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Biomedical subjects

G Lee

Publications and source records attributed to G Lee.

At least 235 records · Page 13Linked to original sources
PubMed1993

Measuring the uptake of Azone into excised human stratum corneum from thin polymer films.

The extent of uptake of Azone into excised human stratum corneum from thin polymer films has been measured using a sandwich model. With poly(dimethyl)siloxane, an Azone loading of the stratum corneum of 6-7% w/w was achieved. With Eudragit NE30D, a loading of less than 1% was reached. The extent of uptake into the stratum corneum and acceptor layers of the sandwich model depended on the Azone content of the films. The resulting enhanced uptake and flux of diazepam through the stratum corneum membrane into a polymeric acceptor layer corresponded closely to the amounts of Azone taken up and their known enhancing effects. The uptake of diazepam from the poly(dimethyl)siloxane films was ten times larger than that from Eudragit NE30D films. The extent of uptake is, therefore, controlled by the rate of release from the polymer and partitioning at the interface.

Acrylic Resins↗
PubMed1993

Spontaneous coronary artery dissection: a report of three cases and review of the literature.

We describe the clinical course of three patients who developed spontaneous coronary artery dissection. All patients were young women, one 9 weeks pregnant. All presented with chest pain; one died suddenly proving refractory to resuscitation, another developed unstable angina culminating in myocardial infarction, cardiogenic shock and death, and the third patient underwent coronary artery bypass grafting following diagnosis of a spontaneous coronary dissection of the left anterior descending artery at angiography. Pathological findings in the two fatal cases are reported. This condition, although rare, is a prominent cause of ischaemic coronary events in young women, when it is frequently associated with pregnancy or the puerperium. Most patients die suddenly, but a clinical spectrum is seen including stable and unstable angina, myocardial infarction and cardiogenic shock. The left anterior descending artery is most frequently affected. The classical histological finding is that of a large haematoma occupying the outer third of the media resulting in complete compression of the true lumen. The cause of spontaneous dissection remains unclear but theories of aetiology include a medial eosinophilic angiitis, pregnancy-induced degeneration of collagen in conjunction with the stresses of parturition, and rupture of the vasal vasorum. The diagnosis must be considered when a patient presents with a suggestive clinical profile. Urgent angiography should be undertaken to establish the diagnosis and consideration given to the need for coronary artery bypass grafting, which has been successfully employed in a number of patients. The uneventful long-term survival of cases treated conservatively has been reported.

Adult↗
PubMed1993

Prevalence of antibodies to hepatitis C virus in relation to surrogate markers in a blood donor population of Singapore.

Prevalence of antibodies to HCV is studied among a blood donor population in Singapore and its relationship to surrogate markers was examined. Sequential serum samples from 4,091 blood donors were tested for the presence of anti-HCV using the second generation immunoassay (Abbott). 275 random serum samples were tested for anti-HBc and ALT. All the samples positive for anti-HCV were also tested for anti-HBc and ALT. Only 22 of the 4,091 donor samples (0.54%) were repeatedly reactive for anti-HCV. Of the 275 random samples tested, 43 samples (15.6%) were positive for anti-HBc and 24 (8.7%) had ALT levels more than 45 IU/l. None of these 67 samples were positive for anti-HCV. Only 3 of the 22 anti-HCV positive samples (13.6%) were positive for anti-HBc and only 6 samples (27.2%) had ALT level more than 45 IU/l. The prevalence of anti-HCV among the donors is only 0.54% which is much lower than the prevalence of HBV. An important finding is that about 60% of the donors positive for anti-HCV had no detectable surrogate markers. Exclusion of blood donors positive for anti-HBc, if implemented in an area where the prevalence of HBV infection is relatively high will result in the loss of blood donors estimated to be 15.6% and the use of raised ALT will result in a further loss of 6.1% of the blood donors.

Adolescent↗
PubMed1993

Development of fabrication system of prostheses using electric discharge machining.

