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Biomedical subjects

H Ishihara

Publications and source records attributed to H Ishihara.

At least 181 records · Page 10Linked to original sources

ONO-5046, an elastase inhibitor, attenuates liver mitochondrial dysfunction after endotoxin.

OBJECTIVE: To investigate the effect of ONO-5046, an elastase inhibitor, on liver mitochondrial dysfunction after endotoxin administration. DESIGN: Prospective, randomized, controlled animal study. SETTING: Research laboratory. SUBJECTS: Male Hartley guinea pigs. INTERVENTIONS: Endotoxin shock was induced by intravenous infusion of Escherichia coli lipopolysaccharide endotoxin (50 mg/kg). Six guinea pigs were treated with endotoxin and saline. Twenty-four guinea pigs received 5, 10, and 30 mg/kg/hr of ONO-5046 after endotoxin administration. Six guinea pigs received only saline. MEASUREMENTS AND MAIN RESULTS: We measured oxygen uptake in state 3 (substrate and adenosine 5'-diphosphate [ADP]) and state 4 (excess substrate, no ADP), as well as the respiratory control ratio (state 3/state 4), adenosine 5'-diphosphate/oxygen ratio (ADP/O), and arterial ketone body ratio. ONO-5046 was dose dependently effective in liver mitochondrial oxidative phosphorylation, such as oxygen uptake in stage 4, respiratory control ratio, adenosine triphosphate synthesis, ADP/O, and arterial ketone body ratio when ONO-5046 was started 30 mins after endotoxin. The administration of 30 mg/kg/hr of ONO-5046 improved mean blood pressure, which had decreased after endotoxin. CONCLUSION: ONO-5046 attenuates the endotoxin-induced liver mitochondrial dysfunctions that may be related to increased liver blood flow.

Adenosine Diphosphate↗

Measurements of extracellular fluid volume in highly perfused organs and lung water in hypo- and hypervolaemic dogs.

The purpose of this study was to identify whether the central extracellular fluid volume status following hypo- and hypervolaemia can be measured by the initial distribution volume of glucose or by the extravascular lung water. These two estimates were compared with the initial distribution volume of sucrose which has been used as an indicator for the measurement of the extracellular fluid volume. The above three estimates were determined by the administration of glucose, chilled saline and sucrose solutions, before and after haemorrhage (30 mL kg-1), and subsequent fluid load (lactated Ringer's solution 90 mL kg-1). The distribution volumes of glucose and sucrose decreased after haemorrhage and increased after fluid load compared with normovolaemic values, and a linear correlation was obtained between these two distribution volumes (r = 0.93, P < 0.001, n = 36). However, the extravascular lung water remained statistically unchanged throughout the procedure, despite a weak linear correlation with the sucrose distribution volume (r = 0.38, n = 33, P < 0.05). These results indicate that the initial distribution volume of glucose is more useful as an indicator of the central extracellular fluid volume status than the extravascular lung water.

Animals↗

In vivo spasmolytic effect of ketamine and adrenaline on histamine-induced airway constriction. Direct visualization method with a superfine fibreoptic bronchoscope.

BACKGROUND: Ketamine (K) has been reported to produce bronchodilation in patients suffering from asthma. Although most researchers have used indirect measurements to study the effect of K in vivo, the reliability of these indirect methods are controversial. We have developed a new technique to measure the bronchial cross-sectional area (BCA) in vivo with a superfine fibreoptic bronchoscope (SFB). Employing this method, we evaluated in vivo spasmolytic effect of K and adrenaline (A). METHODS: Twenty-one mongrel dogs were anaesthetized with pentobarbitone (30 mg.kg-1) and paralyzed with pancuronium (200 micrograms.kg-1.h-1). The trachea was intubated with an endotracheal tube that has a second lumen for insertion of a SFB (OD: 2.2 mm) to measure the BCA continuously. The tip of the SFB was placed between the 2nd and 3rd bronchial bifurcation of the right lung. A videoprinter printed the BCA, which was then measured with NIH Image. Bronchoconstriction was produced with histamine (H: 10 micrograms.kg-1 + 500 micrograms.kg-1.h-1) which was administered until the end of the experiment. The BCA was assessed before and 30 min after the start of H infusion. The dogs were randomly allocated to 3 groups of 7 dogs each. In group K, K (0-10 mg.kg-1) was given i.v., and the BCA was measured 5 min after each K dose. In group A, A (0-0.4 microgram.kg-1) was given i.v., and the BCA was measured 1 min after each A dose. In group A + K, K (1 mg.kg-1 i.v. + 1 mg.kg-1.h-1 i.v.) was given followed, 30 min after, by A i.v. in the same doses as in group A. The BCA was assessed 30 min after the start of K and again 1 min after each A dose. RESULTS: K 10 mg.kg-1 reversed H-induced bronchoconstriction. A subthreshold dose of K significantly potentiated the effect of A, reversing the decrease in BCA by H. CONCLUSION: We have found that K could reverse the H-induced bronchoconstriction and potentiate the A-induced bronchial relaxation.

