patients undergoing elective coronary revascularization between 1997-2001 (M:F=55:15, mean age 67.6+/-7.5 years) were randomly allocated into one of 2 groups: Group C (n=35) was given the standard 4:1-diluted blood-crystalloid BCP, and Group M (n=35) was given minimally-diluted BCP supplemented with potassium-chloride and magnesium-sulfate. The BCP temperature was maintained at 30 degrees C. Cardioplegic arrest was induced with 2 minutes of initial antegrade BCP infusion, followed by continuous retrograde BCP infusion. Intermittent antegrade BCP was infused every 30 minutes for 2 minutes. RESULTS: The time required for achieving cardioplegic arrest was significantly shorter in Group M (47.5+/-16.3 vs 62.5+/-17.6 s, p<0.0001) and the number of patients showing spontaneous heart-beat recovery after aortic unclamping was significantly larger in Group M (28 vs 15, p=0.0029). The number of patients suffering from atrial fibrillation during the postoperative period was significantly smaller in Group M (3 vs 11, p=0.034). The total amount of crystalloid solution infused as cardioplegia was significantly smaller in Group M (62.8+/-22.3 vs 733.6+/-382.6 mL, p<0.0001). Postoperative maximum dopamine dose (3.57+/-2.46 vs 5.44+/-2.23 mg/kg/min, p=0.0014) and peak creatine kinase-MB (19.5+/-8.5 vs 25.8+/-11.9 IU/L, p=0.0128) were significantly lower in Group M. The number of patients showing paradoxical movement of the ventricular septum by early postoperative echocardiography was significantly smaller in Group M (9 vs 24, p<0.0007). CONCLUSIONS: These results demonstrate that initial continuous and intermittent bolus administration of minimally-diluted BCP supplemented with potassium and magnesium can be a simple, reliable and effective technique of intraoperative myocardial protection.

Aged↗

Quantification of relationship between health status and physical fitness in middle-aged and elderly males and females.

AIM: The purpose of this study was to quantify the degree of the relationship between health status and physical fitness level in middle-aged and elderly people using multiple discriminant analysis. METHODS: The participants were 3114 males and females aged 30 to 69 years. Ten physical fitness tests and medical checkups were performed. The participants were divided into 2 groups according to health status; the healthy group and the unhealthy group. Multiple discriminant analysis was applied to the multivariate data. RESULTS: Correct discriminant probabilities of multiple discriminant functions to discriminate the healthy group and unhealthy group were 72.3% for males and 71.7% for females. For all age groups, a gender difference was not found (P>0.05). For aging, as a result of the test of proportion, it was found that the correct discriminant probabilities decreased with age for both genders (P<0.05). CONCLUSIONS: These results suggest that there is a relatively strong relationship between health status and the level of physical fitness in both males and females. These findings support daily physical activities and exercise to maintain or improve physical fitness could be useful for the health status of middle-aged and elderly people. From the result that the correct discriminant probability decreased with age, the changes in probability for males and females were calculated and described with correct discriminant probabilities by moving averages with 5 point smoothing.

Adult↗

Robust NADH-regenerator: improved alpha-haloketone-resistant formate dehydrogenase.

Formate dehydrogenases (FDH) are useful for the regeneration of NADH, which is required for asymmetric reduction by several dehydrogenases and reductases. FDHs have relatively low activity and are labile, especially to alpha-haloketones, thus FDH cannot be applied to the industrial manufacture of optically active alpha-haloalcohols. To stabilize a FDH from Mycobacterium vaccae (McFDH) against the alpha-haloketone ethyl 4-chloroacetoacetate (ECAA), a set of cysteine-mutant enzymes was constructed. Sensitivity to ECAA of mutant C6S was similar to that of the wild-type enzyme, and mutants C249S and C355S showed little activity. In contrast, mutant C256S exhibited remarkable tolerance to ECAA. Surprisingly, mutant C146S was activated by several organic compounds such as ethyl acetate. An optimized mutant, C6A/C146S/C256V (McFDH-26), was obtained by combining several effective mutations. Ethyl (S)-4-chloro-3-hydroxybutanoate [(S)-ECHB] was synthesized from ECAA to 49.9 g/l with an optical purity of more than 99% e.e. using recombinant Escherichia coli cells coexpressing McFDH-26 and a carbonyl reductase (KaCR1) from Kluyveromyces aestuarii.