This paper outlines the principles and uses of electric discharge machining (EDM) in the fabrication of prostheses. The three areas of use of EDM are classified as supplementary use, direct fabrication of crowns and bridges and fabrication of titanium copings using a CAD/CAM process. The problems associated with the use of EDM in each area are discussed and the methods employed to overcome these problems are described. The application of numerically controlled (NC) EDM to prosthodontic work is found to be promising. Further refinement and development are necessary before EDM can be widely accepted as a means of fabricating prostheses.

Computer-Aided Design↗
PubMed1993

Study of the in vitro penetration of the topical glucocorticoid betamethasone-17-valerate from solution-type gels into a multilayer membrane system.

The in vitro transport of betamethasone-17-valerate (1) into a multilayer membrane system has been investigated. Subsaturated formulations of 1 were studied as formed by mixing appropriate propylene glycol/water cosolvent systems. The AUC (drug concentration in acce ptor membrane as a function of time) and the diffusivity of the drug in the vehicle were used to evaluate the results of the in vitro transport. The importance and relationship between solubility, partition coefficient, and diffusivity for the process of in vitro penetration of 1 are discussed.

Betamethasone Valerate↗
PubMed1992

Proline-directed phosphorylation of human Tau protein.

The primary sequence of the microtubule-associated protein tau contains multiple repeats of the sequence -X-Ser/Thr-Pro-X-, the consensus sequence for the proline-directed protein kinase (p34cdc2/p58cyclin A). When phosphorylated by proline-directed protein kinase in vitro, tau was found to incorporate up to 4.4 mol of phosphate/mol of protein. Isoelectric focusing of the tryptic phosphopeptides demonstrated the presence of five distinct peptides with pI values of approximately 6.9, 6.5, 5.6-5.9, 4.7, and 3.6. Mapping of the tryptic phosphopeptides by high performance liquid chromatography techniques demonstrated three distinct peaks. Data from gas phase sequencing, amino acid analysis, and phosphoamino acid analysis suggest that proline-directed protein kinase phosphorylates tau at four sites. Each site demonstrates the presence of a proline residue on the carboxyl-terminal side of the phosphorylated residue. Two phosphorylation sites are located adjacent to the three-repeat microtubule-binding domain that has been found to be required for the in vivo co-localization of tau protein to microtubules. Two other putative phosphorylation sites are located within the identified epitope of the monoclonal antibody Tau-1. Phosphorylation of these sites altered the immunoreactivity of tau to Tau-1 antibody. Since the neuronal microtubule-associated protein tau is multiply phosphorylated in Alzheimer's disease, and Tau-1 immunoreactivity is similarly reduced in neurofibrillary tangles and enhanced after dephosphorylation, phosphorylation at one or more of these sites may correlate with abnormally phosphorylated sites in tau protein in Alzheimer's disease.

Amino Acid Sequence↗
PubMed1992

Tumorigenesis mediated by an antigen receptor.

The heavy chain variable region of the immunoglobulin receptors on cells of the B lymphoma NYC are almost identical to that of other independent B-cell tumors of B/W mice. NYC IgM binds a viral antigen produced by the tumor cells; and despite extensive screening, immunoglobulin-negative variants were never found in the NYC cells, suggesting that NYC loses the capacity to grow in culture when it does not synthesize surface immunoglobulin. These findings indicate that the interaction of endogenous antigen with surface IgM continuously stimulates growth and, thus, that the tumorigenesis of B lymphomas in B/W mice is mediated by antigen receptors.

Animals↗
PubMed1992

Human cysteine-rich protein. A member of the LIM/double-finger family displaying coordinate serum induction with c-myc.

