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Biomedical subjects

Y Saitoh

Publications and source records attributed to Y Saitoh.

At least 91 records · Page 5Linked to original sources

Flumazenil abolishes midazolam-induced increase in the work of nasal breathing.

PURPOSE: To evaluate the effects of midazolam sedation followed by flumazenil antagonism on the work of nasal breathing in normal humans. METHODS: We measured minute ventilation through the nasal route, respiratory frequency, nasal resistance (Rn) and the work of nasal breathing under three conditions: awake, during midazolam sedation, and after flumazenil antagonism in eight healthy human subjects. A custom-made, partitioned face mask enabled nasal and oral airflow to be measured separately. To calculate Rn and the work of nasal breathing, nasal mask and oropharyngeal pressure was also measured. RESULTS: Total resistive work spent on the upstream segment of the nasal route per minute (Wn) (J x min(-1)) was greater during midazolam sedation (3.6 +/- 2.9) than while awake (1.6 +/- 0.9) and after flumazenil antagonism (1.7 +/- 0.6), respectively (mean +/- SD) (P < 0.05). Total resistive work spent on the upstream segment of nasal breathing (WnNnE) (JxL(-1)) increased from 0.31 +/- 0.14 to 0.75 +/- 0.61 after midazolam administration (P < 0.05) and decreased to 0.31 +/- 0.10 after flumazenil. Following midazolam administration, a strong correlation was observed between changes in WnNnE and changes in Rn r = 0.852, P < 0.0001), whereas there was no correlation between changes in Wn and changes in Rn r = 0.159, P = 0.279). CONCLUSION: The work of breathing spent on the upstream segment of the nasal route increases during midazolam sedation and returns to baseline after flumazenil antagonism.

Adult↗

Morphogenesis of nonpolypoid colorectal adenomas and early carcinomas assessed by cell proliferation and apoptosis.

Nonpolypoid neoplasms, as well as ordinary polypoid tumours, are occasionally found in the colorectum. To clarify whether cell kinetic status affects the macroscopic morphology of colorectal neoplasms, we investigated proliferative indices (PI), apoptotic indices (AI), and the expression of apoptosis-related gene products. We examined 110 colorectal neoplasms comprised of 36 polypoid, 38 flat elevated and 36 depressed tumours. According to WHO's criteria these tumours consisted of 61 adenomas with low grade dysplasia (LGD), 30 adenomas with high grade dysplasia (HGD) and 19 carcinomas with submucosal invasion. Apoptotic cells were detected by TUNEL staining. Proliferating cells and apoptosis-related gene products were assessed by immunohistochemistry for Ki-67, p53, Bcl-2, and Bax antigens. AI were closely associated with macroscopic morphology in adenomas but not in carcinomas. PI were relatively constant among the three macroscopic types in adenomas and carcinomas. Median AI values of polypoid, flat elevated and depressed tumours were 1.8%, 2.1% and 4.6% for adenomas with LGD, 0.8%, 2.4% and 6.2% for adenomas with HGD and 2.9%, 4.0% and 3.6% for carcinomas, respectively. Overall PI were significantly higher in carcinomas than in adenomas with LGD, whereas AI were not different. Although the incidence of expression was significantly higher in carcinomas for p53 and in adenomas for Bcl-2 than the others, the expression of apoptosis-related gene products (p53, Bcl-2 and Bax) was similar among polypoid, flat elevated and depressed tumours. Macroscopic morphology of colorectal adenomas is determined by the apoptosis not by proliferation, and high apoptosis found in depressed adenomas implies their low net growth.

Adenoma↗

Heart preservation in HTK solution: role of coronary vasculature in recovery of cardiac function.

