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Biomedical subjects

H Ishihara

Publications and source records attributed to H Ishihara.

At least 109 records · Page 6Linked to original sources
PubMed2000

Spasmolytic effects of prostaglandin E1 on serotonin-induced bronchoconstriction and pulmonary hypertension in dogs.

In this study, we simultaneously evaluated the spasmolytic effects of prostaglandin E1 (PGE1) on serotonin-induced bronchoconstriction and pulmonary hypertension. Eleven mongrel dogs (8-12 kg) anaesthetized with pentobarbital were assigned to two groups: saline (n = 4) and PGE1 (n = 7). Bronchoconstriction and pulmonary hypertension were elicited with serotonin 10 micrograms kg-1 + 1 mg kg-1 h-1 and assessed as the percentage change in bronchial cross-sectional area (BCA) measured by bronchoscopy and pulmonary vascular resistance (PVR), respectively. Thirty minutes after starting the serotonin infusion, saline or PGE1 0 (saline), 0.01, 0.1, 1.0 or 10 micrograms kg-1 i.v. was given. %BCA and %PVR (basal = 100%) were assessed before and 30 min after serotonin, and 30 and 60 min after saline (saline group) or 5 min after each dose of PGE1 (PGE1 group). In the saline group, pulmonary hypertension and bronchoconstriction were stable. In the PGE1 group, PGE1 at > or = 0.1 microgram kg-1 significantly decreased %BCA and 10 micrograms kg-1 almost fully reversed the constriction (from mean (SEM) 56.2% (4.9%) to 94.4% (3.7%)). %PVR was significantly decreased at 10 micrograms kg-1 (from 230% (24%) to 176% (11%)) only. We suggest that PGE1 may produce bronchodilation rather than pulmonary vasodilation.

Alprostadil↗
PubMed2000

A comparison of the spasmolytic effects of olprinone and aminophylline on serotonin-induced pulmonary hypertension and bronchoconstriction with or without beta-blockade in dogs.

In the present study in dogs, we compared with aminophylline the spasmolytic effects of olprinone, a novel phosphodiesterase 3 inhibitor, on serotonin-induced pulmonary hypertension (PH) and bronchoconstriction. Mongrel dogs were anesthetized with pentobarbital. PH and bronchoconstriction were induced with serotonin: 10 microg/kg + 1 mg x kg(-1) x h(-1), and assessed as % changes in pulmonary vascular resistance and bronchial cross-sectional area (basal = 100%). Initially, the relaxant effects of olprinone (n = 8: 0-1000 microg/kg) and aminophylline (n = 8: 0-100 mg/kg) were compared. Pulmonary vascular resistance and bronchial cross-sectional area were assessed before and 30 min after serotonin infusion began and 5 min after each dose of olprinone or aminophylline. We then determined whether propranolol (0.4 mg/kg) reversed the relaxation induced by olprinone (1000 microg/kg, n = 6) or aminophylline (100 mg/kg, n = 6) compared with saline (n = 6 each). Olprinone and aminophylline dose-dependently attenuated both PH and bronchoconstriction (olprinone > aminophylline: -logED(50)[mean] for PH and bronchoconstriction 5.37+/- 0.35[4.24 microg/kg] vs. 1.60+/-0.23[25.4 mg/kg] and 4.06+/-0.12[87.8 microg/kg] vs. 1.51+/-0.21[30.6 mg/kg], respectively). In addition, olprinone produced more potent pulmonary vasodilation than bronchodilation while aminophylline was equipotent. In addition, there was a significant increase in plasma catecholamines after olprinone (> or =100 microg/kg) and aminophylline (> or =10 mg/kg). With the exception of aminophylline-induced bronchodilation, propranolol did not reverse any of the other effects measured. Therefore, the spasmolytic effects of olprinone are independent of plasma catecholamines, while the bronchodilating effect of aminophylline may partially involve increased levels of circulating catecholamines.

Adrenergic beta-Antagonists↗
PubMed2000

Detection of capillary protein leakage by indocyanine green and glucose dilutions in septic patients.

