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Biomedical subjects

Shin Saito

Publications and source records attributed to Shin Saito.

At least 19 recordsLinked to original sources

Progress report on The Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study: status at February 2004.

The Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) Study is the first large-scale intervention trial in Japan using a PROBE design to determine an optimal target blood pressure (BP) level on the basis of self-measured BP at home and optimal initial antihypertensive medication. The registered patients are randomized to one of two different BP levels and to initial antihypertensive regimens (i.e., calcium antagonist [Ca-A], angiotensin-converting enzyme inhibitor [ACE-I], or angiotensin II receptor antagonist [ARB]). At the end of February 2004, 2729, 1687, and 971 patients were recruited, randomized, and followed-up for 12 months or more. Among the 971 patients, mean systolic/diastolic BP levels at randomization in the Ca-A, ACE-I, and ARB groups were 150/90, 152/89, and 151/89 mmHg, respectively. These values reduced after six months of Ca-A-, ACE-I-, and ARB-based treatment (133/81 mmHg, 135/80 mmHg, and 134/79 mmHg, respectively) and further reduced after 12 months (131/80 mmHg, 134/79 mmHg, and 132/79 mmHg, respectively) without any significant differences among groups. In more intensive and less intensive BP-lowering groups, mean systolic/diastolic BP levels at randomization were 151/90 and 150/89 mmHg, respectively. Although BP levels reduced after 6-month (135/80 mmHg and 133/80 mmHg, respectively) and 12-month treatment (133/79 mmHg and 132/80 mmHg, respectively) in each target group, no significant difference in BP values was observed between groups. These results indicate the necessity of additional interventional strategies to improve the achievement of target BP levels, especially in the more intensive BP-lowering group.

Aged↗

Multiple primer extension by DNA polymerase on a novel plastic DNA array coated with a biocompatible polymer.

DNA microarrays are routinely used to monitor gene expression profiling and single nucleotide polymorphisms (SNPs). However, for practically useful high performance, the detection sensitivity is still not adequate, leaving low expression genes undetected. To resolve this issue, we have developed a new plastic S-BIO PrimeSurface with a biocompatible polymer; its surface chemistry offers an extraordinarily stable thermal property for a lack of pre-activated glass slide surface. The oligonucleotides immobilized on this substrate are robust in boiling water and show no significant loss of hybridization activity during dissociation treatment. This allowed us to hybridize the templates, extend the 3' end of the immobilized DNA primers on the S-Bio by DNA polymerase using deoxynucleotidyl triphosphates (dNTP) as extender units, release the templates by denaturalization and use the same templates for a second round of reactions similar to that of the PCR method. By repeating this cycle, the picomolar concentration range of the template oligonucleotide can be detected as stable signals via the incorporation of labeled dUTP into primers. This method of Multiple Primer EXtension (MPEX) could be further extended as an alternative route for producing DNA microarrays for SNP analyses via simple template preparation such as reverse transcript cDNA or restriction enzyme treatment of genome DNA.

DNA Primers↗

ICV melatonin reduces acute stress responses in neonatal chicks.

Melatonin is involved in a variety of biological functions including sleep and stress. Our previous study indicated that neonatal layer chicks were more susceptible to stress than broilers. However, it is not clear whether differences exist in melatonin concentrations between both types of chickens, nor is it known whether melatonin is directly involved in stress in neonatal chickens. In the present study we first compared melatonin concentrations in brain tissues (pineal gland, brain stem, telencephalon, and optic lobe) between neonatal broiler and layer chicks raised under either 12 h light:12 h dark cycle (lights on at 07:00 h) or continuous illumination. Although melatonin concentrations were much higher in broilers than layers at night under the alternative light-dark cycle, these differences disappeared under the 24 h illumination. We thus chose neonatal layers for a test system. We then investigated if intracerebroventricular (ICV) injection of melatonin modulated plasma corticosterone concentrations under continuous illumination. Neonatal layer chicks housed in groups were ICV injected (1) with melatonin (0, 0.116 and 1.16 microg) or with nothing as an intact control followed by isolation in an open-field environment for 10 min; and (2) were given one of the followings treatments: nothing (intact control), control (0 microg), corticotropin-releasing factor (CRF) (0.01 microg), melatonin (1.16 microg), or CRF (0.01 microg) + melatonin (1.16 microg). Ten minutes thereafter blood was collected via heart puncture to determine plasma corticosterone content. Isolation resulted in a significant increase in corticosterone concentration, and both doses of ICV melatonin completely suppressed this increase (P<0.01). CRF injection resulted in a strong increase in plasma corticosterone concentrations (P<0.01). Co-injection with melatonin attenuated the CRF-induced corticosterone elevation in plasma (P<0.01). Our findings provide direct evidence that melatonin modulates the activity of the hypothalamo-pituitary-adrenal axis in chicks.