BACKGROUND: Poor myocardial tolerance to prolonged cold ischemia remains a major concern in heart transplantation. In this study, we estimated superiority of Histidine-Tryptophan-Ketoglutarate (HTK) over University of Wisconsin (UW) as a cardiac preservation solution. METHODS: Isolated rat hearts were mounted on a Langendorff apparatus to estimate the baseline cardiac function. The hearts were arrested and stored at 4 degrees C in UW and HTK solution for 8 hours, and then reperfused. The aortic flow, coronary flow, cardiac output, rate pressure product, and left ventricular dp/dt in the HTK group recovered significantly more than the UW group. The values of myocardial total adenine nucleotides and the adenosine triphosphate to adenosine diphosphate ratio were higher in the HTK than in the UW group. We also examined coronary vascular responsiveness using left coronary arteries dissected from the rat hearts before flushing, before storage, after storage, and after reperfusion. RESULTS: The maximal relaxation response to acetylcholine was significantly higher in the HTK than in the UW group after reperfusion, although there were no significant differences at each stage before reperfusion. In addition, the endothelium-independent relaxation response to sodium nitroprusside in the HTK group was also well preserved after reperfusion. CONCLUSIONS: These results indicate that HTK is superior to UW solution for cardiac preservation. HTK protects coronary vasculature during preservation, which together with reperfusion might lead to improved functional cardiac recovery following preservation.

Adenosine↗

Endothelin-1 concentration increases in the cerebrospinal fluid in cerebral vasospasm caused by subarachnoid hemorrhage.

BACKGROUND: Endothelin-1 (ET-1) was originally identified as a potent vasoconstrictor peptide. Numerous reports have suggested its roles in various disorders. Although there is a great deal of evidence establishing the relationship between ET-1 and cerebral vasospasm in animals, this relationship still remains to be clarified in humans. METHODS: The concentration of ET-1 in cerebrospinal fluid (CSF) was measured by radioimmunoassay in 23 subarachnoid hemorrhage patients. CSF samples were collected every 10 days after surgery from the cisternal drainage tube. RESULTS: Initial concentrations of ET-1 in the CSF collected the first day after operation were all increased compared with the control CSF. In seven of the eight vasospasm patients, the concentrations of ET-1 had increased before the observation of vasospasm and then decreased before the disappearance of the vasospasm. In 13 out of the 15 patients without vasospasm, the concentrations of ET-1 in CSF decreased with time. CONCLUSION: We confirmed that the concentration of ET-1 in CSF increased before the onset of cerebral vasospasm caused by subarachnoid hemorrhage. The ET-1 concentration in the CSF could be a useful marker to detect cerebral vasospasm after subarachnoid hemorrhage.

Adult↗

A triphasic curve characterizes the retention of lever-pressing behavior rewarded by lateral hypothalamic stimulation during the immediate-post-trial period in rats: implications for a transient-intermediate stage between short- and long-term memory.

We investigated the retention of lever-pressing behavior in rats rewarded by lateral hypothalamic (LHT) stimulation. Rats with electrodes implanted into the lateral hypothalamus were trained to press a lever to receive LHT stimulation. More than 90% of rats which had self-stimulated for longer than 30 min retained this behavior when tested 1 or 7 days later, indicating that intracranial self-stimulation (ICSS) produced a stable long-term memory lasting for at least 7 days. Subsequently, we examined retention at shorter ICSS-test intervals. Retention rates were measured 15, 30, 60, 90, 120, 180 or 360 min after the end of a 90-min period of ICSS, using a different group of 15 rats for each interval. Unexpectedly, retention rates in shorter interval tests were lower than those observed after 1 or 7 days. We observed a characteristic fluctuation in retention rates with lower rates at 30 and 180 min, giving a triphasic form to the retention curve with peaks at 15, 90 and 360 min. When a group of rats that had been previously stimulated and shown to have retained the lever-pressing behavior was allowed to re-stimulate a second time, no fluctuations were observed in short-term interval tests. This indicates that the fluctuations in the retention curve immediately after initial ICSS are closely related to the initial acquisition of the memory. Our results support a three-phase model of memory formation that includes a transient-intermediate stage between short- and long-term memory.

Animals↗

Altered expression of the ERM proteins in lung adenocarcinoma.

