[Two cases of ocular damage associated with proton pump inhibitors].
Explore the source record for details and available documents.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Biomedical subjects
M Kohno
Publications and source records attributed to M Kohno.
Evaluation of the Space Collaboration System: its history, image quality and effectiveness for joint case conference.
A joint case-conference was conducted between the Departments of Radiology at Nagoya and Kobe Universities using the Space Collaboration System (SCS), which connects 39 national universities and institutes by communication satellite. In the conference, both sides presented cases using medical images such as those from CT, MRI, and DSA, and the cases were discussed between participants at the two universities. After the final conference, we distributed a questionnaire to solicit responses from the 43 participating radiologists on the quality of the transferred images and their overall impression of the conference. The responses showed that the CT, MRI, and DSA images were clear enough to allow discussion, whereas the plain X-ray images were not. Hence from the standpoint of image quality, the SCS may be unsuited for medical image diagnosis, but useful for presentation of case images in joint conferences and seminars.
Evaluation Studies as Topic↗
[Constitutive activation of the ERK-MAP kinase pathway in human tumors].
Explore the source record for details and available documents.
Apoptosis↗
Cephalometric comparisons of craniofacial and upper airway structures in young children with obstructive sleep apnea syndrome.
We studied 15 children of preschool age who had obstructive sleep apnea syndrome to evaluate their dentofacial morphology in relation to the pharyngeal airway space. We found that (1) sleep apnea was often associated with mandibular retrognathia, (2) the lower incisors tended to exhibit a retrocline, (3) there were no significant differences in angular and linear measurements in the cranial base between patients with sleep apnea and a control group of 30 nonapneic children, and (4) the apneic children had a narrower epipharyngeal airway space than did the controls. These findings suggest that obstructive sleep apnea is probably caused by both adenoidal hypertrophy and abnormal development of the facial skeleton. We highly recommend cephalometric analysis as a valuable tool for conducting the presurgical evaluation of sleep apnea in children of preschool age.
Adenoids↗
[Definition, classification and severity of hypertension].
Explore the source record for details and available documents.
Adolescent↗
[Radiotherapy for outpatients].
Radiotherapy can be done on an outpatient basis depending on the patient's cancer stage, radiation method, concurrent therapy, treatment purpose and general condition. Daily treatment time takes only about 1 minute, but the patient has to come 5 times a week for about 6 weeks for radical treatment and about 3 weeks for palliative treatment. If treated with radiotherapy alone, most patients suffer no severe adverse effects in their daily life. Therefore, radiotherapy can be done on an outpatient basis only if the patient is able to come frequently to the clinic for several weeks. Breast cancer patients commonly undergo radiotherapy in the outpatient clinic, such as breast conserving therapy, postoperative therapy and radiotherapy for local recurrence after mastectomy. Prostate cancer is also commonly treated with radical radiotherapy, postoperative therapy and radiotherapy for local recurrence after prostatectomy. Usually, postoperative irradiation for other cancers and radiotherapy for bone metastases are also undergone on an outpatient basis. During outpatient treatment, it is important to predict and avoid severe normal tissue reactions to radiotherapy, such as myelosuppression and/or pneumonitis, before they are apparent by watching the patient carefully.
Ambulatory Care↗
Age invariant of Gompertz function and exponential decay of populations commensuration with CLOV experiments.
The exponential decay law of populations is further examined on the basis of new observations of Japanese and Swedish cohorts. It is shown that the populations decrease exponentially at higher ages in accordance with the theoretical prediction, which confirms the previous conclusion. The theory is applied to recent experiments on Mediterranean fruit flies by Carey et al., (1992, Science, 258, 457-460), the results showing that the exponential decay law holds in sufficient approximation. All the evidences accumulated so far suggest that the decay law is a general theorem. On the basis of this information, we derive a general expression that estimates the limit age as a function of population. The predicted curve is in excellent agreement with the observed limit ages in Japan.
