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Biomedical subjects

S Uematsu

Publications and source records attributed to S Uematsu.

At least 37 records · Page 2Linked to original sources

Interleukin (IL)-1 beta, IL-6, tumor necrosis factor-alpha, epidermal growth factor, and beta 2-microglobulin levels are elevated in gingival crevicular fluid during human orthodontic tooth movement.

Bone remodeling is a complex process regulated by several mediators. Recent work has revealed that cytokines and growth factors have significant effects on bone cell metabolism. However, little information is available concerning the production of cytokines during orthodontic tooth movement in human subjects, and there is no non-invasive model for determining the production of cytokines. Therefore, the purpose of this study was to identify and quantify the various cytokines in human gingival crevicular fluid (GCF), and to investigate the changes in their levels during orthodontic tooth movement. Twelve patients (mean age, 14.4 years) were used as subjects. An upper canine of each patient having one treatment for distal movement served as the experimental tooth, whereas the contralateral and antagonistic canines were used as controls. The GCF around the experimental and the two control teeth was taken from each subject immediately before activation, and at 1, 24, and 168 hr after the initiation of tooth movement. Cytokine levels were determined by ELISAs. The concentrations of interleukin (IL)-1 beta, IL-6, tumor necrosis factor-alpha, epidermal growth factor, and beta 2-microglobulin were significantly higher in the experimental group than in the controls at 24 hr after the experiment was initiated. All the cytokines remained at baseline levels throughout the experiment for the two control groups. In contrast to cytokine alteration, the amount of total protein in the GCF exhibited a gradual increase, but no significant difference was observed between the control and experimental groups. Since all cytokines in GCF play an important role in the bone remodeling processes in vitro, the present results indicate that the changes in cytokines in GCF are associated with orthodontic tooth movement.

Adolescent↗

Does the central sulcus divide motor and sensory functions? Cortical mapping of human hand areas as revealed by electrical stimulation through subdural grid electrodes.

To clarify the exact anatomic relationship of electrically identified hand areas to the central sulcus, we constructed cortical surface renderings of magnetic resonance images (MRI) to locate the central sulcus accurately and measured the distances of stimulated points from the central sulcus and the Sylvian fissure. We obtained hand responses in 33 patients who underwent implantation of subdural grid electrodes for evaluation and surgical treatment of intractable epilepsy and analyzed these responses according to the presence of motor, sensory, mixed motor and sensory, and arrest responses. Hand motor responses occurred not only in the precentral gyrus but also in the postcentral gyrus, with great variability in superior-to-inferior distribution. Sensory responses also occurred in both the precentral and postcentral gyri with a distribution more ventral than that of motor responses. Mixed motor and sensory responses tended to be limited to the middle part of the central sulcus. Sites where electrical stimulation arrested simple hand repetitive voluntary movements occurred widely throughout the premotor and primary sensorimotor cortices. These data indicate a marked variability in the location of the human cortical hand area, and suggest that motor and sensory hand cortices overlap and are not divided in a simple manner by the central sulcus.

Brain Mapping↗

Cathepsin B in the growth of colorectal cancer: suppressive effect of leupeptin on the growth of DMH-induced rat colon neoplasm.

Cathepsin B, a thiol protease, has been reported to be involved in cancer progression and metastasis. The suppressive effects of two kinds of protease inhibitors, leupeptin and dietary camostate (FOY-305), on tumorigenesis and progression in 1, 2-dimethylhydrazine (DMH)-induced rat colon neoplasm were examined in relation to tissue cathepsin B activity. Male Donryu rats were treated with leupeptin or FOY-305 during or after the administration of DMH. There were no significant differences in average tumor numbers among all DMH-treated groups. However, the percentage of small tumors was significantly higher in the group in which leupeptin was supplied during DMH administration. This trend was not recognized in the FOY-305-treated groups. The ratio of cathepsin B activity in the tumors to that in the tumor-bearing tissue (T/Tb) was significantly increased with increasing tumor size (P = 0.009). The cathepsin B activity levels in the tumor-bearing mucosa in the groups which received leupeptin or FOY-305 following DMH treatment were both significantly lower than that in the group which received neither protease inhibitor (P = 0.046 and P = 0.0067, respectively). The results obtained indicate that leupeptin may have suppressed tumor growth by lowering the tissue cathepsin B activity.

