Simplified way of counselling parents about outcome of extremely premature babies.
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Counseling↗
Biomedical subjects
T Koh
Publications and source records attributed to T Koh.
The novel untranslated first exon "exon 0N" of the rat estrogen receptor gene.
The 5'-untranslated region (UTR) of the estrogen receptor (ER) mRNA in the rat liver was analyzed by the use of the 5'-rapid amplification of the cDNA ends (5'-RACE) method. The nucleotide sequence of one of the positive RACE clones (clone 9) revealed that the existence of the novel untranslated first exon (termed "exon N") being spliced onto the exon 1 of the rat ER mRNA. We further analyzed the distribution of the ER mRNA containing the "exon 0N" (ER mRNA (0N-1)) and the ER mRNA containing the previously reported exon 0 (ER mRNA (0-1)) in the rat brain and peripheral tissues. In contrast to the wide distribution of the ER mRNA (0-1), the distribution of the ER mRNA (0N-1) was almost limited in the peripheral tissues. These results indicate that the "exon 0N" is the novel untranslated first exon of the rat ER gene, and the tissue specific expression of the ER is regulated, at least in part, by differential promoter usage in the rat.
Animals↗
Motility-related protein-1 (MRP-1/CD9) reduction as a factor of poor prognosis in breast cancer.
The application of reliable markers is of major importance for predicting the prognosis of and instituting the appropriate postsurgical treatment of patients with breast cancer. Previously we showed that motility-related protein-1 (MRP-1), which is identical to CD9, regulates cell motility, and that cultured tumor cells transfected with MRP-1/CD9 cDNA have low motility and low metastatic potential. In addition, MRP-1/CD9 immunoblotting and immunohistochemical study with breast cancer revealed that MRP-1/CD9 expression diminished as the clinical stage of a given breast cancer advanced and that the MRP-1/CD9 gene and protein expression in the metastatic lymph nodes was strikingly lower than in the primary breast cancers. In this study, we also investigated the expression of MRP-1/CD9 by immunoblotting and immunohistochemical analysis in 143 freshly resected invasive ductal carcinomas of the breast: 52 tumors were stage I, 61 were stage II, and 30 were stage III. Tumors were classified as MRP-1/CD9 positive when a band intensity of >30% compared with positive control cells, ZR-75-30 were evaluated with the antibody M31-15, and those with intensities <30% as negative. Moreover, these results were ascertained by immunostaining. Tumor specimens classified as MRP-1/CD9 positive using Western blotting had >50% of the cancer cells immunostained with M31-15, and those classified as MRP-1/CD9 reduced had <50% of the cancer cells immunostained with M31-15. There were 97 patients with MRP-1/CD9 positive tumors and 46 patients whose tumors had reduced MRP-1/CD9 levels. The disease-free rate of the former group of patients was strikingly higher than that of the latter (84.7% versus 51.4%, P<0.001). Similarly, the overall survival rate was also significantly different between the two groups (93.6% versus 69.6%, P=0.004). Multivariate analysis with the Cox regression model indicated that MRP-1/CD9 positively correlated better with disease-free survival (P<0.001) than estrogen receptor, tumor, and lymph node status. Our data suggest that low MRP-1/CD9 expression by tumors of the breast may be associated with poor prognosis. It is conceivable that testing for MRP-1/CD9 may identify node-negative breast cancer patients who are at high risk for early disease recurrence.
Antigens, CD↗
Specific N-ras mutation in bone marrow within 48 H of 7,12-dimethylbenz[a]anthracene treatment in Huggins-Sugiyama rat leukemogenesis.
7,12-Dimethylbenz[a]anthracene (DMBA)-induced leukemias in Long-Evans rats consistently have an A --> T transversion at the second base of codon 61 in the N-ras gene. This mutation is also detected in the preleukemic stage. To determine when this specific N-ras mutation occurs in the early stages of leukemogenesis, we designed the mutant allele-specific amplification method, which was sensitive enough to detect one mutant cell among 10(6) normal cells. In the study reported here, N-ras mutation was found in bone-marrow cells 2 d after a single DMBA injection and thereafter throughout the preleukemic stage. These results show that DMBA induces a specific N-ras mutation soon after one DMBA injection and that this mutation is probably the first event in DMBA leukemogenesis.