Aging↗
Auranofin inhibits interleukin-1beta-induced transcript of cyclooxygenase-2 on cultured human synoviocytes.
The aim of this study was to characterize the effects of auranofin (2,3,4,6-tetra-O-acetyl-l-thio-beta-D-gluco-pyranosato-S) on cyclooxygenase expression and prostaglandin E(2) synthesis on cultured human synovial fibroblast-like cells (synoviocytes). Synoviocytes were treated with auranofin in the presence or absence of interleukin-1beta. Cultured supernatants were harvested for prostaglandin E(2) synthesis. Cyclooxygenase-1 and -2 expression was analyzed with Western and Northern blotting. Translocation of nuclear factor-kappa B p65 was determined by immunostaining. Cytotoxicity was measured with 51Cr release assay. Auranofin attenuated interleukin-1beta-induced prostaglandin E(2) production of the cells in a dose-dependent fashion. Auranofin selectively suppressed interleukin-1beta-induced cyclooxygenase-2 mRNA and protein expression of the cells without alteration of cyclooxygenase-1 expression. Also, auranofin interfered with interleukin-1beta-induced translocation of nuclear factor-kappa B. These inhibitory effects did not originate in the cytotoxicity of the agent. Our data indicate that auranofin inhibits interleukin-1beta-induced prostaglandin E(2) synthesis and cyclooxygenase-2 expression via suppression of nuclear factor-kappa B activation on synoviocytes.
Auranofin↗
Specific activation of the p38 mitogen-activated protein kinase signaling pathway and induction of neurite outgrowth in PC12 cells by bone morphogenetic protein-2.
Bone morphogenetic protein (BMP)-2 has the capacity to induce the neuronal differentiation of PC12 cells. Unlike nerve growth factor, however, BMP-2 failed to induce the activation of the 41-/43-kDa mitogen-activated protein (MAP) kinase pathway in these cells. In contrast, BMP-2 characteristically induced the sustained activation of the p38 MAP kinase pathway. Pretreatment of PC12 cells with SB203580 inhibited the BMP-2-induced neurite outgrowth formation in a dose-dependent manner; this inhibition coincided well with the ability of SB203580 to inihibit the BMP-2-induced activation of the p38 MAP kinase pathway. Overexpression in PC12 cells of wild-type MAP kinase kinase (MKK)-6 enhanced the BMP-2-induced activation of p38 MAP kinase, whose activation correlated well with the ability of these cells to induce neurite outgrowth in response to BMP-2. Transient expression of kinase-negative forms of MKK3/6 inhibited the formation of neurite outgrowth in response to BMP-2. Furthermore, expression of constitutively active forms of MKK3/6 induced neurite outgrowth without BMP-2 stimulation, and SB203580 inhibited this induction. These results clearly indicate that activation of the p38 MAP kinase pathway is necessary for BMP-2-induced neuronal differentiation of PC12 cells. Our results also suggest that activation of the p38 MAP kinase pathway alone can induce the neuronal differentiation of PC12 cells.
Amino Acid Sequence↗
Protective role of nitric oxide synthase against ischemia-reperfusion injury in guinea pig myocardial mitochondria.