1,2-Dimethylhydrazine↗

Cathepsin B in the growth of colorectal cancer: increased activity of cathepsin B in human colorectal cancer.

Cathepsin B, a thiol protease, is involved in cancer metastasis. To clarify the role of cathepsin B in tumor progression in human colorectal cancer, the relationship between its activity, immunohistochemical staining, and clinical tumor progression was investigated. Cathepsin B activity in adenocarcinomas was significantly elevated compared with that in the tumor-bearing tissue. Furthermore, the tumor/tumor-bearing tissue (T/Tb) ratio of the activity was significantly higher than that of colorectal adenoma. Immunohistochemical studies demonstrated intense staining in the cancerous tissue. With respect to the clinical stage of tumors, the activity tended to be higher in tumors that had invaded the serosa or subserosa than in those that invaded the proper muscle. The results suggest that cathepsin B participates in the progression of human colorectal cancer, and its increased expression is a sensitive marker of the differentiation between colorectal adenoma and adenocarcinoma.

Adenocarcinoma↗

Relation between micellar structure of model bile and activity of esterase.

In a model bile solution composed of lecithin (L)-bile salt (B), the solubilization of lipid and the accessibility of enzyme to the lipid were examined by observation of EPR spectra and measurement of enzyme activity. The lifetime of the spin probe in the micellar phase was estimated to be approx. 1 microsecond by means of line shape analysis. Both population and lifetime increased with temperature and the molar ratio of lecithin to bile salt (L/B). The EPR data indicated that simple micelle of bile salt, mixed disk micelle of bile salt-lecithin, and multi-lamellar mixed disk micelle can exist in a model bile solution, depending on the L/B molar ratio across a range from 0 to 1.5. The maximal power of the mixed disk micelle to solubilize cholesteryl ester in the model bile at a L/B molar ratio of 1:1 was confirmed by EPR measurement of cholesteryl 12-DOXYL-stearate. Observation of the enzyme activity on a mixture of model bile and substrate at 37 degrees C revealed selective accessibility of cholesterol esterase (bovine pancreas) to mixed disk micelle, of cholesterol oxidase (Streptomyces cinnamomeus) to both simple and mixed disk micelle, and of pancreatic lipase (porcine pancreas) to both simple micelle and an oil droplet of substrate. The temperature-dependent activity of cholesterol oxidase to cholesterol in mixed disk micelle can be explained in terms of mesomorphic phase transition of lecithin side chains followed with fluidity of liquid crystal phase. Regarding phospholipase C from Bacillus cereus, though the selective accessibility to the micelles was not observed at 37 degrees C, a decrease in activity for mixed disk micelle could be found at lower temperatures.

Bile↗

Induction of apoptotic DNA fragmentation and cell death by natural ceramide.

We have found that a solvent mixture of ethanol and dodecane was able to disperse natural ceramide (Cer) into aqueous solution. In U937 cells, addition of natural Cer to medium caused a characteristic pattern of DNA fragmentation, which is indistinguishable from that caused by TNF alpha. The effective concentration of Cer is as low as 25 nM. The present study provides direct evidence that natural Cer functions as a second messenger mediating TNF alpha-induced DNA fragmentation. The use of this solvent to deliver hydrophobic natural Cer to cells will contribute to the elucidation of the biological function of Cer.

Apoptosis↗

Brainstem auditory evoked potentials recorded around the human upper brainstem area.