Acetates↗

Vertical transmission of Neospora caninum in BALB/c mice in both acute and chronic infection.

To examine the frequency of congenital infection by Neospora caninum, BALB/c mice were inoculated intraperitoneally with tachyzoites of N. caninum either during pregnancy (Group 1) or 4 weeks or more before pregnancy (Group 2). Further, the mice inoculated during pregnancy were bred at 4 weeks or more after delivery to form Group 3. Congenital transmission was observed in 76% of the neonates of the mice in Group 1 and in 50% of the neonates of the mice in Group 2. Interestingly, congenital transmission was observed in 86% of the neonates from Group 3. These results suggest that chronically-infected BALB/c mice efficiently transmit N. caninum infection to their offspring.

Animals↗

Fluorescence detection of a new photosensitizer, PAD-S31, in tumour tissues and its use as a photodynamic treatment for skin tumours in dogs and a cat: a preliminary report.

We describe here the detection by fluorescence of a new photosensitizer, PAD-S31, in tumours in dogs and cats and the effect of photodynamic therapy (PDT) by using PAD-S31 for skin tumours in two dogs and one cat. PAD-S31 is a hydrophilic photosensitizer that has two peaks at absorption wavelengths 406 and 665 nm in distilled water. In a preliminary experiment in mice transplanted with SCCVII and colon 26, PAD-S31 was retained in tumour tissues rather than in other organs. The tumours resected from dogs and cats after intravenous administration of PAD-S31 at a dose of 15 mg/kg emitted strong red fluorescence under light illumination of 402 nm wavelength. Animals given PAD-S31 showed no cutaneous photosensitivity under room light illumination. Irradiation at laser light 670 nm wavelength (fluence rate 150 mW/cm2 and total light dosage 150 J/cm2) on cutaneous mast cell tumours in dogs ( n=2 ) and a cutaneous basal cell tumour in a cat induced complete remission. These results suggest PAD-S31 could be a promising photosensitizer for use in a small animal veterinary practice.

Animals↗

Involvement of MIP-2 and CXCR2 in neutrophil infiltration following injection of late apoptotic cells into the peritoneal cavity.

Apoptotic cells are cleared by phagocytes, such as macrophages, as soon as they appear in vivo. If apoptosis occurs acutely, however, macrophages may be outnumbered by apoptotic cells, which causes late apoptosis. We previously showed that injection of late apoptotic cells into the peritoneal cavity led to transient infiltration of neutrophils. In this study, we examined the involvement of MIP-2 and CXCR2 in the neutrophil infiltration. We first produced a recombinant MIP-2 protein, and a fusion protein between CXCR2 and GST in E. coli, and then generated anti-MIP-2 antibodies and anti-CXCR2 antibodies in rabbits. We then confirmed their specificity by Western blotting analysis and flow cytometry. Injection of late apoptotic cells, such as P388 cells treated with etoposide for 24 hours and CTLL-2 cells cultured in IL-2-free medium for 28 hours, induced neutrophil infiltration into the peritoneal cavity, as expected. The antibodies, but not control antibodies against GST, suppressed the neutrophil infiltration to the level caused by injection of normal (viable) cells, suggesting that MIP-2 and CXCR2 are mainly involved in the neutrophil infiltration caused by late apoptotic cells.

Animals↗

A nationwide survey of deep fungal infections and fungal prophylaxis after hematopoietic stem cell transplantation in Japan.

We conducted a nationwide survey to define incidence of deep fungal infections and fungal prophylaxis practices after HSCT. In all, 63 institutions responded. Total number of in-patient transplantations was 935: 367 autologous, 414 allogeneic myeloablative, and 154 allogeneic reduced-intensity (RIST) (n=154). Number of patients who were cared for in a clean room at transplant was 261 (71%) in autologous, 409 (99%) in conventional and 93 (66%) in RIST, respectively. All patients received prophylactic antifungal agents; 89% fluconazole. Number of patients who received the dosage recommended in the CDC guidelines (400 mg/day) was 135 (42%) in conventional transplant and 34 (30%) in RIST (P=0.037). Number of patients who received fluconazole until engraftment and beyond day 75 in conventional transplant vs RIST was, respectively, 324 (100%) vs 109 (97%), and 39 (12%) vs 18 (16%), with no significant difference between the two groups. A total of 37 patients (4.0%) were diagnosed with deep fungal infections; autologous transplantation (0.03%), conventional transplantation (6.0%) and RIST (7.1%). Wide variations in antifungal prophylaxis practice according to the type of transplant and the institutions, and deep fungal infection remain significant problems in RIST.

