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Biomedical subjects

H Ishihara

Publications and source records attributed to H Ishihara.

At least 73 records · Page 4Linked to original sources

Unventilated airway is time-dependently constricted in paralyzed dogs.

BACKGROUND: Apnea has been reported to produce bronchoconstriction and to cause hypoxia, hypercapnia, and modulation of vagal afferent nerves, which also change airway tone. In this study, the authors determined the mechanism of apnea-induced bronchoconstriction. METHODS: Twenty-eight dogs anesthetized and paralyzed were assigned to four groups (n = 7 each): apnea after artificial ventilation with 50% and 100% O2 groups (apnea-50% O2 and apnea-100% O2 groups, respectively), an apnea plus vagotomy group (fraction of inspired oxygen [FiO2] = 1.0), and a one-lung ventilation group (FiO2 = 1.0). The trachea was intubated with a single- or double-lumen tube in the three apnea groups or the one-lung ventilation group, respectively. The bronchial cross-sectional area (BCA) was assessed by the authors' bronchoscopic method. In the apnea-100% O2 and apnea plus vagotomy groups, a respirator was turned off for 5 min to produce apnea. In the apnea-50% O2 group, apnea was produced for 3 min. In the one-lung ventilation group, the right lumen was blocked for 5 min, and 15 min later, the left lumen was blocked for 5 min. BCA, arterial oxygen tension (PaO2), and arterial carbon dioxide tension (PaCO2) were assessed every minute. RESULTS: The BCA in intact dogs time-dependently decreased by approximately 20% and 40% at 3 and 5 min after apnea started, respectively, whereas they did not in vagotomized dogs. In the apnea-50% O2 and apnea-100% O2 groups, bronchoconstriction could occur without hypoxemia, although hypercapnia was observed in all dogs. In the one-lung ventilation group, despite the fact that PaCO2 increased by only 2 mmHg without hypoxemia, unventilated BCA time-dependently decreased by 33.6 +/- 10.3%, whereas ventilated BCA did not. CONCLUSION: The current study suggests that the unventilated airway may constrict spontaneously. In addition, the airway constriction could be vagally mediated but not due to hypoxia and hypercapnia.

Animals↗

Minimum 10-year follow-up study of anterior lumbar interbody fusion for isthmic spondylolisthesis.

The aims of the current study were to evaluate the long-term clinical and radiologic results of anterior lumbar interbody fusion (ALIF) for isthmic spondylolisthesis. Between 1981 and 1988, a total of 35 patients underwent ALIF for isthmic spondylolisthesis. Of these, 23 patients were followed clinically and radiographically for more than 10 years (average, 13.3 years). The Japanese Orthopaedic Association low-back pain score was used to evaluate the outcome of subjective symptoms and clinical signs. The preoperative and postoperative percentage of slip, preoperative and postoperative intervertebral disk height, interbody graft union, and pars defect union were evaluated by serial radiographs. The adjacent disk degeneration was also evaluated by radiographs and magnetic resonance imaging. Although the low-back pain score worsened after 5 years, ALIF provides satisfactory overall long-term clinical results. The preoperative percentage of slip and the disk height were corrected after surgery, but at the time of interbody graft union, slip and disk height recurred as a result of grafted bone collapse. The rate of union in the grafted area was 83%. In the nonunion cases, the scores gradually deteriorated with time, but the overall results were not different from those of union cases. Radiographs showed adjacent disk degeneration in 52% of cases in the upper adjacent level and in 70% of cases in the lower adjacent level, but these changes were not correlated with clinical outcomes.

Adolescent↗

Serial changes of herniated intervertebral discs after posterior lumbar discectomy: the relation between magnetic resonance imaging of the postoperative intervertebral discs and clinical outcome.

To evaluate the relation between the morphologic changes of postoperative intervertebral discs and the clinical outcome after posterior lumbar discectomy, the size of the bulging disc was analyzed prospectively on serial follow-up magnetic resonance images in 26 randomly selected patients. The bulging of postoperative intervertebral discs involved three patterns of reduction: early reduction (n = 15), gradual reduction (n = 6), and late reduction (n = 5). There was a significant difference in the serial changes of subjective symptoms and neurologic function among the three patterns. A late reduction of postoperative disc bulging could cause late recovery of subjective symptoms and neurologic disturbance.

