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Biomedical subjects

R Ando

Publications and source records attributed to R Ando.

At least 37 records · Page 2Linked to original sources

Central bombesin inhibits food intake and the orexigenic effect of neuropeptide Y in the neonatal chick.

It is well known that central injection of bombesin (BN) suppresses feeding in mammalian and avian species, but the anorexigenic effect of central BN are still open with special reference to the chick. The dose response (0, 0.1 and 0.5 microg) of intracerebroventricular (ICV) injection of BN was examined in Experiment 1. ICV injection of BN inhibited food intake in a dose-dependent manner. Experiment 2 was done to determine whether BN interacts with the orexigenic effect of neuropeptide Y (NPY) in the neonatal chick. Central administration of NPY (2.5 microg) greatly enhanced food intake, but co-injection of BN (0.5 microg) suppressed food intake. The dose response of NPY (2.5 microg) co-injected with three levels of BN (0, 0.1 and 0.5 microg) was examined in Experiment 3. ICV injection of BN attenuated the hyperphagia by NPY in a dose-related fashion. It is suggested that central BN may interact with NPY for the regulation of feeding in the neonatal chick.

Animals↗

Central administration of alpha-melanocyte stimulating hormone inhibits fasting- and neuropeptide Y-induced feeding in neonatal chicks.

In the present study, the effect of intracerebroventricular (i.c.v.) administration of alpha-melanocyte stimulating hormone (alpha-MSH) on food intake of neonatal chicks was examined. In experiment 1, i.c. v. injection of alpha-MSH (0.04, 0.2 and 1 microg) significantly inhibited food intake of 3-h fasted chicks in a dose-dependent manner. In experiment 2, alpha-MSH strongly inhibited neuropeptide Y-induced feeding when neuropeptide Y (2.5 microg) and several doses of alpha-MSH were given simultaneously i.c.v. These results suggest that alpha-MSH plays an important role in the regulation of food intake of neonatal chicks.

Animals↗

Brain-derived mast cells could mediate histamine-induced inhibition of food intake in neonatal chicks.

In the present study, the effect of intracerebroventricular (i.c.v.) administration of histamine on food intake of neonatal chicks was examined over 2 h. Histamine (100, 200 or 400 nmol, respectively) was injected in the lateral ventricle of 2-day-old chicks, and cumulative food intakes were measured. i.c.v. injection of histamine significantly inhibited food intake in a dose-dependent manner. In addition, compound 48/80, which causes degranulation of mast cells and release of histamine, or thioperamide, which is an antagonist of the histamine H3 autoreceptor and increases histamine release from histaminergic nerve terminals, was injected i.c.v. to clarify whether mast cell- or neuron-derived histamine in the central nervous system of chicks is essential to the feeding inhibition. Central administration of compound 48/80 inhibited food intake with a dose-dependent manner, but thioperamide had no effect on feeding. An inhibitor of mast cell degranulation, sodium cromoglycate, somewhat attenuated food intake inhibited by compound 48/80. These results suggest that brain-derived mast cells could be a major source of histamine in the inhibition of food intake of neonatal chicks.

Animals↗

Intracerebroventricular injection of mammalian motilin, melanin-concentrating hormone or galanin does not stimulate food intake in neonatal chicks.

1. Several neural peptides are known to stimulate feeding behaviour in mammalian species. The aim of this study was to elucidate whether central injection of mammalian motilin, melanin-concentrating hormone (MCH) or galanin stimulates feeding in the neonatal chick. 2. None of the peptides applied here enhanced the food intake of the chick. 3. It is suggested that motilin, MCH and galanin, at least those of mammalian origin, may not regulate feeding in neonatal chicks, when administered to the central nervous system.

Animals↗

Central gastrin inhibits feeding behavior and food passage in neonatal chicks.

The gastrin/cholecystokinin (CCK) family is recognized as the principal family of hormones involved in regulation of the gastrointestinal tract CCK is recognized as a satiety hormone in mammalian species, but it has been suggested that gastrin rather CCK may have an important role in controlling feeding behavior in the neonatal chick through a poorly developed blood brain barrier. So far, however, there is no direct evidence that central gastrin inhibits food intake in neonatal chicks. The aim of this study was to elucidate whether central administration of gastrin 1) inhibits feeding behavior and 2) alters food passage from the crop. The effects of central administration of gastrin on food intake were investigated in experiment 1. Birds (2-day-old) were food-deprived for 3 h and then gastrin or saline was injected intracerebroventricularly. Gastrin strongly inhibited food intake in a dose-dependent fashion for 2 h. Thereafter, the effects of central gastrin on feeding behavior and serum corticosterone concentration were examined in experiment 2. Following central administration of gastrin, food intake was depressed and pecking behavior was inhibited. Serum corticosterone concentration was not altered by central administration of gastrin. The influence of central gastrin on food passage from the crop was investigated in experiment 3. Central administration of gastrin clearly delayed food passage. In conclusion, central gastrin appears to have a strong effect for the satiety and gastrointestinal motility in the neonatal chick.