Antifungal Agents↗

Two states of the triple helix in the thermal transition of the collagen model peptide (Pro-Pro-Gly)10.

The collagen model peptide (Pro-Pro-Gly)10 is known to fold into a triple helix in solution. So far, the triple helix has been considered to exist as a single state. However, our previous study of (Pro-Pro-Gly)10 in solution has indicated the presence of two different states of the triple helix, a lower (HL) and a higher temperature state (HH). In the present study, these triple-helical states were investigated in more detail by NMR. Complete stereospecific assignments of the methylene protons of the proline residues were accomplished by the use of NOESY and TOCSY spectra. The temperature dependence of the 1H chemical shifts showed that the HL-to-HH thermal transition can be attributed to a conformational change of the first proline (Pro1) residues of the (Pro-Pro-Gly) triplets. Since TOCSY spectra with a 10 ms mixing-time confirmed a down puckering of these Pro residues in the HL state, but interconverting down and up puckerings in the HH state, the HL-to-HH thermal transition corresponds to conformational changes of the pyrrolidine rings of the Pro1 residues from an uniform down puckering to a more flexible state. The results confirm that thermal unfolding of the triple helix proceeds through the intermediate HH state.

Collagen↗

A case of Kawasaki disease associated with syndrome of inappropriate secretion of antidiuretic hormone.

UNLABELLED: Kawasaki disease (KD) is an acute vasculitis of unknown aetiology with varied clinical manifestations. Although coronary arteritis is common in the course of KD, central nervous system involvement is rare. We report a case of KD in an infant who developed convulsions and apnoea during his illness associated with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). CONCLUSION: The possibility of severe hyponatraemia should be anticipated in children with KD. Infants with KD are at risk of SIADH and should be monitored closely for its development.

Humans↗

Japanese multicenter phase II and pharmacokinetic study of rituximab in relapsed or refractory patients with aggressive B-cell lymphoma.

BACKGROUND: To evaluate the efficacy and feasibility of rituximab monotherapy in Japanese patients with relapsed or refractory aggressive B-cell lymphoma. PATIENTS AND METHODS: Sixty-eight patients were treated with rituximab at 375 mg/m(2) by eight consecutive weekly infusions. Pretreatment variables affecting overall response rate (ORR) and progression-free survival (PFS) and the relationship between pharmacokinetic parameters and efficacy were analyzed. RESULTS: The ORRs of 68 enrolled patients and 57 eligible patients were 35% [95% confidence interval (CI) 24% to 48%] and 37% (95% CI 25% to 51%), respectively. Median PFS of 53 evaluable patients was 52 days, whereas time to progression of 21 eligible responders was 245 days. Mild to moderate infusion-related toxicities were observed frequently at the first infusion, but all of them were reversible. Elevated lactate dehydrogenase (LDH) and refractoriness to prior chemotherapy were unfavorable factors affecting ORR and PFS (P <0.01). Serum trough levels of rituximab and area under the concentration-time curve for responders were higher than for non-responders (P <0.05). CONCLUSIONS: Eight consecutive weekly infusions of rituximab have significant anti-lymphoma activity for relapsed or refractory aggressive B-cell lymphoma. Several pretreatment variables and serum rituximab levels are useful for predicting its efficacy.

Adult↗

A novel and effective approach of developing aggressive experimental autoimmune gastritis in neonatal thymectomized BALB/c mouse by polyinosinic:polycytidylic acid.

