Age effects on pupil dilation among Alzheimer's patients.
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Acetaminophen↗
Biomedical subjects
H Toyoshima
Publications and source records attributed to H Toyoshima.
Cerebral blood volume in acute brain infarction: A combined study with dynamic susceptibility contrast MRI and 99mTc-HMPAO-SPECT.
BACKGROUND AND PURPOSE: The aim of this study was to correlate the abnormality in cerebral blood volume (CBV) measured by dynamic susceptibility contrast-enhanced MRI with that in cerebral blood flow (CBF) estimated by single-photon emission CT with [99mTc]hexamethylpropylenamine-oxime in patients with acute ischemic stroke. METHODS: Nine patients with unilateral occlusion of either the middle cerebral artery or the internal carotid artery (4 men and 5 women; mean+/-SD age, 74.4+/-11.6 years) were studied within 6 hours after stroke onset. The relative CBV (relCBV) and CBF (relCBF) in the lesions were defined relative to the contralateral mirror regions. RESULTS: In the brain regions with mild (relCBF >/=0.60), moderate (0.40</=relCBF<0.60), and severe (relCBF <0.40) hypoperfusion, the mean relCBV values were 1.29+/-0.31, 0.94+/-0.49, and 0.30+/-0.22, respectively. The relCBV was significantly elevated in the brain areas with mild hypoperfusion (P<0.001) and significantly reduced in the brain areas with severe hypoperfusion (P<0.001). The relCBF was significantly better than the relCBV in predicting the evolution of infarction (P<0.02). The probability of evolving infarction for the hypervolemic (relCBV >1.0) regions was significantly lower than that for hypovolemic (relCBV <1.0) regions in the relCBF range between 0.40 and 0.50 (P<0.02). CONCLUSIONS: In acute ischemic stroke within 6 hours of onset the CBV can be either increased, normal, or decreased, depending on the severity of hypoperfusion. The increased CBV has a protective effect on evolving infarction. Although the CBF is a better predictor of tissue outcome, the CBV measurement may help detect potentially salvageable brain tissue in the penumbra with compromised blood flow.
Acute Disease↗
The effect of chronic treatment with trandolapril on cyclic AMP-and cyclic GMP-dependent relaxations in aortic segments of rats with chronic heart failure.
1 Characteristics of cyclic GMP- and cyclic AMP-mediated relaxation in aortic segments of rats with chronic heart failure (CHF) and the effects of chronic treatment with an angiotensin I converting enzyme (ACE) inhibitor, trandolapril, were examined 8 weeks after coronary artery ligation. 2 Cardiac output indices of coronary artery-ligated and sham-operated rats were 125+/-8 and 189+/-10 ml min(-1) kg(-1), respectively (P<0.05), indicating the development of CHF at this period. 3 The maximal relaxant response of aortic segments to 10 microM acetylcholine in rats with CHF and sham-operated rats was 64.0+/-5.7 and 86.9+/-1.9%, respectively (P<0.05), whereas the relaxant response to sodium nitroprusside (SNP) remained unchanged. Tissue cyclic GMP content in rats with CHF was lower than that of sham-operated rats. 4 In endothelium-intact segments of rats with CHF, the maximal relaxant response to 10 microM isoprenaline (44.5+/-6.7%) was lower that sham-operated rats (81.3+/-2.5%, P<0.05) and the concentration-response curve for NKH477, a water-soluble forskolin, was shifted to the right without a reduction in the maximal response. Isoprenaline-induced relaxation of aortic segments was attenuated by NG-nitro-L-arginine methyl ester (L-NAME) in sham-operated rats, but not in rats with CHF. Relaxation to 30 microM dibutyryl cyclic AMP in rats with CHF (26.8+/-2.7%) was lower than that in sham-operated rats (63.4+/-11.8%, P<0.05). 5 Trandolapril (3 mg kg(-1) day(-1)) was orally administered from the 2nd to 8th week after the operation. Aortic blood flow of rats with CHF (38.5+/-3.6 ml min(-1)) was lower than that of sham-operated rats (55.0+/-3.0 ml min(-1)), and this reduction was reversed (54.1+/-3.4 ml min(-1)) by treatment with trandolapril. The diminished responsiveness described above was normalized in the trandolapril-treated rat with CHF (i.e., the maximal relaxation to acetylcholine, 94.7+/-1.0%; that to isoprenaline, 80.5+/-2.8%; that to dibutyryl cyclic AMP, 54.7+/-6.2%). However, aortic segments of trandolapril-treated rats with CHF, L-NAME did not attenuate isoprenaline-induced relaxation and the tissue cyclic GMP level was not fully restored, suggesting that the ability of the endothelium to produce NO was still partially damaged. 6 The results suggest that vasorelaxation in CHF, diminished mainly due to dysfunction in endothelial nitric oxide (NO) production and cyclic AMP-mediated signal transduction, was partially restored by long-term treatment with trandolapril. The mechanism underlying the restoration may be attributed in part to prevention of CHF-induced endothelial dysfunction.
