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Biomedical subjects

E Lee

Publications and source records attributed to E Lee.

At least 235 records · Page 13Linked to original sources

Extensive areas of aneuploidy are present in the respiratory epithelium of lung cancer patients.

According to the field cancerisation theory the entire upper aerodigestive tract has been mutagenised, thereby placing the affected individual at risk for the development of one or more cancers. To investigate this concept we studied the respiratory epithelium in lungs bearing cancer, including bronchi, bronchioles and alveoli. After identifying preneoplastic and preinvasive lesions by light microscopy, we determined the DNA content of their nuclei in Feulgen-stained sections using a high-performance digitised image analyser. Archival material from 35 resected cases of non-small-cell lung cancer (NSCLC) was selected, including 16 central tumours (mainly squamous cell carcinomas) and 19 peripheral tumours (mainly adenocarcinomas) and five resected cases of metastatic tumour from extrathoracic primary sites. Of the NSCLCs, 31/35 (89%) were aneuploid, as were 60% of the metastases from extrathoracic sites. Multiple, focal areas of preneoplasia or preinvasive carcinoma were present in the selected cases. The lesions ranged in severity from hyperplasia through metaplasia and dysplasia to carcinoma in situ. Aneuploid preinvasive lesions were not noted in association with the four diploid tumours but were present only when the accompanying NSCLC was aneuploid. With both central and peripheral tumours, aneuploid preneoplastic lesions were more frequent in the peripheral parts of the lung (bronchioles or alveoli) than in the central bronchi. Both the degree and incidence of aneuploidy increased with progressive severity of morphological change. Aneuploidy was not found in preinvasive lesions accompanying the five metastatic cases. Our findings provide strong support for the concept of field cancerisation.

Adenocarcinoma↗

Effects of aging and gastritis on gastric acid and pepsin secretion in humans: a prospective study.

BACKGROUND & AIMS: Recent studies suggesting that gastric secretion does not decrease with aging included few elderly individuals and measured only acid secretion. The aims of this study were to measure gastric acid and pepsin output in 206 health Americans (age range, 18-98 years) and to compare secretion rates with gastric histology. METHODS: Immediately after basal and pentagastrin-stimulated acid and pepsin outputs were measured, oxyntic biopsy samples were obtained. RESULTS: Gastric acid and pepsin output rates were similar in young (age range, 18-34 years) and middle-aged (age range, 35-64 years) groups. Stimulated acid output was reduced approximately 30% in the elderly (age range, 65-98 years). However, after adjustment for histology, Helicobacter pylori infection, and other variables, age had no independent effect on acid output. The decline in acid secretion in the elderly was primarily related to a higher prevalence of chronic atrophic gastritis and a lower prevalence of smoking. Pepsin output was reduced by approximately 40% in the elderly. After adjustment for other variables, age remained a robust predictor of reduced pepsin output. CONCLUSION: Although advancing age has no independent effect on gastric acid secretion, it is associated with reduced pepsin output independent of atrophic gastritis, H. pylori infection, and smoking.

Adolescent↗

The male facelift: considerations and techniques.

Facelift in the male patient presents unique challenges with respect to maintenance of normal hairline and management of bearded skin. With careful psychological preparation, surgical planning, and attention to detail, these male characteristics can be retained with a good rejuvenative result. The combination of a deep-plane rhytidectomy technique with modified incisions and endoscopic brow intervention has provided the authors with consistent surgical results. Complications have been minimal, with no significant hematomas, skin loss, or nerve injuries to date.

Face↗

A novel DNA cleaving agent, 2,2'-bis(2-aminoethyl)-4,4'-bithiazole, induces thymocyte apoptosis.

The incubation of rat immature thymocytes with 2,2-bis(2-aminoethyl)-4,4'-bithiazole, which possesses the cleaving activity toward plasmid DNA in the presence of Co2+, resulted in an increase in DNA fragmentation. No DNA fragmentation of the cells was induced by 2,2-bis(3-aminopropyl)-4,4'-bithiazole, which has little cleaving activity toward plasmid DNA. Analysis of fragmented DNA from thymocytes treated with 2,2-bis(2-aminoethyl)-4,4'-bithiazole by agarose gel electrophoresis revealed that the compound produced 50 kbp DNA fragments and caused internucleosomal DNA fragmentation. In addition, the confocal microscopic images of thymocytes treated with the compound showed condensation of chromatin. These results indicate that bithiazole derivative induces thymocyte apoptosis with the biochemical and morphological characteristics through triggering DNA scission.

