Biomedical subjects
K Satoh
Publications and source records attributed to K Satoh.
Helicobacter pylori detected deep in gastric glands: an ultrastructural quantitative study.
To determine the presence of Helicobacter pylori deep in the gastric glands and in the parietal cell canaliculi, biopsied specimens from 15 patients were observed by electron microscopy. In the specimens, 818 H. pylori and 1,846 parietal cells were detected. Most of the H. pylori (93.9%, 768/818) were present on the mucosal surface. However, a few organisms (50/818, 6.1%) were detected deep in the mucosa. The mean number of H. pylori per specimen was 2.13 (32/818, 3.9%) and 1.20 (18/818, 2.2%), deep in the gland and in the parietal cell canaliculi, respectively. All appeared morphologically intact. Although the combination of culture and histology from biopsy tissues is usually used for isolation of H. pylori in most laboratories, such organisms are considered difficult to detect with conventional methods and to dislodge with antimicrobial therapy. Therefore, H. pylori present deep in the mucosa are suggested to be one of the factors in recrudescence after eradication therapy. In addition, H. pylori in the parietal cell canaliculi may affect parietal cell function or alter gastric physiology.
[The effect of occult hyperprolactinemia (OHP) on gonadotropin secretion system].
The present study was conducted to investigate the effects of the transient increase of serum prolactin levels on the gonadotropin secretion system in patients with occult hyperprolactinemia (OHP). 216 cases of normoprolactinemic hypothalamic anovulatious were selected by LH-RH and TRH loading tests, and 5mg/day of bromocriptine was administered for more than 8 weeks. The effectiveness of the bromocriptine administration was estimated by the ultrasonic examination of the follicular development. The endocrinological backgrounds were compared between bromocriptine effective (154 cases, group A) and non-effective (62 cases, group B) patients. Serum prolactin levels 30min. after LH-RH and TRH loading (PRL30 in group A were significantly higher than those of group B (74.1 +/- 36.5 vs. 38.0 +/- 18.2ng/ml, p < 0.01). From this result, it was thought that many of the OHP patients were selected in group A. Serum LH levels 30min. after loading test (LH30) in group A also increased compared to those of group B (65.0 +/- 66.5 vs. 43.1 +/- 34.3mIU/ml, p < 0.02). The LH/FSH ratio before loading was also higher in group A (1.3 +/- 0.6) than that of group B (1.0 +/- 0.5, p < 0.02). This fact showed that group A also contained patients with hyper-LH hypothalamic anovulation, which is known as the endocrinological PCOD. There were also significant inverse correlations between serum levels of prolactin and FSH in group A (before loading values: r = 0.272, 30min. after loading: r = 0.224, p < 0.01). By the administration of bromocriptine, serum prolactin levels decreased both in group A and B, and the elevated serum LH/FSH ratio (1.0 +/- 0.4, p < = 0.02), LH30 (46.1 +/- 37.0mIU/ml, p < 0.005) also decreased significantly. Serum levels of FSH in group A increased significantly with treatment (before loading: 5.4 +/- 2.6-->6.2 +/- 2.0, 30min. after loading: 10.6 +/- 6.0-->14.6 +/- 9.9mIU/ml, p < 0.005). From these facts, it was concluded that FSH secretion was suppressed even by a slight increase of serum prolactin levels which was usually seen in the OHP, and bromocriptine administration was effective not only for the suppression of serum prolactin and LH levels, but also for the improvement of FSH secretion in the OHP patients.
Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis by dietary curcumin and hesperidin: comparison with the protective effect of beta-carotene.