Animals↗

Spinal actions of GR73632, a novel tachykinin NK1 receptor agonist.

Behavioral characterization of GR73632, a newly synthesized tachykinin NK1 receptor agonist, was examined in mice. Intrathecal (IT) injection of GR73632 in the spinal subarachnoid space of mice elicited a dose-dependent behavioral syndrome, consisting of scratching, biting and licking. The time course of the response to GR73632 was almost similar to that of substance P. GR73632 evoked much more licking and biting than did substance P, that in turn caused less scratching. GR73632 was approximately 200-fold more potent than substance P in inducing the characteristic behavioral response. The GR73632-induced behavioral response was inhibited by IT co-administration of CP-96,345, a non-peptide NK1 receptor antagonist, but not its inactive enantiomer CP-96,344. CP-96,345, co-injected IT with substance P, also inhibited the behavioral response to substance P. These results demonstrate that the scratching, biting and licking response induced by IT GR73632 may be mediated by the NK1 receptor in the spinal cord. These findings suggest that GR73632 may be useful as a tachykinin NK1 receptor agonist and also for evaluating spinal pharmacological activities of NK1 receptor antagonists.

Animals↗

Cyclopropenone-containing cysteine proteinase inhibitors. Synthesis and enzyme inhibitory activities.

By focusing on the amphiphilic properties of cyclopropenone (e.g. a good electrophile and a precursor for a stable 2pi-aromatic hydroxycyclopropenium cation), a new class of cysteine proteinase inhibitors containing a cyclopropenone moiety was designed. For the purpose of the present research, we needed to devise a new method to introduce a peptide-related moiety as a substituent on the cyclopropenone residue. We investigated the reaction of metalated cyclopropenone acetal derivatives (2, R2 = metal) with N-protected alpha-aminoaldehydes 4 to obtain the adduct 5, and succeeded in the preparation of highly potentiated cysteine proteinase inhibitors 8 after several steps transformations. They showed strong inhibitory activities only to cysteine proteinases such as calpain, papain, cathepsin B, and cathepsin L and not to serine (e.g. thrombin and cathepsin G) and aspartic proteinases (e.g. cathepsin D). Kinetic studies indicated that they are competitive inhibitors, and by the examinations of their inhibitory mechanism it became clear that they are reversible inhibitors.

Calpain↗

Intracerebroventricular injection of orexins does not stimulate food intake in neonatal chicks.

1. Recently, 2 novel neuropeptides were discovered, both derived from the same precursor by proteolytic processing, which bind and activate 2 closely related orphan G protein-coupled receptors, Named orexin-A and -B (Sakurai et al., 1998). Both stimulate food intake when administered centrally to rats. 2. Our aim was to elucidate whether central injection of mammalian orexin-A or -B stimulates food intake in the chick. 3. Under conditions of free access to food, orexin-A did not alter the food intake of chicks, but cumulative food intake was significantly suppressed by orexin-B. 4. The orexin-B was then administered to chicks deprived of food for 3 h to confirm its suppressive effect. No significant effect of orexin-B on food intake was detected. 5. Central injection of orexin-B did not modify food intake when appetite was stimulated by fasting. 6. Neither of these orexins appears to stimulate feeding in chicks.

Animals↗

Pentanucleotide repeat and size polymorphisms in the apolipoprotein(a) gene are associated with the lipoprotein(a) concentration in chronic hemodialysis patients.

