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Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 811 records · Page 45Linked to original sources
PubMed1995

A modification of the local lymph node assay for contact allergenicity screening: measurement of interleukin-2 as an alternative to radioisotope-dependent proliferation assay.

The local lymph node assay is an effective prediction method for contact allergenicity, but employs radioisotopes. We investigated whether measurement of interleukin-2 (IL-2) production by lymph node cells could be used instead to predict contact allergenicity of chemicals. Test chemicals were applied for three consecutive days to both ears of Balb/c mice and the auricular lymph nodes were obtained on either the fourth or fifth day after the first application. Both IL-2 concentration in supernatant of the suspension and proliferative activity of lymph node cells were determined after 24-, 48-, 72-h cell culture in RPMI-1640 medium by ELISA and by measuring [3H]methylthymidine incorporation, respectively. These two methods detected allergenicity similarly except in the case of TNCB and oxazolone, which showed excessive proliferation-inducing capacity as compared to IL-2 release-increasing effect. Flow cytometry showed that these two chemicals also increased the percentage of Iad-positive cells in the lymph nodes, suggesting that these chemicals might induce not only cellular immunity but also humoral immunity. We conclude that interleukin-2 assay is a convenient and dependable method for screening strong contact allergens without using radioisotopes.

Allergens↗
PubMed1995

Location of regions of the opioid receptor involved in selective agonist binding.

To elucidate which portions of the opioid receptor molecules are involved in the ligand selectivity, we have expressed chimeric receptors between the rat delta- and mu-opioid receptors from cDNAs and analysed their ligand binding properties. We demonstrate that the major binding determinant for the delta-selective enkephalin-related peptide, [D-Pen2,D-Pen5]enkephalin, resides within the region comprising the transmembrane segments V-VII and the intervening loop regions. On the other hand, the region spanning from the intracellular loop I to the amino-terminal half of the transmembrane segment III is shown to be involved in determining high-affinity binding of the mu-selective enkephalin-related peptides, [D-Ala2, MePhe4,Gly-ol5]enkephalin and [D-Ala2,MePhe4,Met-ol5]enkephalin, whereas the major determinant for binding of the mu-selective alkaloids, morphine and codeine, is demonstrated to exist in the region spanning the transmembrane segments V-VII. These results indicate that distinct regions of the opioid receptor determine the selectivity for the delta- and the mu-selective enkephalin-related peptides and that the binding determinant for the mu-selective alkaloids is distinct from that for the mu-selective enkephalin-related peptides.

Animals↗
PubMed1995

A critical mutation in both WT1 alleles is not sufficient to cause Wilms' tumor.

The WT1 gene is a tumor suppressor gene for Wilms' tumor (WT). Inactivation of both alleles has been proposed as the cause of WT. We encountered a patient with Denys-Drash syndrome associated with WT whose WT1 gene had a homozygous point mutation not only in WT but also in renal tissue adjacent to the WT and in the germline. These findings indicate that factor(s) other than the loss of WT1 are required for WT to develop.

Alleles↗
PubMed1995

Cloning and sequencing of the gene encoding the mouse vitamin D receptor.

The mouse vitamin D receptor (VDR)-encoding cDNA was cloned and the coding regions were sequenced. Comparison of the amino-acid sequence to that of humans and rats revealed high homology in the DNA- and ligand-binding domains. Divergence appeared in the internal region between the two domains.

Amino Acid Sequence↗
PubMed1995

Altered functions of ion channels in diabetic beta cells.

Selective impairment of glucose-induced insulin secretion and hyper-responsiveness to arginine are known features of GK rats, a genetic model of NIDDM. We focus on the ionic mechanism underlying these phenomena using patch-clamp techniques. Pancreatic islets were isolated from male GK rats and age-matched control Wistar rats and were subjected to dispersion and culture. Single channel recordings of KATP channels were performed using either on-cell mode or inside-out patch mode. Ca2+ channel currents were recorded under conventional whole-cell mode. In GK beta cells, ATP sensitivity of KATP channels itself was not altered, although glucose-induced closure of KATP channels was severely impaired. Among substrates for fuel metabolism, only dehydroxyacetone (DHA) reproduced this anomaly. On the other hand, current densities of L-type Ca2+ channels were increased in GK beta cells. Since DHA is a known substrate for glycerol phosphate shuttle, current data suggest that major metabolic deficit of GK beta cells resides in this shuttle. On the other hand, increased L-type Ca2+ channel activities might be an ionic basis for augmented insulin response to nonglucose depolarizing stimuli in GK beta cells.