OBJECTIVE: To determine whether indocyanine green (ICG) and glucose dilutions can detect generalized capillary protein leakage in septic patients without requiring repeated measurements. DESIGN: Prospective, clinical study. SETTING: General intensive care unit. PATIENTS: Twelve consecutive patients who met the criteria of sepsis and 16 consecutive acute myocardial infarction (AMI) patients without any underlying pathology inducing generalized protein capillary leakage. INTERVENTIONS: Both ICG 25 mg and glucose 5 g were administered simultaneously, to calculate the plasma volume determined by the ICG dilution method (PV-ICG) and the initial distribution volume of glucose (IDVG), on day 1 of sepsis or on day 1 of hospitalization for the AMI patients. The relationship between these two volumes and the PV-ICG/IDVG ratio was evaluated in two patient groups. MEASUREMENTS AND MAIN RESULTS: Although the IDVG of the two patient groups was not statistically different, the PV-ICG in the septic patients was higher than that in the AMI patients (p < .01). Consequently, the PV-ICG/IDVG ratio in the septic patients was higher than that in the AMI patients (p < .01). Eight of the 12 septic patients had a PV-ICG/IDVG ratio of >0.45, which was not observed in any of the AMI patients. The PV-ICG/IDVG ratio in the septic patients correlated inversely with the total plasma protein concentration (r2 = .46, p < .025) and mean arterial pressure (r2 = .42, p < .05). CONCLUSIONS: Our results indicate that overestimation of the PV-ICG can occur in septic patients and, further, suggest that simultaneous measurement of the two distribution volumes would help predict generalized capillary protein leakage in septic patients without repeated measurement.

Adult↗
PubMed2000

Phenotypic variation of familial hypertrophic cardiomyopathy caused by the Phe(110)-->Ile mutation in cardiac troponin T.

Mutation of the cardiac troponin T (cTnT) gene is a genetic determinant of familial hypertrophic cardiomyopathy (HCM). A Japanese family of 14 individuals, including 6 with HCM, was subjected to genetic and clinical assessment. Five exons of the cTnT gene were sequenced in all family members. A heterozygous or homozygous T(340)-->A (Phe(110)-->Ile) mutation in exon 9 of the cTnT gene was detected in 11 subjects. Morphological and functional evaluation of the left and right ventricles by echocardiography revealed that 4 of 9 individuals heterozygous for the mutant allele exhibited HCM with moderate cardiac hypertrophy. Cardiac hypertrophy and other clinical features in the 2 subjects homozygous for the mutation were more severe than were those in heterozygous individuals with HCM. Thus, the clinical features of HCM due to the Phe(110)-->Ile mutation in the cTnT gene appear to be modified by a gene dosage effect.

Adolescent↗
PubMed2000

Expression of leptin receptor in human endometrium and fluctuation during the menstrual cycle.

Leptin is secreted by adipocytes and regulates appetite through interaction with hypothalamic leptin receptors (OB-R). Accumulated evidence shows that leptin is involved in the stimulation of reproductive functions and that local expression of leptin and OB-R in the ovary, oocyte, embryo, and placenta plays a role in early development. To investigate the role of leptin in implantation, we examined the expression of OB-R and leptin in the human endometrium. Northern and Western blot analyses and RT-PCR showed that the long form of OB-R (OB-R(L)) messenger ribonucleic acid (mRNA) and protein were expressed. In contrast, leptin mRNA or protein was not detected. All of the splice variants of OB-R (OB-R(T)) and OB-R(L) transcripts were expressed in 90% and 84% of the cases, respectively. OB-R mRNA expression peaked in the early secretory phase. Decidual tissue of early gestation also expressed OB-R(T) and OB-R(L). Their incidence and abundance were comparable among endometria with benign uterine diseases and disease-free endometria and were not related to a body mass index within the normal range. The present results indicate that OB-R, but not leptin, is expressed in the human endometrium.

Carrier Proteins↗
PubMed2000

Progesterone induction of 17beta-hydroxysteroid dehydrogenase type 2 during the secretory phase occurs in the endometrium of estrogen-dependent benign diseases but not in normal endometrium.