The modifying effects of two natural products, curcumin and hesperidin, given during the initiation and postinitiation phases of oral carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats and compared with that of beta-carotene. At 6 weeks of age, rats were divided into experimental and control groups and fed the diet containing beta-carotene, hesperidin, or curcumin at a dose of 0.5 g/kg diet (500 ppm). At 7 weeks of age, all animals except those treated with each test chemical alone and control groups were given 4-NQO (20 ppm) in the drinking water for 8 weeks to induce oral cancer. Seven days after the 4-NQO exposure, groups of animals fed the diets containing test chemicals were switched to the basal diet and continued on this diet until the end of the study. Starting 1 week after the stop of 4-NQO exposure, the groups given 4-NQO and a basal diet were switched to the diets containing beta-carotene, hesperidin, and curcumin and maintained on these diets for 22 weeks. The other groups consisted of rats given 500 ppm beta-carotene, hesperidin, or curcumin alone or untreated rats. All animals were necropsied at the termination of the experiment (week 32). The incidences of tongue neoplasms and preneoplastic lesions, polyamine levels in the tongue tissue, and cell proliferation activity estimated by bromodeoxyuridine-labeling index and by morphometric analysis of silver-stained nucleolar organizer region proteins were compared among the groups. Feeding of curcumin and beta-carotene during the initiation and postinitiation phases and hesperidin at the initiation stage caused a significant reduction in the frequency of tongue carcinoma (41-91% reduction, P < 0.05) and the order of chemopreventive efficacy was curcumin > beta-carotene > hesperidin. The incidences of oral preneoplasia in rats fed the diets mixed with these compounds were also decreased (P < 0.05). There were no such lesions in rats treated with test compounds alone or those in an untreated control group. Dietary administration of these compounds significantly decreased the labeling index of bromodeoxyuridine and the number and area of silver-stained nucleolar organizer region proteins per cell nucleus that are proliferation biomarkers, of the tongue squamous epithelium (P < 0.05). In addition, polyamine levels in the oral mucosa were lowered in rats treated with 4-NQO and three test compounds when compared to those give 4-NQO alone (P < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of sulfonylurea agents on platelet arachidonic acid metabolism; study on platelet homogenates.
Effects of three sulfonylurea agents on arachidonic acid metabolism of platelet homogenates were evaluated using HPLC. Gliclazide had no significant inhibitory effects on arachidonic acid metabolism. Glibenclamide and glimepiride both inhibited the production of cyclooxygenase-related metabolites, thromboxane B2 (TXB2) and 12-hydroxy 5,8,10-heptadecatrienoic acid (HHT), whereas 12-hydroxy 5,8,10,14-eicosatetraenoic acid (12-HETE), a 12-lipoxygenase-related product, was unaffected. These findings confirmed part of our previous report using intact platelets, except that we found in the present study that glibenclamide had no inhibitory effect on 12-lipoxygenase.
Nearest neighbor analysis of D1 and D2 subunits in the photosystem II reaction center using a bifunctional cross-linker, hexamethylene diisocyanate.
A cross-linked product between the D1 and D2 subunits was generated by treating isolated spinach PS II reaction center with a bifunctional cross-linker, 1,6-hexamethylene diisocyanate. To obtain information on the contact site(s) between D1 and D2 proteins, the cross-linked product was cleaved by CNBr, the resultant fragments were separated using a reverse-phase HPLC, and then the partial sequence of the cross-linked polypeptide fragments were determined. By comparing the results with the deduced amino acid sequence of the D1 and D2 proteins from spinach, it is concluded that the C-terminal domains of the D1 subunit (D308-A334) and that of the D2 subunit (Y297-L353) are in close proximity.
Influence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on mitochondrial respiration in rat liver during ischemia.
Effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin and simvastatin, on mitochondrial respiration in ischemic rat liver were examined. Either vehicle, pravastatin (2 or 4 mg/kg per day), or simvastatin (1 or 2 mg/kg per day) was orally administered for 3 weeks. Liver ischemia was induced by cessation of the systemic circulation for 60 min. Liver mitochondria were isolated and the respiration was determined by polarography using glutamate and succinate as substrates. In the vehicle-treated group, ischemia drcreased ZO3, respiratory control index (RCI: QO3/QO4), and ADP/O ratio. Pretreatments with pravastatin and simvastatin enhanced the decreases in QO3 measured with either glutamate or succinate, and in ADP/O ratio measured with succinate. Because of decreasing QO4, HMG-CoA reductase inhibitors did not modify the changes in RCI due to ischemia. There were no significant differences in respiratory indices between pravastatin- and simvastatin-treated groups. In conclusion, HMG-CoA reductase inhibitors may enhance respiratory impairment of liver mitochondria under pathophysiological conditions, such as ischemia.
Synthesis of phosphatidylinositol 3,4-bisphosphate is regulated by protein-tyrosine phosphorylation but the p85 alpha subunit of phosphatidylinositol 3-kinase may not be a target for tyrosine kinases in thrombin-stimulated human platelets.