Acetylcholine↗
Modulation of cAMP-mediated vasorelaxation by endothelial nitric oxide and basal cGMP in vascular smooth muscle.
Recent in vitro evidence shows a role of endothelial nitric oxide (NO) in the modulation of isoproterenol-induced vasorelaxation. To elucidate roles of endothelial cells and NO in cyclic adenosine monophosphate (cAMP)-mediated vasodilators we examined the effects of removal of endothelium and a NO synthase (NOS) inhibitor on relaxant responses in vitro of rat aortic strips to beta-adrenoceptor stimulants and colforsin dapropate, a water-soluble forskolin, and changes in cAMP and cyclic guanosine monophosphate (cGMP) contents. Relaxant responses of rat aorta to isoproterenol, denopamine, salbutamol, colforsin, and dibutyryl cAMP (dbcAMP) were blunted by removal of endothelial cells or treatment with NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). Relaxant response of endothelium-intact segments to isoproterenol was associated with increases in tissue cAMP and cGMP contents. Removal of endothelium or treatment with L-NAME markedly reduced basal cGMP and abolished the isoproterenol-induced increase in cGMP but not cAMP content. In endothelium-removed segments, pretreatment with sodium nitroprusside (SNP) restored the diminished relaxant response to isoproterenol and increased basal cGMP (from 0.08 +/- 0.01 to 0.16 +/- 0.02 pmol/mg protein), whereas it did not affect the isoproterenol-induced increase in cAMP. The diminished relaxant response of endothelium-removed segments to dbcAMP was not restored by SNP pretreatment. The results suggest that relaxant response of rat aorta to cAMP-mediated vasodilators is mediated, in part, by NO production in endothelium and subsequent increase in cGMP in vascular smooth-muscle cells.
Adrenergic beta-Agonists↗
Rheological properties and lipid oxidation of rice decontaminated with low-energy electrons.
Microbial load and quality of rice grains which were exposed to electrons at different acceleration voltages of 170 to 200 kV were examined to evaluate the efficacy of decontaminating rice with low-energy electrons. Electrons at any acceleration voltage between 170 and 200 kV reduced microbial loads of brown rice grains to levels lower than 10 colony-forming units (CFU)/g. Higher acceleration voltages resulted in a lower viscosity and a higher thiobarbituric acid value (TBA). Milling at a yield of 90 or 88% after electron treatment made the viscosity and TBA of rice treated with electrons at 170 kV almost the same as untreated rice. Low and high compression analyses of rice grains which were exposed to electrons at 170 to 180 kV and milled at a yield of 90% followed by cooking showed almost the same hardness and stickiness as untreated grains which were milled at 90%. The results indicate that milling at a yield of 90% or lower removes the portion of rice exposed to electrons at 170 kV and that treatment of brown rice with low-energy electrons enables the preparation of milled rice with extremely low levels of microbial load and little quality deterioration.
