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Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

At least 361 records · Page 20Linked to original sources
PubMed1998

Fluid shear stress increases transforming growth factor beta 1 expression in human osteoblast-like cells: modulation by cation channel blockades.

Mechanical stress is an important regulator of bone metabolism. Fluid shear stress caused by mechanical load in bone tissue has been shown to be important to both the bone structure and function through its effects on osteocytes and osteoblasts. We explored the effects of the fluid shear stress on the expression of growth factors and cytokines in human osteoblast-like SaOS-2 cells with a purpose-built cone-plate viscometer. We showed that the physiological level (1.7-2.0 Pascal) of fluid shear stress increased the mRNA expression of TGF-beta1 about threefold after 3 hours and also increased TGF-beta1 protein about threefold after 24 hours in the SaOS-2 cells. However, no mRNA expression of PDGF-A, IGF-I, IGF-II, or IL-6 was detected. To explore the mechanism of up-regulation of TGF-beta1 expression, we examined the effects of a stretch activated cation nonselective (SA-cat) channel blockade with gadolinium and a voltage-dependent L-type Ca2+ channel blockade with verapamil on the TGF-beta1 expression at the mRNA levels. The fluid shear stress-induced increase in the TGF-beta1 mRNA levels was significantly inhibited by both gadolinium and verapamil. These findings suggest that the physiological level of fluid shear stress induces the production of TGF-beta1 by the SaOS-2 cells via the cation channel function and, as a result, may therefore promote bone formation.

Calcium Channel Blockers↗
PubMed1998

MRI of enlarged endolymphatic sacs in the large vestibular aqueduct syndrome.

We studied ten inner ears of five patients with a bilateral large vestibular aqueduct syndrome, using CT and MRI. Although the large vestibular aqueduct varied in size, a markedly dilated endolymphatic sac extending to the sigmoid sinus was demonstrated bilaterally on MRI in all patients. The cause of hearing loss in this syndrome is unclear. However, it is suggested that reflux of the protein-rich, hyperosmolar endolymph from the enlarged endolymphatic sac (EES) into the cochlea through a widely patent endolymphatic duct may damage the neuroepithelium. CT density and spin-echo MRI signal intensity of the endolymph in EES were markedly higher than those of CSF in eight inner ears of four patients. Increased density and high signal may indicate protein-rich, hyperosmolar endolymph. In some patients with sensorineural hearing loss and EES, the vestibular aqueduct may not appear dilated on CT. MRI is therefore necessary for correct diagnosis of this syndrome, which should more correctly be termed "large endolymphatic duct and sac syndrome". Prominent EES may predict poor prognosis in this syndrome.

Adolescent↗
PubMed1998

Development of extrahepatic arterial blood supply to the liver during hepatic arterial infusion chemotherapy.

The aim of this study was to evaluate the correlation of development of the collateral circulation to the liver during hepatic arterial infusion chemotherapy (HAIC) with the presence of hepatic tumours adjacent to the hepatic surface, and with pretreatment occlusion of aberrant hepatic arteries. In 102 patients with unresectable malignant hepatic tumours treated with HAIC using an implantable port system, development of collaterals to the liver was assessed with CT arteriography using the implantable port and pre- and postoperative angiography. Aberrant hepatic arteries, if present, were occluded prior to treatment for hepatic arterial redistribution. Collaterals to the liver were seen in 29 patients, who had 35 areas with collateral perfusion: 22 areas were in the right posterosuperior area, 6 in the left peripheral area and 7 in the right or left lobar area. Collaterals were revealed more frequently in patients with hepatic tumours adjacent to the hepatic surface than in those without hepatic tumours in peripheral areas in the liver (p < 0.0001). In addition, collaterals developed more frequently in patients with an aberrant hepatic arterial anatomy compared with those with conventional anatomy (p = 0.0007). Our results indicated that patients with hepatic tumours adjacent to the hepatic surface and with pretreatment occlusion of aberrant hepatic arteries had the potential to develop collaterals to the liver during HAIC.