The elevation of serum or plasma lipoprotein(a) [Lp(a)] levels is regarded as an independent risk factor for cardiovascular disease, and many previous reports demonstrated that Lp(a) levels in hemodialysis patients were significantly higher than in controls. The purpose of this study was to investigate the effect of a pentanucleotide repeat polymorphism [(TTTTA)n] in the 5'-flanking region of the apolipoprotein(a) [apo(a)] gene and of a size polymorphism of apo(a) for elevated Lp(a) concentrations observed in chronic hemodialysis patients. We studied 172 patients on chronic hemodialysis and 199 healthy adults. For analysis of the pentanucleotide repeat polymorphism, polymerase chain reaction products were loaded on polyacrylamide gel for electrophoresis. apo(a) size phenotyping was performed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. The median level of Lp(a) in the patients was 14.2 mg/dl which was significantly higher than that in controls (12.0 mg/dl; p < 0.05). In the genotype of (TTTTA)8/8, the median Lp(a) level in the patients (15.9 mg/dl) was significantly higher than that in controls (13.0 mg/dl; p < 0.05). In the genotype of (TTTTA)8/8 with large-sized apo(a) isoforms (A16-A25), the patients had significantly higher Lp(a) levels than the controls (p < 0.05). In conclusion, increased Lp(a) levels in chronic hemodialysis patients were mainly attributed to the combination of eight repeats of the pentanucleotide polymorphism and large-sized isoforms of apo(a).

Apolipoproteins A↗

Controlled trial of falecalcitriol versus alfacalcidol in suppression of parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism.

Active vitamin D3 is extensively used for the treatment of secondary hyperparathyroidism in hemodialysis patients. But it is often impossible to administer enough dose to suppress parathyroid hormone (PTH) level, because of hypercalcemia and hyperphosphatemia. New modalities with higher specificity for PTH suppression are desirable. We conducted a crossover comparative study of falecalcitriol, an active vitamin D3 analog, and alfacalcidol (1alpha[OH]D3). In this study, 25 hemodialysis patients with moderate to severe secondary hyperparathyroidism who had normal serum calcium levels were enrolled. They received daily oral doses of alfacalcidol during an 8-week observation period. Based on serum calcium levels and intact PTH, the subjects were allocated into two groups, and a comparative study was conducted using unmasked crossover design of two drugs x two periods. The dosage of both drugs was adjusted to maintain the initial serum calcium levels, and the relative change (%change) of serum biochemical parameters were compared. Comparison of two drugs in period 1 was taken as primary efficacy evaluation. Reproducibility of drug action was confirmed by comparing the effect of falecalcitriol between period 1 and 2. The percent change of PTH of falecalcitriol was lower than that of alfacalcidol: Those were, respectively, -7.89% and +30.42% for c-terminal PTH (P = 0.022), -4.39% and +38.88% for i-PTH (P = 0.077), and +3.68% and +30.52% for midregion PTH (P = 0.099). The similar changes were observed in the falecalcitriol group during period 2, confirming the reproducibility. Falecalcitriol was found to be superior to alfacalcidol in suppression of PTH levels in patients with moderate to severe secondary hyperparathyroidism when it is administered in equivalent doses that might maintain similar serum calcium levels.

Adult↗

Extended HLA haplotypes in Japanese homozygous typing cells.

We have defined extended HLA haplotypes including the HLA class II genes, the non-HLA genes such as TAP1, TAP2 and LMP2, and the (CTG)n microsatellite repeats within the NOTCH4 gene between DRA and 21OH in 33 Japanese HLA homozygous typing cells (HTC). These conserved haplotypes characterized by unique linkage might be maintained as a result of functional co-operation among them in the antigen presentation pathway. These HTCs can be served as an original and ethnic-specific standard panel, providing useful genetic markers in haplotypic diversity, disease association, and anthropology studies.

HLA Antigens↗

[Vocalization response used for evaluation of pain-related behavior in guinea pigs].

In general, pain has been defined as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage", and hence pain is a subjective and emotional experience for each individual. For this reason, it is difficult to study pain in nonverbal animals. However, painful stimuli (noxious stimuli) can cause both a simple and an overt emotional behavior such as self-defense reaction and vocalization in animals. Therefore, we are able to measure these behaviors as nonverbal communication of pain. The vocalization responses is the natural nociceptive reaction of conscious animals and prelingual children. In the present overview, we described the methodology for objective assessment of guinea pig's vocalization response to arterial algogenics and its characteristics.

Animals↗

Dihydropyridine type calcium channel blocker-induced turbid dialysate in patients undergoing peritoneal dialysis.