Animals↗

Increased plasma vasopressin and atrial natriuretic peptide in chronic schizophrenic patients during abdominal surgery.

Chronic schizophrenic patients are reported to develop imbalanced water homeostasis by the pathological secretion of vasopressin and aldosterone. We measured plasma vasopressin, aldosterone and atrial natriuretic peptide in schizophrenic patients to elucidate the role of these hormones during a perioperative period. Eighteen schizophrenic patients with chronic antipsychotic drugs over 10 years and 22 as a control group who underwent elective lower abdominal surgery were the subjects of this study. In the schizophrenic patients, plasma aldosterone secretion was significantly inhibited, while plasma vasopressin and atrial natriuretic peptide were significantly increased during surgery. A good relationship (r = 0.69, p < 0.01) between plasma atrial natriuretic peptide and plasma osmolality was obtained 60 min after skin incision, but not before the induction of anesthesia. The findings suggest that chronic schizophrenic patients may develop an abnormal secretion of vasopressin, aldosterone and atrial natriuretic peptide during anesthesia.

Adult↗

The measurement of physiological tooth displacement in function.

The purpose of this work was to investigate the physiological tooth displacement in function. We developed the tooth displacement transducer Type M-3 and measured the three dimensional displacement of the upper and lower left first molars in function. The summary is as follows: 1. Magnesensors were used in the tooth displacement transducer Type M-3. Its total weight was 48.7 g. and the measuring pressure was kept less than 0.4 g. It was fixed at the labial surface of the anterior teeth using a paraocclusal splint. 2. The linearity error of the transducer was less than 2% within a range of +/-200 microm. 3. The upper left first molar showed displacement in the palatal and apical direction during clenching at the intercuspal position with habitual occlusal force or during the biting of articulating papers. The displacement varied between 40 and 136 microm. 4. The lower left first molar showed displacement in the apical and lingual direction during clenching at the intercuspal position or during the biting of articulating papers. The displacement varied between 29 and 65 microm. 5. The upper left first molar showed displacement in the palatal and apical direction during mastication. The displacement varied between 68 microm and 79 microm. The upper teeth moved first in the apical direction, then moved toward the labial direction. 6. In the lingual direction, the lower left first molar showed displacement ranging from 11 to 71 microm and 17 to 39 microm in the buccal direction during mastication.

Adult↗

[Perioperative management of a patient with cryoglobulinemia for open heart surgery].

A 57-year-old male with cryoglobulinemia underwent an aortic valve replacement for aortic regurgitation under total intravenous anesthesia with droperidol, fentanyl and ketamine in combination with mild hypothermic cardiopulmonary bypass (esophageal temperature = 34 degrees C). Preoperative steroid therapy with prednisolone of daily dose from 40 to 7.5 mg for six months and plasma exchange (3200 ml) on the day before the operation were performed to attenuate the degree of cryoglobulinemia. He showed an uneventful intraoperative course and there was no postoperative complication associated with cryoglobulinemia.

Anesthesia, Intravenous↗

[Two cases of circulatory failure after local infiltration of epinephrine during tonsillectomy].

