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Biomedical subjects

Y Kishi

Publications and source records attributed to Y Kishi.

At least 163 records · Page 9Linked to original sources

Visceral leishmaniasis misdiagnosed as malignant lymphoma.

Visceral leishmaniasis is a chronic infectious disease caused by a protozoan parasite of the genus Leishmania, characterized by intermittent fever, monocytosis, hepatosplenomegaly and hypergammaglobulinemia. This morbid condition is rather difficult to diagnose correctly, especially at its early stage, because it is rarely encountered in Japan. Recently we treated a case of visceral leishmaniasis in which the patient was misdiagnosed as malignant lymphoma, and went through splenectomy and steroid administration, which made the diagnosis more difficult.

Adult↗

Estimation of EDRF and nitric oxide release using [3H]GTP-labeled human platelets.

We have developed a new bioassay for endothelium-derived relaxing factor (EDRF) or nitric oxide (NO) using human [3H]guanosine triphosphate (GTP)-labeled platelets. The labeled platelets were preincubated with isobutyl-methylxanthine and co-cultured with endothelial cells and the [3H]cyclic guanosine monophosphate (cGMP) formed was isolated by ion-exchange chromatography. Endothelial cells, either in monolayer cells or in suspension, increased platelet cGMP accumulation dose-dependently, a significant increase being detected with 5000 endothelial cells or more/assay when suspended cells were used. Co-culturing with the same number of skin fibroblasts failed to elevate platelet cGMP. Preincubation of endothelial cells with bradykinin and superoxide dismutase (SOD) synergistically potentiated the increase in platelet cGMP, but was attenuated by Nomega-nitro-L-arginine, with partial restoration by L-arginine but not by D-arginine. These compounds, however, did not affect cGMP accumulation by sodium nitroprusside. Moreover, preincubation of the labeled platelets with the NO synthase inhibitor prior to EDRF assay had no effect. We conclude that [3H]GTP-labeled platelets could provide a simple, sensitive and specific bioassay for estimating EDRF or NO release.

Animals↗

Ingested arsenic and internal cancer: a historical cohort study followed for 33 years.

A historical cohort study was conducted to investigate the long-term effect of exposure to ingested arsenic. The 454 residents who had been identified in a list made in 1959 were followed until 1992. They lived in an arsenic-polluted area, called Namiki-cho, Nakajo-machi, in Niigata Prefecture, Japan, and used well water containing inorganic arsenic. The exposure period was estimated to be about 5 years (1955-1959). Death certificates for the people who died between 1959 and 1992 were examined, and a total of 113 of the 454 residents were estimated to have drunk well water containing a high dose of arsenic (> or = 1 ppm). The standardized mortality rate ratios of these 113 residents were 15.69 for lung cancer (observed/expected = 8/0.51; 95% confidence interval (CI) 7.38-31.02) and 31.18 for urinary tract cancer (observed/expected = 3/0.10; 95% CI 8.62-91.75). Cox's proportional hazard analyses demonstrated that the hazard ratios of the highest exposure level group (> or = 1 ppm) versus the background exposure level group (0.001 ppm) were 1.74 (95% CI 1.10-2.74) for all deaths and 4.82 (95% CI 2.09-11.14) for all cancers. The analysis according to the skin signs of chronic arsenicism in 1959 showed that they were useful risk indicators for subsequent cancer development. In the development of lung cancer, there was evidence of synergism between arsenic intake and smoking habit.

Adolescent↗

What effect does controlling platelets have on atherosclerosis?

Platelets play important roles for hemostasis with activated platelets adhering to the injured vessel wall to initiate platelet aggregation. At the same time, our study revealed the cytotoxic effect on endothelial cells characterized by an increase of intracellular Ca++ and a decrease of EDRF production, which may cause plasmal infiltration including blood cells and lipids. Our clinical survey using a small dose of aspirin as an antiplatelet therapy clearly demonstrated its suppressive effect on platelet aggregation and its favorable effect on fibrinolysis. These data suggest that the therapeutic effect of aspirin in vascular disease could be applied to the prevention of thrombus formation and the protection of endothelial cells from the cytotoxic effect of activated platelets.