Adult↗
PubMed1998

Double cardiac rupture after direct infarct coronary angioplasty: report of a case.

The occurrence of double cardiac rupture (DCR) after a successful direct infarct coronary angioplasty (DICA) is extremely uncommon. We describe herein the case of a patient who underwent delayed DICA and despite successful recanalization, subsequently suffered DCR, as a postinfarction ventricular septal defect (PIVSD) with left ventricular free wall rupture (LVFWR). Emergency surgery was performed, and the patient is now doing well more than 2 years after his operation. The possible mechanisms of DCR after delayed DICA are discussed following the presentation of this unusual case.

Aged↗
PubMed1998

Soluble interleukin-2 receptor in children with reflux nephropathy.

PURPOSE: Serum soluble interleukin-2 receptor level is a sensitive and quantitative marker of lymphocyte activation. We determined levels of serum soluble interleukin-2 receptor in children with reflux nephropathy to evaluate its clinical significance in the prediction for the progression of renal injuries. MATERIALS AND METHODS: Serum soluble interleukin-2 receptor values were determined in 63 children with reflux nephropathy. The group consisted of 37 boys and 26 girls 10 to 18 years old. T cells (naive and memory), B cells and macrophages were evaluated immunohistochemically in the scarred kidneys of 4 other patients (3 boys and 1 girl 5 to 16 years old) who underwent nephrectomy due to severe reflux nephropathy with little function seen on (99m)technetium-dimercapto-succinic acid (DMSA) renal scan. Levels of serum soluble interleukin-2 receptor were measured by an enzyme-linked immunosorbent assay. We simultaneously determined serum levels of creatinine and beta2-microglobulin, and urinary levels of alpha1-microglobulin and microalbumin. Individual functions of the right and left kidneys were estimated by renal dimercaptosuccinic acid uptake. RESULTS: Levels of serum soluble interleukin-2 receptor in the patients who had low total uptake of DMSA (right uptake plus left uptake) were significantly higher than those from patients with normal total uptake. Levels of serum soluble interleukin-2 receptor correlated significantly with levels of creatinine (r=0.616, p <0.0001) and beta2-microglobulin (r=0.803, p <0.0001), and levels of urinary alpha1-microglobulin (r=0.753, p <0.0001) and microalbumin (r=0.673, p <0.0001). A significant negative correlation was observed between levels of serum soluble interleukin-2 receptor and total DMSA uptake values (right uptake plus left uptake r=-0.678, p <0.0001). In the scarred kidneys leukocyte infiltrates were markedly increased in fibrosed spaces. The predominant cell type in these lesions was memory T cells. CONCLUSIONS: These results suggest that elevated levels of serum soluble interleukin-2 receptor are likely to reflect activated T cells in the kidneys of patients with reflux nephropathy and may be a useful predictor of progression of renal injury in these children.

Adolescent↗
PubMed1998

L-DOPA does not facilitate nitric oxide production in the rat striatum and substantia nigra: in vivo microdialysis study.

Using in vivo microdialysis and flow-injection, we evaluated the production of nitric oxide (NO) in the striatum and substantia nigra of freely moving rats in response to challenge doses of L-dihydroxyphenylalanine (L-DOPA) by measuring the NO metabolite levels of nitrate and nitrite. The dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations also were determined in the same perfusates. Intraperitoneal injection of L-DOPA produced a significant, dose-dependent increase in the extracellular levels of dopamine and DOPAC in these areas, but did not modify the extracellular levels of the NO metabolites. An acute dose of L-DOPA does not appear to facilitate NO production in the rat striatum and substantia nigra.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Effect of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline on methamphetamine- and cocaine-induced behavioral sensitization.