9,10-Dimethyl-1,2-benzanthracene↗
Transfection of wild-type TP53 induces differentiation in human gingival carcinoma cells.
We investigated the effects of transfection of wild-type TP53 on the growth properties of a human gingival carcinoma cell line, KOSC-3, in which the TP53 gene is mutated at codon 248 and overexpressed. The wild-type TP53 expression plasmid, pCDM8-p53/neo and the control plasmid, pCDM8/neo, were each stably transfected into KOSC-3 cells by using the calcium phosphate method. The number of G418-resistant colonies from wild-type TP53-transfected cells was approximately half that from plasmid controls. Exogenous wild-type TP53 transcripts were identified in four of the 20 G418-resistant clones analysed by reverse transcription PCR. Although the growth rates of the wild-type TP53+ clones did not drastically change during log phase, their saturation density was significantly reduced. The wild-type TP53+ cells were morphologically flat and enlarged when cultured in vitro, and were less able to form colonies in soft agar. In nude mice, the wild-type TP53+ clones formed subcutaneous tumours with conspicuous keratinisation and notable cell death that was not manifested in the parental and plasmid control cells. These findings indicate that the wild-type TP53 gene, even when it coexists with a mutated form, may function as a growth suppressor and differentiation inducer under restricted conditions in gingival squamous cell carcinoma.
Animals↗
Familial isolated hypoparathyroidism: case report with serum PTHrP examination.
We report a family, with isolated hypoparathyroidism. The proband was a 24-year-old woman, who presented with paresthesia of both hands. She had a mild degree of extrapyramidal signs, such as rigidity and decrease in arm swinging. Laboratory examinations revealed low PTH levels, mild hypocalcemia and hyperphosphatemia in the proband, her father, a younger brother and a younger sister, whereas her mother had normal serum calcium, phosphorus and PTH levels. These results indicate that four members of the family were affected, suggesting autosomal dominant inheritance. Brain CT revealed calcification of basal ganglia in the proband, her father and a younger sister, but not in her younger brother. Serum PTH-related protein (PTHrP) levels were examined, and found to be slightly high only in the father of the proband.
Adult↗
[Discrepancy of platelet numbers between automated blood cell analysis and manual counting in the patients with thrombocytopenia].
Automated blood cell analyzer can measure the numbers of blood cell and a histogram patterns of WBC, RBC and Platelet (PLT), and calculate the blood cell indices (RDW, MPV, PDW, etc). It is important clinically in the patients with thrombocytopenia (below 10 x 10(4)/microliter) to measure correct platelet number. However platelet number with automated blood cell analyzer was influenced by the changes in erythrocyte morphology or various PLT conditions. We subclassified the patients with thrombocytopenia into 5 groups according to the histogram pattern of PLT, and compared platelet numbers among NE-8000 analysis (Sysmex), H*2 analysis (Bayer's) and manual method in each group. In the group of abnormal histogram pattern of PLT, platelet numbers obtained with NE-8000 or H*2 were significantly low comparing to manual numbers. About 70% of samples of which Platelet Distribution Width (PDW) was abnormal showed discrepant values between automated analysis and manual eye count. In conclusion, discrepant low platelet count would be obtained by automated analysis and therefore should be carefully interpreted in the patients with thrombocytopenia and abnormal platelet histogram pattern.
Automation↗
Reduced motility related protein-1 (MRP-1/CD9) gene expression as a factor of poor prognosis in non-small cell lung cancer.