We previously reported that manidipine, a new dihydropyridine type calcium channel blocker, produced chylous peritoneal dialysate being visually indistinguishable from infective peritonitis in 5 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) [Yoshimoto et al. 1993]. To study whether such an adverse drug reaction would also be elicited by other commonly prescribed calcium channel blockers in CAPD patients, we have conducted postal inquiry to 15 collaborating hospitals and an institutional survey in International Medical Center of Japan as to the possible occurrence of calcium channel blocker-associated non-infective, turbid peritoneal dialysate in CAPD patients. Our diagnostic criteria for drug-induced turbidity of dialysate as a) it developed within 48 h after the administration of a newly introduced calcium channel blocker to the therapeutic regimen, b) absence of clinical symptoms of peritoneal inflammation (i.e., pyrexia, abdominal pain, nausea or vomiting), c) the fluid containing normal leukocyte counts and being negative for bacterial and fungal culture of the fluid, and d) it disappeared shortly after the withdrawal of the assumed causative agent. Results showed that 19 out of 251 CAPD patients given one of the calcium channel blockers developed non-infective turbid peritoneal dialysis that fulfilled all the above criteria. Four calcium channel blockers were suspected to be associated with the events: benidipine [2 out of 2 (100%) patients given the drug], manidipine [15 out of 36 (42%) patients], nisoldipine [1 out of 11 (9%) patients] and nifedipine [1 out of 159 (0.6%)] in descending order of frequency. None of the patients who received nicardipine, nilvadipine, nitrendipine, barnidipine and diltiazem (25, 7, 2, 1 and 8 patients, respectively) exhibited turbid dialysate. In conclusion, we consider that certain dihydropyridine type calcium channel blockers would cause turbid peritoneal dialysate being similar to that observed in patients developing infective peritonitis. To avoid unnecessary antibiotic therapy the possibility of this adverse reaction should be ruled out whenever a CAPD patient receiving a dihydropyridine type calcium channel blocker develops turbid dialysate.

Calcium Channel Blockers↗

[Current status of cancer pain control in home hospice care--assessment by family members].

To improve the quality of life of terminally ill cancer patients, we care for them in the home whenever possible, making use of home parenteral nutrition (HPN) and continuous intravenous infusion of morphine. The purpose of this study was to assess the current status of and problems associated with our home hospice care program, with emphasis placed on the effectiveness of cancer pain control as viewed by the family of the patient. A questionnaire was sent to six families of patients who died at home. The members of each family were divided into two groups (spouse group or non-spouse group) and evaluated for their reaction to the patient's suffering. It was found that the two groups displayed a different reaction to the patient's suffering. The difference may have derived from the different mixture of objectivity and affection in each group. Therefore, we believe it is necessary to provide emotional support to each group based on this point of view. All respondents expressed a desire to receive home hospice care if they themselves were afflicted with end-stage cancer. This result showed that overall our home hospice care was successful. We intend to proceed with our program to provide patients and their families with more comfortable care, paying due regard to the difference in the reaction of family members to the patient's suffering depending on their relation to patient.

Aged↗

HLA-DRB4 genotyping by PCR-RFLP: diversity in the associations between HLA-DRB4 and DRB1 alleles.

The serologically defined HLA-DR53 antigen is associated with HLA-DR4, -DR7, and -DR9 antigens, and these haplotypes contain two functional genes, DRB1 and DRB4, and two pseudogenes, DRB7 and DRB8. The DRB4 gene encodes the DR53 antigen, and has been officially recognized to contain three allelic variants (DRB4*0101, 0102, and 0103). In this study, we have established the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for DRB4 genotyping and analyzed genetic polymorphism of the DRB4 gene in Japanese population. DRB4*0101, DRB4*0102, and DRB4*0103 could be observed at the frequencies of 0.5%, 1.1% and 32.7%, respectively. The same DRB1 allele does not necessarily share an identical DRB4 allele. Further, a tight linkage disequilibrium was found between DRB4*0102 and DRB1*0401 in Japanese population, whereas DRB1*0401 was associated with DRB4*0101 or *0103 in Caucasian population. These findings reveal extensive diversity of the HLA-DRB1 and -DRB4 haplotypes and may have important implications for HLA-disease associations and donor selection in unrelated transplantation.

Alleles↗

Response of fibrinolytic proteins and endothelin 1 to venous occlusion in patients on chronic hemodialysis.