The intracranial spatiotemporal distributions of brainstem auditory evoked potentials were analyzed in two patients with epilepsy to study the dipole directions of waves III and V, previously found to have a horizontal and a vertical dipole, respectively. Depth electrodes were implanted bilaterally into the frontal and temporal lobes of these patients, the targets including the amygdala and hippocampus which are close to the upper pons and midbrain. Recordings around the upper pons and from the subcortical area downwards along the dorsal aspect of the upper pons indicated that waves III and V are constructed of mixed dipoles, wave III also having a vertical dipole segment and wave V also a horizontal one. These results suggest that several neural activities from the upper pons to midbrain contribute to the generation of waves III and V.

Adult↗

Arachidonic acid release and permeability changes induced by endothelins in human cerebromicrovascular endothelium.

The vasoactive peptide endothelin-1 (ET-1) dose-dependently increased release of 51Cr from human cerebromicrovascular endothelial cells (HBEC), without affecting cell viability as assessed by lactate dehydrogenase release. ET-1 also induced transient accumulation of inositol triphosphate (IP3) and release of [3H] arachidonic acid (AA) from HBEC. The ET-1-induced 51Cr release, formation of IP3, and AA release from HBEC were competitively inhibited by selective ETA subtype receptor antagonist BQ-123. ET-1-stimulated 51Cr- and AA release from HBEC were potentiated by proteinkinase C (PKC) activator phorbol-myristate ester, and abolished by H7, an inhibitor of PKC. Dexamethasone, indomethacin, acetylsalicylic acid, imidazole, as well as the inhibitor of protein kinase A, H8, had no effect on 51Cr release. The results suggest that ETA-receptor mediated activation of PKC and increase in the HBEC 'permeability' for low molecular weight molecules in response to excessive release of endothelins from either HBEC or surrounding tissues during pathologic conditions may contribute to the formation of cerebral edema.

Arachidonic Acid↗

Vasoactive peptides and prostaglandin D2 in human cerebromicrovascular endothelium.

Prostaglandin D2 (PGD2) is the major prostanoid formed among other prostanoids in cultured microvascular endothelium derived from human brain (HBEC). Angiotensin II, arginine vasopressin and endothelium-1 stimulated the production of PGD2 and PGF2 alpha in a concentration-dependent manner, and this effect was inhibited by their specific receptor antagonists or dexamethasone (inhibitor of phospholipase A2/cyclooxygenase II). Both the peptidergic-induced PGD2 and the exogenously added PGD2 were converted in HBEC to 9 alpha, 11 beta-PGF2, a potent vasoconstrictor. Exogenous PGD2 also dose-dependently enhanced the production of vasoconstrictive PGF2 alpha, thromboxane B2, vasodilatory prostaglandin PGE2, and cAMP in these cells. The PGD2 stimulated formation of the prostanoids was inhibited by acetylsalicylic acid or indomethacin (inhibitors of cyclooxygenase I) but not dexamethasone, demonstrating for the first time that PGD2 may contribute to the production of prostanoids in HBEC. These findings strongly suggest that PGD2 may play a pivotal role in the regulation of cerebromicrovascular function.

Capillaries↗

Endothelin-1 receptor binding and cellular signal transduction in cultured human brain endothelial cells.