We experienced two cases of circulatory failure after local infiltration of 0.0005% epinephrine solution for the purpose of prophylactic hemostasis during tonsillectomy under sevoflurane anesthesia. Case 1: A 14 year-old girl developed ventricular bigeminy, tachycardia and hypertension following infiltration of the epinephrine solution 6ml around the tonsil. Sinus rhythm returned with intravenous lidocaine 40 mg and propranolol 0.4 mg. However, the patient showed gradually decreasing heart rate, depressed ST segments and inverted T waves and poor peripheral circulation. Her blood pressure decreased abruptly at the same time and finally the pulsation of the radial and femoral arteries was not palpable. She was treated with intravenous ephedrine in vain. Therefore, she received intravenous epinephrine and cardiac massage, and then recovered from the circulatory failure with her ECG showing normal sinus rhythms. Emergence from the anesthesia was smooth. Her cardiac failure may have been caused by the decreasing cardiac contraction and the increasing afterload due to the vasoconstriction after the intravenous beta-blocker. Case 2: An eleven year-old boy showed ventricular tachycardia and hypertension after infiltration of the epinephrine solution 11.5 ml around the tonsil. Lidocaine was given intravenously. This restored sinus rhythm but the ST segments on his ECG were elevated. ST segments became normalized after intravenous nitroglycerin. However, pulmonary edema developed suddenly, and it was cured by intensive treatment. His ventricular tachycardia and hypertension after the local administration of epinephrine were presumably responsible for the acute heart failure causing the pulmonary edema. Our experience suggests that the maintenance of cardiac function and the reduction of afterload are important to overcome the circulatory disaster following the local infiltration of epinephrine.

Adolescent↗

Novel compounds, 1,3-selenazine derivatives, as antibacterial agents against Escherichia coli and Staphylococcus aureus.

The antibacterial activities of several kinds of novel 4H-5,6-dihydro-1,3-selenazine derivatives against Escherichia coli and Staphylococcus aureus were investigated. 4-Hydroxy-4-methyl-2-p-tolyl-4H-5,6-dihydro-1,3-selenazine (TS-1), 4-ethyl-4-hydroxy-2-p-tolyl-4H-5,6-dihydro-1,3-selenazine (TS-2), and 4-hydroxy-4-methyl-2-pentyl-4H-5,6-dihydro-1,3-selenazine (PS-1) exhibited strong inhibitory activity against E. coli, and TS-1, TS-2, PS-1, 4-hydroxy-4-methyl-2-pentyl-6-propyl-4H-5,6-dihydro-1,3-selenazine (PS-6) and 4-hydroxy-4-methyl-2-pentyl-6-phenyl-4H-5,6-dihydro-1,3-selenazine (PS-8) also showed inhibitory activity against S. aureus. 4H-5,6-dihydro-1,3-thiazines and 1,3-selenazole had no inhibitory activities against both bacteria. TS-1, TS-2, and PS-1 exhibited marked antibacterial activities against both Gram-negative and Gram-positive bacteria.

Anti-Bacterial Agents↗

[Polymyositis-induced respiratory failure in the presence of antecedent pleural effusion].

Pulmonary involvement is generally recognized to be an important determinant of the clinical course in cases of polymyositis. A patient with bilateral pleural effusion as an initial symptom developed respiratory failure due to muscle weakness. Polymyositis was diagnosed on the basis of a muscle biopsy. A chemotherapy regimen consisting of methyl prednisolone (1 g/day for 3 days) followed by prednisolone (60 mg/day) alleviated, the pleural effusion and respiratory failure. Though pleural complications in polymyositis have been described mostly in association with concomitant interstitial lung disease, our patient exhibited only bilateral pleural effusion. Given that pleural effusion can be an initial symptom of polymyositis, it seems necessary that polymyositis be taken into consideration by differential diagnoses of pleural effusion of unknown etiology.

Aged↗

[Severe pneumococcal pneumonia with acute respiratory failure and neutropenia].