Radixin is a member of the ERM (ezrin/radixin/moesin) protein family that is proposed to function as a membrane-cytoskeletal linker. Using differential display analysis, we have identified radixin as a gene down-regulated in primary lung adenocarcinoma. Real-time quantitative reverse transcription polymerase chain reaction confirmed that radixin mRNA was decreased, both in 10 early-stage bronchioloalveolar carcinomas and in 16 invasive lung adenocarcinomas, by 69% (p = 0.0002) and 82% (p < 0.0001), respectively, compared with 9 nontumor lung tissues. Similarly, moesin and ezrin mRNA levels were reduced in lung adenocarcinoma. Immunohistochemistry confirmed that cancer cells expressed very little radixin and moesin, whereas non-neoplastic alveolar and bronchiolar epithelial cells, and endothelial cells, including those within the tumor stroma, were consistently positive for these two proteins. Ezrin was localized in the apical surface of non-neoplastic bronchiolar and alveolar epithelial cells and, in contrast to radixin and moesin, the majority of tumor cells retained expression of ezrin. Localization of ezrin was altered in a significant proportion of tumor cells: whereas tumor cells forming lumina displayed membranous staining on the apical side, tumor cells with disorganized structures were either negative or diffusely positive for ezrin in the cytoplasm. Furthermore, a fraction of tumor cells invading the stroma in a scattered manner were strongly positive for ezrin. In conclusion, expression of radixin and moesin is down-regulated in lung adenocarcinoma, including early-stage bronchioloalveolar carcinoma. An intriguing implication of this finding is that these two genes may function as tumor suppressors in lung adenocarcinoma oncogenesis. Although structurally related to radixin and moesin, ezrin may have a distinct function in tumor-cell invasion.

Adenocarcinoma↗

Widespread gene transfection into the central nervous system of primates.

We attempted in vivo gene transfection into the central nervous system (CNS) of non-human primates using the hemagglutinating virus of Japan (HVJ)-AVE liposome, a newly constructed anionic type liposome with a lipid composition similar to that of HIV envelopes and coated by the fusogenic envelope proteins of inactivated HVJ. HVJ-AVE liposomes containing the lacZ gene were applied intrathecally through the cisterna magna of Japanese macaques. Widespread transgene expression was observed mainly in the neurons. The lacZ gene was highly expressed in the medial temporal lobe, brainstem, Purkinje cells of cerebellar vermis and upper cervical cord (29.0 to 59.4% of neurons). Intrastriatal injection of an HVJ-AVE liposome-lacZ complex made a focal transfection around the injection sites up to 15 mm. We conclude that the infusion of HVJ-AVE liposomes into the cerebrospinal fluid (CSF) space is applicable for widespread gene delivery into the CNS of large animals. Gene Therapy (2000) 7, 759-763.

Animals↗

Impaired beta-cell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients.

OBJECTIVE: Abnormal glucose tolerance is often demonstrated in acromegalic patients. Although insulin resistance is a common feature of acromegaly, it remains unclear whether the extent of insulin resistance per se determines the abnormal glucose tolerance. In order to elucidate this issue, we investigated insulin sensitivity and beta-cell function in acromegalic patients. DESIGN: Twenty-four acromegalic patients were studied in comparison with 24 healthy control subjects. To estimate insulin sensitivity and beta-cell function, we used correct homeostasis model assessment (HOMA) model, a computer-solved model. We also investigated the effects of surgical success on both parameters. RESULTS: HOMA insulin sensitivity (HOMA-%S) in the acromegalic patients was 74 +/- 51 (SD)%, significantly lower than that in 24 healthy controls (144 +/- 49%). HOMA-%S in 12 normal glucose tolerance (NGT) patients was 54 +/- 31%, not significantly different from that in impaired glucose tolerance (IGT; n = 11) or diabetes mellitus (DM; n = 1) patients (93 +/- 60%). By contrast, HOMA beta-cell function (HOMA-%beta) in the NGT acromegalic patients was 163 +/- 67%, significantly higher than the IGT/DM acromegalic patients (89 +/- 34%) and the healthy controls (72 +/- 19%). In 11 patients who achieved complete normalization of GH excess after surgery, HOMA-%S significantly increased to control ranges (from 76 +/- 26 to 159 +/- 61%) within 2 weeks after the surgical success. CONCLUSIONS: We conclude that insulin sensitivity is reduced to a similar extent in acromegalic patients with normal glucose tolerance and those with impaired glucose tolerance or diabetes. Compensatory hyperfunction of beta-cells appears to counterbalance the reduced insulin sensitivity in the acromegalic patients with normal glucose tolerance but not in those with impaired glucose tolerance or diabetes.