Decontamination↗
[Epidemiology of acute coronary syndrome].
We reviewed the epidemiology of ischemic heart disease (IHD) focusing on acute myocardial infarction (AMI) in Japan. The age-adjusted mortality from IHD and the age-adjusted incidence of AMI in Japan were nearly the lowest in the world. Vital statistics of Japan showed that the age-adjusted mortality from IHD and AMI had been decreasing since the 1970's until 1993. Rates of new patients of AMI per day have been stable since the early 1980's according to "patient survey". Several population-based studies reported the unchanged age-adjusted incidence of AMI since the late 1950's. In conclusion, the mortality from IHD and the incidence of AMI are very low in Japan, and there is no epidemiological evidence showing an increase in either one.
Acute Disease↗
Longitudinal study on factors related to the course of vibration-induced white finger.
Follow-up surveys were conducted in 1982 and 1988 to investigate factors affecting the course of vibration-induced white finger (VWF). Subjects were 353 patients, aged 40 to 70 at the start of the 1982 survey, who were receiving treatment for hand-arm vibration syndrome. Between 1982 and 1988, the attacks of VWF decreased, while numbness and pain in the hand changed slightly. Finger skin temperature showed a tendency to increase, but recovery time in nail compression tests was unchanged. Vibration perception threshold and grasping power tended to become worse. Of the 177 patients with VWF in 1982, 55 (31%) had no VWF in 1988. The improvement in VWF depended on its severity assessed by the frequency of attacks, the extent of the affected finger phalanges and the Stockholm vascular (V) stage at the start of the 1982 survey. The improvement was observed in 46% of the 1V (mild) stage cases, against only 17% of the 3V (severe) stage cases. Patients in the 2V (moderate) and 3V stages had lower finger skin temperature than those without VWF (the 0V stage). Patients with milder VWF seemed more likely to improve. Continued use of vibratory tools was found to be an unfavourable factor for improvement of VWF. Age, smoking and drinking habits, and medical complications showed no significant effects on the course of VWF.
Adult↗
Thickness of the basement membrane of bronchial epithelial cells in lung diseases as determined by transbronchial biopsy.
The thickness of the basement membranes of bronchial epithelial cells varies under various pathological conditions. It has been reported that this membrane is thickened in patients with bronchial asthma. By light microscopy, this parameter was measured in biopsy specimens of bronchial mucosa obtained by fibre-optic bronchoscopy. These specimens were obtained from 171 patients who had undergone bronchial biopsy between 1984 and 1994. It was demonstrated that the thickness of the basement membrane of bronchial epithelial cells was weakly correlated with the patient's age, when thickness was examined in patients with lung cancer (r = 0.242, P = 0.0268). The basement membranes in patients with bronchial asthma (8.193 +/- 1.362 mu, mean +/- SEM) were significantly thicker than those without bronchial asthma (5.145 +/- 0.233 mu) (P = 0.0180, Mann-Whitney's U-test). In addition, it is noteworthy that the basement membranes in patients with diabetes mellitus (7.217 +/- 0.753 mu) were also significantly thicker than those without diabetes mellitus (4.968 +/- 0.235 mu) (P = 0.0038, Mann-Whitney's U-test). The background or underlying pathophysiology in such patients should be studied further, with attention directed towards the thickness of the bronchial basement membrane in bronchial biopsy specimens.
Aged↗
Familial aggregation and covariation of diseases in a Japanese rural community: comparison of stomach cancer with other diseases.