Severe pneumococcal pneumonia may precipitate both respiratory failure and neutropenia. The prognoses are considered to be very poor in such cases. We encountered three patients with pneumococcal pneumonia presenting respiratory failure and neutropenia, and successfully treated two. All three patients showed disseminated intravascular coagulation, and respiratory failure requiring mechanical ventilation. Neutropenia was treated with granulyte-colony stimulating factor (G-CSF), with methylpredonisolone administered by pulse therapy for 3 days to treat severe respiratory failure during the clinical course. All 3 patients were relieved of their respiratory failure at least for a few days following treatment. As a result of treatment with antibiotics and G-CSF, pneumococci disappeared from the patients' sputum. However, it has been reported that disintegration of the bacterial cell walls can release inflammatory components capable of causing secondary inflammatory reactions in the lung tissue. This suggested that the worsening respiratory failure experienced by our patients during their clinical course was a result of such reactions, and that methylpredonisolone was effective as the treatment of inflammation.

Aged↗

A regional variation of acetylcholine-induced relaxation in different segments of rat aorta.

The tension of the isolated thoracic aorta of the rat was measured isometrically to determine if there is a regional variation of the relaxation to acetylcholine (ACh). Endothelium-derived nitric oxide (NO)-dependent relaxation to ACh in the thoracic aorta precontracted with norepinephrine was significantly greater in the middle and distal segments than in the proximal segments. The relaxation to ACh was inhibited by NG-nitro-L-arginine methyl ester, an inhibitor of NO synthase. The relaxation to the NO donor sodium nitroprusside did not differ between the same three segments of the thoracic aorta. These results suggest that there are regional variations in the ACh-induced release of endothelium-derived NO in the rat thoracic aorta.

Acetylcholine↗

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an islet substance serving as an intra-islet amplifier of glucose-induced insulin secretion in rats.

1. We examined whether pituitary adenylate cyclase-activating polypeptide with 38 or 27 residues (PACAP-38 or PACAP-27) serves as an intra-islet regulator of glucose-induced insulin secretion in rats. PACAP antiserum specific for PACAP-38 and PACAP-27 was used to neutralize the effect of endogenous PACAP in islets. PACAP release from islets was bioassayed using the response of cytosolic Ca2+ concentration ([Ca2+]i) in single beta-cells, monitored by dual-wavelength fura-2 microfluorometry. Expression of PACAP mRNA was studied by reverse transcription-polymerase chain reaction (RT-PCR), while expression of PACAP was studied by metabolic labelling and immunoblotting. Localization of PACAP receptors was studied immunohistochemically. 2. High glucose-stimulated insulin release from isolated islets was attenuated by PACAP antiserum but not by non-immune sera. 3. The islet incubation medium with high glucose (Med) possessed a capacity, which was neutralized by PACAP antiserum, to increase [Ca2+]i in beta-cells. PACAP antiserum also neutralized the [Ca2+]i-increasing action of synthetic PACAP-38 and PACAP-27, but not that of vasoactive intestinal polypeptide (VIP) and glucagon. 4. Both Med and synthetic PACAP increased [Ca2+]i in beta-cells only in the presence of stimulatory, but not basal, glucose concentrations. In contrast, ATP, a substance that is known to be released from beta-cells, increased [Ca2+]i in beta-cells at both and stimulatory glucose concentrations. 5. Expression of PACAP mRNA and biosynthesis of PACAP-38 were detected in islets and a beta-cell line, MIN6. 6. Immunoreactivity for PACAP-selective type-I receptor was observed in islets. 7. [Ca2+]i measurements combined with immunocytochemistry with insulin antiserum revealed a substantial population of glucose-unresponsive beta-cells, many of which were recruited by PACAP-38 into [Ca2+]i responses. 8. These results indicate that PACAP-38 is a novel islet substance that is synthesized and released by islet cells and then, in an autocrine and/or paracrine manner, potentiates and arouses beta-cell responses to glucose, thereby amplifying glucose-induced insulin secretion in islets.

Adenosine Triphosphate↗

Detection and cloning of unique integration sites of retrotransposon, intracisternal A-particle element in the genome of acute myeloid leukemia cells in mice.

We previously found retrotransposition of the intracisternal A-particle (IAP) element in the genome of acute myeloid leukemia (AML) cells induced by X-irradiation of C3H/He mice (FEBS 16333). To analyze the occurrence of the IAP-mediated retrotransposition in AML cells, we compared integration sites of the IAP element by polymerase chain reaction (PCR) in the genomes of five AML strains derived from different C3H mice. Unique PCR products were found in all of the above independent leukemia cells, whereas no such products were detected in normal cells. Results of cloning, sequencing and Southern analyses showed that the PCR products were derived from novel integration sites of the IAP element in the genome. The data suggest that IAP-mediated retrotransposition occurs frequently in radiation-induced AML cells from C3H/He mice.