Animals↗

An unusual facial sinus.

An unusual presentation of a chronic suppurative granuloma on the alar base area originating from a maxillary lateral incisor is reported. Treatment involved adequate endodontic therapy with simultaneous apical surgery and excision of the granuloma and sinus tract. Awareness of the possible dental origin of facial sinuses, despite their unusual location, is emphasized.

Adult↗

Regulation of matrix metalloproteinases and plasminogen activator inhibitor-1 synthesis by plasminogen in cultured human vascular smooth muscle cells.

Plasmin and matrix metalloproteinases (MMPs) both participate in extracellular matrix remodeling. This study examined the effects of tumor necrosis factor-alpha (TNF-alpha) and plasminogen on collagenase, stromelysin, and plasminogen activator inhibitor-1 (PAI-1) synthesis of collagenase and stromelysin, which remained predominantly in proenzyme forms, as determined by Western analysis of culture media. In contrast, plasminogen and plasmin not only increased secretion of MMPs but also induced cleavage to their active forms. The serine protease inhibitor aprotinin inhibited this activation of MMPs by plasminogen and plasmin. TNF-alpha reduced plasminogen-induced activation of MMPs, suggesting induction of an inhibitor or plasmin generation, such as PAI-1. Enzyme-linked immunosorbent assay of culture media showed that TNF-alpha (10 ng/mL) increased PAI-1 secretion by 4.2 fold compared with control (105.5 +/- 9.6) versus 24.9 +/- 1.7 ng/mL, n = 3). Surprisingly plasminogen also increased PAI-1 secretion by vascular SMCs (3.6-fold over control). These results demonstrate coordination of cytokines and serine proteases in regulating MMP secretion and activation. In addition, the induction of PAI-1 by TNF-alpha and plasminogen suggests a negative feedback mechanisms limit both plasmin-mediated and MMP-mediated matrix degradation.

Cells, Cultured↗

Mice homozygous for an insertional mutation in the Zp3 gene lack a zona pellucida and are infertile.

Mammalian oocytes synthesize and secrete a zona pellucida that surrounds the growing oocytes, ovulated eggs and preimplantation embryos. The extracellular zona matrix is composed of three glycoproteins (ZP1, ZP2, ZP3) that are involved in folliculogenesis, species-specific fertilization, and passage of the early embryo down the oviduct. We have established a mouse line in which Zp3 has been inactivated by homologous recombination with an insertional mutation. Neither Zp3 transcripts nor ZP3 protein was detected in female mice homozygous for the mutation (Zp3-/-), whereas both ZP1 and ZP2 were present in mutant oocytes. Homozygous mutant Zp3-/- mice had follicles with germinal-vesicle-intact oocytes but that lacked a zona pellucida matrix and had a disorganized corona radiata. Although mutant oocytes underwent germinal vesicle breakdown (GVBD) prior to ovulation, the cumulus-oocyte complex was markedly disrupted and the oocytes were often separate from the cumulus cells. After hormone-induced ovulation, cumulus masses were present in the oviducts of homozygous mutant mice, but zona-free eggs were observed in only half of the females and, in these, less than 10% of the normal number [correction of mumber] of eggs were detected. No zona-free 2-cell embryos were recovered from homozygous mutant Zp3-/- female mice after mating with males proven to be fertile, and none became visibly pregnant or produced offspring. These results demonstrate that a genetic defect in a zona pellucida gene causes infertility and, given the conserved nature of the zona pellucida, a similar phenotype is expected in other mammals.

Animals↗

Adjustment of urinary mercury in health risk assessment of mercury.

The determination of adjustment method of urinary mercury in spot urine is one of the important issues in assessing the health risks of mercury workers. But there have been debates about whether creatinine or other forms of correction for urinary concentration are better in reducing the variation of urinary mercury. We evaluated four adjustment methods-specific gravity, creatinine, log creatinine and excretion rate-by correlation between values adjusted by the four methods and individual exposure levels which were the geometric mean of daily air mercury level for 2 or 5 days, and mercury concentrations in 24 hour urine were also investigated to compare the results of spot urine. The correlation between values of spot urine and mercury exposure level was over 0.8 in all adjustment methods for workers who worked over 1 year. All four adjustment methods for urinary mercury were found to be similar in assessing the exposure, log creatinine and excretion rate method however were not practical to use due to lack of reference values, and variable standard values of specific gravity. And the creatinine adjusted values were more sensitive in low mercury exposure level. We therefore recommend the creatinine adjustment method for adjustment of urinary mercury.