To elucidate the mechanism involving synthesis of phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2), which is the main species of 3-phosphorylated phosphoinositides in activated blood platelets, we observed a correlation among protein-tyrosine phosphorylation, protein kinase C (PKC) activation, and PtdIns(3,4)P2 synthesis in these anucleate cells. Thrombin (1 U/ml) elicited marked protein-tyrosine phosphorylation, PKC activation, and PtdIns(3,4)P2 synthesis. In contrast, 1 microM 12-O-tetrade-canoylphorbol 13-acetate barely induced tyrosine phosphorylation and PtdIns(3,4)P2 synthesis although it strongly activated PKC. A variety of kinase inhibitors were tested for their ability to inhibit the thrombin effects. Both staurosporine and tyrphostin inhibited thrombin-stimulated tyrosine phosphorylation and PtdIns(3,4)P2 synthesis. H-7, which specifically, although weakly, inhibited PKC activation, had no effect on tyrosine phosphorylation and PtdIns(3,4)P2 production. Among the various kinase inhibitors tested, staurosporine was the most potent inhibitor of protein tyrosine phosphorylation and PtdIns(3,4)P2 synthesis, and there was a good correlation of the inhibition between these two parameters, although it also inhibited PKC activation. To examine the involvement of PtdIns 3-kinase, which is believed to play an important role in 3-phosphorylated phosphoinositide synthesis, we studied tyrosine phosphorylation and the association with tyrosine-phosphorylated proteins of the p85 alpha subunit of PtdIns 3-kinase in thrombin-stimulated platelets. We did not detect tyrosine-phosphorylated protein by Western blotting where p85 alpha was located. Similarly, when platelet lysates were precipitated with anti-p85 alpha antibodies and then blotted with anti-phosphotyrosine antibodies, tyrosine-phosphorylated p85 alpha was undetectable. Furthermore, when the cell lysates were precipitated with anti-phosphotyrosine antibodies, no p85 alpha was found in the immunoprecipitates. These results show that PtdIns(3,4)P2 synthesis in stimulated platelets is mediated by tyrosine phosphorylation, as it is in proliferating cells, but the p85 alpha subunit of PtdIns 3-kinase may not be a target for tyrosine kinases and that staurosporine, though non-specific, would be a useful tool for elucidating signal transduction involving D-3-phosphorylated phosphoinositide generation and protein-tyrosine phosphorylation in blood platelets.
Detection of platelet aggregates with a particle counting method using light scattering.
A novel method to detect platelet aggregation by means of the particle counting technique using light scattering has been developed. An optical device designed to focus on a limited area of platelet-rich plasma measured the intensity of light scattered by particles passing through the area, minimizing multiple light scattering. The use of polystyrene spheres of different diameters confirmed that the light scattering intensity increases in proportion to the particle size in a suspension. Platelet activation induced by various agonists resulted in light scattering of higher intensities, which correlated well with the number and size of aggregates as observed under a microscope. These findings confirmed that the intensity of light scattering detected by the new device provides information on the number and size of aggregates in a suspension. The new method was compared with conventional platelet aggregometry using overall light scattering or changes in light transmission (optical density). The new device appeared to be particularly sensitive to small aggregates such as those formed in platelet activation induced by low concentrations of agonists. Furthermore, the new method has an advantage over the conventional aggregometry, in that it allows the aggregate size distribution and the extent of aggregation to be estimated.
Simultaneous racemization and isomerization at specific aspartic acid residues in alpha B-crystallin from the aged human lens.
We provide evidence that the racemization and isomerization of aspartyl(Asp) residues occur simultaneously in the alpha B-crystallin in the lens of aged (mean age: 80 years) and young (age: 11 months) humans. We purified alpha B-crystallin and subjected it to tryptic digestion. The resulting peptides were separated by reverse-phase high-performance chromatography (RP-HPLC) and were characterized by amino-acid composition, sequence analysis and mass spectrometry. Two specific sites, Asp-36 (D/L of Asp: 0.92) and Asp-62(D/L of Asp: 0.57), among 13 Asp/asparginyl (Asn) residues in aged alpha B-crystallin, were found to be highly racemized and isomerized to form beta-Asp residues. The beta-Asp-containing peptides were clearly distinguished from normal Asp-containing (alpha-Asp) peptides by RP-HPLC. The racemization and isomerization of Asp residues in aged alpha B-crystallin may occur via a succinimide intermediate. In young alpha B-crystallin, we observed neither racemization nor isomerization. We also found that Met-68 was oxidized to form Met sulfoxide to a greater extent in aged alpha B-crystallin than in young alpha B-crystallin. We concluded that racemization, isomerization, and oxidation of alpha B-crystallin occur spontaneously in the aging process.