In guinea-pig myocardial mitochondria preparation, lowering the Ca2+ concentration or pH level in the perfusate rapidly elevated the fura-2 Ca2+ signal ([Ca2+]m). Pretreatment with 10(-4) M L-Arg inhibited the rapid [Ca2+]m influx, whereas administration of 10(-4) M L-NAME did not, suggesting some association between nitric oxide (NO*) synthase (NOS) activation and Ca2+ kinetics in mitochondria. Immunoblotting analysis showed that endothelial (e)-NOS was present in mitochondria, but not inducible (i)-NOS or brain (b)-NOS. Electron microscopy observations revealed that the e-NOS antibody-reactive site in the mitochondria was the inner cristae. The production of reactive oxygen species and NO* in isolated mitochondria was detected by the spin trapping technique with electron paramagnetic resonance (EPR) spectrometry. Pretreatment with 10(-5) M S-nitroso-N-acetyl-DL-penicillamine (SNAP) and 10(-5) M 3-[2-Hydroxy-1-(1-methylethyl)-2-nitrosohydrazino]-1-propananin e (NOC 5), which spontaneously generate NO*, completely inhibited the [Ca2+]m uptake. In addition, N-morpholino sydnonimine hydrochloride (SIN-1) (10(-5) M), which simultaneously generates NO* as well as *O2- and peroxynitrite anion (ONOO-), inhibited the increase in [Ca2+]m. ONOO- (3 x 10(-4) M) itself also inhibited this increase. Pretreatment with the *O2(-)-scavenger manganese superoxide dismutase or catalase (200 units/ml) completely inhibited the increase in [Ca2+]m caused by lowering of either the Ca2+ concentration or the pH in the perfusate. These results suggested that the formation of reactive oxygen species promoted the [Ca2+]m influx. The agents that inhibited the [Ca2+]m influx improved contractility even in Langendorff preparations after ischemia. Based on these findings, we concluded that e-NOS exists in mitochondria and that NO* may play an important protective role in reperfusion cardiac injury after ischemia, by inhibiting the Ca2+ influx into mitochondria which are otherwise damaged by *O2-.
Animals↗
Antioxidants improve impaired insulin-mediated glucose uptake and prevent migration and proliferation of cultured rabbit coronary smooth muscle cells induced by high glucose.
BACKGROUND: To explore the role of intracellular oxidative stress in high glucose-induced atherogenesis, we examined the effect of probucol and/or alpha-tocopherol on the migration and growth characteristics of cultured rabbit coronary vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: Chronic high-glucose-medium (22. 2 mmol/L) treatment increased platelet-derived growth factor (PDGF)-BB-mediated VSMC migration, [3H]thymidine incorporation, and cell number compared with VSMCs treated with normal-glucose medium (5.6 mmol/L+16.6 mmol/L mannose). Probucol and alpha-tocopherol significantly suppressed high glucose-induced increase in VSMC migration, cell number, and [3H]thymidine incorporation. Probucol and alpha-tocopherol suppressed high glucose-induced elevation of the cytosolic ratio of NADH/NAD+, phospholipase D, and membrane-bound protein kinase C activation. Probucol, alpha-tocopherol, and calphostin C improved the high glucose-induced suppression of insulin-mediated [3H]deoxyglucose uptake. Chronic high-glucose treatment increased the oxidative stress, which was significantly suppressed by probucol, alpha-tocopherol, suramin, and calphostin C. CONCLUSIONS: These findings suggest that probucol and alpha-tocopherol may suppress high glucose-induced VSMC migration and proliferation via suppression of increases in the cytosolic ratio of free NADH/NAD+, phospholipase D, and protein kinase C activation induced by high glucose, which result in reduction in intracellular oxidative stress.
Animals↗
Constitutive activation of the 41-/43-kDa mitogen-activated protein kinase signaling pathway in human tumors.
The 41-kDa and 43-kDa mitogen-activated protein (MAP) kinases play a pivotal role in the mitogenic signal transduction pathway and are essential components of the MAP kinase cascade, which includes MAP kinase kinase (MEK) and Raf-1. As aberrant activation of signal transducing molecules such as Ras and Raf-1 has been linked with cancer, we examined whether constitutive activation of the 41-/43-kDa MAP kinases is associated with the neoplastic phenotype of 138 tumor cell lines and 102 primary tumors derived from various human organs. Constitutive activation of the MAP kinases was observed in 50 tumor cell lines (36.2%) in a rather tissue-specific manner: cell lines derived from pancreas, colon, lung, ovary and kidney showed especially high frequencies with a high degree of MAP kinase activation, while those derived from brain, esophagus, stomach, liver and of hematopoietic origin showed low frequencies with a limited degree of MAP kinase activation. We also detected constitutive activation of the 41-/43-kDa MAP kinases in a relatively large number of primary human tumors derived from kidney, colon and lung tissues but not from liver tissue. Many tumor cells, in which point mutations of ras genes were detected, showed constitutive activation of MAP kinases, however, there were also many exceptions to this observation. In contrast, the activation of the 41-/43-kDa MAP kinases was accompanied by the activation of Raf-1 in the majority of tumor cells and was completely associated with the activation of MEK and p90rsk in all the tumor cells examined. These results suggest that the constitutive activation of 41-/43-kDa MAP kinases in tumor cells is not due to the disorder of MAP kinases themselves, but is due to the disorder of Raf-1, Ras, or some other signaling molecules upstream of Ras.