Adult↗

Methemoglobinemia secondary to benzocaine topical anesthetic.

An 80-year-old white woman with a history of hypertension presented to the Emergency Department with bright red bleeding from the rectum. She was treated with 5 mg of midazolam and benzocaine topical anesthetic spray prior to undergoing colonoscopy and esophageal gastroduodenoscopy. Thirty minutes after endoscopy, the patient became cyanotic and dyspneic; she was suffering from methemoglobinemia, a rare complication secondary to the use of benzocaine topical anesthetic spray. After i.v. administration of methylene blue, 120 mg (2 mg/kg) in 100 cc of normal saline solution, the cyanosis and dyspnea resolved.

Aged↗

Interleukin-2 activated lymphocytes show improved sensitivity for class 1 HLA typing.

The use of phytohemagglutinin (PHA)/interleukin-2 (IL-2) activated lymphocytes for HLA typing and the comparison with those of fresh peripheral blood lymphocytes are described. For detecting class 1 HLA antigens, PHA/IL-2 activated lymphocytes showed higher sensitivity than fresh lymphocytes of the peripheral blood in serological microcytotoxicity testing method. Their reaction specificity for the panel of alloantisera for class 1 HLA antigens was the same. On the contrary, for detecting class 2 HLA antigens, PHA/IL-2 activated lymphocytes showed lower sensitivity than those with fresh B-cells. For class 2 HLA typing, the typing with DNA methods showed the best results. Thus, we conclude that a combination of a serological typing method using PHA/IL-2 activated lymphocytes for class 1 HLA antigens with a DNA method for typing class 2 HLA antigens currently offers the best approach for the detection of HLA antigens.

Adult↗

The structure of the G protein heterotrimer Gi alpha 1 beta 1 gamma 2.

The crystallographic structure of the G protein heterotrimer Gi alpha 1(GDP)beta 1 gamma 2 (at 2.3 A) reveals two nonoverlapping regions of contact between alpha and beta, an extended interface between beta and nearly all of gamma, and limited interaction of alpha with gamma. The major alpha/beta interface covers switch II of alpha, and GTP-induced rearrangement of switch II causes subunit dissociation during signaling. Alterations in GDP binding in the heterotrimer (compared with alpha-GDP) explain stabilization of the inactive conformation of alpha by beta gamma. Repeated WD motifs in beta form a circularized sevenfold beta propeller. The conserved cores of these motifs are a scaffold for display of their more variable linkers on the exterior face of each propeller blade.

Amino Acid Sequence↗

Allelotype analysis of childhood acute lymphoblastic leukemia.

To identify the genetic events that may play an important role in leukemogenesis of childhood ALL, we report for the first time the allelotyping of childhood ALL. Twenty-four cases of childhood ALL were screened for loss of heterozygosity (LOH) using 101 highly polymorphic microsatellite markers, which are distributed among all autosomal chromosomes. For LOH analysis on both chromosomes 9 and 12, 54 childhood ALL samples were examined. The most frequent allelic loss was found on chromosomal arm 9p, where 20 of 50 (40%) informative samples showed LOH. Moreover, nearly 30% of samples that did not have either homozygous deletions or point mutations of the putative tumor suppressor genes CDKN2/INK4A/p16 and INK4B/p15 on chromosomal arm 9p had LOH at D9S171. Loss of chromosomal arm 12p was also frequent (26%). Mutational analysis suggested that the altered gene on 12p is not the cyclin-dependent kinase inhibitor p27/Kip1, which is also on 12p. Several other regions that had LOH included 1p, 4q, 5p, 6q, 7p, 8p, 9q, 10q, 13q, 17p, 17q, 18q, 19q, and 22q. Of 24 patients, 19 (79%) showed allelic loss on at least one chromosomal arm. Samples of two patients (8%) showed LOH on almost all chromosomes. Fractional allelic loss, calculated for each sample as the total number of chromosomal arms lost/total number of arms with information, showed a median value of 0.04 and a mean of 0.123 (range, 0 to 0.95). This fractional allelic loss is lower than those reported for many solid tumors. This analysis shows the extreme power of LOH analysis using microsatellite markers in childhood ALL.

