[Congenital lymphopenia].
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Genes, T-Cell Receptor↗
Biomedical subjects
K Imai
Publications and source records attributed to K Imai.
[Idiopathic CD4+ T-lymphocytopenia].
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Diagnosis, Differential↗
[The slope of hemoglobin-oxygen equilibrium curve: implications hidden in the sigmoid curve].
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Allosteric Site↗
[Recent advance of prognostic factor in human colorectal cancer].
It has become clear that cancers develop and progress through the accumulation of various genetic alterations. Among various human malignancies, none is better understood at the molecular genetic level than colorectal cancer. Colorectal cancer is one of the commonest malignant tumors and has a relatively poor prognosis. Recent advances in the molecular genetics of colorectal cancer have stimulated attempts to evaluate the prognostic significance of specific genetic alterations in this tumor. Although conventional pathological staging has served as the standard measure of prognosis in colorectal cancer, certain molecular genetic markers are now considered to be useful for predicting the behavior of cancer and the clinical outcome of patients. We have described the recent advances in prognostic factors of colorectal cancer, such as oncogenes, tumor suppressor genes, chromosomal deletions, adhesion molecules, proteinases, DNA replication error, and others. The latest improvements in detecting these molecular markers have made it possible to apply them to the clinical setting with relative ease. Some of these markers are considered to be susceptible to, or modifiable by, direct therapeutic intervention. For instance, matrix metalloproteinases could be targets for therapeutic intervention using their inhibitors. We hope that these molecular genetic markers with prognostic significance play an important role in disease management of patients with colorectal cancer in future.
Cell Adhesion Molecules↗
[A case of juvenile type dentatorubral-pallidoluysian atrophy (DRPLA) with psychomotor retardation since infancy].
We report here a case of an 11-year-old boy with juvenile type of dentatorubral-pallidoluysian atrophy (DRPLA). His psychomotor development has been delayed since infancy and cerebellar ataxia was noted at the age of 2 years, indicating an early onset. At the age of 6 years, he had progressive myoclonus epilepsy (PME) and underwent a series of neuroradiological, electrophysiological and pathological examinations, which failed to reveal the etiology. Gene analysis performed at the age of 11 years revealed an expanded CAG repeat at the DRPLA locus in both the patient and his asymptomatic father. In the absence of a positive family history, a diagnosis of DRPLA may be difficult due to its clinical variability. We conclude that DRPLA should be taken into account in the differential diagnosis of childhood PME and that gene analysis should be performed to confirm a diagnosis of DRPLA.
Anticipation, Genetic↗
[Clinical utility of the free prostate specific antigen (PSA), alpha 1-antichymotrypsin-complexed PSA, and free/total PSA ratio using the specific and sensitive enzyme-linked immunosorbent assay "E-plate EIKEN PSA"].
We studied the clinical significance of serum prostate specific antigen (PSA) ratio: free-PSA/total-PSA and free-PSA/complex-PSA to discriminate between prostate cancer (PC) and prostate benign disease (non-PCa) by using total-PSA, alpha 1-antichymotrypsin complexed (complex)-PSA and free-PSA enzyme-linked immunosorbent assay (ELISA) kits newly developed at EIKEN Chemical Co, Ltd. Fre-PSA and complex-PSA ELISA kits demonstrated high sensitivity and specificity. Total-PSA ELISA kit also demonstrated equimolarity for free-PSA and complex-PSA. On the total-PSA range of 4-10 ng/ml, free-PSA/total-PSA% (f/t%) and free-PSA/complex-PSA% (f/c%) were very useful to discriminate between PCa and non-PCa by receiver operating characteristic curve analysis as well as PSA density (PSA-D) but not free-PSA level. F/t% and f/c% were even useful to discriminate early stage PCa (i.e. A1 or B0) from non-PCa by the Mann-Whitney U-test.
Enzyme-Linked Immunosorbent Assay↗
[IgG, IgA, Bence Jones protein (BJP) myeloma].
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Bence Jones Protein↗
[IgD myeloma].
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Antineoplastic Agents, Alkylating↗
[Evaluation of the safety and clinical feasibility of exercise 99mTc-MIBI SPECT using one day protocol--multicenter phase III clinical trial report].
We evaluated the safety and clinical usefulness of the same day protocol of exercise 99mTc-MIBI SPECT in 107 patients with heart diseases. No adverse event was observed except for one case of transient hypotension caused by the exercise. More than 95% of stress images and all of the rest images were judged as "Excellent" or "Good" in image quality. Overall sensitivity was 84.3% in detecting coronary artery disease, and no statistical difference was observed between the results obtained with Re-Ex and Ex-Re protocols. The examination was "Quite Effective" or "Effective" in diagnostic efficacy in 96.2% of the cases. We concluded that the same day protocol is a safe and useful method for diagnosing myocardial ischemia, which provides high image quality and valuable information.
