Magnetoluminescence studies of InyAl1-yAs self-assembled quantum dots in AlxGa1-xAs matrices.
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Journal Article↗
Biomedical subjects
K Uchida
Publications and source records attributed to K Uchida.
Somatic in vivo alterations of the DPC4 gene at 18q21 in human lung cancers.
The chromosome region 18q21 has been shown to be frequently deleted in lung cancers. Recent identification at this locus of DPC4, a gene whose inactivation has been suggested to play a role in pancreatic carcinogenesis, prompted as to examine whether it might also be altered in lung cancers. Two missense and 2-bp frameshift somatic mutations in DPC4 were detected among 42 lung cancer specimens taken directly from patients. DPC4 mutations, however, were not present in all lung cancers carrying l8q21 deletions. These findings suggest that DPC4 may play a role in a limited fraction of lung cancers and that another tumor suppressor gene may also exist in this chromosome region.
Base Sequence↗
Oxidative stress response in iron-induced renal carcinogenesis: acute nephrotoxicity mediates the enhanced expression of glutathione S-transferase Yp isozyme.
An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces acute renal proximal tubular necrosis, a consequence of free radical-mediated oxidative tissue damage, that eventually leads to a high incidence of renal adenocarcinoma in rodents. In the present study, we investigated the free radical-induced oxidative stress response in this carcinogenesis model, focusing on the expression of glutathione S-transferases (GSTs) which catalyze the conjugation of reactive chemicals with glutathione and play an important role in protecting cells. A single intraperitoneal Fe-NTA treatment (15 mg Fe/kg body weight) induced a rapid oxidative stress, which was monitored by the accumulation of lipid peroxidation products and the loss of sulfhydryl contents in the kidneys, resulting in a 30% reduction of GST activity 1 h after an Fe-NTA treatment. The enzyme activity returned to the control level after 16 h. The immunoblot analysis of GST isozymes demonstrated that the level of alpha-class GSTs (GST-Ya and GST-Yc) and pi-class GST (GST-Yp), major GST isozymes constitutively produced in the kidney, decreased immediately within 1 h of the Fe-NTA treatment. The onset of the recovery of GST-Yp protein levels was detected 3 h after the Fe-NTA treatment. The enhanced production of GST-Yp in gene expression was evident in the drastic elevation of mRNA levels and these increases coincided with a substantial rise in the GST activity and protein levels. The alpha-class GSTs were not inducible by treatment with Fe-NTA. The immunohistochemical analysis demonstrated that the expression of GST-Yp was strongly induced in the regenerating proximal tubular cells. A steady accumulation of GST-Yp protein was observed in the subacute toxicity experiments with multiple injections of Fe-NTA. These results suggest that the enhanced expression of GST-Yp is important in mediating cell repairs or increasing the resistance to subsequent injury.
Adenocarcinoma↗
Daily rhythm of serum melatonin in patients with dementia of the degenerate type.
The daily rhythm in serum melatonin levels was measured in patients with dementia of the degenerate type (Alzheimer's disease, Pick's disease and senile dementia of the Alzheimer type) by radioimmunoassay. Thirteen patients (age: 69.0 +/- 8.0 years, mean +/- S.D.) were studied. All patients were hospitalized at the time of the study and had a history of sleep-wake disturbances, nocturnal wandering and/or delirium. We also studied 13 age-matched healthy control subjects (control group 1), ten young adults (control group 2), and nine hospitalized patients without dementia (control group 3). Two subjects in the control groups showed no measurable changes in melatonin level throughout the day, while the other 30 control subjects exhibited a clear daily rhythm with the peak concentration occurring during the night. On the other hand, four out of the 13 patients with dementia did not show any melatonin rhythm. Two of the demented patients who did not exhibit melatonin rhythm displayed clinical symptoms of rhythm disorders. One out of the nine patients with melatonin rhythm presented with clinical symptoms, such as delirium and sleep-wake disturbance. Our results suggest that the probability of absent melatonin rhythm is higher in demented patients compared with subjects without dementia. However, a lack of melatonin rhythm is not always associated with symptomatic rhythm disorders. Since the melatonin rhythm reflects that of the suprachiasmatic nucleus, it follows that the SCN function of the patients having a history of rhythm disorders was not always severely damaged.
Aged↗
Aberrant hypermethylation at the bcl-2 locus at 18q21 in human lung cancers.