Acromegaly↗

Granisetron/dexamethasone combination for the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy.

Dexamethasone decreases chemotherapy-induced emesis when added to an antiemetic regimen. This study was undertaken to evaluate the efficacy of granisetron/dexamethasone combination for preventing postoperative nausea and vomiting (PONV) after lapIaroscopic cholecystectomy (LC). In a prospective, randomized, double-blind manner, 120 patients (83 females), aged 25-65 years, were assigned to receive granisetron 40 microg kg-1 alone or granisetron 40 microg kg-1 plus dexamethasone 8 mg (n=60 of each) intravenously immediately before the induction of anaesthesia. A standardized general anaesthetic procedure and postoperative analgesia were used. A complete response, defined as no PONV and no need for another rescue antiemetic, during 0-3 h after anaesthesia was 83% with granisetron and 98% with granisetron plus dexamethasone, respectively (P=0.008); the corresponding incidence during 3-24 h after anaesthesia was 83% and 98% (P=0.008). No clinically important adverse events were observed in any of the group. In conclusion, prophylactic therapy with granisetron/dexamethasone combination is more effective than granisetron alone for the prevention of PONV after LC.

Adult↗

Nicorandil stimulates release of adenyl purines from porcine coronary artery.

1. To clarify the mechanism of the cardioprotective effect of nicorandil (2-nicotinamidoethyl-nitrate ester), the effects of nicorandil and nitric oxide (NO) donors on the release of ATP, ADP, AMP and adenosine from arterial segments and cultured endothelial cells of the porcine coronary artery were examined. 2. Nicorandil significantly increased the release of total adenyl purines from arterial segments and from cultured endothelial cells. 3. Cromakalim, an ATP-sensitive K+ channel opener, did not affect the release of total adenyl purines from coronary artery segments. 4. s-Nitroso-N-acetyl-D,L-penicillamine and isosorbide dinitrate, NO donors, significantly increased the release of total adenyl purines from coronary artery segments. 5. These results demonstrate that nicorandil stimulates ATP release from the coronary artery by acting not as an ATP-sensitive K+ channel opener, but as a nitrate, thus suggesting the cardioprotective properties of nicorandil.

Adenine Nucleotides↗

Pretreatment with oral clonidine attenuates cardiovascular responses to tracheal extubation in children.

This study was designed to evaluate the effects of diazepam and clonidine orally given preoperatively on cardiovascular responses to tracheal extubation in children. Fifty children, ASA physical status I, aged 4-10 years, undergoing minor elective surgery (inguinal hernia, phimosis) received orally, in a randomized, double-blind manner, diazepam 0.4 mg.kg-1 or clonidine 4 microgram.kg-1 (n=25 of each). These drugs were administered 105 min before an inhalational induction of anaesthesia. The same standard general anaesthetic technique was employed throughout. The maximum changes in heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were less in patients who had received clonidine than in those who had received diazepam (HR, 12 vs 24; SBP, 14 vs 26; DBP, 9 vs 16; mean, P < 0.05). In conclusion, compared to diazepam given orally, pretreatment with oral clonidine attenuates haemodynamic changes associated with tracheal extubation in children.

Administration, Oral↗

Identification and cataloging of genes induced by long-lasting long-term potentiation in awake rats.