Neonatal thymectomy induces autoimmune gastritis (AIG) in 40-70% of BALB/c mice. We presumed that induction of autoimmunity by polyinosinic:polycytidylic acid (poly I:C) might allow development of a more aggressive model of AIG. A group of BALB/c mice were thymectomized on day 3 after birth. Neonatal thymectomized mice were either injected with poly I:C or phosphate-buffered saline (PBS). Non thymectomized neonatal BALB/c mice were injected with only poly I:C. All neonatal thymectomized mice injected with poly I:C developed 3 cardinal features of AIG: (1) moderate to severe degree gastritis (2) presence of autoantibody to H(+)/K(+) ATPase and (3) loss of parietal cells. However, only 70% of the PBS-treated neonatal thymectomized BALB/c mice developed some, but not, all features of AIG. A mild degree of AIG was seen in 12 of 31 nonthymectomized BALB/c mice administered with only poly I:C. Administration of poly I:C in neonatal thymectomized BALB/c mice in the first and second week appeared to be the most effective for induction of aggressive AIG. The levels of interleukin (IL)-6, IL-12p70, interferon-gamma and tumour necrosis factor-alpha were significantly higher in poly I:C-injected thymectomized mice compared to PBS-injected neonatal thymectomized mice (P < 0.05). The frequencies of CD4(+)CD25(+) regulatory T cells in the spleen were significantly decreased in neonatal thymectomized mice administered with poly I:C compared to PBS-treated neonatal thymectomized mice (P < 0.01). Taken together, these results suggest that induction of inflammatory cytokines and reduction of regulatory T cells by poly I:C might contribute to the development of an aggressive model of AIG in neonatal thymectomized BALB/c mice.

Animals↗

Comprehensive gene expression analysis of the response to straight-chain alcohols in Saccharomyces cerevisiae using cDNA microarray.

AIMS: The purpose of this study was to examine the gene expression profiles of yeast Saccharomyces cerevisiae subjected to straight-chain alcohols. METHODS AND RESULTS: Lipophilic alcohols with high log Pow values were more toxic to yeast than those with low log Pow values. Morphological changes after exposure to ethanol, 1-pentanol, 1-octanol were observed, whereas n-pentane as a model hydrocarbon affected the surface of the outer membrane, with little change in organelles. Using cDNA microarrays, quite a few up-regulated gene categories were classified into the category 'cell rescue, defence and virulence' by ethanol, and the category 'energy' and 'metabolism' by 1-pentanol. Meanwhile, the characteristic genes up-regulated by n-pentane were not observed, and the expression profile was distantly related to ethanol, 1-pentanol and 1-octanol. CONCLUSIONS: This study suggests that gene expression profiles at the whole genome level were intimately associated with the cell growth inhibition and morphological changes by straight-chain alcohols with differing log Pow values. SIGNIFICANCE AND IMPACT OF THE STUDY: The study of comprehensive gene expression profiles by cDNA microarrays elucidates the straight-chain alcohol adaptation mechanisms.

1-Octanol↗

Implications of plasma concentrations of adiponectin in patients with coronary artery disease.

OBJECTIVE: To investigate whether concentrations of plasma adiponectin constitute a significant coronary risk factor, with particular focus on the relation between plasma concentrations of adiponectin and the development of acute coronary syndrome (ACS). SUBJECTS AND METHODS: Plasma concentrations of adiponectin were measured in 123 patients with coronary artery disease (CAD) and in 17 control participants. Patients were divided into three groups according to condition type: acute myocardial infarction (AMI) group (n = 59), unstable angina pectoris (UAP) group (n = 28), and stable angina pectoris (SAP) group (n = 36). RESULTS: Plasma concentrations of adiponectin correlated negatively with body mass index (r = -0.18, p < 0.05), serum triglyceride (r = -0.25, p < 0.01), and fasting glucose concentrations (r = -0.21, p < 0.05), but correlated positively with age (r = 0.26, p < 0.01), high density lipoprotein cholesterol concentrations (r = 0.35, p < 0.01), and low density lipoprotein particle size (r = 0.37, p < 0.01). Plasma concentrations of adiponectin in patients with ACS, in both the AMI and UAP groups, were significantly lower than those in patients with SAP and in the control group (ACS, 6.5 (3.0) microg/ml; SAP, 11.3 (5.9) micro g/ml; control 12.8 (4.3) microg/ml; p < 0.01). Additionally, plasma concentrations of adiponectin in patients with CAD (7.9 (4.6) microg/ml, p < 0.01) were significantly lower than in the control group. There were, however, no significant differences between patients with SAP and the control group (p = 0.36). Multiple logistic regression analysis showed that smoking, fasting glucose concentration, and low log adiponectin concentration correlated independently with the development of an ACS. CONCLUSIONS: The findings suggest that measurement of plasma concentrations of adiponectin may be of use for assessing the risk of CAD and may be related to the development of ACS.

Adiponectin↗