Biomedical subjects

E Lee

Publications and source records attributed to E Lee.

At least 217 records · Page 12Linked to original sources

PubMed1997

A high-risk group for prostatism: a population-based epidemiological study in Korea.

OBJECTIVE: To evaluate the effect of sociodemographic, dietary and physical factors on prostatism in Korean men aged 50 and over. SUBJECTS AND METHODS: A community-based cross-sectional epidemiological study was performed in Yonchon County, Korea. The Korean version of the International Prostate Symptom Score (IPSS) was used to assess the severity of prostatism. Data on occupation, marital status, education, smoking habits, alcohol intake, daily consumption of nutrients, body mass index, abdominal circumference, waist-to-hip ratio, blood pressure, serum glucose, cholesterol, triglyceride and high-density lipoprotein (HDL) levels were analysed. The age-adjusted relative risk of these factors was calculated for moderate to severe prostatism (IPSS > or = 8). A multivariate analysis of all significant factors was performed to examine the joint effect of risk factors. RESULTS: Of 514 subjects, 119 (23.2%) had moderate to severe prostatism, the risk for which was related to age and alcohol consumption; waist-to-hip ratio (which represents the degree of abdominal obesity) and the serum level of HDL showed a biphasic association with prostatism in the multivariate analysis. CONCLUSION: In addition to previously reported risk factors, these data suggest that there might be an association between the development of prostatism and abnormal lipid metabolism.

Age Factors↗

PubMed1997

Clinical comparison of selective and non-selective alpha 1A-adrenoreceptor antagonists in benign prostatic hyperplasia: studies on tamsulosin in a fixed dose and terazosin in increasing doses.

OBJECTIVE: To compare the efficacy and safety of a fixed dose (0.2 mg) of tamsulosin, a selective alpha 1A-adrenoreceptor antagonist, with an increasing dose (1-5 mg) of terazosin, a non-selective antagonist, in the treatment of urinary outflow obstruction associated with benign prostatic hyperplasia (BPH) in Korean patients. PATIENTS AND METHODS: The study comprised a single-blind and randomized design with tamsulosin or terazosin taken once daily for 8 weeks. A total of 98 patients was enrolled, with 72 patients included in the analyses after 4 and 8 weeks. The primary variables assessed were changes in the maximum urinary flow rate Qmax and the total International Prostate Symptom Score (IPSS), with the post-void residual urine volume, 'obstructive' and 'irritative' questions in the IPSS, and the investigators' global assessment of efficacy also determined. The number of patients with a clinically significant response to treatment with tamsulosin or terazosin was determined and defined as those with > 20% improvement from the baseline Qmax or > 20% decrease in total IPSS. Adverse reactions possibly or probably related to study medication were recorded throughout the treatment period. RESULTS: Both tamsulosin and terazosin produced similar significant improvements in subjective and objective symptoms of urinary outflow obstruction (P > 0.05). Systolic and diastolic (standing) blood pressures decreased significantly in patients treated with terazosin (P < 0.05). The adverse reactions, most frequently dry mouth and dizziness which were usually mild and transient, were significantly higher in patients on terazosin (18 patients, versus one on tamsulosin, P < 0.001). The changes led to discontinuation of therapy in two patients on terazosin. CONCLUSION: Tamsulosin was as effective as terazosin in treating urinary outflow obstruction associated with BPH, but had a markedly better safety profile.

Adrenergic alpha-Antagonists↗

PubMed1997

Differential expression of ferritin heavy chain in THP-1 cells infected with Mycobacterium bovis BCG.

To identify the host genes induced or suppressed by infection of mycobacteria, the reverse transcriptase polymerase chain reaction (RT-PCR) and the differential display reverse transcriptase polymerase chain reaction (DD RT-PCR) methods were used. In this study, cDNAs complement to mRNA extracted from human peripheral monocyte derived naive THP-1 cells, THP-1 cells infected with live Mycobacterium bovis BCG, THP-1 cells treated with heat-killed BCG, and THP-1 cells incubated with IgG-coated glass-beads were compared on the sequencing gel. One (TG2-1) of the clones selected by DD RT-PCR is 446 bp long and is identical to human ferritin heavy (H) chain gene. Northern blot analysis confirmed that ferritin H chain gene has been markedly over-expressed in monocytic THP-1 cells incubated with live and dead M. bovis BCG. Differential display techniques of host genes whose expression levels were varied by infection of mycobacteria could provide information about the response of macrophages to mycobacterial infection.

Amino Acid Sequence↗

PubMed1997

Immune response to a Murray Valley encephalitis virus epitope expressed in the flagellin of an attenuated strain of Salmonella.

Recent developments in vaccine construction include the use of attenuated, avirulent strains of Salmonella as carriers of foreign antigens. These recombinant strains can elicit a heterologous immune response when injected into animals, demonstrating potential for their use in the construction of many vaccines. In the present study, a B-cell epitope of Murray Valley encephalitis virus (MVE) was identified and expressed in a Salmonella strain to evaluate its potential to induce a specific immune response to MVE. A synthetic oligonucleotide encoding the B-cell epitope (residues E201-224) of the envelope protein of MVE was inserted into the cloned flagellin gene of the Salmonella strain. The construct was sequenced to ensure correct orientation of the epitope. Expression of the epitope was demonstrated by Western blot analysis and immunogold electron microscopy with monoclonal antibody specific to the epitope. Electron microscopy analysis revealed multiple copies of the epitope along the flagella. The recombinant Salmonella carrying the hybrid flagellin gene elicited an immune response to the MVE epitope in a mouse model. The MVE-specific antibodies partially neutralised the virus in vitro. The significance of this system for engineering vaccines for other medically important flaviviruses is discussed.