Accumulating evidence suggests that altered DNA methylation may play a role in the oncogenesis of human neoplasms, including lung cancer. The presence of aberrant hypermthylations at 3p, 9p, 11p, ad 17p, which are known to be hot spots for allele loss in lung cancers, is suggested to be a reflection of the existence of tumor suppressor genes in these chromosomal regions. In the present study, we investigated the methylation status of the Rb locus at 13q14 as well as that of the bcl-2 locus at 18q21 in 134 lung cancer specimens, representing all major histological subtypes. As a result, 18q21 was identified to be the fifth chromosomal region affected by frequent tumor-specific aberrant hypermethylation in lung cancers. The occurrence of aberrant hypermethylation at the bcl-2 locus at 18q21 was restricted to non-small cell lung cancers, and among non-small cell lung cancers, such epigenetic aberrations were observed most frequently in adenocarcinomas without any association with bcl-2 expression. Interestingly, allelic loss at the bcl-2 locus was also seen in 40% (7 of 17 informative cases) of adenocarcinomas; this frequency was also the highest among values for the various histological subtypes of lung cancers. These results suggest that aberrant hypermethylation at the bcl-2 locus may be a reflection of a putative tumor suppressor gene residing at 18q21, and aberrant hypermethylation might play a role in its inactivation. In contrast, altered methylation status of the Rb locus appears to be quite rare in lung cancers, if present at all.
Adenocarcinoma↗
Capillary column high-performance liquid chromatographic-electrospray ionization triple-stage quadrupole mass spectrometric analysis of proteins separated by two-dimensional polyacrylamide gel electrophoresis. Application to cerebellar protein mapping.
A method is presented for the structural characterization of proteins separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). The method includes separation of a protein mixture by 2D-PAGE, recovery of proteins from the gel spots revealed by copper staining and analysis of the proteins by triple-stage quadrupole mass spectrometry using an electrospray ionization interface (ESI-TSQMS). Prior to the mass spectrometric analysis, the extracted proteins were passed through a small reversed-phase column (10 x 4.0 mm I.D.) to remove salts and gel-derived contaminants and then introduced into the mass spectrometer through a reversed-phase capillary column with 0.25 mm I.D. Application of the method to the analysis of rat cerebellar proteins suggests that the molecular mass could be accurately determined with sub-picomole amounts of protein samples derived from one or two 2D gels. The method was also useful for peptide mapping and determination of amino acid sequences of proteins micro-prepared from the 2D gel. Because 2D-PAGE has an excellent resolving power in protein separation and because capillary LC-ESI-TSQMS provides structural information with very small amounts of samples, the combined system of 2D-PAGE and capillary LC-ESI-TSQMS described here should allow wide applications to molecular studies of genes and proteins, such as identifications of protein spots on 2D gels, confirmation of gene/protein sequences and analysis of post-translational modification of proteins present naturally in tissue/cell extracts or expressed by recombinant DNA techniques.
Amino Acid Sequence↗
Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease.
There is growing evidence that oxidative stress and mitochondrial respiratory failure with attendant decrease in energy output are implicated in nigral neuronal death in Parkinson disease (PD). It is not known, however, which cellular elements (neurons or glial cells) are major targets of oxygen-mediated damage. 4-Hydroxy-2-nonenal (HNE) was shown earlier to react with proteins to form stable adducts that can be used as markers of oxidative stress-induced cellular damage. We report here results of immunochemical studies using polyclonal antibodies directed against HNE-protein conjugates to label the site of oxidative damage in control subjects (ages 18-99 years) and seven patients that died of PD (ages 57-78 years). All the nigral melanized neurons in one of the midbrain sections were counted and classified into three groups according to the intensity of immunostaining for HNE-modified proteins--i.e., no staining, weak staining, and intensely positive staining. On average, 58% of nigral neurons were positively stained for HNE-modified proteins in PD; in contrast only 9% of nigral neurons were positive in the control subjects; the difference was statistically significant (Mann-Whitney U test; P < 0.01). In contrast to the substantia nigra, the oculomotor neurons in the same midbrain sections showed no or only weak staining for HNE-modified proteins in both PD and control subjects; young control subjects did not show any immunostaining; however, aged control subjects showed weak staining in the oculomotor nucleus, suggesting age-related accumulation of HNE-modified proteins in the neuron. Our results indicate the presence of oxidative stress within nigral neurons in PD, and this oxidative stress may contribute to nigral cell death.