The present study investigated the effect of pretreatment with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, on behavioral sensitization induced by methamphetamine (METH) and cocaine at doses that are transitional relative to the induction of an acute response of locomotion and interrupting episodes of sniffing and head movement. Male Sprague-Dawley rats were randomly assigned to four groups that received daily either 20 mg/kg NBQX + 3 mg/kg METH, 40 mg/kg NBQX + 3 mg/kg METH, vehicle + 3 mg/kg METH, or vehicle + saline daily for 10 days. In another experiment, rats of four groups received daily either 20 mg/kg NBQX + 15 mg/kg cocaine, 40 mg/kg NBQX + 15 mg/kg cocaine, vehicle + 15 mg/kg cocaine, or vehicle + saline daily for 10 days. NBQX did not attenuate activity/stereotypy induced by acute administration of either psychostimulant. Pretreatment with NBQX did not affect augmentation of activity/stereotypy scores by repeated administration of METH or cocaine. There was no significant difference in the intensity of activity/stereotypy between the NBQX + METH and vehicle + METH groups and between the NBQX + cocaine and vehicle + cocaine groups following a challenge injection with 2 mg/kg METH alone or 15 mg/kg cocaine alone, respectively, given 7 days after the last dose of repeated treatment session. Pretreatment with NBQX alone for 10 days (20 mg/kg for 5 days and 40 mg/kg for subsequent 5 days) did not affect the intensity of activity/stereotypy induced by a challenge injection with 2 mg/kg METH given 7 days after the last dose of repeated injection session. NBQX at 40 mg/kg had no apparent effect on acute METH (3 mg/kg)-induced dopamine release in the striatum. These results suggest tht AMPA receptors are unlikely to be involved in induction of behavioral sensitization that is manifested as augmented activity/stereotypy following repeated administration of METH or cocaine.

Animals↗
PubMed1998

Kainic acid may enhance hippocampal NO generation of awake rats in a seizure stage-related fashion.

Temporal changes in kainate-induced seizure activity and hippocampal NO generation were evaluated simultaneously in conscious rats by using in vivo microdialysis and by determining the concentrations of nitrite and nitrate in perfusates. Intraperitoneal injection of kainic acid produced 'wet dog shake', focal seizure of the limbs and neck, hypersalivation, or generalized convulsion. These behavioral changes peaked at 120 min after the drug challenge and lasted for about 100 min. In contrast, the concentrations of NO metabolites, nitrite and nitrate, in the hippocampal perfusates increased rapidly and reached a plateau level at 40 min after the injection, and the level remained high for over 220 min. The increase was more marked in animals presenting severe seizures than those presenting mild ones. Pre-treatment with 25 mg/kg N(G)-nitro-L-arginine methyl ester promoted the severity of kainate-induced seizures, but it suppressed the increase in NO metabolites. These results suggest that kainic acid enhances hippocampal NO generation in a severity-related manner of the induced seizures. The enhanced NO generation upon kainate challenge appears mainly to be involved in seizure suppression.

Animals↗
PubMed1998

Cooling effect of continuous renal replacement therapy in critically ill patients.

Hypothermia is reported to increase intensive care unit (ICU) mortality. The heat loss that occurs during continuous renal replacement therapy (CRRT) favors the development of hypothermia. In an effort to assess the influence of CRRT on body temperature, we reviewed the records of 72 consecutive ICU patients treated with CRRT and further prospectively studied the temperature in the inlet and outlet lines for blood and dialysate of 27 other patients at various flow settings during continuous venovenous hemodialysis (CVVHD). Among the 72 retrospective cases, 36 episodes of hypothermia (core body temperature <35.5 degrees C) occurred and persisted for a mean of 2.6+/-1.8 days. It was more frequent during venovenous than arteriovenous modalities (31 of 67 v5 of 20, respectively); no patients developed hypothermia during arteriovenous slow continuous ultrafiltration (AVSCUS), whereas 48% of the patients undergoing CVVHD became hypothermic, occurring earlier in the therapy course (days 2 to 4). Mean arterial pressure (MAP) tended to increase after CRRT initiation, but absolute changes were not statistically significant. In the prospective arm, the CVVHD circuit temperatures were directly measured. Whereas no attempt was made to change body temperature, stepwise changes in blood (Qb) and dialysate flow rate (Qd) produced venous circuit temperature changes: the higher the Qb, the smaller the arteriovenous temperature differences independent of changes in Qd (P < 0.001). Also, venous circuit temperature varied directly with Qd at fixed Qb (P < 0.001). This relationship also held for temperature conversion to lost energy units per minute. Using room temperature dialysate, CRRT may significantly lower patients' core temperatures. Although the clinical significance of this effect is not clear at this point, energy loss during CVVHD may be important in hemodynamic stability or patient prognosis.