Analysis of Variance↗

ICV CRF and isolation stress differentially enhance plasma corticosterone concentrations in layer- and meat-type neonatal chicks.

The present study compared the plasma corticosterone concentrations between meat- and layer-type neonatal chicks (Gallus gallus) (1) exposed to isolation-induced stress or (2) injected intracerebroventricularly (ICV) with corticotropin-releasing factor (CRF). Both types of neonatal chicks housed in groups were individually introduced to an open field arena and locomotion and distress-induced vocalizations were monitored for 10 min. The responses of the two strains were remarkably different, with meat-type chicks being less active than layer-type chicks. Distress-induced vocalizations were drastically decreased over time in meat-type chicks while they remained high in layer-type chicks throughout the test. Plasma corticosterone concentrations measured at the end of the test were significantly higher in layer-type chicks than in meat-type ones. Plasma corticosterone concentrations measured 10 min after the ICV injection of CRF were significantly higher in layer- than meat-type chicks. These results indicate that meat-type chicks have either a greater capability to acclimatize to novel environments, or a blunted HPA axis compared with layer-type chicks.

Animals↗

Central administration of phosphatidylserine attenuates isolation stress-induced behavior in chicks.

The present study investigated whether centrally administered phosphatidylserine (PS) could modify the behavior of chicks under isolation-induced stress. Isolation stress-induced vocalization and spontaneous activity for 10 min, which were attenuated by intracerebroventricular (i.c.v.) injection of PS. The effect of PS was compared with other phospholipids or L-serine, a constituent of PS. Phosphatidylcholine (PC) had no effect on these behavior, but phosphatidylethanolamine (PE) significantly increased vocalizations and spontaneous activity compared with PS. L-Serine similarly decreased isolation-induced vocalizations and spontaneous activity. To clarify the mechanism by which central PS attenuates isolation-induced stress behavior, the contribution of the acetylcholine (ACh) receptor (AChR) was also investigated. PS was co-injected i.c.v. with the muscarinic AChR (M-AChR) antagonist scopolamine or the nicotinic AChR (N-AChR) antagonist hexamethonium. The suppression of vocalizations and spontaneous activity by PS was partially attenuated by scopolamine, but not hexamethonium. These findings indicate that isolation-induced stress behavior are attenuated by PS, acting partially through the M-AChR.

Animals↗

Ambulatory blood pressure and 10-year risk of cardiovascular and noncardiovascular mortality: the Ohasama study.

The objective of this study was to elucidate the long-term prognostic significance of ambulatory blood pressure. Ambulatory and casual blood pressure values were obtained from 1332 subjects (872 women and 460 men) aged >or=40 years from the general population of a rural Japanese community. Survival was then followed for 14 370 patient years and analyzed by a Cox hazard model adjusted for possible confounding factors. There were 72 cardiovascular deaths during the 10.8-year follow-up. The relationship between 24-hour systolic blood pressure and the cardiovascular mortality risk was U-shaped in the first 5 years, then changed to J-shaped over the rest of the 10.8-year follow-up. After censoring the first 2 years of data, the risk flattened until it again increased for the fifth quintile of 24-hour systolic blood pressure for the 10.8-year follow-up period. For 24-hour diastolic blood pressure, the J-shaped relationship remained unchanged, regardless of follow-up duration and censoring. Ambulatory systolic blood pressure values consistently showed stronger predictive power for cardiovascular mortality risk than did casual systolic blood pressure in the 10.8-year follow-up data, whereas such relationships became more marked after censoring the first 2 years. When nighttime and daytime systolic blood pressure values were simultaneously included in the same Cox model, only nighttime blood pressure significantly predicted the cardiovascular mortality risk for the 10.8-year follow-up data. We conclude that the relationship between ambulatory systolic blood pressure and cardiovascular mortality is not U-shaped or J-shaped, and that nighttime blood pressure has better prognostic value than daytime blood pressure.