The main purpose of the present study was to determine whether any abnormalities in the response of fibrinolytic activity to venous occlusion could be observed in patients undergoing chronic hemodialysis (HD patients). A 10-min venous occlusion test was performed in 13 HD patients and in 9 healthy subjects. The arm opposite to the arteriovenous fistula was occluded in HD patients. The following factors were measured: tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), plasmin-alpha2-plasmin inhibitor complex (PIC), stabilized fibrin degradation product (D-dimer), and von Willebrand factor antigen determined by enzyme immunoassay, and endothelin 1 by radioimmunoassay with two antibodies. Preocclusion levels of PIC, D-dimer, von Willebrand factor, and endothelin 1 were significantly higher and those of t-PA significantly lower in HD patients than in controls. During the occlusion, there was a positive correlation between the percent changes in t-PA and von Willebrand factor and between those in von Willebrand factor and PIC. There was no correlation between percent and absolute changes during the occlusion in endothelin 1 and those in t-PA, PAI-1, PIC, D-dimer, or von Willebrand factor. There was no significant difference between HD patients and controls as to the percent changes in hematocrit, t-PA, PIC, D-dimer and von Willebrand factor. HD patients demonstrated a significantly greater percent change in PAI-1 than controls. The mechanism by which endothelin 1 is released in response to the occlusion appears to differ from that for t-PA, PAI-1, and von Willebrand factor. PAI-1 may be readily released in response to stimuli to blood vessels in HD patients.

Blood Vessels↗

Is the bone mass of hemodialysis patients genetically determined?

Polymorphism of the vitamin D receptor gene (VDR) has been linked to bone mineral density in twins, postmenopausal osteoporosis, and premenopausal woman. We examined the possibility that the bone mass in hemodialysis (HD) patients might be determined by VDR. The study consisted of 229 HD patients with a mean age of 53.3 years (range 21 to 83), who were dialyzed three times a week for an average of 8.65 (range 0.2 to 24) years. We determined their VDR using DNA of peripheral white blood cells by restriction enzyme BsmI and the polymerase chain reaction-restriction fragment length polymorphism method. Bone mineral content (BMC) was estimated at 1/3 of the radius using dual energy X-ray bone absorptiometry, and expressed in z-scores standardized by gender and age. Distributions of VDR in this hemodialysis population were BB (9.9%), Bb (13.1%), and bb (77.0%), showing no significant different from those in 105 healthy volunteers (BB, 7.6%; Bb, 13.3%; and bb, 79.0%). Multiple regression analysis revealed that gender, age, duration on HD, and serum osteocalcin are major determinants of BMC (r = 0.762, P < 0.001), while VDR and serum parathyroid hormone are not. In a subgroup with younger (< 65 years) patients dialyzed for less than 8.65 years, the z-score of BMC of patients with BB allele was less than those with Bb and bb allele (N = 77, P = 0.020). We conclude that vitamin D receptor polymorphism is not one of the main determinants of BMC of HD patients, though it might partially effect bone mass in a subgroup of younger HD patients with shorter HD histories. Further studies with longitudinal observation will be needed to confirm these possibilities.

Adult↗

Fibrinogen, coagulation factor VII, tissue plasminogen activator, plasminogen activator inhibitor-1, and lipid as cardiovascular risk factors in chronic hemodialysis and continuous ambulatory peritoneal dialysis patients.

Mortality rates associated with cardiovascular disease (CVD) are high in long-term dialysis patients. Increased levels of plasma fibrinogen (FBG), coagulation factor VII (FVII), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) as well as hyperlipidemia are regarded as important risk factors for CVD. To investigate whether there are differences in the risk of CVD between chronic hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients, serum lipid levels and plasma FBG, FVII, t-PA, and PAI-1 levels were measured in 17 patients on HD and 17 patients on CAPD. FBG was measured by the thrombin time method, FVII activity (FVIIc) by the chromogenic prothrombin time method, and t-PA and PAI-1 activity by the chromogenic substrate assay. No difference was found in body mass index (BMI) between HD and CAPD patients. Total cholesterol (TC), TC/high-density lipoprotein (HDL)-C ratio, low-density lipoprotein (LDL)-C, and triglycerides (TG) were significantly increased, and HDL-C was significantly decreased in CAPD patients compared with HD patients. FBG and FVIIc were significantly elevated in CAPD patients compared with controls or HD patients. T-PA activities were significantly higher in HD and CAPD patients than in controls. CAPD patients showed significantly higher PAI-1 activities than controls or HD patients. Significant positive correlations were found between FBG or FVIIc and TC, between FBG and LDL-C or TG, and between FVIIc and LDL-C in these patients. T-PA showed significant negative correlations with FBG, PAI-1, TC, LDL-C, and TG. There was a significant positive correlation between PAI-1 and TG and a significant negative correlation between PAI-1 and HDL-C. We conclude that CAPD patients may have a greater risk of CVD than do HD patients, and that coagulation and fibrinolytic activity are correlated with lipid disorders in these patients.

Adult↗