Relaxant mechanisms of cyclic AMP-increasing agents in porcine coronary artery.
We investigated the relaxant mechanisms of the cyclic AMP (cAMP)-increasing agents, isoproterenol, T-0509, forskolin and 3-isobutyl-1-methylxanthine (IBMX), on porcine coronary arteries contracted with U46619 (300 nM), a thromboxane A2 analogue, or 30 mM KCl, by measuring force simultaneously with intracellular Ca2+ concentration ([Ca2+]i) or cAMP and cyclic GMP (cGMP) levels. In U46619-contracted arteries, these agents decreased [Ca2+]i and force of contraction to almost the same extent in a concentration-dependent manner, whereas in KCl-contracted arteries these agents, except IBMX at higher concentrations, produced a relaxation with little change in [Ca2+]i. These agents all elevated tissue cAMP levels, and in addition, IBMX at higher concentrations increased cGMP levels. In Ca(2+)-free medium, these agents produced a concentration-dependent inhibition of Ca2+ release from intracellular Ca2+ stores induced by U46619 but not by 25 mM caffeine. Isoproterenol at a high concentration (3 microM) transiently decreased [Ca2+]i but steadily relaxed KCl-contracted arteries. This decrease in [Ca2+]i, but not the relaxation was inhibited by ryanodine and caffeine treatments. These results suggest that the relaxant mechanism of these agents on KCl-contracted arteries is mainly due to phosphorylation of myosin light chain kinase via cAMP-dependent protein kinase, resulting in a reduction of the Ca2+ sensitivity of contractile elements. Their relaxant mechanism in U46619-contracted arteries seems due to the inhibition of signal transduction of the agonist, resulting in a decrease in [Ca2+]i and inhibition of the Ca2+ sensitization.
Magnetic behavior of YbNiSb.
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Aspergilloma formation in a pneumatocele in a patient with acute lymphoblastic leukemia.
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Alteration in the JC polyomavirus genome is enhanced in immunosuppressed renal transplant patients.
JC polyomavirus (JCV) DNAs derived from urine generally contain an archetypal regulatory sequence, whereas regulatory regions of JCVs in the brain with progressive multifocal leukoencephalopathy (PML) have specifically altered regulatory regions. However, JCV DNAs with regulatory regions that deviate from the archetype sometimes occur in the urine of non-PML patients. In this study, we compared the incidence of these rearranged regulatory regions between immunosuppressed (renal transplant recipients) and nonimmunosuppressed patients. We found that the incidence of rearranged JCV regulatory regions was significantly higher in renal transplant patients than that in nonimmunosuppressed patients. This finding suggests that immunosuppression would permit accumulation of JCV with rearranged regulatory regions. On the other hand, from the following observations, we conclude that rearranged regulatory regions unique to PML-type JCVs rarely occur even in renal transplant patients: (1) rearrangements in JCVs from these patients were almost exclusively simple, that is deletions or duplications; (2) duplication of domain A or deletion of domain B, each being a feature common to most PML-type regulatory regions, was rarely detected in JCVs from the patients. The data are consistent with the fact that PML is a rare disease in patients with decreased immune competence and support the hypothesis that changes in the JCV regulatory region may be involved with the etiology of PML.
A further study of the vasodilator and negative inotropic mechanisms of action of nicorandil and its congeners in the canine heart.
The vasodilator and negative inotropic mechanisms of action of nicorandil and its congeners (SG-209, SG-103, and SG-86) were investigated in isolated canine papillary muscle preparations cross-circulated through the anterior septal artery with support dogs. SG-209, SG-103, and SG-86 were obtained by replacement of the nitroxyl group of nicorandil by acetoxyl, nicotinoyloxyl, and hydroxyl groups, respectively. Nicorandil (0.03-10 mumol), SG-209 (0.1-10 mumol), SG-103 (1-30 mumol), and SG-86 (3-100 mumol) all produced an increase in coronary blood flow through the anterior septal artery. Both nicorandil and SG-209 produced a near-maximal increase in coronary blood flow, the latter being about 5.5 times less potent than the former. SG-103 and SG-86 were far less potent than SG-209 in that order. The vasodilator actions of nicorandil and SG-209 were antagonized by glibenclamide given IV to support dogs, but those of SG-103 and SG-86 were not. The pKB values of glibenclamide were 6.34 toward nicorandil and 6.49 toward SG-209. Developed tension of the papillary muscle was reduced by nicorandil, SG-209, and SG-103, but not by SG-86. In this respect SG-209 was about 4.7 times less potent than nicorandil, and SG-103 was much less potent than SG-209. The negative inotropic effects of nicorandil and SG-209 were antagonized by glibenclamide, but that of SG-103 was not.(ABSTRACT TRUNCATED AT 250 WORDS)
A long surviving case of recurrent medulloblastoma displaying effectiveness of ACNU/vincristine chemotherapy.