In the human endometrium, inactivation of 17beta-estradiol to estrone is catalyzed by 17beta-hydroxysteroid dehydrogenase type 2 (17betaHSD2). Previous studies have shown that the 17betaHSD2 activity in the endometrium is elevated during the secretory phase, as compared with the level during the proliferative phase, and that the elevation is in response to progesterone via the progesterone receptors. Recently, it has been demonstrated that aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis, is not present in the endometrium obtained from normal menstruating women with cervical cancer in situ showing no other gynecological disease (defined as "disease free"), but present in the endometrium obtained from patients with endometriosis, adenomyosis, and/or leiomyomas (defined as "diseased"). However, the previous 17betaHSD studies have been performed without distinguishing between disease-free and diseased endometria. We, therefore, analyzed 17betaHSD2 distinguishing between disease-free and diseased endometria. During the proliferative phase, the abundance of messenger RNA (mRNA) and activity of 17betaHSD2 were comparable in both disease-free and diseased endometrium. However, during the secretory phase, while the abundance of mRNA and activity of 17betaHSD2 increased 4- to 6-fold in diseased endometrium, the 17betaHSD2 remained unchanged in the disease-free endometrium. Kinetic studies showed that the Km was identical among the four groups of endometria, suggesting that the elevation of 17betaHSD2 simply resulted from increased mRNA transcription. Organ culture of proliferative endometria in the presence of progestins resulted in the stimulation of 17betaHSD2 in diseased endometria via the progesterone receptors, whereas disease-free endometrium was not stimulated by progestins. These results suggest that the previous paradigm that 17betaHSD2 activity in the endometrium is elevated during the secretory phase is confined to diseased endometrium but not to disease-free endometrium and that the estrogen metabolism is altered in the endometria of the patients with estrogen-dependent benign diseases.

17-Hydroxysteroid Dehydrogenases↗
PubMed2000

Insulin-like growth factor-I (IGF-I)/IGF-I receptor axis and increased invasion activity of fibroblasts in keloid.

Activation of signals for insulin-like growth factor-I receptor (IGF-IR) is thought to be closely linked to abnormal cell proliferation and differentiation in various diseases. The keloid in which fibroblasts invade beyond the margins of the original wound, is a dermal fibroproliferative tissue of unknown etiology. Clinically, keloids are most commonly observed in subjects at ages between 10 and 30 years. Interestingly, plasma levels of growth hormone and IGF-I are also high during the same period, suggesting that IGF-I might be involved in the patho-physiology of keloid fibroblasts. We therefore first examined the expression level of IGF-IR in normal and keloid tissues. Immunohistochemical analysis confirmed increased expression of IGF-IR in keloid fibroblasts, but not in normal fibroblasts. On the other hand, the staining intensity of IGF-IR in the epidermis of normal tissues was almost equal to that in keloids. Next, to study the functional properties of the IGF-I/IGF-IR axis in both normal and keloid fibroblasts, we investigated invasion activities. The invasive activity of IGF-IR overexpressing keloid fibroblasts was greatly increased in the presence of IGF-I, and inhibited by a neutralizing antibody to IGF-I. In contrast, its activity of IGF-IR weak-expressing normal fibroblasts was not changed. Our results indicate the involvement of the activated IGF-I/IGF-IR axis in the pathogenesis of the invasive activity of fibroblasts.

Adolescent↗
PubMed2000

Increased expression of intracisternal A-particle RNA in regenerated myeloid cells after X irradiation in C3H/He inbred mice.

Myeloid Cells after X Irradiation in C3H/He Inbred Mice. Myeloid leukemia cells were derived from regenerated hematopoietic cells damaged by sublethal doses of X radiation in C3H/He inbred mice. We previously found that within the genome of the myeloid leukemia cells, a retrotransposon, the intracisternal A-particle (IAP) element, is integrated. Levels of IAP RNA, the source of cDNA for the integration, were analyzed quantitatively in C3H mice. Higher levels of IAP transcripts were observed in normal cells, particularly in hematopoietic cells, from C3H/He mice, than in those from C57BL/6J and STS/A mice. In the C3H/He mice, an approximately twofold increase in IAP RNA was found in the regenerated spleen and bone marrow cells at 5 days and from 12 to 90 days after whole-body X irradiation. In addition, an increased level of IAP RNA was observed in all the myeloid leukemia cells derived from C3H/He mice. This suggests that the elevated levels of IAP RNA in the regenerated hematopoietic cells after irradiation contribute to the increase in retrotransposition of IAP found in myeloid leukemia cells from C3H/He mice.