Maintenance of long-term potentiation (LTP) requires de novo gene expression. Here we report the direct isolation, using PCR-differential display, of genes whose expression level was altered after induction of long-lasting LTP in the hippocampus of freely moving awake rats. Differential display using 480 primer combinations revealed 17 cDNA bands that showed a reproducible change in expression level. These cDNAs represented at least 10 different genes (termed RM1-10), all of which showed up-regulation at 75 min after LTP induction and a return to basal expression levels within 24 h. Three of these genes were known only from expressed sequence tags (RM1-3), two were known genes whose up-regulation by LTP has not been described (GADD153/CHOP and ler5), and five were known genes whose up-regulation by LTP has already been reported (MAPK phosphatase, NGFI-A/zif268, vesl-1S/homer-1a, Ag2, and krox-20). We characterized the expression profiles of genes in the two former categories with respect to NMDA receptor dependency, tissue specificity, and developmental regulation using northern blotting and semiquantitative RT-PCR. The up-regulation of all five of these genes was NMDA receptor-dependent and correlated with the persistence of LTP, suggesting that these genes may play functional roles in prolonged LTP maintenance.

Animals↗

Clinical outcome of endoscopic mucosal resection for superficial GI lesions and the role of high-frequency US probe sonography in an American population.

BACKGROUND: Endoscopic mucosal resection, a major advance in endoscopy, provides an endoscopic option for management of focal and superficial lesions of the gastrointestinal tract. Although popular in the Orient due to the high incidence of superficial neoplasia, there are scant data on its use in the United States. Our aim was to assess the efficacy and safety of endoscopic mucosal resection in our patient population and evaluate whether high-frequency ultrasound (US) probe sonography provides useful information relative to the procedure. METHODS: Endoscopic mucosal resection was performed in 32 of 33 patients referred for endoscopic management of superficial neoplastic or submucosal lesions. High-frequency US probe sonography was performed with a 20 MHz US probe. Endoscopic mucosal resection was performed after submucosal saline solution injection with the strip biopsy technique. RESULTS: Thirty-two superficial lesions were resected. Of 24 epithelial lesions resected, 22 were intramucosal and 2 had early submucosal invasion (SM1); the 2 patients with the latter 2 lesions were poor candidates for surgery. Depth of penetration of 25 of 26 lesions scanned was accurately predicted by high-frequency US probe sonography. Eight lesions raised from the submucosa. Minor complications were limited to the colon. Of the 7 patients with carcinomas, 6 had no evidence of recurrence at a mean follow-up of 12 months; 1 died of a second primary cancer. CONCLUSIONS: Endoscopic mucosal resection provided definitive therapy for 24 early-stage neoplastic lesions and provided a diagnosis in the remaining 8. In our study, the technique proved to be safe with only three minor complications noted. High-frequency US probe sonography accurately delineated the depth of penetration of all lesions scanned, therefore making it an ideal imaging modality for selecting patients who may benefit from endoscopic mucosal resection.

Biopsy↗

Evaluation of pulmonary gas exchange after lobectomy and simple thoracotomy.

Postoperative influence of simple thoracotomy and lobectomy on pulmonary gas exchange was investigated in 10 patients undergoing thoracotomy and lobectomy (L group) and 10 patients with simple thoracotomy (ST group). Gas exchange was assessed with hot-wire mass spectrometry and blood gas analyses preoperatively and postoperatively at 1, 3, 6, 12, 24 and 48 h and on days 4, 6 and 13. The preoperative values of alveolar-arterial oxygen tension gradient (AaDO2), ventilation-perfusion mismatch (V(A)/Q) and circulatory shunt (Qs/Qt) were maintained in the ST group. In the L group, however, AaDO2 and Qs/Qt showed good maintenance of gas exchange for only 6-12h after lobectomy and then deteriorated because of peripheral atelectasis, resulting in poorer values than those in the ST group on days 4 and 13. Careful postoperative management, including pulmonary toilet, is essential for maintenance of gas exchange and prevention of pulmonary complications.

Adult↗

Synthesis and structure-activity relationships of selective ligands for P3 purinoceptor-like protein (P3LP).