A favorable case of recurrent medulloblastoma, in which 19 years has elapsed with combination therapy due to surgery, radiation and chemotherapy since the initial operation, is reported. The case was a male of age 12 who was admitted due to medulloblastoma of the classical type. Tumor recurrences were observed 3 times within 7 years after the initial operation and radiation treatment. At the 3rd recurrence, a large tumor was found in the cerebellar vermis and left cerebellar hemisphere on CT with CSF dissemination and a high NSE level in the CSF (62 ng/ml). Only chemotherapy by intravenous administration of 2 courses of 120-150 mg ACNU (1.7-2.2 mg/kg) and 4 mg vincristine (0.06 mg/kg) with intrathecal administration of methotrexate was given at this time. The tumor image and gait disturbance with radicular pain disappeared completely and the NSE level in the CSF improved to within the normal range (5.4 ng/ml). The patient continues in complete remission, with a Karnovsky performance status of 100% at 4 years after the 3rd recurrence. We report full details of this case in which active treatments consisting mainly of chemotherapy proved to be effective for recurrent medulloblastoma, even though its prognosis is generally very unfavorable.
Density-associated changes in platelet-activating factor acetylhydrolase activity and membrane fluidity of human erythrocytes.
Platelet-activating factor acetylhydrolase is known to degrade oxidatively fragmented phospholipids which are similar in structure to platelet-activating factor. We examined changes of acetylhydrolase activity during in vivo aging of human erythrocytes and tried to assess its role in maintaining the membrane properties of erythrocytes. Higher-density erythrocytes are enriched with older cells. Erythrocytes obtained from seven healthy colleagues were separated into four density fractions by centrifugation in discontinuous Percoll density gradients. Both membrane and cytosolic acetylhydrolase decreased with increasing erythrocyte density. Membrane and cytosolic acetylhydrolase activities in the lightest fraction were 2.0 +/- 1.0 (SD) nkat/g protein and 362 +/- 58 pkat/g protein, respectively, and these values were significantly higher than those in the densest fraction: 1.3 +/- 0.7 nkat/g protein and 286 +/- 70 pkat/g protein, respectively. Membrane acyltransferase activity also decreased with red cell density and the average values in the lightest and densest fractions were 51.2 +/- 23.6 and 27.0 +/- 20.2 mukat/g protein, respectively. Generation of thiobarbituric acid-reactive substances induced by t-butyl hydroperoxide treatment decreased with increasing cell density, and the inhibition of acetylhydrolase with diisopropylfluorophosphate resulted in enhanced peroxide-induced lipid oxidation, particularly in lower-density fractions. There was no significant change in basal levels of thiobarbituric acid-reactive substances in red cell membrane. Membrane fluidity was evaluated by fluorescence recovery after photo-bleaching and it decreased as erythrocyte density increased. We conclude that the activity of the deacylation/reacylation cycle maintained by acetylhydrolase and acyltransferase is gradually reduced during in vivo aging of erythrocytes. This may be connected with decreases of polyunsaturated fatty acids and membrane fluidity in old erythrocytes.
Occurrence of multiple JC virus variants with distinctive regulatory sequences in the brain of a single patient with progressive multifocal leukoencephalopathy.
We established 99 JC virus (JCV) DNA clones directly from the brain of a single patient with progressive multifocal leukoencephalopathy (PML). Based upon restriction patterns, the cloned viral DNAs were classified into two major groups (NY-1A and -1B) containing 53 and 35 clones, respectively, and several minor groups containing one or a few clones. The regulatory sequences of representative clones were compared with the archetypal regulatory sequence, which has been detected in JCV DNAs cloned from the urine of healthy and nonimmunosuppressed individuals. The regulatory sequence of NY-1B had the two structural features common to most PML-type regulatory regions, duplication and deletion of specific segments in the archetypal sequence, while that of NY-1A contained a small deletion and an insertion of a 29-bp sequence originating from the early region of the JCV genome. A regulatory region similar to that of NY-1A has never been detected in JCV isolates obtained thus far.