Animals↗
PubMed2000

[Influence of occlusal contacts on tooth displacement].

During function, the tooth displacement path depends on occlusal contacts of the upper and lower teeth. Therefore, we must reconstruct occlusal relation carefully so as not to disturb physiological tooth displacement. In this investigation, tooth displacements were measured with the Displacement Transducer type M-3 in varying occlusal contact. The following conclusions were obtained. 1. The location of occlusal contacts influenced the tooth displacement of the upper first molar. Especially, an occlusal contact on the lingual inclination of the lingual cusp, buccal cusp had great influence. The tooth showed displacement toward the buccal direction, and it differed from the physiological tooth displacement path during clenching at the intercuspal position. 2. The location of occlusal contacts had little influence on the tooth displacement of the lower first molar. The tooth showed displacement toward the lingual direction. It was similar to the physiological tooth displacement. 3. On the upper first molar, the location of occlusal force influenced the Stress-Strain curve. Especially, the occlusal force on the buccal cusp had great influence on the amount of tooth displacement. 4. On the lower first molar, the location of occlusal force influenced the Stress-Strain curve. Especially, the occlusal force on the lingual cusp brought much displacement and a 2-phase displacement path, at times. Therefore, occlusal contacts have close relation to tooth displacement, and any occlusal reconstruction should harmonize with tooth displacement representing periodontal tissue distortion.

Adult↗
PubMed1999

Association between an aggrecan gene polymorphism and lumbar disc degeneration.

STUDY DESIGN: A case-control study using magnetic resonance imaging findings and a polymerase chain reaction assay to investigate the association between aggrecan gene polymorphism and lumbar disc degeneration. OBJECTIVE: To analyze whether the aggrecan gene polymorphism is related to lumbar disc disease in young women. SUMMARY OF BACKGROUND DATA: It has been suggested that a genetic factor or familial predisposition contributes to the development of lumbar disc herniation. However, the precise genetic component related to disc disease remains unclear. Recently, a polymorphism has been identified in the region of the human aggrecan gene. The expressed variable numbers of tandem repeat polymorphism occur in the highly conserved repeat region. METHODS: The participants were 64 young women with or without low back problems. Magnetic resonance imaging was used to evaluate the degeneration and herniation of the intervertebral disc. Genomic deoxyribonucleic acid was extracted from all participants. A polymerase chain reaction assay was carried out to detect the alleles of the aggrecan gene. The association of intervertebral disc degeneration and herniation with the distribution of the aggrecan gene alleles was analyzed. RESULTS: Findings showed an overrepresentation of alleles with small numbers of repeats in subjects with multilevel disc degeneration, thus indicating a significant distribution difference. There also was a significant difference between the distribution of alleles and the severity of disc degeneration. No significant association was found between any of the alleles either in number or type of disc herniation. CONCLUSIONS: The current study showed that multilevel and severe disc degeneration was present in the participants with shorter variable numbers of tandem repeat length of the aggrecan gene. This suggests that subjects with shorter variable numbers of tandem repeat length of the aggrecan gene have a risk of having multilevel disc degeneration develop at an early age.

Adult↗
PubMed1999

Molecular cloning of rat SH2-containing inositol phosphatase 2 (SHIP2) and its role in the regulation of insulin signaling.