Adolescent↗

Clinical symptoms and surgical outcome in lumbar spinal stenosis patients with neuropathic bladder.

We evaluated the clinical and radiologic features of patients with lumbar spinal stenosis with neuropathic bladder. Based on cystometrogram analysis, the patients were divided into two groups--the neuropathic bladder (NB) group: the NB+ group (23 patients), and the nonneuropathic bladder group: the NB- group (14 patients). The symptom of incontinence was characteristic in patients in the NB+ group. Patients in the NB+ group had a more severe neurologic disturbance, compared with those in the NB- group. The more severe neurologic disturbance was caused by the more striking finding of degenerative spinal stenosis associated with developmental narrowing of the spinal canal. Decompressive surgery had a beneficial effect on the recovery of the neurologic symptoms in both groups. Residual urine volume was reduced after surgery. Postoperative cystometrogram was carried out in nine patients in the NB+ group. It showed a normal pattern in six patients; however, three patients remained in an underactive pattern. Furthermore, four patients still required clear intermittent self-catheterization after surgery.

Aged↗

Comparison of initial distribution volume of glucose and plasma volume in thoracic fluid-accumulated patients.

OBJECTIVE: We have reported that initial distribution volume of glucose indicates the central extracellular fluid volume in the presence of fluid gain or loss. The purpose of this study was to describe changes in initial distribution volume of glucose, plasma volume determined by the indocyanine green dilution method (PV-ICG), and thoracic fluid content by thoracic electrical bioimpedance in patients with or without apparent thoracic fluid accumulation in the absence of pleural effusion. We also sought to test whether initial distribution volume of glucose rather than PV-ICG mirrors thoracic fluid content. DESIGN: Prospective, clinical study. SETTING: General intensive care unit. PATIENTS: Eleven consecutive patients with apparent thoracic fluid accumulation as judged by thoracic fluid content >0.05/ohm and underlying pathology and 20 consecutive acute myocardial infarction patients within 24 hrs after its onset were selected for study. None of the acute myocardial infarction patients had thoracic fluid content >0.05/ohm. INTERVENTIONS: Five grams of glucose and 25 mg of indocyanine green were administered simultaneously to calculate initial distribution volume of glucose and PV-ICG daily for the fluid-accumulated patients, and the same dosages were administered to the acute myocardial infarction patients immediately after their admission to the intensive care unit after percutaneous coronary angioplasty. Only the data on the day of the maximal and minimal thoracic fluid content in the fluid-accumulated patients were used for the study. The relationship between these two fluid volumes and thoracic fluid content was evaluated in the two patient groups. MEASUREMENTS AND MAIN RESULTS: Initial distribution volume of glucose and thoracic fluid content rather than PV-ICG and thoracic fluid content moved together in the same direction in each fluid-accumulated patient. Neither pulmonary artery occlusion pressure, central venous pressure, nor PV-ICG produced a better correlation with cardiac index when compared with initial distribution volume of glucose in patients with or without thoracic fluid accumulation. CONCLUSIONS: We suggest that initial distribution volume of glucose rather than PV-ICG is a better indicator of the intrathoracic blood volume status, even although intravenously administered glucose cannot stay in the intravascular compartment.

APACHE↗

Overexpression of SH2-containing inositol phosphatase 2 results in negative regulation of insulin-induced metabolic actions in 3T3-L1 adipocytes via its 5'-phosphatase catalytic activity.