PURPOSE: We investigated familial aggregation as well as familial covariation of diseases by means of a questionnaire survey dealing with family histories of stomach cancer, stroke, hypertension, diabetes and tuberculosis as well as life style among 2,769 inhabitants of a rural community (84% of census population). METHODS: The strength of familial aggregation was shown by an odds ratio (OR) that compared the number of families in which siblings suffered from one of the above diseases among families in which at least one parent suffered from it, and among families in which neither did. Probands were divided into two groups for analysis: an under-55 "young group," and a 55-and-older "old group." RESULTS: The OR for stomach cancer was lowest and insignificant in the young group, and significant (2.2, p < 0.05) only in the old group. The OR for stroke, hypertension, and tuberculosis was 4.5-5.1 (p < 0.05) in the young group but decreased to 2.3-3.2 in the old group. Diabetes increased from 3.9 to 5.7 (p < 0.05) with advancing age. Age-related OR trends were not affected by exposure to cigarette smoke in the past. Stomach cancer showed a borderline familial covariation with diabetes and a borderline inverse covariation with hypertension. Hypertension showed a familial covariation with stroke and diabetes. CONCLUSIONS: Among the investigated diseases, familial aggregation was weakest for stomach cancer. The results suggest that stomach cancer may share a common familial etiologic factor with diabetes and hypotension.
Adult↗
Subcortical hypoperfusion associated with asymptomatic white matter lesions on magnetic resonance imaging.
BACKGROUND AND PURPOSE: We examined whether hemodynamic and metabolic abnormalities in the cerebral white matter, basal ganglia, and thalamus are associated with asymptomatic white matter lesions (WML) depicted on MR images. METHODS: A positron emission tomographic study with H2(15)O, C15O, and 15O2 was performed in eight normal control subjects without any WML (mean +/- 1 SD age, 68.5 +/- 10.2 years) and in 15 asymptomatic subjects with WML (71.3 +/- 8.5 years) to measure regional cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and oxygen metabolic rate. RESULTS: In the cerebral white matter in the asymptomatic subjects with WML, significantly lower CBF (20.3 +/- 3.9 mL/100 mL per minute; P < .05) and significantly higher OEF (0.43 +/- 0.08; P < .05) were found compared with those for control subjects (23.5 +/- 2.6 mL/100 mL per minute and 0.37 +/- 0.06, respectively). The severity of WML was not related to the magnitude of hypoperfusion. In the basal ganglia, significantly lower CBF (44.9 +/- 6.9 mL/100 mL per minute; P < .01) and significantly higher OEF (0.54 +/- 0.08; P < .01) were found in the WML group than in control subjects (70.1 +/- 12.0 mL/100 mL/min and 0.39 +/- 0.03, respectively). In the thalamus, there was no significant difference in CBF and OEF between the control and WML groups. CONCLUSIONS: Hypoperfusion of the cerebral white matter and basal ganglia in asymptomatic WML subjects may be induced by the arteriosclerosis of long penetrating medullary arteries and lenticulostriate arteries but may not be directly related to the production of WML. The role of hypoperfusion in the production of WML and acceleration of its development remains to be elucidated.
Aged↗
Seasonal variation in the incidence of sudden death according to occupation of householder in Japan.
To examine the relationship between overwork and the occurrence of sudden death, the relation between occupation and seasonal variation in sudden death was studied. A total of 8481 cases of sudden death (among subjects aged over 24 years) were selected from all deaths between 1984 and 1986 in the Niigata Prefecture, Japan, based on a death certificate survey. Sudden death was defined as death within 24 h of the onset of the underlying disease. We divided subjects into 4 groups according to the occupation of the householder: agricultural workers, employees, the self-employed, and other occupations. As the incidence of sudden death in the 'other occupation' group did not show any significant seasonal variation, this group was considered to be a control group. Among young to middle-aged men (25-65 year old), the incidence of sudden death was higher than in the control group for agricultural workers in April and September and for employees in March and September. However, in older men (over 65) the incidence for agricultural workers was higher only in April. Among women, there was no such spring rise in the incidence of sudden death in any occupational group. The months featuring a high incidence of sudden death coincided with the busiest occupational months only for people who were actually working and not for those who had already retired.