Motility related protein-1 (MRP-1) is a transmembrane glycoprotein that is identical to the CD9 antigen. In previous studies, we showed that various types of cultured tumor cells transfected with MRP-1/CD9 cDNA have low motility and diminished metastatic potential to the lung. More recently we used immunohistochemical procedures, immunoblotting, and reverse transcription-PCR to demonstrate that the level of MRP-1/CD9 expression was inversely related to the clinical stage of a given carcinoma of the breast. In addition, we found that the primary tumors of almost 50% of the patients had higher MRP-1/CD9 levels than their respective metastatic lymph nodes. In consideration of these findings, we have now applied reverse transcription-PCR to determine MRP-1/CD9 gene expression in lung cancer. We analyzed tumor tissues of 109 patients: 49 tumors were stage I; 15 were stage II; and 45 were stage III. We found that 67 patients had MRP-1/CD9-positive tumors, and that gene expression was reduced in the tumors of the remaining 42 individuals. The overall rate of survival was strikingly higher among patients with positive tumors than in those whose tumors had reduced gene expression (62.3 versus 34.9%; P < 0.001). This also pertained to patients with adenocarcinomas of the lung (55.4 versus 26.0%; P < 0.001). Multivariate analysis with the Cox regression model indicated that MRP-1/CD9 positivity correlated better with overall survival rate than did other variables, except lymph node status. Our data suggest that low MRP-1/CD9 expression by tumors of the lung may be associated with poor prognosis. It is conceivable that testing for MRP-1/CD9 may identify node-negative lung cancer patients and patients with adenocarcinomas who are at high risk for early disease recurrence.
Antigens, CD↗
Induction of Fas-mediated apoptosis in p53-transfected human colon carcinoma cells.
To investigate the biological function of p53 in colon carcinoma cells, a wild-type p53 expression plasmid under the control of the human cytomegalovirus promoter was stably transfected into the human colon adenocarcinoma cell line WiDr, which carries a mutation of the p53 gene at codon 273. Exogenous wild-type p53 transcripts were detected at various expression levels in 8 of 117 G418-resistant clones. The growth rates of the wild-type p53+ clones in culture did not change significantly. The efficiency of colony formation in soft agar, however, was completely suppressed in two wild-type p53+ clones. This is the first to demonstrate the feasibility of stable transfection of the wild-type p53 gene under the control of non-inducible promoter in human colon cancer cells. The major alteration found was that wild-type p53+ cells which were incubated with anti-Fas IgM showed marked cytolysis with preferential over-expression of wild-type p53 accompanied by overexpression of a cyclin-dependent kinase inhibitor, WAF1, whereas the endogenous mutant p53 retained its expression level. The findings suggest that a Fas-initiated pathway is incidentally linked to a p53-dependent apoptotic pathway through the reconstituted wild-type p53 gene in WiDr cells. This model should help elucidating the additional role of the p53 tumor suppressor gene and the mechanism of apoptosis in colon carcinoma cells.
Adenocarcinoma↗
Motility related protein 1 (MRP-1/CD9) expression: inverse correlation with metastases in breast cancer.
In our previous studies we showed that motility related protein 1 (MRP-1) is a glycoprotein recognized by mAb M31-15, and that the sequence of MRP-1 is identical to that of CD9, a WBC differentiation antigen. Transfection of MRP-1/CD9 cDNA into cultured nonhematopoietic cells suppresses cell motility. The extent of suppression is directly related to the level of MRP-1/CD9 expression. In addition, the metastatic potential of MRP-1/CD9-transfected melanoma BL6 cells is lower than that of control BL6 cells. To determine whether these experimental results are of relevance with respect to actual human tumors, we investigated MRP-1/CD9 expression in 143 invasive ductal carcinomas of the breast. Of 97 patients with MRP-1/CD9-positive tumors, only 36 (37.1%) had lymph node involvement. In contrast, 21 of 39 (53.8%) patients whose tumors had reduced MRP-1/CD9 immunoreactivity and 5 of 7 patients whose primary carcinomas were not stained by the anti-MRP-1/CD9 MAb had lymph node metastases. The comparison of protein expression by 62 primary tumors and their respective metastatic lymph nodes revealed that in almost 50% of the cases, the latter had lower MRP-1/CD9 levels than the former. Moreover, reverse transcriptase-PCR-based analysis disclosed that MRP-1/CD9 gene expression in the metastatic lymph nodes of 17 of 32 patients was strikingly lower than in the primary invasive ductal carcinomas. Gene overexpression was not observed in any of the samples studied. Our data suggest that low MRP-1/CD9 expression may be associated with the metastatic potential of certain human tumors.
Adult↗
N-ras mutation in 7,12-dimethylbenz[a]anthracene (DMBA)-induced erythroleukemia in Long-Evans rats.