Phosphatidylinositol (PI) 3-kinase plays an important role in various metabolic actions of insulin including glucose uptake and glycogen synthesis. Although PI 3-kinase primarily functions as a lipid kinase which preferentially phosphorylates the D-3 position of phospholipids, the effect of hydrolysis of the key PI 3-kinase product PI 3,4,5-triphosphate [PI(3,4,5)P3] on these biological responses is unknown. We recently cloned rat SH2-containing inositol phosphatase 2 (SHIP2) cDNA which possesses the 5'-phosphatase activity to hydrolyze PI(3,4,5)P3 to PI 3,4-bisphosphate [PI(3,4)P2] and which is mainly expressed in the target tissues of insulin. To study the role of SHIP2 in insulin signaling, wild-type SHIP2 (WT-SHIP2) and 5'-phosphatase-defective SHIP2 (Delta IP-SHIP2) were overexpressed in 3T3-L1 adipocytes by means of adenovirus-mediated gene transfer. Early events of insulin signaling including insulin-induced tyrosine phosphorylation of the insulin receptor beta subunit and IRS-1, IRS-1 association with the p85 subunit, and PI 3-kinase activity were not affected by expression of either WT-SHIP2 or Delta IP-SHIP2. Because WT-SHIP2 possesses the 5'-phosphatase catalytic region, its overexpression marked by decreased insulin-induced PI(3,4,5)P3 production, as expected. In contrast, the amount of PI(3,4,5)P3 was increased by the expression of Delta IP-SHIP2, indicating that Delta IP-SHIP2 functions in a dominant-negative manner in 3T3-L1 adipocytes. Both PI(3,4,5)P3 and PI(3,4)P2 were known to possibly activate downstream targets Akt and protein kinase C lambda in vitro. Importantly, expression of WT-SHIP2 inhibited insulin-induced activation of Akt and protein kinase C lambda, whereas these activations were increased by expression of Delta IP-SHIP2 in vivo. Consistent with the regulation of downstream molecules of PI 3-kinase, insulin-induced 2-deoxyglucose uptake and Glut4 translocation were decreased by expression of WT-SHIP2 and increased by expression of Delta IP-SHIP2. In addition, insulin-induced phosphorylation of GSK-3beta and activation of PP1 followed by activation of glycogen synthase and glycogen synthesis were decreased by expression of WT-SHIP2 and increased by the expression of Delta IP-SHIP2. These results indicate that SHIP2 negatively regulates metabolic signaling of insulin via the 5'-phosphatase activity and that PI(3,4,5)P3 rather than PI(3,4)P2 is important for in vivo regulation of insulin-induced activation of downstream molecules of PI 3-kinase leading to glucose uptake and glycogen synthesis.

3T3 Cells↗

Tyrosine phosphorylation-dependent and -independent role of Shc in the regulation of IGF-1-induced mitogenesis and glycogen synthesis.

To examine the functional role of Shc tyrosine phosphorylation in IGF-1 signaling, wild-type (WT)-Shc and Y239,240,317F (3F)-Shc were transiently transfected into L6 myoblasts. IGF-1 signaling was compared among the transfected cells. IGF-1-induced tyrosine phosphorylation of Shc and its subsequent association with Grb2 were increased in WT-Shc cells, whereas they were decreased in 3F-Shc cells compared with those in parental L6 cells. Consistent with their changes, IGF-1-induced MAPK activation and thymidine incorporation were enhanced in WT-Shc cells, whereas they were again decreased in 3F-Shc cells. It is possible that Shc and insulin receptor substrate (IRS)-1 can interact competitively, via their phosphotyrosine binding (PTB) domains, with the activated IGF-1 receptor. In this regard, IGF-1-induced tyrosine phosphorylation of IRS-1 was decreased by overexpressing both WT-Shc and 3F-Shc cells. Consistent with the decrease, IGF-1-induced IRS-1 association with the p85 subunit of PI3K and activation of PI3K and Akt were reduced in both WT-Shc and 3F-Shc cells. As a result, IGF-1-induced glycogen synthesis was also decreased in both cells. Furthermore, expression of Shc PTB domain alone inhibited IGF-1 stimulation of Akt and glycogen synthesis. These results indicate that tyrosine phosphorylation of Shc is important for IGF-1 stimulation of MAPK leading to mitogenesis and that Shc, via its PTB domain, negatively regulates IGF-1-induced glycogen synthesis by competing with IRS-1, which is not relevant to Shc tyrosine phosphorylation.

Adaptor Proteins, Signal Transducing↗

Beta-cell-targeted expression of a dominant-negative hepatocyte nuclear factor-1 alpha induces a maturity-onset diabetes of the young (MODY)3-like phenotype in transgenic mice.