We examined the structure-activity relationship of various 5'-N-substituted-carboxamidoadenosine derivatives toward P3 purinoceptor-like protein (P3LP), which has affinity for both adenine nucleosides and nucleotides. We discovered a hydrophobic binding region near the 5'-N-substituted-carboxamide group. From the linear alkyl N-substituted derivatives, 1-(adenin-9-yl)-1-deoxy-N-n-pentyl-beta-D-ribofuranuronamide (6) was found to be the most potent ligand. In the series of the N-cycloalkyl derivatives, 1-(adenin-9-yl)-1-deoxy-N-cyclohexyl-beta-D-ribofuranuronamide (8) was the strongest ligand. We also examined the receptor selectivity for the selected nucleosides 6 and 8 with 1 (HAK2701) and N-ethylcarboxamidoadenosine (NECA) versus P1 purinoceptor subtypes, such as adenosine A1, A2A, A2B, and A3 receptors and found 8 is the most selective ligand for P3LP.

Adenosine↗

Ramosetron for preventing postoperative nausea and vomiting in women undergoing gynecological surgery.

UNLABELLED: In a prospective, randomized, double-blinded, placebo-controlled trial, we evaluated the efficacy of ramosetron at three different doses (0.15, 0.3, and 0.6 mg) for the prevention of postoperative nausea and vomiting (PONV) after gynecological surgery. One hundred twenty women, ASA physical status I or II, aged 21-63 yr, received IV either placebo or ramosetron 0.15, 0.3, or 0.6 mg (n = 30 of each) at the completion of surgery. A standard general anesthetic technique and postoperative analgesia were used. A complete response, defined as no PONV and no need for another rescue antiemetic, during 0-3 h after anesthesia occurred in 40%, 47%, 87%, and 90% of patients who had received placebo and ramosetron 0.15, 0.3, and 0.6 mg, respectively. Corresponding results during 3-24 h after anesthesia were 43%, 50%, 87%, and 90%, and 24-48 h after anesthesia were 50%, 53%, 90%, and 93% (P < 0.05). Patients who had received ramosetron 0.3 or 0.6 mg were satisfied compared with those who had received placebo (P < 0.05). There were no serious clinical adverse events caused by the study drug in any of the groups. In conclusion, ramosetron 0.3 mg is an effective antiemetic for preventing PONV during 0-48 h after anesthesia in female patients undergoing gynecological surgery. Increasing the dose to 0.6 mg provided no further benefit. IMPLICATIONS: This randomized, double-blinded, placebo-controlled trial in 120 women found the effective dose of ramosetron for preventing postoperative nausea and vomiting after gynecological surgery to be 0.3 mg.

Adult↗

Symbiobacterium thermophilum gen. nov., sp. nov., a symbiotic thermophile that depends on co-culture with a Bacillus strain for growth.

A Gram-negative and tryptophanase-positive thermophile, whose growth is dependent on co-culture with an associating Bacillus strain, had been reported and tentatively named Symbiobacterium thermophilum strain T(T). Axenic culture of strain T(T) was recently established by dialysing cultures with the supporting bacterial strains or adding their culture broth. Phylogenetic analysis of strain T(T), based on the 16S rDNA sequence, was conducted for the validation of S. thermophilum. The sequence of strain T(T) was located at the outermost position in the high-G+C Gram-positive group distinctly isolated from any other branches hitherto known. Ten sequences identical to that of strain T(T), and one sequence closely related to it, were identified for the first time from soil and compost samples. The outer membrane of strain T(T) had a three-layered structure, outside the cytoplasmic membrane, which is similar to the S-layer in the cells of members of the Bacillaceae. Chemical analysis of the cells revealed that menaquinone-6 is a major component of the quinone system. According to these results, along with several previous observations (i.e. a G+C DNA content of 65 mol% and the identification of iso-C15:0 and iso-C17:0 acids as major cellular fatty acids), the new taxon Symbiobacterium thermophilum gen. nov., sp. nov. is proposed. The type strain is S. thermophilum strain T(T) (= IAM 14863T).

Bacillus↗