Adult↗
Ergonomic evaluation of working posture of VDT operation using personal computer with flat panel display.
The aim of this study was to evaluate working conditions using a personal computer with a flat panel display (FPD) in terms of visual and musculoskeletal comfort. Measurements of viewing distance, viewing angle, head angle, neck angle and electromyogram (EMG) activities of the neck, shoulder and back muscles of visual display terminal (VDT) operators were compared at workstations using an FPD and a desktop personal computer (DPC). A notebook personal computer (NPC) with a 10.4 inches FPD, was used in this experiment. Each of 10 healthy subjects performed word processing tasks using both NPC and DPC workstations. Significant differences in the work posture while using the NPC and DPC were seen with viewing distance, viewing angle and head angle. The characteristic features of the work posture using the NPC were a remarkably short viewing distance and a forward inclination of the head. The value of integrated EMG (IEMG) of the neck muscle was greater while using the NPC than when using the DPC. These phenomena were caused by the structure of NPCs; most NPCs have a display and keyboard which cannot be separated and are not adjustable without tilt and swivel mechanisms. VDT devices that cannot be adjusted may potentially make operators assume a poor posture while working, which could cause visual and musculoskeletal disorders. To prevent visual and musculoskeletal problems using NPCs, a more upright head and neck position was recommended. The addition of a mechanism for adjustment of the height of an NPC display would allow a comfortable downward gaze without the loss of correct posture.
Adolescent↗
On the masking of signals on immunoblots by cellular proteins.
When determining the concentration of a particular protein in a cell extract, or when comparing the amount of a protein in different samples, it is a common practice to use specific antibodies in immunoblotting to compare the samples side by side with known amounts of purified protein. Here we show that with many antibodies, in particular monoclonal antibodies, the sensitivity of detecting the cognate antigen on immunoblots can be significantly reduced when the antigen is in a mixture with other cellular proteins. The signals on the immunoblots are masked by other endogenous proteins in the cell lysate, making the amount of the protein on the immunoblot appear to be less than the actual amount, thus invalidating direct comparison with purified protein.
3T3 Cells↗
Cyclin-dependent kinases are inactivated by a combination of p21 and Thr-14/Tyr-15 phosphorylation after UV-induced DNA damage.
The cyclin-dependent kinase (CDK) inhibitor p21 is induced by the tumor suppressor gene product p53 and is thought to be important for the arrest of the cell cycle following DNA damage. Here we have investigated the contribution of p21 in inhibiting different cyclin-CDK complexes that drive different cell cycle transitions following UV irradiation-induced DNA damage in normal human fibroblasts and immortalized rodent fibroblasts. When cells were exposed to a low dose of UV irradiation, both p53 and p21 were induced; the protein kinase activities associated with Cdc2, Cdk2, and Cdk4 were inhibited; and there was a good correlation between their inhibition and binding to p21. p21 alone is likely to be sufficient for the inhibition of Cdk2 because all the cyclin-complexed forms of Cdk2 were associated with p21 after irradiation. In contrast, only a small proportion of Cdk4 and Cdc2 was complexed with p21, although the level of Cdk4 associated with either p21 or p27 was increased after irradiation. Furthermore, recombinant p21 added to an unirradiated cell lysate at the same level as that induced by irradiation damage inhibited only the kinase activity associated with Cdk2. Cdc2 is likely to be inhibited by Thr-14/Tyr-15 phosphorylation after irradiation because Cdc2 was tyrosine-phosphorylated, and recombinant Cdc25 was able to increase its kinase activity significantly. Taken together, these results suggest that different CDKs are inhibited by different mechanisms following UV-induced DNA damage: Cdk2 is inhibited by the elevated level of p21; Cdk4 is inhibited by cooperation of p21 with other CDK inhibitors, like p27, and possibly by phosphorylation; and Cdc2 is inhibited by Thr-14/Tyr-15 phosphorylation. It is likely that these underlying mechanisms that inactivate CDKs are similar for other kinds of DNA damage.