Amino Acid Sequence↗
High-level expression of Rhizopus niveus lipase in the yeast Saccharomyces cerevisiae and structural properties of the expressed enzyme.
Rhizopus niveus lipase (RNL) has a unique structure consisting of two noncovalently bound polypeptides (A-chain and B-chain). To improve this enzyme's properties by protein engineering, we have developed a new expression system for the production of recombinant lipase in the yeast Saccharomyces cerevisiae. For the present study, we developed a more efficient expression system using the strain ND-12B and the multicopy-type plasmid pJDB219. We purified two types of recombinant lipases, each to a single peak by gel-filtration HPLC, although they were found to be heterogeneous by SDS-PAGE. Analysis of reversed-phase HPLC, N-terminal amino acid sequence, and sugar content showed that the difference between the two types of lipases was due mainly to their sugar content (high or low mannose type). Moreover, there were two species within each type of lipase. One kind was processed to the A-chain and B-chain as in the native lipase, while the other remained unprocessed. Although these yeast-purified lipases contained several posttranslational modifications and different glycosylations, their secondary structures were the same as those of the native lipase as measured by circular dichroism spectra and determination of disulfide bonding. This suggests that protein folding of the recombinant lipase occurred correctly in yeast.
Amino Acid Sequence↗
A dopamine-secreting pheochromocytoma.
Explore the source record for details and available documents.
Adrenal Gland Neoplasms↗
Association between angiotensin-converting enzyme gene polymorphisms and regression of left ventricular hypertrophy in patients treated with angiotensin-converting enzyme inhibitors.
PURPOSE: An insertion/deletion (ID) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with left ventricular hypertrophy. The present study examined polymorphisms of the ACE gene in patients with essential hypertension and left ventricular hypertrophy who were participants in a long-term trial of therapy with an ACE inhibitor. PATIENTS AND METHODS: ACE inhibitor therapy was administered for >2 years to 54 patients with hypertension who had moderate or severe left ventricular hypertrophy. Cardiac dimensions were monitored by echocardiography before the initiation of therapy and after 1 and 2 years of treatment. Serum ACE activity and plasma concentrations of brain natriuretic peptide, a marker for left ventricular hypertrophy, were also monitored. RESULTS: Eighteen patients had the II genotype for the angiotensin-converting enzyme gene, 19 had the ID genotype, and 17 had the DD genotype. Baseline (mean +/- SD) serum ACE activity was significantly greater (P <0.05) in the DD (18 +/- 7 IU/L) group than in the II (7 +/- 4 IU/L) or ID (12 +/- 6 IU/L) groups. ACE inhibitor therapy was effective in controlling blood pressure, and it reduced posterior and septal wall thickness, left ventricular mass index, and plasma brain natriuretic peptide concentration in all three groups. Despite similar blood pressure reductions, after 2 years, mean (+/- SD) regression in posterior wall thickness was significantly less (P <0.05) in the DD group (-9% +/- 5%) than in the ID (-21% +/- 7%) and II (-21% +/- 9%) groups. Similar results were seen for the reductions in brain natriuretic peptide levels. The magnitudes of regression of septal wall thickness and left ventricular mass index during therapy were less in the DD group than the II group (P <0.05). CONCLUSION: Hypertensive patients with the DD genotype are less likely to have regression of left ventricular hypertrophy when treated with ACE inhibitors than are patients with other ACE genotypes.