SH2-containing inositol 5'-phosphatase (SHIP) plays a negative regulatory role in hematopoietic cells. We have now cloned the rat SHIP isozyme (SHIP2) cDNA from skeletal muscle, which is one of the most important target tissue of insulin action. Rat SHIP2 cDNA encodes a 1183-amino-acid protein that is 45% identical with rat SHIP. Rat SHIP2 contains an amino-terminal SH2 domain, a central 5'-phosphoinositol phosphatase activity domain, and a phosphotyrosine binding (PTB) consensus sequence and a proline-rich region at the carboxyl tail. Specific antibodies to SHIP2 were raised and the function of SHIP2 was studied by stably overexpressing rat SHIP2 in Rat1 fibroblasts expressing human insulin receptors (HIRc). Endogenous SHIP2 underwent insulin-mediated tyrosine phosphorylation and phosphorylation was markedly increased when SHIP2 was overexpressed. Although overexpression of SHIP2 did not affect insulin-induced tyrosine phosphorylation of the insulin receptor beta-subunit and Shc, subsequent association of Shc with Grb2 was inhibited, possibly by competition between the SH2 domains of SHIP2 and Grb2 for the Shc phosphotyrosine. As a result, insulin-stimulated MAP kinase activation was reduced in SHIP2-overexpressing cells. Insulin-induced tyrosine phosphorylation of IRS-1, IRS-1 association with the p85 subunit of PI3-kinase, and PI3-kinase activation were not affected by overexpression of SHIP2. Interestingly, although both PtdIns-(3,4,5)P3 and PtdIns(3,4)P2 have been implicated in the regulation of Akt activity in vitro, overexpression of SHIP2 inhibited insulin-induced Akt activation, presumably by its 5'-inositol phosphatase activity. Furthermore, insulin-induced thymidine incorporation was decreased by overexpression of SHIP2. These results indicate that SHIP2 plays a negative regulatory role in insulin-induced mitogenesis, and regulation of the Shc. Grb2 complex and of the downstream products of PI3-kinase provides possible mechanisms of SHIP2 action in insulin signaling.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Serial changes in trunk muscle performance after posterior lumbar surgery.

STUDY DESIGN: Serial changes in trunk muscle performance were prospectively studied in 20 patients who underwent posterior lumbar surgery. OBJECTIVE: To evaluate the influence of back muscle injury on postoperative trunk muscle performance and low back pain, to clarify the significance of minimization of back muscle injury during surgery. SUMMARY OF BACKGROUND DATA: The current investigators have reported examination of iatrogenic back muscle injury in an animal model and in humans. However, definite impairment caused by such back muscle injury has not been clarified. METHODS: The patients were divided into a short-retraction-time group (< 80 minutes; n = 12) and a long-retraction-time group (> or = 80 minutes; n = 8). Before surgery and 3 and 6 months after surgery, the degree of back muscle injury was estimated by magnetic resonance imaging, and trunk muscle strength was measured. In addition, the incidence and severity of low back pain were serially analyzed. RESULTS: Back muscle injury was directly related to the muscle retraction time during surgery. The damage to the multifidus muscle was more severe, and the recovery of extensor muscle strength was delayed in the long-retraction-time group. In addition, the incidence of postoperative low back pain was significantly higher in the long-retraction-time group. CONCLUSIONS: Postoperative trunk muscle performance is dependent on the muscle retraction time. Thus, it is beneficial to shorten the retraction time to minimize back muscle injury and subsequent postoperative low back pain.

Adolescent↗
PubMed1999

The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23.

The vitronectin receptor, alphavbeta3 integrin, plays an important role in tumor cell invasion, angiogenesis, and phagocytosis of apoptotic cells. CD47, a member of the multispan transmembrane receptor family, physically and functionally associates with vitronectin receptor (VnR). Although vitronectin (Vn) is not a ligand of CD47, anti-CD47 and beta3 mAbs suppress Vn, but not fibronectin (Fn) binding and function. Here, we show that anti-CD47, anti-beta3 mAb and Vn, but not Fn, inhibit sCD23-mediated proinflammatory function (TNF-alpha, IL-12, and IFN-gamma release). Surprisingly, anti-CD47 and beta3 mAbs do not block sCD23 binding to alphav+beta3+ T cell lines, whereas Vn and an alphav mAb (clone AMF7) do inhibit sCD23 binding, suggesting the VnR complex may be a functional receptor for sCD23. sCD23 directly binds alphav+beta3+/CD47(-) cell lines, but coexpression of CD47 increases binding. Moreover, sCD23 binds purified alphav protein and a single human alphav chain CHO transfectant. We conclude that the VnR and its associated CD47 molecule may function as a novel receptor for sCD23 to mediate its proinflammatory activity and, as such, may be involved in the inflammatory process of the immune response.

Animals↗
PubMed1999

Enhanced phosphoinositide hydrolysis via overexpression of phospholipase C beta1 or delta1 inhibits stimulus-induced insulin release in insulinoma MIN6 cells.

