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Biomedical subjects

S Lee

Publications and source records attributed to S Lee.

At least 973 records · Page 54Linked to original sources

An immunohistochemical study of the expression of p53 protein in colon cancer.

A total of 471 cases of colonic adenocarcinomas and 28 cases of colonic adenomas were examined immunohistochemically to evaluate the expression of p53 protein in the light of their relationship with various prognostic factors. A monoclonal antibody, p53 DO-7, was used in the study. Two hundred and fourteen adenocarcinomas (45.5%) showed positive staining for p53, however only three of the adenomas (10.3%) were positive (P < 0.05). p53 was stained to neoplastic nuclei. Adjacent normal mucosal cells were negative. There were no significant correlations between p53 expression and prognostic parameters such as age, sex, gross configuration, modified Astler-Coller stages, microscopic tumor growth patterns, tumor depth, tumor size and lymph node involvements. However, left sided adenocarcinomas (49.3%) expressed p53 more often than right sided adenocarcinomas (35.6%) (P = 0.01). The positive rates were different according to the histologic differentiation; 45.2% in well differentiated, 51.3% in moderately well differentiated, 23.8% in poorly differentiated, and 26.5% in mucinous carcinomas (P = 0.011). The mean survival periods of the p53 positive and negative groups were 29 months and 32 months, respectively (P = 0.385). However, overall survival for patients with grade one and two positive p53 was better than those of grade three and four positive cases (P = 0.028). In conclusion, the result of this multivariate analysis suggests that immunohistochemically strong p53 protein expression (more than 30% of tumor cells) has value in estimating a prognosis for patients with colorectal adenocarcinomas.

Adenocarcinoma↗

Altered p53 expression in Epstein Barr virus positive T cell lymphomas.

Recent studies have suggested a probable association between Epstein-Barr virus (EBV) and nasal/nasopharyngeal T cell lymphomas but the role of oncogenes or tumor suppressor genes is poorly understood. We have studied the frequency of p53 expression and its relation to the EBV infection in 33 Korean patients with head and neck (H&N) lymphomas. All cases (23 B cell & 10 T cell) were immunostained for p53 protein using the mAb D07 (Novocastra) and the avidin biotin peroxidase method. EBER in situ hybridization was performed using a fluorescein conjugated EBV oligonucleotide probe (Dako). Among 33 lymphomas, 16 cases stained positively for p53 protein. P53 expression was frequent both in higher grade lymphomas and in advanced stage. Nine cases were EBER positive, EBER was more commonly found in T cell lymphomas than in B cell lymphomas (70% vs 8.7%). EBER positive lymphomas showed a higher frequency of p53 positivity than EBER negative lymphomas (78% vs 38%), although the difference was not statistically significant (p = 0.095). These findings indicate altered expression of p53 protein occurs in H&N lymphomas, especially in late event lymphoma progression and appears to play a role in the development of EBER positive T cell lymphomas.

Follow-Up Studies↗

Differential responses of CD34-positive acute myelogenous leukemic blasts to the costimulating effects of stem cell factor with GM-CSF and/or IL-3.