Mutations in the transcription factor hepatocyte nuclear factor-1 alpha (HNF-1 alpha) cause maturity-onset diabetes of the young 3, a severe form of diabetes characterized by pancreatic beta-cell dysfunction. We have used targeted expression of a dominant-negative mutant of HNF-1 alpha to specifically suppress HNF-1 alpha function in beta-cells of transgenic mice. We show that males expressing the mutant protein became overtly diabetic within 6 wk of age, whereas females displayed glucose intolerance. Transgenic males exhibited impaired glucose-stimulated insulin secretion, detected both in vivo and in the perfused pancreas. Pancreatic insulin content was markedly decreased in diabetic animals, whereas the glucagon content was increased. Postnatal islet development was altered, with an increased alpha-cell to beta-cell ratio. beta-Cell ultrastructure showed signs of severe beta-cell damage, including mitochondrial swelling. This animal model of maturity-onset diabetes of the young 3 should be useful for the further elucidation of the mechanism by which HNF-1 alpha deficiency causes beta-cell dysfunction in this disease.

Animals↗

Kojic acid production in an airlift bioreactor using partially hydrolyzed raw corn starch.

In a culture of Aspergillus oryzae MK-107-39 in a 3-l airlift bioreactor, kojic acid was not produced when glucose/wheat germ medium (GM1) was used. However, when a jar fermentor was used, the kojic acid yield was high. A suitable medium for culture in an airlift bioreactor consisting of partially hydrolyzed corn starch and a small amount of corn steep liquor (CSL) (SM1) was selected. In the cultivation in the airlift bioreactor using SM1, nearly 40 g/l of kojic acid was produced, which was the same as the amount produced in the jar fermentor containing GM1. The optimum aeration rate for the airlift bioreactor was 2.0 vvm (0.66 cm/s of superficial linear velocity (Vs)). The cost of SM1 using the airlift bioreactor was reduced to 40% that of GM1 using the jar fermentor. Furthermore, the energy cost of kojic acid production using SM1 in the airlift bioreactor was less than one-fourth of that for the jar fermentor using GM1.

Journal Article↗

Standardization of laboratory data and establishment of reference intervals in the Fukuoka Prefecture: a Japanese perspective.

Standardization of 22 clinical chemistry analytes and five serum protein constituents has been performed in the Fukuoka Prefecture, which has a population of approximately five million. The standardization project was established to determine reference intervals for these analytes by educating physicians, medical technologists and staff of medical institutions, and by daily or monthly monitoring the use of common control samples through e-mail. Standardization extended to 97% of the institutions in the prefecture. Results for 14 of the 22 clinical chemistry analytes have become highly reliable and differences between institutions decreased. Standardization of other analytes is now in progress. Regional collaboration based on international guidelines led to a significant improvement in interlaboratory comparability. Areas where further improvements are needed have been identified.

Adolescent↗

Progression of ossification of the posterior longitudinal ligament following en bloc cervical laminoplasty.

BACKGROUND: Ossification of the posterior longitudinal ligament often causes compressive myelopathy. Ossification is a progressive disease, and it has been reported that the area of ossification increases after decompressive surgery. However, it is uncertain how the progression of ossification affects the long-term outcome after cervical laminoplasty. This study was performed to clarify the relationship between the progression of ossification of the posterior longitudinal ligament and the clinical results following en bloc cervical laminoplasty. METHODS: Forty-five patients who were followed for more than ten years after laminoplasty participated in this study. Radiographs and tomograms of the cervical spine of each patient were made before and after the operation and at the time of the latest follow-up. The extent of ossification in the longitudinal and sagittal axes was evaluated. Neurological function was graded with use of the Japanese Orthopaedic Association scoring system. The relationship between the progression of ossification and the score-based rate of recovery was analyzed. RESULTS: Thirty-three (73%) of the patients had progression of ossification of the posterior longitudinal ligament after laminoplasty. Progression was frequent in patients with the mixed type of ossification and in those with the continuous type, whereas it was rare in patients with the segmental type. The patients with progression of the ossification were significantly younger than those without progression (p = 0.018). The Japanese Orthopaedic Association score improved rapidly within one year and continued to improve up to five years after surgery. The score tended to decrease thereafter. For thirteen patients, the score had worsened at the time of the latest follow-up. Three patients had neurological deterioration following an increase in the thickness of the ossification. CONCLUSIONS: Progression of ossification of the posterior longitudinal ligament was often observed during the long-term follow-up period after laminoplasty. Young patients with mixed and continuous types of ossification had the greatest risk for progression. Preventive measures, such as the use of a wider laminar opening during the laminoplasty, should be considered for patients who are at risk for progression of ossification.