Adenosine Triphosphate↗
PubMed1995

Fine structure and distribution of lymphatics in the synovial membrane of monkey and human knee joints. A study using an enzyme-histochemical method.

The fine structure and distribution of lymphatics in the synovial membrane of monkey knee joints, and human knees with osteoarthritis and rheumatoid arthritis, were studied by light and electron microscopy using an enzyme-histochemical method. Whole mount preparations and tissue sections were doubly stained for 5'-nucleotidase and alkaline phosphatase. The 5'-nucleotidase positive lymphatics could be distinguished from the alkaline phosphatase positive blood vessels. In monkey specimens the 5'-nucleotidase lymphatics were densely distributed in the medial and lateral parts of the suprapatellar pouch and infrapatellar fat pad, in both the superficial and deep of the sublining cell layers. Collecting lymphatics were well developed in the deep fibrous layer and in the merging epimysium. In the knees with both types of arthritis, the patterns of distribution were the same as in the monkey. No lymphatics were found in well developed villi in rheumatoid arthritis, but many blood vessels were present.

Animals↗
PubMed1995

Stress-response (heat-shock) protein 90 expression in tumors of the central nervous system: an immunohistochemical study.

This retrospective study deals with the expression of stress-response (heat-shock) protein 90 (srp 90) in a series of 148 human brain tumors. Immunohistochemical procedures were employed; cells of the human breast cancer line MCF7 exposed to hyperosmolar stress served as positive controls. Deposits of reaction products were found in the cytoplasm and they displayed a granular pattern. srp 90 was detected in 14/31 meningiomas and 5/10 breast cancer metastases to the brain. The protein was also present in 6/13 glioblastomas and 7/18 astrocytomas. In addition, a positive reaction was found in 2/10 medulloblastomas, 2/14 primitive neuroectodermal tumors, 1/11 pituitary tumor, 2/21 schwannomas and 2/11 lung tumor metastases; however, oligodendrogliomas and primary malignant lymphomas were not stained. The srp 90 was detected in Western blots of meningioma tissue homogenates. No significant immunohistochemical reaction was seen with sections of normal human cerebra, brain stem, cerebella, pituitary glands and spinal cords. These results document the expression of srp 90 by a variety of primary and metastatic intracranial tumors.

Autopsy↗
PubMed1995

Effect of stopping fluoride administration on the distribution profiles of fluoride in three different kinds of rat bones.

The aim of this work was to explore the reduction of fluoride concentrations in the skeleton after stopping experimental fluoride administration. Fluoride was administered to the rats at varying doses (0, 50, 100 ppm in drinking water) and for different lengths of time (4, 13, 25 weeks). A series of fluoride concentrations across the full thickness of humerus, parietal bone, and vertebra arch in rats were measured by means of an abrasive micro-sampling technique. The distribution profiles of fluoride from periosteal to endosteal surfaces, which were apparently related to the histological structure of these bones, were U shaped in the humerus, V shaped in the parietal bone, and W shaped in the vertebra arch. The average fluoride concentrations in the bones increased significantly with each increasing dose and length of fluoride administration. The relative increments were similar between the different regions or the different bones. After stopping fluoride administration, on the other hand, the relative reduction of the average fluoride concentrations in the bones were 30-100%. They were greatly related to the length after stopping fluoride administration and the dose and length of fluoride administration, but also dependent upon the type of bone and the region examined.

Animals↗
PubMed1995

Detection of Helicobacter pylori DNA in gastric juice by the polymerase chain reaction: comparison with findings in bacterial culture and the detection of tissue IgA and serum IgG antibodies against Helicobacter pylori.