Stem cell factor (SCF), a c-kit ligand, has a preferential effect on the proliferation of several classes of immature hematopoietic progenitor cells in combination with GM-CSF or IL-3. To analyze the costimulatory role of SCF in leukemic growth, we investigated the effect of SCF in the presence of GM-CSF and/or IL-3 on isolated CD34-positive (CD34+) leukemic blasts from 15 patients with acute myelogenous leukemia (AML). Cultures of CD34+ cells from normal bone marrow were used as controls. When the proliferation of CD34+ AML blasts in the presence of GM-CSF and/or IL-3 were evaluated in vitro for the effects of SCF, two patterns emerged. In one pattern, CD34+ AML blasts responded with a significant increase in DNA synthesis and/or colony formation when SCF was used with GM-CSF and/or IL-3 relative to the growth with SCF alone; This result is consistent with those CD34+ bone marrow cells from normal donors. Six patients (40%) were included in this category. The addition of SCF as a single factor resulted in colony formation in all six of these cases. In the other pattern, nine of the patients (60%) had CD34+ leukemic cells whose growth with SCF plus either GM-CSF, IL-3, or GM-CSF+IL-3, was not significantly different from the growth noted in the presence of SCF alone. Among them seven cases that did not form colonies in response to SCF alone, and one case showing autocrine, background growth were included. In the six cases in which the costimulating effects of SCF were documented, CD34+ c-kit+ blasts comprised 50.5 +/- 18.7% of the CD34+ leukemic blasts-higher than 21.8 +/- 19.4% of cases in which the costimulating effect of SCF was not documented. In the cases showing high c-kit antigen expression (> or = 40%), SCF had a costimulatory effect in 71% (5/7) of the patients. In conclusion, our data indicate that CD34+ leukemic blasts from a good proportion of patients with AML did not respond to the costimulating effects of SCF in the presence of GM-CSF adn/or IL-3, in contrast to those CD34+ bone marrow cells from normal donors. The possible use of SCF for acute leukemia must await further cytogenetic and molecular studies, which should clarify the preferential costimulating role of SCF in normal hematopoiesis.

Antigens, CD↗

Neuroimaging in head injury.

This article reviews the neuroradiologic manifestations of acute nonpenetrating head injury. The pathophysiology of the various types of neurotrauma is correlated with the imaging features. Computed tomography (CT) remains the initial imaging modality of choice, allowing rapid diagnosis of the majority of injuries. Magnetic resonance imaging is useful in the subacute and chronic stages (particularly in a patient whose initial CT scan is unremarkable) to assess brainstem and white matter shearing injuries.

Brain Injuries↗

DNA aneuploidy in morphologically normal colons from patients with colon cancer.

DNA aneuploidy is common in colon carcinoma, colonic polyps, and ulcerative colitis. We found an interesting subset of patients with colon cancer. These individuals (14 of 230 cases, 6%) had hypodiploid aneuploidy in their morphologically normal-appearing colonic tissue. The aneuploid fractions were small, making up between 10 to 15% of the total events, and the ploidy pattern was not related to the ploidy pattern of the tumor. The clinical findings of the 14 patients were compared with those of patients who had diploid normal colons by age, location of the tumor, Dukes stage, and percent aneuploidy in the main tumor; the two groups were comparable. Both the normal colon and carcinomas of the 14 cases were studied by a newly developed "enriched" polymerase chain reaction for K-ras mutations. No K-ras mutations were found in the normal tissues, but mutations were found in the tumors of four cases. Cells from some colon cancers have a high degree of genetic instability, as shown by numerous mutations throughout the genome. Analysis of eight matched colon cancers and aneuploid, morphologically normal-appearing colons for genetic alterations, as measured by shifts in the electrophoretic mobility of microsatellite repeat fragments, showed that only one of eight colon cancer samples had microsatellite instability, which is the expected frequency. Taken together, the data suggest that individuals with colon cancer may have morphologically normal colonic tissue, which is genetically abnormal, and this abnormality may precede the development of mutations in K-ras.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Protein binding of acetylsalicylic acid and salicylic acid in porcine and human serum.

As part of a pilot project establishing a porcine model for aspirin overdose, the percentage protein binding of acetylsalicylate (ASA) and salicylate (SA) in porcine and human sera was evaluated in vitro over a range of concentrations. Serum from 2 pigs and 4 humans were spiked with ASA concentrations of 0.5-100 mg/dL and SA concentrations of 1-120 mg/dL. Protein binding for each concentration of ASA and SA was determined using radiolabeled drug and ultrafiltration with the Centrifree micropartition system. The percentage protein binding for ASA in pig and human sera were similarly low (< 50%) for all concentrations evaluated. Percentage protein binding for SA for pig and human sera were high (approximately 90% and 80%) at low therapeutic concentrations, but then declined to approximately 30% at higher toxic concentrations (120 mg/dL). The protein binding of ASA and SA over a range of concentrations was similar for porcine and human sera.

Animals↗

Electron microscopic observation of erythema nodosum with the eosinophilic infiltration. A case report.