Adolescent↗

Tertiary and quaternary structural changes in Gi alpha 1 induced by GTP hydrolysis.

Crystallographic analysis of 2.2 angstrom resolution shows that guanosine triphosphate (GTP) hydrolysis triggers conformational changes in the heterotrimeric G-protein alpha subunit, Gi alpha 1. The switch II and switch III segments become disordered, and linker II connecting the Ras and alpha helical domains moves, thus altering the structures of potential effector and beta gamma binding regions. Contacts between the alpha-helical and Ras domains are weakened, possibly facilitating the release of guanosine diphosphate (GDP). The amino and carboxyl termini, which contain receptor and beta gamma binding determinants, are disordered in the complex with GTP, but are organized into a compact microdomain on GDP hydrolysis. The amino terminus also forms extensive quaternary contacts with neighboring alpha subunits in the lattice, suggesting that multimers of alpha subunits or heterotrimers may play a role in signal transduction.

Binding Sites↗

Murray valley encephalitis virus envelope protein antigenic variants with altered hemagglutination properties and reduced neuroinvasiveness in mice.

Neutralization escape variants of Murray Valley encephalitis virus were selected using a type-specific, neutralizing, and passively protective anti-envelope protein (E) monoclonal antibody (4B6C-2) which defines epitope E-1c. Nucleotide sequence analysis revealed single nucleotide changes in the E genes of 15 variants resulting in nonconservative amino acid substitutions in all cases. One variant had a three-nucleotide deletion in the E gene which resulted in loss of serine at residue 277. Changes were clustered into two separate regions of the E polypeptide (residues 126-128 and 274-277), indicating that E-1c is a discontinuous epitope. One variant (BHv1), altered at residue 277 (Ser-->Ile), failed to hemagglutinate across the pH range 5.5-7.5, in contrast to parental virus and the other escape variants which hemagglutinated at an optimal pH of 6.6. BHv1 was also of reduced neuroinvasiveness in 21-day-old mice following intraperitoneal inoculation compared to the other viruses. Parental virus and the neutralization escape variants grew equally well in both vertebrate and invertebrate cell cultures, indicating that the reduced neuroinvasiveness of BHv1 was not due to a major abnormality of replication.

Amino Acid Sequence↗

The modulation of phosphatidylinositol biosynthesis in hamster hearts by methyl lidocaine.

Methyl lidocaine is an experimental anti-arrhythmic drug which has been shown to enhance the biosynthesis of phosphatidyl-inositol (PI) in the hamster heart. In this study, the effect of methyl lidocaine on enzymes involved in the biosynthesis of PI in the heart was examined. When the hamster heart was perfused with labelled methyl lidocaine, the majority of the compound was not metabolized after perfusion. The direct action of methyl lidocaine on an enzyme was studied by the presence of the drug in enzyme assays, whereas its indirect action was studied by assaying the enzyme activity in the heart after methyl lidocaine perfusion. CTP:phosphatidic acid cytidylyl-transferase, a rate-limiting enzyme in PI biosynthesis, was stimulated by methyl lidocaine in a direct manner. Kinetic studies revealed that methyl lidocaine caused a change in the affinity between the enzyme and phosphatidic acid and resulted in the enhancement of the reaction. Alternatively, acyl-CoA:lysophosphatidic acid acyltransferase, another key enzyme for PI biosynthesis, was not activated by the presence of methyl lidocaine. However, the enzyme activity was stimulated in hearts perfused with methyl lidocaine. The enhancement of the acyl-transferase by methyl lidocaine perfusion was found to be mediated via the adenylate cyclase cascade with the elevation of the cyclic AMP level. The stimulation of protein kinase A activity by cyclic AMP resulted in the phosphorylation and activation of the acyltransferase. Interestingly, the activity of protein kinase C was not stimulated by methyl lidocaine perfusion. We conclude that the enhancement of PI biosynthesis by methyl lidocaine in the hamster heart resulted from the direct activation of the cytidylyltransferase, as well as the phosphorylation and subsequent activation of the acyltransferase.

Acyltransferases↗