Adolescent↗
Modulation of cell death pathways to apoptosis and necrosis of H2O2-treated rat thymocytes by lipocortin I.
Lipocortin I, also called annexin I, a calcium and phospholipid binding protein, protected rat thymocytes from H2O2-elicited necrosis and facilitated H2O2-induced apoptosis, while anti-lipocortin I antibody enhanced H202-elicited necrosis by blocking H202-induced apoptosis. Essentially similar results were obtained with phospholipase A2 inhibitors and activators such as 3,4-octyadecyl-benzylacrylic acid and melittin, respectively. Available evidence suggests that lipocortin I modulates signals for cell death pathways of H2O2-treated rat thymocytes to apoptosis and necrosis by regulating cellular phospholipase A2 activities but not by inhibiting membrane lipid peroxidation.
Animals↗
Selective maternal-allele loss in human lung cancers of the maternally expressed p57KIP2 gene at 11p15.5.
Genomic imprinting at 11p15 is suggested to play a role in certain pediatric tumors such as Wilms' tumor, based on the findings of selective maternal loss of this chromosomal region. Although the allele loss at 11p15 is also frequent in a number of cancers of adults including lung, breast, and bladder cancers, possible involvement of genomic imprinting in these tumors has not been investigated extensively. p57KIP2, a newly described member of the p21 cyclin-dependent kinase (CDK) inhibitor family which is thought to negatively regulate the cell cycle at the G1 checkpoint, has been mapped to 11p15. In the present study, we searched for somatic p57KIP2 mutations in lung cancer, but failed to find such alterations. Interestingly, however, we found that the p57KIP2 gene is imprinted with maternal expression and that the maternal alleles had been selectively lost in 11 of 13 (85%) lung cancer cases carrying 11p15 deletions, this being a significant bias (p=0.01). These data provide the first evidence that genomic imprinting may play a role in the oncogenesis of not only rare pediatric tumors but also this common cancer of adults, suggesting that the imprinted p57KIP2 CDK inhibitor gene is a potential target for maternally biased 11p15 deletions.
Adult↗
Photoluminescence spectra of GaP/AlP short-period superlattices under high magnetic fields.
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Journal Article↗
Oxidative stress response in iron-induced acute nephrotoxicity: enhanced expression of heat shock protein 90.
Iron overload with ferric nitrilotriacetate (Fe-NTA) induces acute renal proximal tubular necrosis, a consequence of oxidative tissue damage, that leads to a high incidence of renal adenocarcinoma in rodents. In the present study, we determined the proteins preferentially produced in response to the Fe-NTA-induced oxidative injury. A single intraperitoneal Fe-NTA treatment led to the enhanced production of a number of proteins with molecular masses of 85-95 kDa. These included heat shock protein 90 (HSP90) as determined by immunoprecipitation. The enhanced production of HSP90 was prominent in the renal tubular cells. Steady accumulation of HSP90 was observed in the subacute toxicity experiments with multiple injections of Fe-NTA, suggesting that the enhanced production of HSP90 is important in increasing resistance to subsequent injury caused by the Fe-NTA-induced oxidative stress.
Animals↗
Laminoplasty with foraminotomy for coexisting cervical myelopathy and unilateral radiculopathy: a preliminary report.
STUDY DESIGN: An assessment was made of the efficacy of a combined laminoplasty and foraminotomy operation for patients with coexisting myelopathy and unilateral radiculopathy. The procedure was done in 17 patients. OBJECTIVES: The patients were followed with lateral flexion and extension radiographs, computed tomography scans, and an assessment system specially designed to qualitatively evaluate the patients' neurologic status. Follow-up period averaged 4 years (range, 2.1-9.3 years). SUMMARY OF BACKGROUND DATA: Excellent-to-good results were obtained for 76% (13 of 17) of the patients without any significant functional compromise based on the radiographs. Sixteen nerve roots were decompressed with a less than 25% foraminotomy, whereas eight were decompressed by a 25%-50% foraminotomy without serious neurologic damage, except for one patient. The neurologic results appeared unrelated to the extent of foraminotomy. METHODS: A refined procedure for combined laminoplasty and foraminotomy was reviewed retrospectively in terms of neurologic outcome and radiographic data. RESULTS: The present series is small, and results are not comparable directly with other methods. The procedure appears effective for myelopathy and radiculopathy. This procedure is applicable to patients with myelopathy and coexisting nerve root impingement anterolaterally or in the neural foramen. CONCLUSION: The combined laminoplasty and foraminotomy operation may provide greater neurologic improvement in patients with coexisting myelopathy and unilateral radiculopathy, while maintaining cervical spine stability after surgery.