The presence of eosinophils localized within an inflammatory skin lesion of a patient with erythema nodosum has been studied by electron microscopy. Among the intact eosinophils seen in the cellular infiltration, some underwent necrosis and released membrane-bound, free eosinophil granules into the interlobular septa of the subcutaneous fat. Such granules, identified by their central crystalline cores, often showed granular changes with core dissolution and were found scattered in the edematous space between the collagen bundles. A few intact eosinophils that showed minor alterations of cytoplasmic granules were also present. The significance of these findings, which may enhance endothelial permeability, is discussed.

Adult↗

Simultaneous detection of both hepatitis B virus DNA and hepatitis C virus RNA using a combined one-step polymerase chain reaction technique.

Hepatitis C virus (HCV) RNA polymerase chain reaction (PCR) is widely used for diagnosis of HCV infection and evaluation of therapy. The sensitive hepatitis B virus (HBV) DNA PCR is often reserved for detection of quantities of HBV DNA that are insufficient for hybridization. Application of both PCR techniques is limited by their labor-intensity, potential for contamination, and substantial time required for analysis. To study HCV and HBV infections, occurring alone or in combination, we developed a combined one-step PCR method to detect HCV RNA and HBV DNA in a single serum specimen using oligoprimers from the HCV 5' untranslated region and the HBV preS/S region. Specificity of the HBV and HCV PCR products was confirmed on the basis of their molecular sizes in positive samples, Southern blot hybridization, and negative controls. The sensitivities of the combined PCR were assessed using samples containing a wide range of defined amounts of HBV DNA and HCV RNA and were comparable with those obtained with conventional HBV DNA or HCV RNA PCR methods. The sensitivity of the combined method was further validated by the 100% concordance between results of its HBV and HCV components and those of conventional PCR methods in patients with HBV and/or HCV infections. The combined one-step HBV/HCV PCR is a sensitive, specific, rapid, and cost-effective method, especially suited for epidemiological screening and clinical diagnosis of HBV and HCV infections occurring alone or in combination.

Base Sequence↗

Superiority of neural networks over discriminant functions for thalassemia minor screening of red blood cell microcytosis.

We compared the utility of screening red blood cell (RBC) microcytosis for thalassemia minor using backpropagation neural networks, linear and quadratic discriminant functions, and previously reported discriminant functions based on RBC indices. Screening classification of cases representing possible thalassemia minor (n = 60) and non-thalassemic microcytosis (n = 60) were studied. Among eight RBC indices evaluated, the RBC count was the best univariate discriminant function. Multivariate stepwise discriminant analysis selected the RBC count, the mean corpuscular volume, and the percentage of hypochromic cells as the most discriminatory subset of RBC indices. Optimized linear and quadratic discriminant functions based on these indices performed better than seven previously reported multivariate discriminant functions. However, optimized neural networks were superior to all other discriminant methods studied, averaging 94.1% discriminant efficiency, 94.2% sensitivity, and 94.2% specificity.

Analysis of Variance↗

Violence and schizophrenia: clozapine as a specific antiaggressive agent.

Pharmacological management of persistent aggression in patients with schizophrenia is a difficult clinical dilemma. Clozapine has been shown to be an effective agent in this regard. This study sought to compare the symptomatic response on the Brief Psychiatric Rating Scale (BPRS) between hostile schizophrenic patients and patients without aggression. While dramatic improvements were evident in aggression, both groups were indistinguishable with respect to BPRS response. These results suggest that clozapine may have a selective antiaggressive effect.

Adult↗

Polypharmacy.

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Dose-Response Relationship, Drug↗

Serine acetyltransferase from Arabidopsis thaliana can functionally complement the cysteine requirement of a cysE mutant strain of Escherichia coli.