Adult↗

[The effect of celiprolol hydrochloride for lipid metabolism--especially for the low density lipoprotein particle size].

Recently, much attention has been paid to small sized low density lipoprotein (LDL) as a risk factor for ischemic heart disease. We investigated the effect of celiprolol hydrochloride (CH), which is a beta 1 selective beta-blocker with high intrinsic sympathomimetic activity (ISA), on the LDL particle size. We treated 41 hypertensive patients with CH and studied the change in LDL particle size according to the score of fast beta lipoprotein and LDL relative mobility value (LDL-Rm) measured by lipoprotein polyacrylamide gel disc electrophoresis (PAGE). We also studied changes in blood pressure, total cholesterol (TC), trygiyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and midband on PAGE. Systolic and dyastolic blood pressure and pulse significantly decreased during treatment. TC levels were significantly decreased at 8 weeks in all subjects and at 4, 8 and 12 weeks in patients with a TC value of over 220 mg/dl. TG levels were significantly decreased at 4 and 8 weeks in patients with initial levels of over 150 mg/dl, and significantly increased at 4 and 8 weeks in those with initial levels of under 150 mg/dl of TG. HDL-C levels did not significantly change during treatment. LDL-C levels were significantly decreased at 4, 8 and 12 weeks in patients with initial levels of over 150 mg/dl. Apo AI, AII, B, CII, CIII and E levels did not significantly change during treatment. Fast beta lipoprotein scores did not significantly change overall during treatment, but were significantly decreased at 4 and 8 weeks in patients initial TG levels of over 150 mg/dl and at 4 and 12 weeks in those with initial levels of over 220 mg/dl of TC. LDL-Rm scores did not significantly change during treatment. Midband scores were significantly reduced overall at 8 weeks, and after 4 and 8 weeks in patients with initial TG levels of over 150 mg/dl and at 4, 8 and 12 weeks in those with initial TC levels of over 220 mg/dl. These results indicated that CH did not change LDL particle size. It was suggested that CH might be a beneficial beta-blocker from the standpoint of prevention for atherosclerosis.

Aged↗

Antitumor activity of ER-51785, a new peptidomimetic inhibitor of farnesyl transferase: synergistic effect in combination with paclitaxel.

Inhibitors of ras farnesylation have been extensively studied in the preclinical stage, and some of them are being developed in the clinic. Herein, we describe the antitumor activity of a new farnesyl transferase inhibitor, ER-51785. In vitro, ER-51785 selectively inhibited farnesyl transferase activity (IC50 = 77 nM) compared with geranylgeranyl transferase I activity (IC50 = 4200 nM). In cells, ER-51785 inhibited posttranslational processing of H-ras with IC50 = 28 nM, but not that of rap 1A at concentrations up to 50 microM. This compound also strongly inhibited colony formation of H-ras-transformed NIH 3T3 fibroblasts and EJ-1 bladder carcinoma cells. In vivo, ER-51785 showed potent tumor regression activity against EJ-1 xenografts but only modest activity against MIA PaCa-2 xenografts. Treatment of ER-51785 in combination with paclitaxel exhibited synergistic effects against colony formation and tumor growth of MIA PaCa-2 cells. The results presented herein support the idea that farnesyl transferase inhibitors alone and in combination with other chemotherapeutic agents have the potential to be developed as therapies for tumors expressing H-ras or K-ras oncogenes.

3T3 Cells↗

[Marked bradycardia during anesthetic induction treated with temporary cardiac pacing in a patient with latent sick sinus syndrome].