Intravenous injections of 7,12-dimethylbenz[a]anthracene (DMBA) induce erythroblastic leukemia (erythroleukemia) with No.2 trisomy in Long-Evans rats. Activation of some oncogenes such as abl and Ha-ras has been reported to occur in relation to the secondary chromosomal translocations. In the present studies, a consistent type of mutation, A to T transversion in codon 61 of N-ras gene, was found in all of 6 cultured leukemia cell lines and 5 primary leukemias induced by DMBA. The N-ras mutation was also found in bone marrow cells of 2 out of 8 preleukemias. On the contrary, no mutation was observed in Ha- and Ki-ras genes in all leukemias and preleukemias. The consistent occurrence of above N-ras mutation in leukemias indicates that it plays an important role in DMBA-leukemogenesis.
9,10-Dimethyl-1,2-benzanthracene↗
Alternative splicing of the neurofibromatosis 1 gene correlates with growth patterns and neuroendocrine properties of human small-cell lung-carcinoma cells.
Two distinct transcripts, type I and type II, of the neurofibromatosis I (NFI) gene are generated by alternative splicing in the region corresponding to the gene's GTPase-activating protein-related domain (GRD). Relative expression levels of these 2 transcripts were previously correlated to neural differentiation. Since small-cell lung carcinoma (SCLC) often exhibits neuroendocrine properties, we analyzed the type-I to type-II mRNA ratio in 15 SCLC cell lines, using reverse transcriptase and polymerase chain reaction methods. The type-I mRNA was predominant in 10 cell lines; 8 of them grew as floating aggregates in culture and had high L-dopa decarboxylase (DDC) activity. The other 5 lines predominantly expressed type-II mRNA, adhered to the culture substrate, and expressed low or undetectable levels of neural cell-adhesion molecule (NCAM) antigen and DDC activity. N2+, one of the subclones of NCI-N417 cells, exhibited a higher type-I to type-II ratio after the cells had adhered to a laminin-coated plate and had emitted neurite-like processes. These findings provide evidence that alternative splicing patterns of NFI mRNA correlate with the mechanisms that regulate the growth patterns and neuroendocrine properties of SCLC cells in vitro.
Alternative Splicing↗
Platelet satellitism found by an abnormal leukocyte cytogram with an automated cell counter.
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Adult↗
The failure of retrograde continuous warm-blood cardioplegia to resuscitate cardiac function in experimental acute coronary artery occlusion and reperfusion.
The effects of retrograde continuous warm-blood cardioplegia (RCWBC) on myocardial preservation during surgical revascularization for acute coronary artery occlusion were investigated using an isolated in-situ dog heart model. The left anterior descending artery (LAD) was occluded for 60 minutes followed by 60 minutes of cardioplegic arrest and reperfusion after release of the coronary artery occlusion. Thirty one animals were divided into 3 groups according to the manner of cardioplegic arrest. The first group of animals (n=10) received multiple doses of cold St. Thomas' Hospital solution delivered antegradely through the aortic root. The second group of animals (n=11) received the same dose of the crystalloid solution delivered retrogradely through the coronary sinus. The third group of animals (n=10) received RCWBC through the coronary sinus. In the animals which were capable of supporting the working mode after reperfusion (8 hearts in each group), regional myocardial function in the occluded LAD distribution measured by sonomicrometer as well as global myocardial function evaluated by left-ventricular stroke-work index were not significantly improved during reperfusion by RCWBC. Corresponding to the functional data, myocardial pH in the occluded LAD distribution was not significantly increased by RCWBC. Although RCWBC maintained myocardial pH in the circumflex artery distribution at a significantly higher level than the other two groups of hearts undergoing cold crystalloid cardioplegia, RCWBC resulted in a substantial decline of myocardial pH in the right-ventricular free wall. These results suggest that RCWBC after 60 minutes of LAD occlusion may not provide a significant benefit in myocardial preservation compared to cold crystalloid cardioplegia delivered through either an antegrade or retrograde manner.
Animals↗
Three cases of primary hyperparathyroidism associated with nonmedullary thyroid carcinoma.