APACHE↗
PubMed1998

Chronic olanzapine or sertindole treatment results in reduced oral chewing movements in rats compared to haloperidol.

Chronic haloperidol treatment typically produces late-onset, purposeless oral chewing movements in laboratory rats with a prevalence of 40 to 60%. Chronic clozapine does not produce these movements. Based on the phenomenologic and pharmacologic similarities between these rat chewing movements and human tardive dyskinesia (TD), the animal movements are often used as a model of tardive dyskinesia (TD). Here we report results of the association of oral chewing movements in rats with chronic administration of two new antipsychotic drugs, olanzapine and sertindole. Because each of these antipsychotic drugs has a very low incidence of acute Parkinsonism in human studies, they are candidates for showing a low tardive dyskinesia risk. Neither new drug produced a significant incidence of haloperidol-like chewing in rats, nor did movement ratings after their chronic administration differ from placebo; whereas, haloperidol produced a 60% prevalence of purposeless chewing and a prevalence significantly increased from placebo. This low rate of oral dyskinesias in rats is consistent with several of the preclinical characteristics of the drugs and correlates with their low acute motor side effects in clinical trials. We propose, although have not yet tested in humans, that these animal results will predict low TD liability of these drugs.

Animals↗
PubMed1998

Cortico-cortical inhibition of the motor cortical area projecting to sternocleidomastoid muscle in normals and patients with spasmodic torticollis or essential tremor.

OBJECTIVES: To investigate whether the cortico-cortical inhibition originally reported for the human hand motor area is present in the motor cortex for sternocleidomastoid muscle (SCM) and to evaluate the amount of inhibition in spasmodic torticollis and essential tremor. METHODS: Subjects were 14 normal healthy volunteers, 10 patients with spasmodic torticollis and 5 with essential tremor involving neck muscles. A paired-pulse magnetic stimulation was performed for the SCMs and first dorsal interosseous muscles (FDIs). RESULTS: In normal subjects, a subthreshold magnetic conditioning stimulus suppressed responses to a suprathreshold magnetic test stimulus when their interval was 1-5 ms in SCM. This indicates that the similar cortico-cortical inhibitory mechanism is present in the motor cortex for SCM as in the hand motor area. In the patients with spasmodic torticollis, the cortico-cortical inhibitory effect was reduced or absent in SCM, but normal in the FDI. In contrast, in patients with essential tremor, normal cortico-cortical inhibition was seen in both the SCM and FDI. CONCLUSIONS: The cortico-cortical inhibitory mechanisms of the motor cortex for SCM can be studied by a paired-pulse magnetic stimulation method. Our result of reduced cortico-cortical inhibition in torticollis patients suggests abnormal excitability (hyperexcitable or disinhibited) of the motor cortex for SCM in spasmodic torticollis.

Adult↗
PubMed1998

Restricted localization of thrombospondin-2 protein during mouse embryogenesis: a comparison to thrombospondin-1.