Amino Acid Sequence↗
Inactivation of p27Kip1 by the viral E1A oncoprotein in TGFbeta-treated cells.
The adenovirus oncoprotein E1A and the simian virus SV40 large T antigen can both reverse the strong growth-inhibitory effect of transforming growth factor(TGF)-beta on mink lung epithelial cells: exposure of TGF-beta causes these cells to arrest late in the G1 phase of the cell cycle (ref. 3). This arrest correlates with an increase in expression of the protein p15Ink4B (ref. 4), inactivation of the cyclin E/A-cdk2 complex by the inhibitory protein p27Kip1 (refs 5-7), and with the accumulation of unphosphorylated retinoblastoma protein. The rescue by E1A of cells from TGF-beta arrest is partly independent of its binding to retinoblastoma protein. Here we show that E1A directly affects the cyclin-dependent kinase inhibitor p27Kip1 in TGF-beta-treated cells by binding to it and blocking its inhibitory effect, thereby restoring the activity of the cyclin-cdk2 kinase complex. In this way, E1A can overcome the effect of TGF-beta and modulate the cell cycle. To our knowledge, E1A provides the first example of a viral oncoprotein that can disable a cellular protein whose function is to inhibit the activity of cyclin-dependent kinases.
Adenovirus E1A Proteins↗
Composite carcinoid-adenocarcinoma tumor of the stomach: report of a case.
We describe herein the case of an extremely unusual composite carcinoid-adenocarcinoma tumor of the stomach, most of which was found to be carcinoid. The carcinoid tumor component exhibited argyrophilic granules, immunohistochemical localization of chromogranin, and serotonin immunoreaction. Conversely, none of the adenocarcinoma component reacted with argyrophilia, chromogranin, or serotonin. DNA flow cytometric analysis revealed a near-diploid pattern in the carcinoid element and an aneuploid pattern in the adenocarcinoma element. The transitional zone and continuity between the two tumor components were observed. These findings suggest that the tumor originated from the endocrine system, although part of it showed nonendocrine differentiation. The patient died approximately 6 months after the onset of symptoms and an autopsy could not be performed.
Adenocarcinoma↗
D-type cyclin expression is decreased and p21 and p27 CDK inhibitor expression is increased when tsBN462 CCG1/TAFII250 mutant cells arrest in G1 at the restrictive temperature.
BACKGROUND: The tsBN462 temperature-sensitive mutant hamster cell line exhibits cell cycle arrest and apoptosis at the restrictive temperature of 39.5 degrees C, due to a point mutation in the CCG1/TAFII250 gene, which encodes a component of the general transcription factor TFIID. RESULTS: We now report that CCG1/TAFII250 persisted as a complex with TBP and associated proteins (TAFs) in tsBN462 cells at the restrictive temperature. FACScan analysis revealed that the tsBN462 mutation resulted in a failure to progress out of G0 into G1. Using two-dimensional gel electrophoresis we observed a decrease in the synthesis of several proteins, starting in the middle of the G1 phase, becoming very pronounced during late G1. The expression of the immediate early genes c-fos, c-jun and c-myc was normally induced by serum treatment of quiescent cells at the restrictive temperature, whereas expression of cyclins A, D1 and D3 was reduced. Expression of the cyclin-dependent kinase (CDK) inhibitor proteins p21 and p27 was enhanced. Consistent with the decreased cyclin D and increased p21/p27 expression, we found that phosphorylation of Rb was decreased at 39.5 degrees C. Cyclin A-, E- and Cdk2-associated histone H1 kinase activity was reduced concomitantly with the increase in p21 protein. CONCLUSION: Decreased cyclin/Cdk kinase activity and decreased Rb phosphorylation are possible causes of G1 cell cycle arrest in tsBN462 cells at the restrictive temperature.
Animals↗