Aged↗

Anorexigenic effects of pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide in the chick brain are mediated by corticotrophin-releasing factor.

Intracerebroventricular (ICV) injection of pituitary adenylate cyclase-activating polypeptide-38 (PACAP) or vasoactive intestinal peptide (VIP) inhibits feeding in chicks. However, the underlying anorexigenic mechanism(s) has not yet been investigated. The present study investigated whether these peptides influence the activity of corticotrophin-releasing factor (CRF) neural pathways in the brain of chicks. Firstly, we found that ICV injections of PACAP and VIP increased plasma corticosterone concentrations. The corticosterone-releasing effect of PACAP was completely attenuated by co-injection of astressin, a CRF receptor antagonist, but this effect was only partial for VIP. These results demonstrated that CRF neurons mediate the actions of PACAP and, to a lesser extent, VIP, and suggest that the signaling mechanisms differ between the two peptides. This difference may arise from the two peptides interacting with different receptors because the corticosterone-releasing effect of PACAP, but not VIP, was completely attenuated by co-injection of PACAP (6-38), a PACAP receptor antagonist. Finally, we examined the effect of ICV co-injection of astressin on the anorexigenic effects of PACAP and VIP and found that the effects of both peptides were attenuated by astressin. Overall, the present study suggests that the anorexigenic effects of PACAP and VIP are mediated by the activation of CRF neurons.

Animals↗

Comparison of brain arginine-vasotocin and corticotrophin-releasing factor for physiological responses in chicks.

Arginine-vasotocin (AVT), a non-mammalian homologue of mammalian arginine-vasopressin, is a stress-related peptide in the brain of birds. The aim of the present study was to determine the effects of intracerebroventricular (ICV) injection of AVT on feeding behavior, body temperature, corticosterone release and several behavioral parameters in chicks. These effects were compared with those of corticotrophin-releasing factor (CRF), another stress-related peptide. The ICV injection of AVT inhibited feeding behavior, increased rectal temperature, and increased plasma corticosterone concentrations, but these effects were weaker than those of CRF. AVT induced hypoactivity as evidenced by decreased vocalization and stepping while CRF induced hyperactivity. The present results demonstrate that some functions of brain AVT are similar to those of CRF, although these effects are weaker than those induced by CRF. However, some AVT-induced behaviors were different from CRF, indicating that the physiological roles of AVT in the regulation of stress behavior are different from those of CRF in chicks.

Animals↗

Effect of central administration of prolactin-releasing peptide on feeding in chicks.

Prolactin-releasing peptide (PrRP) is one of the inhibitory factors in feeding regulation of mammals. However, no information is available for avian species. The present study was done to clarify the effect of intracerebroventricular (ICV) injection of PrRP on feeding in chicks. Firstly, we found that ICV injection of PrRP (94-1500 pmol) significantly increased food intake in chicks. The result was completely different from those obtained in mammals. The orexigenic effect of PrRP was significantly weaker than that of neuropeptide Y (NPY), a potent orexigenic peptide, on an equimolar basis. The orexigenic effect of NPY was further enhanced with coinjection of PrRP. These results suggest the existence of a novel orexigenic mechanism in the chick brain, which might differ from NPY-involved feeding regulatory pathway. In addition, ICV injection of PrRP significantly decreased the rectal temperature, but the effect was weaker than that of NPY, suggesting that PrRP may inhibit energy expenditure in chicks. Taken together, we showed here that PrRP may be involved in the regulation of both feeding behavior and energy metabolism in the chick brain.

Animals↗

Evaluation of calcaneal malposition by magnetic resonance imaging in the infantile clubfoot.