Adenylyl Cyclases↗

Interaction of palytoxin with red cells: structure-function studies.

Palytoxin (PTX), a potent toxin isolated from the marine soft coral Palythoa tuberculosa increases the cationic permeability of red cell membranes and inhibits the (Na+,K+)-activated ATPase, effects that are completely reversed by ouabain. It has also been shown to compete with ouabain for a binding site and it has been suggested that it binds to the Na+,K(+)-pump molecule in cells. In a search for analogues of PTX that would bind covalently and could thus be used to identify and characterize the binding site, we have used compounds which differed from PTX at one end or at both ends simultaneously. In order to determine whether these derivatives could be used to replace palytoxin, we tested their potency to induce an increased cation flux, complete with ouabain for its binding site, and inhibit the isolated, purified (Na+,K(+)-ATPase). The results obtained indicate that departures from the PTX structure at one end or at both ends simultaneously substantially decrease the ability of the compounds to increase the cationic permeability of red blood cells and to inhibit the (Na+,K(+)-ATPase). These actions were found to be completely reversed by ouabain, but the analogues are two to three orders of magnitude less potent than PTX in competing with ouabain for its binding site. These results suggest that both ends of the palytoxin molecule participate in the interactions of the toxin with its receptor and that modifications in these regions of the molecule produce significant alterations in its binding and subsequent action on red cell membranes.

Acrylamides↗

The potencies of synthetic analogues of saxitoxin and the absolute stereoselectivity of decarbamoyl saxitoxin.

The potencies of synthetic saxitoxin (+/- STX) and six of its synthetic analogues, including the enantioselectively synthesized unnatural (-)enantiomer of decarbamoyl saxitoxin (dcSTX), were measured and compared to those of natural saxitoxin [(+)STX]. The analogues, all of which were racemic (+/-) mixtures except for dcSTX, varied in the substituents at the C6 position, the carbamoyl 'moeity', and the C12 position, the hydrated ketone. The ability of the toxins to inhibit the compound action potential (AP) and to displace radiolabeled natural saxitoxin (3H-STX) from nerve membranes at equilibrium were both used as potency assays. Biological activity of both (+)- and (-)dcSTX was analyzed by the kinetics of block of single Na+ channels reconstituted in planar lipid bilayer membranes, where it was demonstrated that only (+)dcSTX had biological activity. The potency of STX analogues fell markedly as the substituent at the C6 position became smaller; Ki values from the binding competition assay (at 4 degrees C) are: (+/-)6-methanolic-STX, 5 x 10(-10) M; (+/-)6-methyl-STX, 1 x 10(-6) M; (+/-)6-dihydro-STX, 3.5 x 10(-5) M. Replacement of the ketone at the C12 position by a methylene group was accomplished in two derivatives, although both also had substituents at the C6 position. The compound (+/-)6-methyl-12-deoxy-STX was about 0.03 as potent as (+/-)6-methyl-STX and only 10(-5) as potent as racemic (+/-)STX. In synthetic compounds where the benzyloxymethyl (-CH2OCH2C6H5) substituent occurred at the C6 position, the C12-methylene derivative still displayed some binding activity (Ki = 6 x 10(-4) M). However, when the same C6 derivatized compounds also contained a 6-membered heterocyclic group (-C3H8S2-) conjugated to carbon 12, the measured binding affinity was even further decreased (Ki = 2 x 10(-3) M). The findings show that substitutions on the carbon 6 position of STX have stronger effects on STX potency than previously believed, and that the toxin may form a hydrogen bond with the sodium channel at this site. Furthermore, the total removal of oxygen from the C12 position does not completely abolish the binding activity of the molecule.