The detection of Helicobacter pylori in gastric juice by the polymerase chain reaction (PCR) was undertaken in 124 patients with peptic ulcer or chronic gastritis. PCR products were evaluated by agarose gel electrophoresis and Southern hybridization of H. pylori-specific DNA sequences. Positive and negative results of the PCR analysis in 72 examinations were compared with those from bacterial culture, and with the detection of tissue IgA antibody against H. pylori by enzyme-linked immunosorbent assay ELISA; Serion, Wuerzburg, Germany, and detection of serum IgG antibody against H. pylori by ELISA; Radim Pomezia, Italy. Thirty-four PCR-positive samples evaluated by electrophoresis and hybridization coincided with positive samples in 56% of bacterial cultures, 59% of tissue IgA antibody identifications, and 94% of serum IgG antibody evaluations; 26 PCR-negative samples coincided with negative samples in 96% of bacterial cultures, 81% of tissue IgA antibody evaluations, and 38% of serum IgG assessments. We compared the detection achieved with the H. pylori PCR assay in gastric juice with that in biopsies taken from the antrum and upper corpus in 90 examinations, and found them to be both positive in 34 (38%) and 36 (40%) of specimens, both negative in 37 (41%) and 30 (33%) specimens, gastric juice-positive but biopsy-negative in 10 (11%) and 12 (13%) specimens, and vice versa in 9 (10%) and 12 (13%) specimens, when detected by electrophoresis and hybridization, respectively, showing equivalent detection rates. In relation to the type of disease, the positive PCR assay results with gastric juice, evaluated by electrophoresis and hybridization, respectively, were: gastric ulcer 34/53 (64%) and 39/53 (74%), duodenal ulcer 23/38 (61%) and 25/38 (66%), and chronic gastritis 20/33 (61%) and 23/33 (70%), showing no significant difference in positive rates between peptic ulcer and chronic gastritis. Of the samples of 16 patients with H. pylori-positive gastric juice by the PCR assay, 7 were negative by PCR assay analyzed by electrophoresis and hybridization after the completion of treatment H. pylori. However, after treatment, 3 were negative on electrophoresis but still had positive results with hybridization, indicating that a minimal number of bacilli may have still remained. Detection of H. pylori in gastric juice has potential advantages for examining H. pylori infection in the entire stomach and for follow up after treatment for the eradication of H. pylori.

Antibodies, Bacterial↗
PubMed1995

Effects of Troglitazone (CS-045) on insulin secretion in isolated rat pancreatic islets and HIT cells: an insulinotropic mechanism distinct from glibenclamide.

In order to elucidate the direct effects of (+/-)-5-[4-(6-hydroxy-2,5,7,8-tetramethylchroman-2-yl-methoxy) benzyl]-2,4-thiazolidinedione (Troglitazone), a newly-developed oral hypoglycaemic agent, on pancreatic beta-cell function, in vitro investigation of isolated rat pancreatic islets and a hamster beta-cell line (HIT cell) were performed. Troglitazone stimulates both glucose, and glibenclamide-induced insulin release at a concentration of 10(-6) mol/l in these cells but, conversely, inhibits insulin secretion at 10(-4) mol/l. Glucose uptake in HIT cells is similarly enhanced by 10(-6) mol/l Troglitazone, but is reduced in the presence of 10(-4) mol/l Troglitazone. However, a quantitative immunoblot analysis with a specific antibody for GLUT 2 glucose transporter revealed no significant change in GLUT 2 protein in HIT cells with 10(-6) mol/l Troglitazone. Specific binding of [3H]-glibenclamide to beta-cell membranes is replaced by Troglitazone in a non-competitive manner, but 10(-6) mol/l Troglitazone failed to eliminate ATP-sensitive K++ channel activity. These results suggest that Troglitazone has a putative non-competitive binding site at, or in the vicinity of, the sulphonylurea receptor in rat pancreatic islets and HIT cells and that the dual effect of Troglitazone on insulin secretory capacity is mediated through the modulation of glucose transport activity, possibly due to the modification of intrinsic activity in glucose transporter in pancreatic beta cells by this novel agent.

ATP-Binding Cassette Transporters↗
PubMed1995

Intraduodenal cholecystokinin octapeptide (CCK-8) can stimulate pancreatic secretion in the calf.