Magnetic resonance imaging (MRI) can clearly visualize both the ossification centers and surrounding cartilage of growing bones and enable a three-dimensional analysis of their positional relationships by using overlapping images. The calcaneal position was evaluated based on five newly proposed parameters of magnetic resonance images in 30 clubfeet of 18 infants with the bimalleolar and lower leg axes as reference lines. Sixteen unaffected feet in the unilateral cases were analyzed as normal feet. MRI showed that the calcaneus in clubfoot rotated internally, medially and posteriorly with reference to the bimallelar axis and that it took an equinus and a varus position with reference to the lower leg axis as compared with the normal foot. These five parameters and their normal values on the calcaneal position should be useful for the evaluation of infantile clubfeet.

Calcaneus↗

The second progress report on the Hypertension Objective treatment based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study.

BACKGROUND: The Hypertension Objective treatment based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study is a large-scale intervention trial to determine both optimal target blood pressure (BP) on the basis of self-measured BP at home, and optimal initial antihypertensive medication. OBJECTIVE: To investigate the quality of randomization at the end of March 2003, and BP-controlled conditions during initial 6 months. METHODS: We evaluated the number of patients randomized by the end of March 2003, and BP changes during the initial 6 months based on intention-to-treat analysis. RESULTS: By the end of March 2003, a total of 1086 patients (12% of a planned randomization of 9000 patients) had been randomized. Among 653 patients who had been followed for > or =6 months after randomization, mean systolic/diastolic BPs at randomization in the calcium antagonist, angiotensin-converting enzyme and angiotensin II receptor blocker groups were 149/89, 150/89 and 149/88 mmHg, respectively. Blood pressures were reduced after 3 months (137/83, 139/82 and 136/82 mmHg, respectively), and further reduced after 6 months (134/81, 135/80 and 133/80 mmHg, respectively), with no significant differences identified between groups. In more- and less-intensive BP-lowering groups, mean systolic/diastolic BPs at randomization were 149/88 and 150/89 mmHg, respectively. Although BPs were reduced after treatment for 3 months (137/83 and 137/82 mmHg, respectively) and 6 months (134/80 and 135/80 mmHg, respectively) in each target group, significant differences were still not observed between groups. CONCLUSIONS: Good quality of randomization was observed at the end of March 2003, but rate of achievement for target BPs was insufficient.

Angiotensin II Type 1 Receptor Blockers↗

Prediction of ischaemic and haemorrhagic stroke by self-measured blood pressure at home: the Ohasama study.

OBJECTIVE: To examine the predictive value of self-measured blood pressure values taken at home (home blood pressure) for risk of stroke and subtypes. METHODS: We obtained home blood pressure measurements from 1702 people, aged > or =40 years, without a history of stroke, in the general population in Japan, and continued follow-up after a mean period of 10.6 years. The prognostic significance of blood pressure for stroke risk was examined using the Cox proportional hazards regression model, which was adjusted for possible confounding factors. RESULTS: There was a linear relationship between home blood pressure and risk of stroke and subtypes. On average, each 10/5 mmHg elevation in home systolic/diastolic blood pressure respectively, was associated with an approximately 30/20% respectively, higher risk of total stroke. A similar relationship was observed for the risk of haemorrhagic stroke (intracerebral and subarachnoid haemorrhage), and the risk of ischaemic stroke [cerebral infarction and transient ischaemic attack (TIA)]. The risk of stroke and subtypes showed a significantly greater relation with home blood pressure values compared to conventional blood pressure values. CONCLUSIONS: This is the first study to demonstrate that home blood pressure is an independent predictor for haemorrhagic and ischaemic stroke, in the general population.

Adult↗

[A case of type 4 gastric cancer with peritoneal dissemination successfully treated over 2 years by alternate-day administration of TS-1].

We report a patient with unresectable advanced gastric cancer who has been being treated by TS-1 administration on alternate days for 2 years. The patient was a 50-year-old female with type 4 gastric cancer accompanied by Schnitzler metastasis and pleural effusion. TS-1 administration was initiated at a daily dose of 100 mg with a schedule of 4-week administration and 2-week suspension. However, grade 2 hepatic dysfunction and leukocytopenia developed. When the daily TS-1 administration was changed to alternate-day administration at the same dose, no side effects were observed, allowing the continuation of treatment. She has maintained a minor response (MR)-no change (NC) for 1 year and 5 months, and is still symptom-free and being treated on an outpatient basis at present, 2 years after treatment. TS-1 is an anti-cancer drug that plays a central role in chemotherapy for gastric cancer. However, in some patients, side effects sometimes develop using the routine administration method, making continuation of administration difficult. Alternate-day TS-1 administration has great potential as a protocol that produces long-term anti-tumor effects while reducing side effects.