Adult↗
Beneficial effect of donor pretreatment with thromboxane A2 synthase inhibitor on the graft survival in pig liver transplantation.
With a known evidence that thromboxane A2 (TxA2) is elevated in the perfusate of the liver transplant (LTx) recipient, TxA2 is likely to play a role in the pathogenesis of preservation reperfusion injury. In this study, effectiveness of donor pretreatment with TxA2 synthase inhibitor, sodium ozagrel (SO), in the prevention of primary nonfunction (PNF) was investigated. LTx was performed for eight pigs which received the grafts treated with SO during harvest surgery (treatment group). Eight other animals were the control group. All of the animals in the treatment group survived longer than 7 days, whereas 37.5% (three of eight) of the control group died from PNF within 3 days postoperative. Significantly lower serum LDH levels were noted in the treatment group than control. Serum thromboxane B2 (TxB2) and 6-keto-PGF1 alpha were both elevated in the control group. However, a significant decrease in TxB2 was noted in the treatment group after reperfusion of the liver graft. Polymorphonuclear leukocyte (PMN) infiltration in the graft after reperfusion was significantly greater in the control group than in the treatment group. Hepatocyte microsteatosis was prominent in the control group after reperfusion. Donor pretreatment with SO was effective in the prevention of PNF after LTx. The beneficial effects of this drug are improvement in microcirculation allowing better perfusion of cold preservative and the blocking effect of platelet-PMN-endothelial interaction which is thought to be a primary etiology in reperfusion injury.
6-Ketoprostaglandin F1 alpha↗
Pravastatin reduces restenosis after coronary angioplasty of high grade stenotic lesions: results of SHIPS (SHIga Pravastatin Study).
We conducted a multicenter prospective, randomized, double-blind, placebo-controlled trial to test whether pravastatin, a hydroxymethyl glutaryl coenzyme A reductase inhibitor, can decrease restenosis after percutaneous transluminal coronary angioplasty (PTCA). Pravastatin 10 mg twice daily was begun at least 10 days prior to elective PTCA in patients with total cholesterol less than 280 mg/dl. The end-point was a between-group comparison of the frequency of restenosis defined as a more than 50% loss of the initial gain in diameter stenosis at the PTCA site at 3 months during follow-up by automated quantitative coronary arteriography. Of 207 patients randomly assigned to study groups, 139 patients underwent PTCA; 133 procedures were successful, and 124 patients underwent follow-up angiography at 3 months, and 179 lesions (85 pravastatin, 94 placebo) in 124 patients (62 pravastatin, 62 placebo) were analyzed. The two groups were comparable for baseline characteristics. Total cholesterol decreased by 19.6% in the pravastatin group (p < 0.001) but not in the placebo group. Although the restenosis rate was not different in the two groups (29.4% in pravastatin vs. 39.4% in placebo, p = 0.215) as a whole, it was reduced to about one fifth (8.8%) in the pravastatin group compared with 44.8% in the placebo group (p = 0.0011) when the comparison was restricted to high grade lesions (> or = 75% diameter stenosis, 34 lesions in pravastatin, 29 lesions in placebo). Pravastatin thus reduces restenosis after PTCA of high grade lesions.
Adult↗
Liberation of vasoactive substances and its prevention with thromboxane A2 synthase inhibitor in pig liver transplantation.
There are multiple causes of liver graft nonfunction in the early post-transplant period. Since a severe microcirculatory disturbance based on ischemia-reperfusion liver injury is considered to be the main underlying pathophysiology, it is suspected that various vasoactive substances are liberated after reperfusion of the graft. In order to investigate this matter, we conducted an experimental study with pig liver allotransplantation. Two groups of animals received donor grafts with or without thromboxane synthase inhibitor (sodium ozagrel), 1.25 mg/ kg body weight intravenously, given at the time of liver harvesting. All of the recipient animals in the treatment group (n = 10) survived longer than 7 days whereas three of ten animals in the control group died within 7 days. Serum lactate dehydrogenase (LDH) in the recipient serum at 1 h after reperfusion was significantly lower in the treatment group (915.1 +/- 167.3 U/l) than in the control group (1264.4 +/- 134.7 U/l). Serum thromboxane B2 (2261.7 +/- 1055.7 pg/ml) and endothelin-1 (6.3 +/- 2.2 pg/ml) after reperfusion in the treatment group were significantly lower than those in the control group (4220.0 +/- 1711.0 pg/ml and 11.2 +/- 3.1 pg/ml, respectively). Although serum angiotensin II after reperfusion tended to be lower in the treatment group than in the controls serum renin activity was less than 3 ng/ml in both groups of animals. There were no differences in the plasma endotoxin levels between the two groups. We conclude that the administration of sodium ozagrel to the donor animals provided better graft function in recipients than no such treatment. We speculate that the inhibition of thromboxane A2 production suppresses the liberation of other vasoconstrictive substances, preventing microcirculatory disturbance and, thereby, contributing to improved graft function after liver transplantation.