Action Potentials↗

Delirium in critical care unit patients admitted through an emergency room.

Two hundred thirty-eight patients admitted consecutively to a critical care unit through an emergency room were assessed prospectively for the presence of delirium. Thirty-eight patients (16%) developed delirium. Delirium occurred with equal frequency in all disease categories. The presence of abnormal head imaging which required medical intervention did not predict the development of delirium. The median delay between admission and the development of delirious was 4 days, however, one-fourth of the patients were delirious on the day of admission. The patients with abnormal head imaging who required medical intervention had a higher frequency of onset of delirium on the first day compared with patients without. The delirium lasted a median of 5 days and resolved within a week in over 70% of patients. These results confirm that delirium is frequently present in patients who require acute critical care after emergency room evaluation. In this population, serious medical disease is a better predictor of the development of delirium than the presence of abnormal brain imaging which required medical intervention. Although delirious patients have longer lengths of stay, the presence of delirium does not predict higher mortality, as has been reported in other populations. This could be because delirious patients admitted to the critical care unit through the emergency room have fewer premorbid medical problems predisposing them to poor outcome.

Adult↗

Effects of cilostazol on development of experimental diabetic neuropathy: functional and structural studies, and Na+ -K+ -ATPase acidity in peripheral nerve in rats with streptozotocin-induced diabetes.

We studied the ability of cilostazol (CL), an antithrombotic and vasodilating agent, to prevent functional, structural and biochemical abnormalities including delayed motor nerve conduction velocity (MNCV), morphological changes in myelinated fibers, and decreased Na(+)-K(+) -ATPase activity in the peripheral nerves of rats with streptozotocin (STZ)-induced diabetes. Cilostazol treatment (30 mg/kg/day p.o.) for 10 weeks significantly prevented the delay in MNCV in the tail nerve, and morphometric analysis of the sural nerves revealed that this dose of cilostazol had a significant effect on reduction of average size of myelinated fibers. In untreated diabetic rats, cyclic AMP content and Na(+)-K(+)-ATPase activity of peripheral nerve were each significantly less than in normal control rats. Cilostazol (30 mg/kg/day) prevented reduction of Na(+)-K(+)-ATPase activity. Decrease in cyclic AMP content was completely prevented with both doses of cilostazol (30 and 10 mg/kg/day). These findings suggest that cilostazol may have beneficial effects in the treatment of diabetic neuropathy, possibly via improvement of nerve Na(+)-K(+) -ATPase activity and cyclic AMP content. Cilostazol may thus be a potent drug for the clinical treatment of diabetic neuropathy.

Animals↗

Analysis of methicillin-resistant and methicillin-susceptible Staphylococcus aureus by a molecular typing method based on coagulase gene polymorphisms.

A molecular typing method for Staphylococcus aureus based on coagulase gene polymorphisms (coagulase gene typing) was evaluated by examining a total of 240 isolates which comprised 210 methicillin-resistant S. aureus (MRSA) and 30 methicillin-susceptible S. aureus (MSSA) collected from a single hospital. By AluI restriction enzyme digestion of the PCR-amplified 3'-end region of the coagulase gene including 81-bp repeated units, the MRSA and MSSA isolates examined were divided into 6 and 12 restriction fragment length polymorphism (RFLP) patterns, respectively, whereas five patterns were commonly detected in MRSA and MSSA. MRSA isolates that showed a particular RFLP pattern were considered to be predominant in the hospital. Coagulase typing with type-specific antisera was also performed for all S. aureus isolates for comparison. Coagulase types II and VII were most frequently detected and included isolates with four and five different AluI RFLP patterns, respectively, whereas each of the other coagulase types corresponded to a single RFLP pattern. These results indicated that RFLP typing was more discriminatory than serological typing, for typing S. aureus and demonstrated its utility in epidemiologic investigation of S. aureus infection in hospitals.

Bacterial Typing Techniques↗

Primary squamous cell carcinoma of the endometrium: a case report and a suggestion of new histogenesis.