Animals↗

Facet joint asymmetry as a radiologic feature of lumbar intervertebral disc herniation in children and adolescents.

STUDY DESIGN: This study compared the incidence of facet joint asymmetry between adult and juvenile patients with lumbar intervertebral disc herniation. OBJECTIVES: To determine the different distribution of the facet joint asymmetry between the adult and juvenile patients. SUMMARY OF BACKGROUND DATA: As early as 1967, it was suggested that asymmetry of the facet joints is correlated with the development of disc herniation. There have been numerous arguments for and against Farfan's hypothesis, however, most studies were carried out on adult patients, and this hypothesis has not been verified in juvenile patients. METHODS: The study group consisted of 29 levels of 25 patients aged 12-20 years (juvenile group) and 50 levels of 33 patients aged 30-49 years (adult group) who underwent posterior discectomy. The shape of facet joints, the facet joint angle, and the moment arm angle and length were measured for each facet joint using computed tomography. Facet joint asymmetry was defined as the difference in facet joint shape or a difference of more than 10 degrees in facet joint angles between the right and left sides. The incidence of facet joint asymmetry and the relationships among the facet joint asymmetry and the location, type of disc herniation, and disc degeneration were examined in juvenile and adult groups. RESULTS: The overall incidence of facet joint asymmetry was significantly higher in the juvenile group (12 levels, 41%) than in the adult group (four levels, 8%; P < 0.01). There were no significant relationships among the facet joint asymmetry, the location, type of disc herniation, and disc degeneration. CONCLUSIONS: This study revealed that the frequency of facet joint asymmetry in the juvenile group was five times higher than that in the adult group. This result indicates that facet joint asymmetry is a radiologic feature of lumbar intervertebral disc herniation in children and adolescents.

Adolescent↗

Lumbar intervertebral disc herniation in children less than 16 years of age. Long-term follow-up study of surgically managed cases.

STUDY DESIGN: In this retrospective study, the long-term clinical results of lumbar intervertebral disc herniation in children less than 16 years of age were reviewed. OBJECTIVES: To evaluate the effectiveness of surgical treatment including posterior discectomy, extraperitoneal anterolateral discectomy, and anterior interbody fusion for lumbar intervertebral disc herniation in children less than 16 years of age. SUMMARY OF BACKGROUND DATA: Although previous follow-up studies on surgically managed lumbar intervertebral disc herniation in children and adolescents generally reveal good outcomes, few reports have focused on the time course of clinical findings and the long-term results. METHODS: The outcome of subjective symptoms, clinical signs, and time-related change of the intervertebral disc space in 11 patients were evaluated with an average follow-up period of 9 years (range, 5-12 years). RESULTS: The posterior discectomy procedure relieved clinical symptoms quickly. In the case of central herniation with or without intervertebral instability, extraperitoneal anterolateral discectomy or anterior interbody fusion led to favorable long-term results. Clinical symptoms (lower back pain, leg pain) and neurologic disturbance disappeared within 3 months after surgery. Recovery of normal straight leg raising test results (tight hamstrings), however, required much more time than recovery of other symptoms. Narrowing of the intervertebral disc space progressed up to 3-6 months after discectomy, but then disc space widening occurred. CONCLUSIONS: Satisfactory long-term clinical results and early return to school life were obtained with each surgical procedure. It is important to aim toward an early return to school via surgical treatment.

Adolescent↗

Effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc.