We previously reported the structure of the placentally derived human cysteine-rich (h crp) cDNA and demonstrated that it encodes a highly conserved and widely distributed zinc finger-like protein. We now report that the expression of both the mouse and human crp genes is induced as a primary response to serum in quiescent Balb/c 3T3 cells and in human fibroblasts. The profile of this primary response is remarkably parallel to that of c-myc in the Balb/c 3T3 cell line. The structure of the 23.2-kilobase h crp gene demonstrates that it is a member of a gene superfamily encoding proteins sharing a highly characteristic 52-amino acid "LIM/double-finger" motif. The evolutionarily conserved structure of cysteine-rich protein, its structural similarity to a number of developmentally critical proteins, its distinctive tissue distribution, and its primary response to early events in the cell cycle suggest that crp plays an important role in cell function.

3T3 Cells↗
PubMed1992

High frequency of myelomonocytic tumors in aging E mu L-myc transgenic mice.

Transgenic mice that contain constructs of the L-myc gene under the transcriptional control of the immunoglobulin heavy chain enhancer (E mu) develop thymic hyperplasia and are predisposed to T cell lymphomas. Here we describe a second form of malignancy that occurs in aging E mu L-myc transgenic mice. The mean latency period for the development of this malignancy is longer compared with the E mu L-myc T cell lymphomas but the overall incidence is increased threefold. The histopathological morphology is that of a highly malignant mesenchymal neoplasm that closely resembles human fibrous histiocytoma. The tumor cells were classified as myelomonocytic on the basis of several lineage-specific markers and the lack of rearrangements of the immunoglobulin heavy chain and the T cell receptor beta loci. Cultured tumor cells produce macrophage colony-stimulating factor (M-CSF) protein and express the M-CSF receptor, suggesting the involvement of an autocrine loop in this malignancy. Similar to the E mu L-myc T cell lymphomas, these tumors show high-level transgene expression but no detectable levels of endogenous c-myc mRNA, directly implicating the deregulated expression of L-myc in the generation of this malignancy. E mu L-myc myelomonocytic tumors show consistent trisomy of chromosome 16, implicating this as a secondary event in the development of this tumor. In the light of recent findings that L-myc is expressed in human myeloid leukemias and in several human myeloid tumor cell lines, the results described here might implicate L-myc in the development of naturally occurring myeloid neoplasias.

Aging↗
PubMed1992

A novel regulatory myosin light chain gene distinguishes pre-B cell subsets and is IL-7 inducible.

We describe a novel regulatory myosin light chain gene (termed precursor lymphocyte-specific regulatory light chain or PLRLC) that is expressed specifically in precursor B and T lymphocytes. PLRLC is the first example of a regulatory myosin light chain gene which displays specific expression in non-muscle cells. PLRLC is expressed in adult bone marrow derived normal and transformed pre-B cells; in the former, PLRLC expression levels are induced by the pre-B cell specific growth factor interleukin-7 (IL-7). PLRLC is not expressed in either transformed pre-B cells derived from fetal liver or in normal fetal liver pre-B clones grown in the presence of IL-7. Therefore this gene provides the first marker that clearly distinguishes these two pre-B subsets. Finally, several of the different PLRLC transcripts potentially encode regulatory myosin light chains with unique structural features. The unique distribution, regulation and structural features of the PLRLC gene products suggest an important role for PLRLC during lymphocyte development.

Amino Acid Sequence↗
PubMed1992

Interaction of SEWA sarcoma cell proteins with the intracisternal A-type particle long terminal repeat DNA sequence.

Intracisternal A-type particle (IAP) transcripts are endogenous retrovirus-like sequences expressed during specific stages of normal development and in a variety of murine tumors. In this study, we have analyzed two cell lines derived originally from the SEWA murine osteosarcoma and grown either as ascites or as solid tumors, for proteins that might regulate IAP expression. We found that subline AA7-NA, originally derived from the ascites tumor, expressed about five times more IAP RNA than the AS12-AD subline, which was derived from a solid tumor. In view of this finding, we examined the binding of cellular proteins from the two cell lines to the 5' end of an IAP long terminal repeat sequence. Gel retardation assays of DNA-protein complexes and DNase I footprinting assays identified several DNA sequences within the long terminal repeat fragment that were protected by protein extracts from both SEWA sublines. Gel retardation assays using specific synthetic oligonucleotide sequences that correspond to two of these protected regions revealed different patterns of DNA-protein complexes with extracts from the two SEWA sublines. These data suggest that expression of IAP sequences is regulated by complex mechanisms involving several proteins that appear to differ between the two sublines.