Adult↗
Occurrence of sustained increase in QT dispersion following exercise in patients with residual myocardial ischemia after healing of anterior wall myocardial infarction.
Our objective was to evaluate the effect of exercise on QT dispersion over the next 3 hours, as seen on a standard 12-lead electrocardiogram in patients with healed myocardial infarction with or without residual ischemia. We measured QT and QTc dispersion before, immediately after, and 1 and 2 hours after symptom-limited, dynamic treadmill exercise tests in 28 patients with healed anterior wall myocardial infarction with (group I, n = 18) and without (group II, n = 10) residual ischemia. The same protocol was followed in 5 group I patients after successful performance of coronary angioplasty. QT and QTc dispersion did not change immediately after exercise in group II. These parameters increased in group I (QT dispersion at rest [mean +/- SD] 57 +/- 22 ms, and after exercise 87 +/- 27 ms; QTc dispersion at rest 62 +/- 25 ms, and after exercise 114 +/- 36 ms). The increases in QT and QTc dispersion were sustained for at least 2 hours. After a successful coronary angioplasty in 5 patients, these parameters no longer increased with exercise. Thus, QT dispersion increased for at least 2 hours after exercise in patients who had residual ischemia after healing of myocardial infarction. Data obtained in 5 of these patients after coronary angioplasty support the idea that residual ischemia plays a key role in the sustained increase in QT dispersion after exercise.
Aged↗
A novel gastric-cancer-associated mucin antigen defined by a monoclonal antibody A3D4.
De-glycosylation of mucins may expose new tumor-associated core protein epitopes. In this study, to attempt to develop useful markers for gastric cancers, we have purified and de-glycosylated gastric mucin and tried to establish monoclonal antibodies (MAbs). A MAb designated A3D4 among established MAbs was shown to react with gastric cancer with high frequency, but not with normal gastric epithelium. Among normal digestive organs, only the colon and gall bladder were positive for MAb A3D4. The incidence of positivity in gastric cancer was 75% for intestinal-type adenocarcinoma (n = 28), 40% for solid-type adenocarcinoma (n = 5) and 33% for signet/scirrhous-type adenocarcinoma (n = 15). Interestingly, adenoma and intestinal metaplasia (IM) with chronic gastritis or peptic ulcer were negative for MAb A3D4, whereas 8 out of 13 cases (62%) of IM with gastric cancer was positive. Western-blot analysis using the lysate from normal colon tissues revealed a high-molecular-weight (> 300-kDa) smear-like band. Immunohistochemical analysis indicated that the reactivity of MAb A3D4 was clearly increased when tissue sections were pre-treated with periodic acid or O-glycanase, while it was decreased by pre-treatment with trypsin or protease V8. There was no reactivity with the synthetic peptide encompassing the tandem-repeat sequence of MUC2 or MUC3. These data suggest that MAb A3D4 detects a novel gastric-cancer-associated mucin antigen whose epitope may be peptide in nature.
Adenocarcinoma↗
Serum levels of prostate-specific antigen among Japanese-American and native Japanese men.
BACKGROUND: Fourfold to sixfold higher prostate cancer rates in Japanese-American men in the United States compared with Japanese men in Japan have been cited to support a role for environmental risk factors in the etiology of the disease. To examine the hypothesis that part or all of the elevated prostate cancer rates in Japanese-American men may reflect more intensive prostate cancer screening in the United States than in Japan, we compared prostate-specific antigen (PSA) levels in community-based samples of serum from men without prostate cancer. METHODS: Japanese-American men aged 40-85 years and native Japanese men aged 40-89 years with no history of prostate cancer provided sera, respectively, in the United States from March 1990 through March 1992 (n = 237) or in Japan from January 1992 through December 1993 (n = 3522). Age-specific PSA levels were used to estimate the prevalences of undetected prostate cancer in the two populations. RESULTS: Age-specific mean PSA levels were significantly lower in Japanese-Americans than in native Japanese (two-sided P<.001). The prevalence of an elevated PSA level increased with age in both populations and exceeded 5% among men aged 60 years or more. Combined with data on prevalence of detected prostate cancer in the two populations, our data suggest that some 10.0% of Japanese-Americans aged 75 years have prostate cancer, with 31% of that fraction remaining undiagnosed. The corresponding estimates in Japan are a total cancer prevalence of 5.4%, of which 81% has not been detected clinically. CONCLUSIONS: The total cancer prevalence ratio 10.0/5.4 = 1.9 (95% confidence interval = 1.5-2.3) in Japanese-American men compared with Japanese men in Japan suggests an increased risk for Japanese-American men, but of less magnitude than the fourfold to sixfold increase indicated by the incidence data.