Angiotensin II↗
Lordotic alignment and posterior migration of the spinal cord following en bloc open-door laminoplasty for cervical myelopathy: a magnetic resonance imaging study.
We investigated lordotic alignment and posterior migration of the spinal cord following en bloc open-door laminoplasty for cervical myelopathy. Fifty-five patients (32 men and 23 women) were studied, with an average follow-up of 2.4 years. Radiological examination included evaluation of lordosis of the cervical spine and spinal cord, degree of enlargement of bony spinal canal, and the magnitude of posterior cord migration. We also correlated these changes with neurological improvement. Postoperatively, there was an average of 5% loss of cervical spine lordosis (P > 0.01) on radiographs and 12% reduction in the lordotic alignment of the spinal cord (P > 0.05) on magnetic resonance imaging. Postoperatively, the size of the bony spinal canal increased by 48%. Posterior cord migration showed a significant correlation with the preoperative cervical spine and spinal cord lordosis (P < 0.05). Thirty-seven (67%) patients with neurological improvement exceeding 50% showed significant posterior cord migration following laminoplasty compared with those demonstrating less than 50% improvement (P = 0.01). Our results suggest that a significant neurological improvement is associated with posterior cord migration after cervical laminoplasty.
Adult↗
Abnormal neuropeptide concentration in rectal mucosa of patients with inflammatory bowel disease.
Regulatory neuropeptides are widely distributed in the gastrointestinal tract, where they play an important role in motility, secretion, and immune and inflammatory responses. In this study, the rectal mucosal content of somatostatin (SOM), substance P (SP), beta-endorphin (BE), and thyrotropin-releasing hormone (TRH) was measured by radioimmunoassay in 56 patients with ulcerative colitis (UC), 15 patients with Crohn's disease (CD), 15 patients with acute infectious colitis (AIC), and 11 controls, who showed no inflammation of the rectal mucosa, nor abnormal bowel movements. The content of immunoreactive (ir)-SOM was decreased in UC patients, especially in those with persistent disease activity, while the levels of ir-SP, BE, and TRH were increased in such patients. Some changes of ir-peptide levels were also observed in CD and AIC patients. The changes in neuropeptide levels were analyzed in relation to histological grades of inflammation in UC patients, grades 4-5 showing the most significant changes. The levels of ir-SOM, SP, BE, and TRH showed no significant change in chronic persistent UC when measured 6-12 months after the initial examination. In contrast, in patients with remitting intermittent UC, the levels of SP and BE decreased during remission. Abnormal intestinal neuropeptide content may be implicated in the continued mucosal immune and inflammatory responses that are manifested in patients with inflammatory bowel disease.
Adult↗
Effects of beta-lactam antibiotics on intestinal microflora and bile acid metabolism in rats.
Wistar male rats were treated for six days with broad spectrum beta-lactam antibiotics, latamoxef, and cefotaxime. On the seventh day, the number of fecal anaerobic microbes decreased, total fecal bile acids decreased, and bile acid pools increased. Secondary bile acids such as beta-hyocholic, hyodeoxycholic, lithocholic, and deoxycholic acids decreased in the feces while the primary bile acids, cholic, beta-muricholic, and chenodeoxycholic acids, became predominant. Coprostanol, a microbial metabolite of cholesterol, also disappeared from the feces during the treatment. The cecum enlarged to almost twice the size of that in control rats, whereas the liver weight was not significantly changed. After treatment was stopped, the number of fecal microbes returned to the initial counts within a week, but restoration of bile acid and cholesterol metabolism required at least three weeks.
Animals↗