Animals↗
PubMed1992

Immunolocalization of synexin (annexin VII) in adrenal chromaffin granules and chromaffin cells: evidence for a dynamic role in the secretory process.

Synexin (annexin VII) is a Ca(2+)- and phospholipid-binding protein which has been proposed to play a role in Ca(2+)-dependent membrane fusion processes. Using a monoclonal antibody against synexin, Mab 10E7, and immunogold, we carried out a semiquantitative localization study of synexin in bovine adrenal medullary chromaffin granules, and in resting and nicotine-stimulated adrenal chromaffin cells. Isolated chromaffin granules contained very little synexin, whereas chromaffin granules aggregated with synexin (24 micrograms/mg) and Ca2+ (1 mM) clearly showed synexin-associated immunogold particles in the vicinity of the granule membrane (1.88 gold particles per granule profile). In isolated, cultured adrenal chromaffin cells, synexin was present in the nucleus (5.5 particles/microns 2) and in the cytosol (5.3 particles/microns 2), but mainly around the granule membrane in the granular cell area (11.7 particles/microns 2). During the active phase of cholinergically stimulated catecholamine secretion, the amount of synexin label was reduced by 33% in the nucleus, by 23% in the cytosol, and by 51% in the granule area. The plasma membrane contained a small amount of synexin, which did not significantly change upon stimulation of the cells. We conclude that synexin is involved in the secretory process in chromaffin cells.

Adrenal Medulla↗
PubMed1992

HLA-DQ beta 57 in Hispanic patients with insulin-dependent diabetes mellitus.

OBJECTIVE: The purpose of our study was to investigate the distribution of HLA-DQ beta-chain amino acid residue 57 (HLA-DQ beta 57) as a genetic marker of susceptibility for insulin-dependent diabetes mellitus in the Hispanic population. STUDY DESIGN: Fifteen patients of Puerto Rican descent with juvenile-onset insulin-dependent diabetes mellitus underwent human leukocyte antigen typing for HLA-DQ beta 57 by polymerase chain reaction amplification of the target genomic DQ sequence followed by hybridization of the polymerase chain reaction product to phosphorus 32-labeled allele-specific oligonucleotide probes. A control group of 44 Hispanic adults without diabetes who were undergoing human leukocyte antigen typing for tissue donation were concurrently typed for comparison. RESULTS: The Hispanic insulin-dependent diabetes mellitus group showed a significant increase in homozygosity for a non-aspartate amino acid (p = 0.023) over a control group of Hispanic subjects without diabetes. A high rate of heterozygosity for aspartate (53.3%) is found in Hispanic subjects with insulin-dependent diabetes mellitus as well. CONCLUSIONS: HLA-DQ beta 57 in the Hispanic population has a distribution distinct from HLA-DQ beta 57 in the Caucasian population. A single aspartate is not protective against insulin-dependent diabetes mellitus in Hispanic subjects.

Amino Acid Sequence↗
PubMed1992

Microtubule-bundling studies revisited: is there a role for MAPs?

The molecular mechanism of microtubule bundling has been enveloped in controversy for the past few years. At the centre of the debate are MAPs: are they necessary for the formation of microtubule bundles? In this article, Gloria Lee and Roland Brandt weigh the evidence and propose that microtubule stability might be the crucial factor in microtubule bundling. Perhaps then MAPs might act as spacer molecules between microtubules.

Journal Article↗