STUDY DESIGN: This study is a unique in vitro study on the effects of hydrostatic pressure on human intervertebral disc metabolism. OBJECTIVE: To investigate the effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc. SUMMARY OF BACKGROUND DATA: Mechanical stress and hydrostatic pressures influence proteoglycan and protein synthesis rates in bovine articular cartilage and coccygeal discs. However, the mechanism of matrix synthesis regulation of the intervertebral disc under mechanical stress has not been elucidated. METHODS: Twenty-eight human lumbar intervertebral discs obtained from surgery and from cadavers at autopsy were used. Each tissue fraction was charged with medium in a plastic syringe and placed in a water-filled hydrostatic pressure-control vessel. The hydrostatic pressures applied were 1 (control), 3, and 30 atm (atm = atmospheres) for 2 hours. The proteoglycan and protein synthesis rates were determined by radioisotope incorporation. The production of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 were measured by a one-step enzyme immunoassay method using monoclonal antibodies. RESULTS: Three atm pressure stimulated proteoglycan synthesis rates in the nucleus pulposus and inner anulus (n = 14 in each tissue). Compared with the control group, 30 atm pressure significantly inhibited proteoglycan synthesis in the inner anulus (P = 0.011). In the nucleus pulposus, matrix metalloproteinase-3 production was stimulated at a pressure of 30 atm relative to 3 atm (P = 0.014, n = 16 in each tissue). The highest tissue inhibitor of metalloproteinases-1 production showed highest values at 3 atm pressure in the inner anulus (n = 16 in each tissue). CONCLUSION: The results suggest that hydrostatic pressure influences intervertebral disc cell metabolism. A physiologic level of hydrostatic pressure (3 atm) may act as an anabolic factor for stimulation of proteoglycan synthesis and tissue inhibitor of metalloproteinases-1 production. This may be essential for maintaining the matrix of the disc. If the pressure was 30 atm or more or 1 atm or less, a catabolic effect will be predominant, with reduction of proteoglycan synthesis rate and increase of matrix metalloproteinase-3 production. Abnormal hydrostatic pressure, therefore, may accelerate disc degeneration.

Cadaver↗

Insulin receptor substrate (IRS)-2 is dephosphorylated more rapidly than IRS-1 via its association with phosphatidylinositol 3-kinase in skeletal muscle cells.

Insulin receptor substrate (IRS)-2 is structurally and functionally similar to IRS-1. Indeed, stimulation with insulin or insulin-like growth factor I led to the rapid tyrosine phosphorylation of both IRS-1 and IRS-2, which in turn activated phosphatidylinositol (PI) 3-kinase in L6 cells and rat skeletal muscle. However, IRS-2 was rapidly dephosphorylated (3-10 min after the addition of insulin/insulin-like growth factor I), whereas IRS-1 phosphorylation continued for at least 60 min. The time courses of the PI 3-kinase activity associated with IRS-1 and IRS-2 paralleled the tyrosine phosphorylation of these proteins. Preincubation with sodium orthovanadate, an inhibitor of protein tyrosine phosphatase, blocked the rapid dephosphorylation of IRS-2, suggesting the involvement of tyrosine phosphatase. The activation of PI 3-kinase apparently plays an important role in the rapid dephosphorylation of IRS-2, as IRS-2 dephosphorylation was inhibited markedly by suppressing PI 3-kinase activity with wortmannin or overexpression of the dominant negative p85 subunit of PI 3-kinase, which cannot bind the p110 catalytic subunit. In addition, platelet-derived growth factor stimulation prior to insulin stimulation decreased IRS-associated PI 3-kinase and significantly inhibited the dephosphorylation of IRS-2. Taken together, these observations suggest that IRS-2 plays a unique role in mediating the signals from the insulin receptor to downstream molecules and that this effect is more transient than that of IRS-1. Tyrosine phosphatase and IRS-associated PI 3-kinase activity thus contribute to the rapid dephosphorylation of IRS-2.

Androstadienes↗

Co-localization of glucokinase with actin filaments.

A portion of glucokinase appeared to be co-localized with actin filaments in the cytoplasm of cultured rat hepatocytes incubated with 25 mM glucose. When liver- or islet-type glucokinase was transiently expressed in COS-7 cells, the expressed glucokinase was also co-localized with actin filaments in the cytoplasm of these transfected cells. Although co-localization of glucokinase with actin filaments was not clearly demonstrated in the pancreatic beta-cell line MIN6, islet glucokinase was found to be present in both the nucleus and the cytoplasm, though predominantly in the nucleus. These findings suggest that subcellular localization of glucokinase, including co-localization with actin filaments, may have an important physiological role in metabolic regulation.

Actins↗