The effect of CCK-8 administered into the duodenal lumen and into the systemic blood on pancreatic secretion and duodenal migrating myoelectric complex (MMC) was studied in four calves. Simultaneous MMC recordings and collections of pancreatic juice were performed on valves that had been fasted overnight. Intraduodenal (0, 100, and 300 pmol/kg body wt) and intravenous (0, 30, and 100/pmol kg) infusions of CCK-8 were made for 5 min during the no spiking activity (NSA) phase of duodenal MMC associated with a nadir of periodic pancreatic secretion. CCK-8 was also administered during continuous atropine infusion (5 micrograms/kg/min). Both intraduodenal and intravenous infusions of CCK-8 resulted in marked pancreatic responses in juice outflow, bicarbonate output, and protein output. Atropine decreased pancreatic response (protein output) to intravenous CCK-8 and markedly inhibited the response (juice flow, bicarbonate, and protein output) to intraduodenal CCK-8. Infusions of CCK-8 did not affect the duration of MMC in the duodenum. Plasma CCK increased significantly after intravenous infusion, but remained unchanged after intraduodenal infusion. In conclusion, CCK-8 can stimulate pancreatic secretion from the duodenal lumen, possibly via a cholinergic mechanism in the calf.

Animals↗
PubMed1995

Hyperresponse in calcium-induced insulin release from electrically permeabilized pancreatic islets of diabetics GK rats and its defective augmentation by glucose.

In spontaneously diabetic GK rats, insulin secretion from pancreatic beta cells in response to glucose is selectively impaired, probably due to deficient intracellular metabolism of glucose and impaired closure of KATP channels during glucose stimulation. By using electrically permeabilized islets of GK rats, we explored the functional modulations in exocytotic steps distal to the rise in [Ca2+]i in the diabetic condition. At 30 nmol/l Ca2+ (basal conditions) insulin release was similar between GK and non-diabetic control Wistar rats. In response to 3.0 mumol/l Ca2+ (maximum stimulatory conditions), insulin release was significantly augmented in permeabilized GK islets (p < 0.01). Raising glucose concentrations from 2.8 to 16.7 mmol/l further augmented insulin release induced by 3.0 mumol/l Ca2+ from permeabilized control islets (p < 0.001), but had no effect on that from permeabilized GK islets. The stimulatory effect of glucose on insulin release from permeabilized control islets was partly inhibited by 2,4-dinitrophenol, an inhibitor of mitochondrial oxidative phosphorylation (p < 0.01). The hyperresponse to Ca2+ in GK islets may play a physiologically compensatory role on the putative functional impairment both in [Ca2+]i rise and energy state in response to glucose in diabetic beta cells, and may explain the relative preservation of insulin release induced by non-glucose depolarizing stimuli, such as arginine, from pancreatic islets in non-insulin-dependent diabetes mellitus.

2,4-Dinitrophenol↗
PubMed1995

Fluoride profiles in different sites of approximal surfaces of second primary molars after topical application of acidulated phosphate fluoride gel in vivo.

Thirty-four (17 paired) extracted second primary molars were obtained from 17 individuals (9 boys and 8 girls) aged from 9 yr 2 months to 12 yr 7 months. A tooth on one side was extracted as a control, and an acidulated phosphate fluoride (APF) gel was then applied to the paired contralateral second primary molar. Three months later, the experimental tooth was extracted. Nine sites were assayed by a microsampling technique from small areas of the approximal enamel surface. The fluoride and phosphorus concentrations were determined by a fluoride electrode and by colorimetric procedure, respectively. Fluoride concentrations were higher in the teeth treated with the APF gel than in the control teeth. The highest fluoride uptake was observed in the central area of the approximal surfaces. Deeper areas (> 10 microns) had a marked uptake of fluoride as compared with surface areas (< 3 microns). It was concluded that the APF gel application increased the fluoride levels of approximal tooth surfaces, particularly the mid-central site, of second primary molars, even at 3 months after application.

Acid Etching, Dental↗
PubMed1995

Decrease of medullary catecholaminergic neurons in multiple system atrophy and Parkinson's disease and their preservation in amyotrophic lateral sclerosis.