Serine acetyltransferase, a key enzyme in the L-cysteine biosynthetic pathway of sulfate assimilating organisms, catalyzes the formation of O-acetylserine, the immediate precursor of L-cysteine. In higher plants, it is thought that sulfur assimilation occurs primarily in leaf chloroplasts; however, serine acetyltransferase is not localized exclusively in this tissue and organelle. At least three genes for serine acetyltransferase have been identified in the higher plant Arabidopsis thaliana. Reported here is a cDNA corresponding to one of these genes, SAT1, a 1,079 bp clone with an open reading frame predicted to encode a 34-kDa protein that is able to functionally complement a serine acetyltransferase mutant strain of Escherichia coli. The predicted amino acid sequence of SAT1 shows significant homology with bacterial serine acetyltransferases. SAT1, expressed as a recombinant protein, shows serine acetyltransferase enzyme activity and cross-reacts with an antibody against the homologous E. coli enzyme. The first 40 amino acids of the SAT1 polypeptide resembles a plastid transit peptide, but the polypeptide is probably not plastid localized. Genomic DNA blot analysis of A. thaliana showed that SAT1 is a single copy gene and RNA blot analysis revealed that SAT1 is expressed in both leaves and roots.

Acetyltransferases↗

Binding of mismatched microsatellite DNA sequences by the human MSH2 protein.

Alteration of the human mismatch repair gene hMSH2 has been linked to the microsatellite DNA instability found in hereditary nonpolyposis colon cancer and several sporadic cancers. This microsatellite DNA instability is thought to arise from defective repair of DNA replication errors that create insertion-deletion loop-type (IDL) mismatched nucleotides. Here, it is shown that purified hMSH2 protein efficiently and specifically binds DNA containing IDL mismatches of up to 14 nucleotides. These results support a direct role for hMSH2 in mutation avoidance and microsatellite stability in human cells.

Base Composition↗

Topology of Kell blood group protein and the expression of multiple antigens by transfected cells.

Kell is one of the major blood group systems in human red blood cells (RBCs). The Kell antigens are carried on a 731 amino acid glycoprotein that is thought to span the erythrocyte membrane once. Rabbit antibodies to three synthetic peptides, derived from different parts of the Kell protein, were used to determine the topology of Kell protein on the RBC. Antibodies to a C-terminal peptide and to a peptide derived from amino acid residues 410 to 439 reacted with RBCs treated with 0.2 mol/L dithiothreitol. An antibody to the N-terminal peptide reacted with inside-out RBC vesicles but not with right-side-out vesicles nor with intact RBCs, showing that Kell is a type II membrane protein and that the extracellular portion of the protein is folded by disulfide bonds. By transfection, Kell protein was expressed on the cell surface of surrogate cells, and the transfected cells expressed similar antigenic properties as native RBCs. Kell protein was expressed in COS-1 and K562 cells and in Sf9 cells infected by the Baculovirus system. Transfected K562 cells expressed several high-incidence antigens but not the low-incidence antigen K1.

Animals↗

Sex and gender bias in anatomy and physical diagnosis text illustrations.

OBJECTIVE: To examine the sex and gender distribution of illustrations in two atlases, five anatomy texts, and five physical diagnosis texts. DESIGN: Of 4060 illustrations that were identifiable by sex and gender in 12 commonly used anatomy and physical diagnosis textbooks, 3827 were categorized by two reviewers as female, male, or neutral. RESULTS: Females were represented, on average, in 21.2% of the anatomy text illustrations; males were represented, on average, in 44.3%; 34.4% of the illustrations were neutral. Of the nonreproductive anatomy illustrations, a mean of 11.1% (range, 4.6% to 23.8%) depicted women and 43.1% (range, 35.4% to 56.2%) depicted men. Of nonreproductive anatomy illustrations, a mean of 45.8% (range, 27.2% to 59.9%) were neutral. Overall, the physical diagnosis text illustrations demonstrated a more equal sex and gender distribution (21.5% female and 24.8% male). However, in the reproductive chapters of the physical diagnosis texts, females were depicted in a mean of 71.1% (range, 63.2% to 79.0%) of the illustrations, while in the nonreproductive chapters, females were depicted in 8.8% of total illustrations. CONCLUSIONS: In anatomy and physical diagnosis texts, women are underrepresented in illustrations of nonreproductive anatomy. The finding that males are depicted in a majority of nonreproductive anatomy illustrations may perpetuate the image of the male body as the normal or standard model for medical education.

Female↗