To study the effects of enhanced phosphoinositide hydrolysis on insulin secretion, phosphoinositide-specific phospholipase Cbeta1 (PLCbeta1) or PLCdelta1 was overexpressed in insulinoma MIN6 cells via adenoviral vectors. Inositol phosphate production stimulated by NaF (with AlCl3) in PLCbeta1-overexpressing cells and that stimulated by KCl or glucose in both PLCbeta1- and PLCdelta1-overexpressing cells were greater than that in control cells. In addition, reduced phosphatidylinositol-4,5-bisphosphate levels were observed in these cells stimulated by NaF or KCl. The greater phosphoinositide hydrolysis was accompanied by 25-45% inhibition of insulin secretion. These data suggest that excessive phosphoinositide hydrolysis inhibits secretagogue-induced insulin release in MIN6 cells.

Adenoviridae↗
PubMed1999

Effects of low oxygen concentrations and metabolic inhibitors on proteoglycan and protein synthesis rates in the intervertebral disc.

The intervertebral disc is the largest asvacular structure in the body; consequently, there are steep gradients in O2 concentration, with PO2 falling to as low as 1% O2 in the centre of the disc. We investigated the effect of O2 concentration on the rates of O2 consumption, lactate production, and sulphate and proline incorporation in bovine caudal discs. We also investigated the effects of metabolic inhibitors of energy production pathways on tracer incorporation. Samples from the outer annulus and nucleus pulposus were incubated for 24 hours in 1-21% O2. Rates were measured during the last 4 hours of incubation. As O2 concentration was reduced from 10 to 1% O2, O2 consumption rates fell by around 75% and lactate production rates almost doubled; the bovine discs thus showed a positive progressive Pasteur effect. Incorporation rates of [3H]proline and [35S]sulphate were lowest at 1% O2. In the nucleus, but not in the outer annulus, the rate of [35S]incorporation peaked at 5% O2, where it was 30% greater than at 21% O2 and 150% greater than at 1% O2. The competitive glycolysis inhibitor 2-deoxyglucose, the oxidative phosphorylation uncoupler 2,4-dinitrophenol, and the oxidative phosphorylation inhibitor sodium azide all markedly reduced sulphate incorporation. These results, together with previous measurements of CO2 production rates, suggest that a functionally significant fraction of the disc's energy is supplied by oxidative phosphorylation. However, low levels of PO2, 2,4-dinitrophenol, and sodium azide have been reported to reduce sulphate incorporation in articular cartilage, a tissue that derives its energy almost entirely from glycolysis.

2,4-Dinitrophenol↗
PubMed1999

Response to surgical stress in elderly patients and Alzheimer's disease.

PURPOSE: To determine the effect of surgical stress on plasma epinephrine, norepinephrine, ACTH and cortisol concentrations in patients aged 80-99 yr and in patients complicated with Alzheimer's disease. METHODS: A prospective controlled study was undertaken in 55 undergoing surgical reduction of femur neck fracture in Hirosaki University hospital and Hakodate Watanabe hospital; 18 patients in 80-99 yr (Group 1) and 18 patients in 40-59 yr (Group 2) and 7 patients (Group A) with and 12 patients (Group B) without Alzheimer's dementia (AD) aged 60-79 yr. RESULTS: The increase in plasma norepinephrine level (274%) of group 1 patients, 15 min after skin incision was higher than that in group 2 (191%) (P < 0.01). Mean plasma cortisol levels (40.4+/-4.7 and 44.1+/-5.2 microg x dl(-1)) of group 1, 15 min after skin incision and 60 min after the end of surgery were significantly higher than the 29.8+/-3.5 and 22.3+/-3.0 microg x dl(-1) of group 2 (P < 0.05). Plasma norepinephrine (1092.9+/-112.0 pg x ml(-1)) and cortisol concentrations (53.4+/-5.8 microg x dl(-1)) in group A were higher than in group B (772.6+/-82.4 pg x ml(-1) and 41.7+/-4.3 microg x dl(-1)) 15 min after skin incision (P < 0.05). CONCLUSIONS: Plasma norepinephrine and cortisol responses to surgical stress are activated in elderly patients and in patients with Alzheimer's disease.

Adrenocorticotropic Hormone↗