A 59 year-old woman with latent sick sinus syndrome was scheduled to undergo ophthalmic surgery including phacoemulsification and aspiration, vitrectomy, photocoagulation and intraocular lens under general anesthesia. Preoperative ECG showed sinus rhythms of 77 bpm without bradycardia or a sinus pause. Total intravenous anesthesia with propofol, fentanyl, ketamine and vecuronium was employed for the induction of anesthesia immediately followed by severe bradycardia with a rate of 36-40 bpm including sinus arrest and atrio/nodal escaped beats. Intravenous atropine was ineffective to restore the heart rate and then urgent temporary pacing was successfully applied to overcome bradycardia. The patient recovered uneventfully from anesthesia. She complained of being dizzy and faint with prominent bradycardia due to sick sinus syndrome three months after the surgery. Therefore she underwent permanent cardiac pacemaker implantation successfully. Temporary pacing is mandatory when anesthesia is given to surgical patients with latent sick sinus syndrome.

Anesthesia, General↗

[Combination of acute normovolemic hemodilution technique with preoperative autologous blood donation prevented allogeneic blood transfusion against 4000 g surgical blood loss in a patient undergoing left partial nephrectomy].

A 41-year-old male patient with well-controlled hypertension underwent a partial nephrectomy under total intravenous anesthesia with propofol, fentanyl and ketamine. To avoid allogeneic blood transfusion, preoperative autologous blood donation (400 g) a week before the surgery and acute normovolemic hemodilution (800 g) after induction of anesthesia were performed. As surgical blood loss was more than 4000 g, blood hemoglobin (Hb) level decreased to 6.4 g.dl-1. However, as intraoperative hemodynamics was relatively stable with no ischemic changes in ECG and arterial blood gas analysis did not show metabolic acidosis, autologous blood transfusion was withheld till hemostasis had been done. After returning the autologous blood, Hb increased to 9.4 g.dl-1. On the 2nd postoperative day, Hb decreased to 7.6 g.dl-1. As the patient's vital signs did not show any severe complications, blood transfusion was not performed. Then, the Hb level increased gradually to 13.9 g.dl-1, 3 month later without allogenic blood transfusion. In addition, any postoperative complications by low Hb level were not recognized so far. This case suggests that combination of autologous transfusion techniques may be effective to avoid allogeneic blood transfusion even against massive hemorrhage. However, to avoid disadvantage of these technique, we should always evaluate preoperative patient conditions.

Adult↗

[Early detection of hypoxia with BIS monitoring during percutaneous cardiopulmonary support].

We report a patient in whom hypoxia developed during percutaneous cardiopulmonary bypass (PCPS) and was detected with the lowering of the bispectral index (BIS) values. A 7-yr-old boy was managed with PCPS for the treatment of cardiogenic shock after cardiac surgery. His circulation was dependent on PCPS and pulse pressure was nearly zero. Signals by pulse oxymetry were undetectable and periodical blood gas analysis was performed to confirm proper oxygenation. BIS was monitored, and a gradual decrease in the value was observed. Careful observation also revealed darkening of the blood in the PCPS circuit and blood gas analysis showed severe hypoxia. Oxygen concentration of the gas to a PCPS oxygenator was increased immediately and new PCPS circuit was prepared. It took almost two minutes to exchange the circuit. Near circulatory arrest might have occurred during the procedure and BIS and suppression ratio (SR) became below 10 and above 90, respectively. Both returned to the previous values 30 min after the replacement of the circuit. Severe hypoxia, otherwise overlooked, was detected with BIS monitoring and BIS reflected the circulatory status of the patient, especially of the brain. This monitoring is useful to confirm proper oxygenation during PCPS.

Cardiopulmonary Bypass↗

[Clinical laboratory data and reference intervals standardized in Fukuoka].

In Fukuoka whose population is approximately five million inhabitants, surveys on the accuracy of laboratory data have been performed by the Fukuoka Prefecture Medical Association for the last 30 years. We have been attempting to evaluate the data for routine use since 1988, and it has become possible to share laboratory data between all institutions in Fukuoka prefectures. As a result, reference intervals for 23 clinical chemistry analytes were established in 1995, to which were added in 1996 five serum protein constituents that have been utilized for clinical examinations. Methods for documentations and monitorings the data obtained in the prefecture were also established, standardization of the above analytes extended to 97% of the institutions in the prefecture. Results for 14 of the 23 clinical chemistry analytes have become highly reliable and clinically useful as differences between institutions in terms of results have narrowed. Standardization of other analytes is now in progress.

Aged↗