A case of primary endometrial squamous cell carcinoma (ESCC) in a 75-year-old woman is reported. In her endometrium, mature stratified squamous epithelium was associated with mucinous glands in which epithelium and glands were identical to those of the uterine cervix, but which were not connected with the cervix. Thus, the endometrial squamous epithelium with mucinous glands was diagnosed as heterotopic cervical tissue. This heterotopia was surrounded by ESCC and connected with it. The present case suggests that some ESCCs may arise in heterotopic cervical epithelium in the endometrium.

Aged↗

Comparison between acute and delayed onset major depression after spinal cord injury.

Sixty patients with spinal cord injury were examined to assess major depression during the in-hospital period and at 3- and 6-month follow-up. Thirteen patients had depression during the initial in-hospital evaluation (acute onset depression) and eight had depression first diagnosed at either 3- or 6-month follow-up (delayed onset depression). Acute onset depression was related to the severity of impairment and premorbid history of psychiatric disorder, suggesting a psychological reaction to impairment or premorbid vulnerability as a possible mechanism for developing depression. Delayed onset depression was not related to severity of physical impairment but was associated with more rostral spinal injury, suggesting the possibility that neurophysiological response to injury more proximal to the brain may play a role in delayed onset depression. These data also suggest that the etiology and pathophysiology of these two types of depression may be different.

Adult↗

Effect of nifedipine on cyclic GMP turnover in cultured coronary smooth muscle cells.

We investigated the effects of nifedipine on cyclic GMP turnover and the pertinent enzyme activities in cultured coronary smooth muscle cells (SMC). Nifedipine at high concentrations slightly decreased basal soluble guanylate cyclase activity and inhibited the action of sodium nitroprusside (SNP) but had no effect on the particulate form of the enzyme. In contrast, nifedipine inhibited cyclic GMP hydrolysis by directly inhibiting the partially purified calmodulin-stimulated isoform of phosphodiesterase (type I PDE) with IC50 of 4.2 microM. Nifedipine > or = 1.0 microM enhanced cyclic GMP accumulation in response to 1.0 microM SNP, although nifedipine alone exerted no influence on cyclic GMP levels. Enhancement of cyclic GMP accumulation by nifedipine in response to SNP was not affected by BAY K 8644, a calcium channel agonist. These properties may be shared by other dihydropyridines since nicardipine and nisoldipine also inhibited type I PDE with similar IC50. However, some other structurally unrelated calcium channel blockers, diltiazem and verapamil, had little effect on cyclic nucleotide hydrolysis or on cyclic GMP accumulation in response to SNP. Nifedipine may synergistically enhance cyclic GMP accumulation in response to nitric oxide (NO)-releasing agents by directly inhibiting type I PDE in coronary SMC. Such effects of nifedipine may partly contribute to coronary vasodilation and prevention of coronary spasm in patients with ischemic heart disease.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Carcinosarcoma of the uterine body of mesonephric origin.

A case of carcinosarcoma of mesonephric origin in a 58 year old woman is reported. A cystic tumor with a solid area, measuring 14 cm in greatest diameter, was detected in the pelvic cavity by computerized tomography and ultrasound. Although it was diagnosed as an ovarian cancer for surgical removal, it was found to be entirely located in the myometrium of the left lateral wall of the uterine body and neither ovary was remarkable. Histologically the tumor was composed of epithelial and sarcomatous components. The former showed low papillary pattern, crowded solid nests and cords of cells, and focal tubular structures. The latter showed a solid growth pattern with differentiation to leiomyosarcoma. In the uterine cervix, a 1.2 cm mesonephric (Gartner's) cyst was found. Neither neoplastic lesions nor endometriosis were identified in the cervix, endometrium, fallopian tubes or ovaries. Based on the histologic features and the specific location of the tumor, the coexistence of Gartner's cyst, and the normal appearance of the endocervical mucosa as well as the endometrium, it was diagnosed as a mesonephric carcinosarcoma. The serum levels of carcinoembryonic antigen, CA125, CA19-9, and CA72-4 were within normal ranges in the clinical course. The patient died of disease 8 months after surgery.