Adenocarcinoma↗

Pituitary adenylate cyclase activating polypeptide and vasoactive intestinal peptide inhibit feeding in the chick brain by different mechanisms.

Intracerebroventricular (ICV) injections of pituitary adenylate cyclase-activating polypeptide-38 (PACAP) and vasoactive intestinal peptide (VIP) inhibit feeding in chicks. However, the precise anorexigenic mechanisms have not been investigated, since both peptides activate the VPAC receptor in mammals. We investigated which receptor mediates the anorexigenic effects of these peptides in chicks. ICV co-injection of PACAP (6-38), a PAC1 receptor antagonist, attenuated the anorexigenic effect of PACAP but not VIP. On the other hand, ICV co-injection of [D-p-Cl-Phe6, Leu17]-VIP, a VPAC receptor antagonist, did not affect the effects of both peptides. Although these results imply that the effect of VIP was not specific, a subsequent experiment demonstrated that ICV injection of anti-chicken VIP antiserum stimulated feeding and suggested that endogenous VIP inhibits feeding in the chick brain. Collectively, the data suggest that the anorexigenic mechanism of PACAP is different from that of VIP and that an undiscovered VIP receptor may be present in the chicken brain.

Animals↗

Central pipecolic acid increases food intake under ad libitum feeding conditions in the neonatal chick.

It has been demonstrated that L-pipecolic acid (L-PA) is a major metabolic intermediate of L-lysine in the mammalian and chicken brain. A previous study showed that intracerebroventricular (i.c.v.) injection of L-PA suppressed feeding in neonatal chicks, and the actions were associated with gamma-aminobutyric acid (GABA)-B receptor activation. It has been reported that endogenous L-PA in the brain fluctuated under different feeding conditions. In the present study, we investigated the effect of i.c.v. injection of L-PA on food intake in the neonatal chick under ad libitum feeding conditions. The food intake was increased by 0.5 or 1.0 mg L-PA under ad libitum feeding conditions contrary to previous studies using fasted birds. A hyperphagic effect of L-PA (0.5 mg) was attenuated by both GABA-A receptor antagonist (picrotoxin, 0.5 microg) and GABA-B receptor antagonist (CGP54626, 21.0 ng). These results indicate that a hyperphagic effect of L-PA is mediated by both GABA-A and GABA-B receptors and L-PA differentially affects food intake under different feeding conditions in the neonatal chick.

Animals↗

Intracerebroventricular injection of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibits feeding in chicks.

Previous research has indicated an involvement of glucagon superfamily peptides in the regulation of feeding in the domestic chick brain. However the possible roles of vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide-38 (PACAP) have not yet been investigated. We therefore examined the effect of intracerebroventricular (ICV) injections of VIP or PACAP on food intake in chicks. ICV injection of both VIP and PACAP significantly inhibited food intake over 4 h at doses ranging from 12 to 188 pmol. Subsequently, we compared the anorexic effect the glucagon superfamily peptides VIP, PACAP, growth hormone-releasing factor (GRF) and glucagon-like peptide-1 (GLP-1) after ICV injection at an equimolar dose (12 pmol). All four peptides significantly inhibited food intake, although the anorexic effects of VIP and PACAP were weaker than those of GRF and GLP-1. These findings support the hypothesis that glucagon superfamily peptides play an important role in the regulation of appetite in the chick brain.

Animals↗

Myelofibrosis after essential thrombocythemia complicated by alveolar proteinosis.

Hematological diseases are often accompanied by respiratory disorders. Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by excessive accumulation of surfactant in the alveolar space. We describe a case of PAP complicated by myelofibrosis following essential thrombocythemia. The patient developed high fever, respiratory failure, and leuko-erythroblastosis during the progressive course of PAP. These symptoms were alleviated by prednisolone. The level of serum IL-6 was elevated when PAP was progressing rapidly. This may explain why the symptoms were alleviated by the steroids.

Bone Marrow↗