Nonmedullary thyroid carcinoma was diagnosed in three of nine cases of primary hyperparathyroidism. In all three cases, diagnosis of primary hyperparathyroidism was made before that of thyroid carcinoma. In the first case, follicular carcinoma was incidentally detected during parathyroidectomy. In the second case, thyroid tumor was discovered during imaging studies for hyperparathyroidism. Papillary carcinoma and ectopic parathyroid was diagnosed postoperatively. In the third case, a thyroid lesion had been mistaken for a putative parathyroid lesion, but the diagnosis of papillary carcinoma was obtained. These cases suggest that preoperative examination for hyperparathyroidism should be carefully evaluated, considering possible concomitant thyroid lesions.
Adenocarcinoma↗
[Intermediate to late results of aortic or mitral valvuloplasty by rasping procedure].
We have proposed Rasping procedure as one of the methods of aortic valvuloplasty (A-Rasping) and defined as debridement of the thickened surface of the rheumato-degenerative aortic valve using an electric rasper since 1986. Furthermore, we have extended this technique to mitral valvuloplasty (M-Rasping). The purpose of this study is to evaluate intermediate to late results of valvuloplasty by Rasping procedure. From 1986 to 1994, this method was carried out on 14 patients with mild-to-moderate aortic valve disease in severe mitral valve disease or coronary artery disease, and on 6 patients with mitral stenosis. In A-Rasping group, aortic regurgitation was found in 10 patients and aortic stenosis was found in 4 patients. The degree of regurgitation, the transvalvular pressure gradient, and the pre- and postoperative cardiac function in both group were investigated chronologically by echocardiography. In this series of patients, no hospital mortally including operative death was observed. Furthermore, reoperation for repaired aortic or mital valve was not required. In A-Rasping group, 2 late deaths (14.2%) occurred at 1 year and 4 years after operation. Cause of 2 late deaths was prosthetic valve endocarditis in mitral position. In A-Rasping group, at 1 year after operation, regurgitation was reduced to degree I or less in all patients. However, at the 3rd postoperative year, regurgitation increased to degree II in 2 patients. As compared with the preoperative values, the transvalvular pressure gradient significantly decreased in 4 patients (29.5 +/- 7.6 mmHg vs 12.5 +/- 5.0 mmHg, p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Evaluation for mitral valvuloplasty using rasping procedure].
From April 1992 through July 1994, 7 patients underwent mitral valvuloplasty using rasping procedure in conjunction with open mitral commissurotomy. All patients had satisfactory postoperative results without the complications such as restenosis, regurgitation, infection. However, thromboembolism was observed in 1 patient at the postoperative 6 months. And no reoperation for repaired mitral valve was observed. Transvalvular pressure gradient significantly decreased from 14.3 +/- 8.5 mmHg to 4.7 +/- 1.6 mmHg after operation. Mitral valve areas significantly increased from 1.01 +/- 0.31 cm2 to 1.78 +/- 0.41 cm2 after operation. As compared with preoperative value of 0.32 +/- 0.02, postoperative left ventricular fractional shortening (LVFS) significantly improved to 0.40 +/- 0.03. The advantages of this method is considered to be equable and safe débridement, and no anticoagulation at late period. Mitral valvuloplasty using rasping procedure, except for transmural calcified lesions, is useful and effective method. And excellent postoperative long-term results could be expected.
Aged↗
[Successful surgical treatment of active infective endocarditis associated with perforation of aortic wall].
A 69-year-old man was transferred to our hospital because of severe progressive heart failure, eyeground hemorrhage due to embolism and uncontrollable inflammation. Emergent operation was suggested. Aortic valve replacement with a 23 mm Carpentier-Edwards bioprosthesis and patch closure of perforation using Dacron double velore was successfully performed. Vegetation was observed from the commissure between left and non coronary cusp to the aortic wall. Perforation (3 mm in diameter) and a moderate amount of bloody pericardial effusion were recognized. However periannular abscess was not detected. Postoperative course was uneventful and no recurrence of infection has been seen. We believe that surgical treatment for active infective endocarditis should be recommended when the bactericidal agents are ineffective and before the hemodynamics is suddenly deteriorated and the embolism occurs to the other organs.
Aged↗