Carcinosarcoma↗

Changes in the vascular network of the oral epithelium and reduced enamel epithelium during tooth eruption.

The purpose of this study was to examine the vascular network beneath the reduced enamel epithelium (REE) and oral epithelium (OE) during tooth eruption. Using the corrosive-resin casting method, vascular resin casts were prepared from premolar and molar teeth of the dog and examined by scanning electron microscopy. The vascular network beneath the REE is arranged in two layers, an inner layer consisting of a dense capillary network and an outer layer composed primarily of arterioles and venules. Throughout tooth eruption, the configuration of the vessels of the inner layer is continually changing from a network of capillary loops to a fishnet pattern, whereas the arrangement of the vessels of the outer layer remains fairly constant. When the crown emerges into the oral cavity, leakage of resin from the vessels provides evidence of increased vascular permeability, suggesting the presence of inflammation within the marginal gingiva. When root development is nearly complete, the vascular network adjacent to the REE becomes continuous with that of the OE. The inner margin of the free gingiva receives its blood supply from this network, and the vessels of this network also give off branches which anastomose with the capillary network of the periodontal ligament.

Animals↗

Cytotoxic effect of activated platelets on endothelial cells.

Modern science has made clear the important roles of endothelial cells in both physiological and biochemical functions of vessel wall and their impairment initiate the process of atherosclerotic changes. Activated platelets also injure endothelial cells which were characterized with energy discharge, the decrease of cAMP content, the Ca++ entry, and dysfunction of No production. These data suggest the protection of endothelial cells from the injury could be the important protective factor from atherosclerosis. From this point of view, antiplatelet therapy is not only for antithrombotic but also for endothelial cell protective therapy.

Animals↗

Anti-endotoxin activity of a novel synthetic lipid A analog.

Lipid As from non-toxic bacteria such as Rhodobacter capsulatus and Rhodobacter sphaeroides have been shown to antagonize the immunostimulatory effects of lipid A and LPS from pathogenic bacteria. We have biologically characterized a series of synthetic LPS antagonists including the proposed structures of the lipid A and R. sphaeroides containing fatty acid side chains ester-linked to the disaccharide backbone, as well as an analog of R. capsulatus lipid A containing ether-linked alkyloxy side chains (E5531). In vitro assays utilizing LPS-stimulated human monocytes or whole blood demonstrated that low nanomolar concentrations of E5531 inhibited cellular activation as indicated by decreased release of the cytokines TNF-a, and interleukins-1, 6, and 8. E5531 also inhibited LPS-induced release of cytokines and nitric oxide from murine macrophages. Synthetic antagonists at up to 100 microM were devoid of agonistic activity in murine and human in vitro systems. In vivo, E5531 blocked induction of TNF-a by LPS and reduced LPS-induced lethality in mice. These in vitro and in vivo results indicate that E5531 may have clinical therapeutic utility as an antagonist of endotoxin-mediated morbidity and mortality.

Animals↗

[Anesthesia for hepatectomy in a patient with glycogen storage disease].

We successfully anesthetized a 19-year-old female with type I glycogen storage disease for hepatectomy. She had hypoglycemia and severe metabolic acidosis before surgery. General anesthesia was performed with epidural anesthesia. We used acetated Ringer solution mainly as intraoperative fluids instead of lactated Ringer solution and controlled administration of glucose determining blood glucose. The patient's plasma lactate levels, pyruvate and base excess during and after operation, were unchanged compared with those before operation. Administration of sodium bicarbonate was not necessary. In the case of metabolic acidosis due to accumulation of lactate as in glycogen storage diseases, it was useful to use acetated Ringer solution for fluid therapy.

Adult↗