The kinetic properties of endothelin-1 (ET-1) binding sites and the production of inositol phosphates (IPs; IP1, IP2, IP3), cyclic AMP, thromboxane B2, and prostaglandin F2 alpha induced by various endothelins (ET-1, ET-2, ET-3, and sarafotoxin S6b) were examined in endothelial cells derived from human brain microvessels (HBECs). The presence of both high- and low-affinity binding sites for ET-1 with KD1 = 122 pM and KD2 = 31 nM, and Bmax1 = 124 fmol/mg of protein and Bmax2 = 909 fmol/mg of protein, respectively, was demonstrated on intact HBECs. ET-1 dose-dependently stimulated IP accumulation with EC50 (IP3) = 0.79 nM, whereas ET-3 was ineffective. The order of potency for displacing ET-1 from high-affinity binding sites (ET-1 > ET-2 > sarafotoxin S6b > ET-3) correlated exponentially with the ability of respective ligands to induce IP3 formation. ET-1-induced IP3 formation by HBEC was inhibited by the ETA receptor antagonist, BQ123. The protein kinase C activator phorbol myristate ester dose-dependently inhibited the ET-1-stimulated production of IPs, whereas pertussis toxin was ineffective. Cyclic AMP production by HBECs was enhanced by both phorbol myristate ester and ET-1, and potentiated by combined treatment with ET-1 and phorbol myristate ester. Data indicate that protein kinase C plays a role in regulating the ET-1-induced activation of phospholipase C, whereas interaction of different messenger systems may regulate ET-1-induced accumulation of cyclic AMP. ET-1 also stimulated endothelial prostaglandin F2 alpha production, suggesting that activation of phospholipase A2 is most likely secondary to IP3-mediated intracellular calcium mobilization because both ET-1-induced IP3 and prostaglandin F2 alpha were inhibited by BQ123. These findings are the first demonstration of ET-1 (ETA-type) receptors linked to phospholipase C and phospholipase A2 activation in HBECs.

Brain↗

Cortical tongue area studied by chronically implanted subdural electrodes--with special reference to parietal motor and frontal sensory responses.

Motor and sensory cortical tongue representations were examined in 40 patients with intractable seizures who underwent chronic subdural electrode grid implantation. Tongue responses were observed in a wide area 4.5 cm anterior and 3 cm posterior to the central sulcus. The distribution of the responses was not influenced by whether the responses were unilateral or bilateral. In patients with fronto-parietal lesions, the tongue motor area was located significantly more superior to the Sylvian fissure and more anterior to the central sulcus than was the tongue motor area of patients without organic lesion. Both motor and sensory responses were found outside of the classic precentral or postcentral area on the lateral surface of the cortex. Motor responses ('parietal motor responses') could occur posterior to the central sulcus and, rarely, sensory responses ('frontal sensory responses') were identified anterior to the central sulcus. These paradoxical parietal motor and frontal sensory responses were seen in 17 out of 40 (42.5%) patients. Nine of these 17 patients had no organic brain lesion on MRI. Clinical factors, such as patient's age, duration of seizures and cognitive functions (IQ, word fluency score), did not influence the frequency of the paradoxical responses. However, patients with brain lesions showed a tendency to have associated paradoxical responses (P < 0.05). In conclusion, paradoxical responses are not uncommon in epilepsy patients, particularly in those with organic lesions. The physiological and clinical implications of the paradoxical responses are discussed.

Adolescent↗

Electrical stimulation and language.

Electrical stimulation has been used for over half a century in clinical settings to facilitate the surgical treatment of patients with intractable seizures and cortical structural lesions. It should be employed as the final result of a stepwise process in patient management but, when called for, can be very accurate in localizing critical functional areas. We discuss the use of this technique in patient evaluation, with an emphasis on the evaluation of patients with seizure disorders.

Cerebral Cortex↗

Vasoconstrictive peptides induce endothelin-1 and prostanoids in human cerebromicrovascular endothelium.