Thrombospondin-1 and -2 (TSP1 and TSP2) are multifunctional, multimodular extracellular matrix proteins encoded by separate genes. We compared the distributions of TSP1 and TSP2 in mouse embryos (day 10 and later) by immunohistochemistry. TSP1 was detected on day 10 in the heart and intestinal epithelium, on day 11 in megakaryocytes, and on day 14 in the lung. TSP2 was not detected until day 14, with strongest staining in mesenchymal condensation that gives rise to cartilage and bone. The distribution of TSP2 was different from but overlapped with the distribution of TSP1. TSP1 was found in cartilage proper with diminished staining around chondrocytes undergoing differentiation and hypertrophy, whereas TSP2 was restricted to the matrix surrounding chondrocytes of the growth zone cartilage. TSP2 and TSP1 were both expressed in centers of intramembranous ossification that form the skull bones, in reticular dermis, on the apical surface of nasal epithelium, in skeletal muscle, and in the sheath surrounding vibrissae. Areas of exclusive staining for TSP2 included the perichondrium surrounding the cartilage of the nasal cavities, developing bone of the lower mandible, and adrenal gland. The distinct localizations of TSP1 and TSP2 indicate that the two proteins have specific functions during mouse embryogenesis.

Animals↗
PubMed1998

Phosphoisoforms of insulin-like growth factor binding protein-1 in appropriate-for-gestational-age and small-for-gestational-age fetuses.

We analysed phosphoisoforms of insulin-like growth factor binding protein-1 (IGFBP-1) in maternal and cord sera from preterm and term fetus with different growth status. Phosphoisoforms were separated by non-SDS-polyacrylamide gel electrophoresis and detected by immunoblot. Phosphoisoforms were also analysed by anion exchange chromatography on HPLC. The proportion of non-phosphorylated IGFBP-1 to total IGFBP-1 was significantly higher in preterm fetus than in their mothers, however, the relative amounts of each IGFBP-1 isoforms were similar between preterm and term fetus. The levels of non-phosphorylated IGFBP-1 were similar between appropriate for gestational age (AGA) and small for gestational age (SGA) fetus at term, however, phosphorylated isoforms of IGFBP-1 were increased in SGA fetus compared to those of AGA fetus and the proportion of non-phosphorylated IGFBP-1 to total IGFBP-1 was lower in SGA fetus than those in AGA fetus. Thus, the profiles of non-phosphorylated and phosphorylated IGFBP-1 in the fetus varies corresponding to fetal growth suggesting that not only total amounts of IGFBP-1 but also the proportion of phosphoisoforms of IGFBP-1 is important for fetal growth.

Biomarkers↗
PubMed1998

Renal ACE immunohistochemical localization in NIDDM patients with nephropathy.

A role of renal angiotensin-converting enzyme (ACE) in diabetic nephropathy has been suggested. Immunohistochemical localization of ACE was studied in 20 non-insulin-dependent diabetes mellitus patients with diabetic nephropathy and 17 healthy kidney transplant donors, with ACE gene insertion/deletion (I/D) polymorphism also examined in the latter. Immunohistochemical studies indicated that ACE staining was significantly (P < 0.01) enhanced in glomeruli and slightly decreased in proximal tubules in diabetic patients. Glomeruli positive for ACE immunostaining were observed in 23.5% of the healthy subjects and in 80% of the diabetic patients. All patients with nodular lesions had ACE-positive glomeruli and showed significantly (P < 0.01) more intense glomerular ACE immunostaining than patients without nodular lesions. Among healthy controls, subjects with the DD genotype had ACE-positive glomeruli more frequently and tended to show slightly increased intensity on proximal tubule ACE immunostaining compared with subjects with other genotypes. These observations suggest that increased ACE localization in glomeruli is likely to be one of the factors in the increased renin-angiotensin system activity in glomeruli in patients with diabetic nephropathy. There is a possibility that ACE gene I/D polymorphism may be related to renal ACE immunohistochemical localization.

Diabetes Mellitus, Type 2↗