Adult↗
IFN-gamma upregulates anti-apoptotic gene expression and inhibits apoptosis in IL-3-dependent hematopoietic cells.
IFN-gamma is a cytokine which functions in a wide range of biological activities by inducing a number of early and delayed genes. In murine IL-3-dependent cell lines BAF-B03 and 32D, IFN-gamma upregulated bag-1 and bcl-xL gene expression. These cells revealed prolonged cell survival against IL-3-deprivation by IFN-gamma stimulation. In contrast, human myeloma cell line RPMI8226, despite expression of IFN-gamma receptor, showed neither induction of their expressions nor prolonged cell survival against serum starvation-induced apoptosis by IFN-gamma stimulation. Gene-transfer-mediated overexpression of BAG-1 protein in BAF-B03 cells led to prolonged cell survival against IL-3-deprived apoptosis compared with control BAF-B03 transfectants, indicating that levels of BAG-1 expression are crucial for cell survival in BAF-B03 cells. Taken together, these studies suggest that induction of anti-apoptotic gene expression is a crucial factor for the anti-apoptotic function of IFN-gamma in IL-3-dependent immature hematopoietic cells.
Animals↗
Biochemical and pharmacological characterization of FK706, a novel elastase inhibitor.
FK706, sodium 2-[4-[[(S)-1-[[(S)-2-[[(RS)-3, 3, 3-trifluoro-1-isopropyl-2-oxopropyl]aminocarbonyl]pyrrolidin -1-yl]carbonyl]-2-methylpropyl] aminocarbonyl] benzoylamino] acetate, C26H32F3N4NaO7, is a synthetic water-soluble inhibitor of human neutrophil elastase. This compound demonstrated a competitive and slow-binding inhibition of human neutrophil elastase with a Ki of 4.2 nM. In studies using synthetic substrates, FK706 inhibited human neutrophil elastase activity and porcine pancreatic elastase activity with respective IC50 values of 83 and 100 nM. FK706, however, inhibited more weakly, (IC50 values > 340 microM) other serine proteinases such as human pancreatic alpha-chymotrypsin, human pancreatic trypsin and human leukocyte cathepsin G. FK706 also effectively inhibited the hydrolysis of bovine neck ligament elastin (2 mg/ml final concentration) by human neutrophil elastase (4 microg/ml final concentration) with an IC50 value of 230 nM. FK706 protected animals against human neutrophil elastase (50 microg/animal)-induced lung hemorrhage with ED50 values of 2.4 microg/animal by intratracheal administration and 36.5 mg/kg by intravenous administration, respectively. Subcutaneous administration of FK706 significantly suppressed human neutrophil elastase (20 microg/paw)-induced paw edema in mice in a dose-dependent manner (47% inhibition at a dose of 100 mg/kg). These results suggest that FK706 would be a useful tool for investigating the role of human neutrophil elastase in inflammatory disorders associated with an excess of elastase, such as pulmonary emphysema, adult respiratory distress syndrome, septic shock, cystic fibrosis, chronic bronchitis and rheumatoid arthritis.
Animals↗
Increased sensitivity of gastric cancer cells to natural killer and lymphokine-activated killer cells by antisense suppression of N-acetylgalactosaminyltransferase.
UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferases (GalNAc transferases) catalyze the initial reaction in O-linked (mucin type) oligosaccharide biosynthesis. To attempt to inhibit the synthesis of O-glycan, we transfected antisense cDNA of GalNAc transferase type 1 (GalNAc-T1) into a human gastric cancer cell line, JRST. A decreased expression of GalNAc-T1 at the level of both mRNA and protein was observed in the resultant transfectants. They demonstrated a significantly increased sensitivity to NK and lymphokine-activated killer cells in vitro compared with parental cells and mock transfectants. Although there was no significant difference in in vitro cell proliferation among parental cells, mock transfectants, or antisense transfectants, the in vivo growth rate of antisense transfectants using SCID mice was clearly lower than that of parental cells and mock transfectants. Furthermore, the treatment of mice with anti-asialo-G(M1) Ab abolished this growth-inhibitory effect of antisense transfection. From these results, we conclude that antisense suppression of GalNAc-T1 could increase the sensitivity of tumor cells to NK and lymphokine-activated killer cells, suggesting that this strategy may be of use as a new immunogene therapy.
Animals↗