Vasoconstrictive peptides and prostanoids have been implicated in the pathogenesis of hypertension and vasospasm. Recently, we have shown that human cerebromicrovascular endothelium [human brain endothelial cells (HBEC)] constitutively produces both endothelin-1 (ET-1) and prostanoids. The vasoactive peptides, arginine vasopressin (AVP) or angiotensin II (ANG II), stimulated secretion of both immunoreactive ET-1 and prostanoids from HBEC by a receptor-mediated induction of phospholipase C (PLC) and PLA2. The release of constitutive or AVP- or ANG II-induced ET-1 occurred at different rates during the 24-h incubation of HBEC in serum-free medium. The temporal profile of AVP-stimulated production of prostanoids differed from that of ANG II. AVP-induced release of prostaglandin D2 (PGD2) persisted for 24 h, whereas ANG II-stimulated PGD2 was only seen during the first 4 h of incubation. ANG II maximally stimulated PGI2 secretion during the 4- to 8-h interval, whereas AVP did not stimulate PGI2 secretion. Dexamethasone (Dxm), indomethacin (Indo), and nordihydroguaiaretic acid, the respective inhibitors of PLA2-cyclooxygenase II, cyclooxygenase, and lipoxygenase, increased both constitutive and AVP- or ANG II-stimulated secretion of ET-1. Dxm also decreased AVP- or ANG II-stimulated production of PGD2 and PGF2 alpha. These results indicate an interrelationship between HBEC production of ET-1 and prostanoids, which may play a role in regulating cerebral microcirculation.

Angiotensin II↗

Reliability of amygdalohippocampal volume measured directly on MRI films.

Volume measurement of the amygdalohippocampus on MRI may provide important information for epilepsy surgery. This study investigated the reliability of direct volume assessment (DVA) versus computer-assisted measurement (CAM) of amygdalohippocampus. DVA was carried out by counting the number of squares occupied by amygdalohippocampus in a transparent mm2 overlay used on both sagittal and coronal films. CAM was achieved using the 'thresholding and tracing' automated technique. Seventeen patients undergoing language-dominant left temporal lobectomy were studied. Mean volume as determined by the CAM was 4.99 +/- 1.31. In DVA, the mean volume was 5.05 +/- 1.23 (r = 0.974). Reproducibility of the volume measurement was tested by repeating measurements 5 times on 5 patient samples of amygdalohippocampal complex in DVA, and 3 times on 4 samples in CAM. The mean coefficient of variation for amygdalohippocampal volume was 6.9 +/- 3.2% in DVA and 3.9 +/- 2.0 in CAM. We also tested a more simplified method of assessing amygdalohippocampal volume by calculating the left to right volume ratio from MRI scans (2-40 films for each sample). Volume ratios determined directly from MRI films made in different months (14 samples) and of different sections (coronal and sagittal series, 18 samples) correlated well with each other (p < 0.01). Direct assessment of amygdalohippocampal volume can be used effectively for preoperative evaluation of the patient with epilepsy.

Adult↗

Total craniospinal decompression in achondroplastic stenosis.

We describe our experience with total craniospinal decompression along the entire neuraxis, extending from the brain stem to the cauda equina, in seven patients with achondroplasia. These patients presented with clinically significant compression at multiple levels. In these patients, there were focal areas of complete myelographic block, typically at the cervicothoracic or thoracolumbar junction, as well as diffuse narrowing of the entire spinal subarachnoid space. In some, there were further complications of basilar impression, Arnold-Chiari malformation, or syringomyelia. Total craniospinal decompression was completed in either one or two stages. Only a small minority of our patients with achondroplasia had critical stenosis over this many levels, requiring total craniospinal decompression. However, with proper preparation and technique, we found that patients can tolerate even such an extensive decompressive procedure and benefit from surgery without suffering postoperative spinal instability.

Achondroplasia↗

Decreased hippocampal muscarinic cholinergic receptor binding measured by 123I-iododexetimide and single-photon emission computed tomography in epilepsy.

Regional binding of 123I-iododexetimide, a muscarinic acetylcholine receptor antagonist, was measured in vivo in the temporal lobes of 4 patients with complex partial seizures using single-photon emission computed tomography. In the anterior hippocampus ipsilateral to the electrical focus, 123I-iododexetimide binding was decreased by 40 +/- 9% (mean +/- SD, p < 0.01) compared with the contralateral hippocampus; 123I-iododexetimide binding in other temporal lobe regions was symmetrical. The data indicate a regionally specific change of muscarinic acetylcholine receptor in anterior hippocampus in complex partial seizures of temporal lobe origin.

Adult↗