We investigated the number of tyrosine hydroxylase (TH)-immunoreactive neurons in the C1 and A2 regions of the medulla, the sites of the baroreflex arc, in 7 patients with multiple system atrophy (MSA), 8 with Parkinson's disease (PD), 9 with amyotrophic lateral sclerosis (ALS), and 12 age-matched normal subjects to analyze the relationship between cardiovascular dysfunction and medullary catecholaminergic neurons. Orthostatic hypotension (OH) was marked in all the MSA patients and moderate in three PD patients. Three of the five ALS patients who had been on respirators showed lability of blood pressure; paroxysmal hypertension and nocturnal hypotension without compensatory tachycardia. All the MSA patients showed extremely marked decrease of TH-immunoreactive neurons in both the C1 and A2 regions. In the patients with Parkinson's disease, numerous TH-immunoreactive neurons contained Lewy bodies that were immunostained by antibody to TH. TH-immunoreactive neurons were decreased very markedly in the A2 regions of two patients with OH, and three patients without OH showed fairly marked decreases in the C1 or A2 region. In contrast, the number of TH-immunoreactive neurons in ALS was the same as in normal subjects. In MSA and some PD patients, orthostatic hypotension may partly be due to the involvement of the medullary catecholaminergic neurons. The lability of blood pressure in ALS probably is not related to the medullary catecholaminergic neurons.

Aged↗
PubMed1995

Role of endogenous CCK in regulation of interdigestive pancreatic exocrine secretion in sheep (Ovis aries).

The role of endogenous cholecystokinin (CCK) in the regulation of pancreatic exocrine secretion during the interdigestive period was studied in conscious sheep. Intravenous infusion of proglumide (15, 30 and 60 mumol/kg/min) for 70 min significantly decreased flow rate, protein and amylase output in pancreatic juice by 80% at the maximum dose, as well as atropine (10 micrograms/kg/min), without a significant decrease in plasma concentration of immunoreactive CCK. Intravenous injection of CCK (114 pmol/kg) increased the pancreatic secretion during atropine infusion, but not during proglumide infusion. These results suggest that the regulation of interdigestive pancreatic exocrine secretion in sheep depends greatly on endogenous CCK as well as on the cholinergic mechanism.

Amylases↗
PubMed1995

Cholecystokinin does not act on the efferent pathway of cholinergic and adrenergic nerves to inhibit ruminal contractions in sheep (Ovis aries).

The effect of exogenous cholecystokinin-octapeptide (CCK-8) on ruminal contractions and the role of efferent pathways of cholinergic and adrenergic nerves on the effect were studied in sheep. Intravenous infusion of CCK-8 at 11.4 and 45.6 pmol/kg/min significantly inhibited the frequency and amplitude of ruminal contractions in conscious sheep. After bilateral cervical vagotomy, intravenous infusion of CCK-8 at 45.6 mol/kg/min had no detectable effect on amplitude of ruminal contractions induced by electric stimulation to the cervical vagus nerve (1 msec, 20 Hz, 5 mA, for 10 sec at 1-min intervals) in anesthetized sheep. The amplitude of contractile responses of ovine ruminal muscle strips to acetylcholine at 5 x 10(-5) M was not inhibited by CCK-8 applied simultaneously at 1 x 10(-9) M. Intravenous infusion of phentolamine at 53.0 nmol/kg/min, propranolol at 101.4 nmol/kg/min, or their combined infusion did not alter the inhibitory action of CCK-8 at either dose on ruminal contractions in conscious sheep. These results suggest that CCK-8, which does not act on the efferent pathway of cholinergic and adrenergic nerves, may reflexively inhibit reticuloruminal contractions via vagal afferent fibers in sheep.

Acetylcholine↗
PubMed1995

Effects of intravenous infusions of cholecystokinin (CCK)-8 on exocrine and endocrine pancreatic secretion in conscious sheep.

The effects of cholecystokinin (CCK)-8 on both exocrine and endocrine pancreatic functions were examined simultaneously in five conscious sheep. Intravenous infusions of CCK-8 (0, 5, 10, 20, 30, 60, 120 and 240 pmol/kg/min for 40 min) induced dose-dependent increases in flow rate, and in protein and amylase outputs in pancreatic juice. The same CCK-8 infusions induced dose-dependent increases in plasma insulin, but no change in plasma glucagon concentrations. The threshold dose (10-30 pmol/kg/min) of CCK-8 infusion for stimulating insulin secretion was similar to that for stimulating amylase output. In conclusion, using amylase output as an indicator of physiological action, CCK is one of the potential candidates as a physiological regulator of insulin, but not glucagon secretion in sheep.

Amylases↗