Aged↗
Abnormal Ca2+ release from cardiac sarcoplasmic reticulum in tachycardia-induced heart failure.
OBJECTIVE: In heart failure, little information is available as to the Ca2+ release function of sarcoplasmic reticulum (SR), which plays a major role in cardiac contractile function. Here, we assessed the rapid kinetics of drug-induced Ca2+ release from cardiac SR in combination with a measurement of ryanodine binding in heart failure. METHODS: The SR vesicles were isolated from dog left ventricular (LV) muscles (normal (N), n = 10; pacing induced heart failure (HF), n = 10). The time course of SR Ca2+ release was continuously monitored by a stopped-flow apparatus using arsenazoIII as a Ca2+ indicator, and Ca2+ uptake and [3H]ryanodine binding assays were done using a filtration method. RESULTS: The amount of Ca2+ uptake was reduced in HF to 55% of N (P < 0.05). Even the more marked and earlier appeared decrease was seen in the rate constant and the initial rate of polylysine (PL; a specific release trigger)-induced Ca2+ release (P < 0.05). However, the PL concentration dependency of the initial rate shifted towards lower concentrations of PL in HF than in N ([PL] at half maximum stimulation = 0.13 vs. 0.35 microM). The [3H]ryanodine binding assay revealed a lower Bmax (pmol/mg) in HF than in N (0.91 +/- 0.19 vs. 2.64 +/- 0.59, P < 0.05), but no difference in Kd (nM) (0.95 +/- 0.29 vs. 0.90 +/- 0.11, P = n.s.). The [PL] dependency on the enhancement of [3H]ryanodine binding again showed a shift towards lower [PL] in HF than in N. CONCLUSIONS: In pacing-induced heart failure, the Ca2+ releasing function of SR is disturbed, which may result in an intra-cellular Ca2+ transient that was slowed down.
Animals↗
Plasma levels of nitric oxide and related vasoactive factors following long-term treatment with angiotensin-converting enzyme inhibitor in patients with essential hypertension.
Several mechanisms other than the inhibition of systemic and local formation of angiotensin II (Ang II) have been proposed to play a role in mediating the hypotensive effects of angiotensin-converting enzyme (ACE) inhibitors. In the present study, we measured plasma levels of nitric oxide (NO) and the related vasoactive factors bradykinin, 6-keto prostaglandin F1alpha (6-keto PGF1alpha) a stable metabolite of prostacyclin, and cyclic guanosine-3',5'-monophosphate (cGMP) before and after a 4-week treatment with the ACE inhibitor lisinopril in 17 patients with essential hypertension. Plasma NO levels were measured by the Griess method after conversion of nitrate to nitrite. Long-term lisinopril treatment significantly reduced blood pressure and increased plasma NO and 6-keto PGF1alpha. The treatment also tended to increase plasma levels of bradykinin and cGMP, but not to a significant extent. The posttreatment NO level was inversely correlated with posttreatment systolic, diastolic, and mean blood pressure (n = 17, r= -.68, P< .01, n = 17, r= -.54, P < .05, and n = 17, r= -.66, P< .01, respectively). The posttreatment bradykinin level was also modestly correlated with posttreatment systolic and mean blood pressure (n = 17, r = -.51, P < .05 and n = 17, r = -.55, P < .05, respectively). In contrast, posttreatment 6-keto PGF1alpha and cGMP levels were not correlated with posttreatment systolic, diastolic, or mean blood pressure. These findings raise the possibility that increased formation of NO and bradykinin, as well as inhibition of the renin-angiotensin system, contribute to the hypotensive effect of the ACE inhibitor observed in our hypertensive patients.
6-Ketoprostaglandin F1 alpha↗
Automated electron spin resonance free radical detector assays for antioxidant activity in natural extracts.
Explore the source record for details and available documents.
Antioxidants↗