Amino Acid Sequence↗

PubMed1997

Prognostic markers of intravesical bacillus Calmette-Guérin therapy for multiple, high-grade, stage T1 bladder cancers.

BACKGROUND: Prediction of a response to intravesical bacillus Calmette-Guérin (BCG) therapy for bladder cancer is clinically important. We determined whether several molecular markers have prognostic value in intravesical BCG therapy for multiple, high-grade, stage T1 bladder cancers. METHODS: The expressions of p53 (clone D07), bcl-2 (100-D5), cathepsin-D (C5), c-myc(9E11), c-erbB-2 (CB11) and Ki-67 (MM1) were determined by immunohistochemistry in paraffin-embedded tissues from 32 multiple, T1, grade II-III bladder cancer patients (15 BCG responders, 17 nonresponders) who had undergone a single course of BCG therapy (Pasteur strain, 5 x 10(8) CFU weekly for 6 weeks) after complete removal of the tumors. The association between the expression of these markers and the response to BCG was assessed by univariate and multivariate analyses. RESULTS: There was no difference in patient and tumor characteristics between the 2 groups. Using multivariate analysis, the only useful marker was p53, with the overexpression of the p53 protein inversely related to the response to BCG therapy (P = 0.0182). CONCLUSION: Our results suggest that the status of p53 expression offers significant clinical information and may be a useful tool in the selection of suitable candidates for BCG therapy in multiple, high-grade stage T1 bladder cancer patients.

Adjuvants, Immunologic↗

PubMed1997

Mitochondrial gene transfer ribonucleic acid (tRNA)Leu(UUR) 3243 and tRNA(Lys) 8344 mutations and diabetes mellitus in Korea.

The high prevalence of diabetic patients with a mutation in the mitochondrial gene (the 3243 and 8344 bp mutations) has been identified in Japan. To determine the prevalence of diabetic patients with those mutations in Korea, we randomly screened selected 503 clinical diabetic patients regardless of their diabetes types. We found only 1 patient with the mitochondrial DNA mutation at position 3243 (percent mutation, 32%), and the mitochondrial DNA mutation at position 8344 was not found in any of the patients. The affected subject was a 22-yr-old man with a history of myoclonic epilepsy and mild sensorineural hearing loss, a 1-yr duration of diabetes mellitus, and a low level C peptide response to oral glucose. Because of the low frequency of these mutations in the Korean diabetic population, we concluded that these particular mutations of mitochondrial DNA may not be a common contributor to diabetes mellitus in Korea.

Adult↗

PubMed1997

Lhx2, a LIM homeobox gene, is required for eye, forebrain, and definitive erythrocyte development.

We investigated the function of Lhx2, a LIM homeobox gene expressed in developing B-cells, forebrain and neural retina, by analyzing embryos deficient in functional Lhx2 protein. Lhx2 mutant embryos are anophthalmic, have malformations of the cerebral cortex, and die in utero due to severe anemia. In Lhx2-/- embryos specification of the optic vesicle occurs; however, development of the eye arrests prior to formation of an optic cup. Deficient cellular proliferation in the forebrain results in hypoplasia of the neocortex and aplasia of the hippocampal anlagen. In addition to the central nervous system malformations, a cell non-autonomous defect of definitive erythropoiesis causes severe anemia in Lhx2-/- embryos. Thus Lhx2 is necessary for normal development of the eye, cerebral cortex, and efficient definitive erythropoiesis.

Anemia↗

PubMed1997

Hsp70 and Hsc70 are preferentially expressed in differentiated epithelial cells in normal human endometrium and ectocervix.

Two highly related 70K heat shock proteins, encoded by the hsc70 and hsp70 genes, are located in the nucleocytoplasmic compartment of mammalian cells. In contrast to recent cell lines, which express Hsp70 only when stressed, many human cell lines constitutively express Hsp70. The degree to which this reflects constitutive expression of Hsp70 in normal human tissues has not been extensively examined. In this study, we show by immunoblotting that human Hsp70 is constitutively expressed in the ovary, cervix, and endometrium and, by immunohistochemical analysis using Hsp70- and Hsc70-specific antibodies, that Hsp70 and Hsc70 are expressed in distinctive and predominantly overlapping patterns in the cervix and endometrium. In these two tissues, the highest levels of both proteins are seen in differentiated, non-proliferating epithelial cells, which is surprising in light of previous studies suggesting growth stimulation of hsp70 gene expression. These observations suggest the possibility that in certain human tissues, basal expression of the hsp70 and hsc70 genes is co-regulated.

Blotting, Western↗

PubMed1997

Tumor-associated antigens in normal mucosa of patients with superficial transitional cell carcinoma of the bladder.

PURPOSE: We identified premalignant lesions in tumor-surrounding histologically normal bladder mucosa from patients with superficial and muscle-invasive bladder cancer to look for "premalignant" lesions as the source of tumor recurrence. MATERIALS AND METHODS: Tumor-associated antigen expression in histologically normal bladder mucosa in 23 patients with superficial bladder cancer was studied. Histologically normal bladder specimens from 21 patients with muscle-invasive bladder cancer and from 30 prostatic cancer patients served as controls. Tumor-related antigens 486p 3/12, LBS8, 19A211 and M344 were mapped quantitatively with monoclonal antibodies and immunohistological techniques. RESULTS: Expression of all four bladder tumor-associated antigens was significantly enhanced and more than two antigens were expressed simultaneously in histologically normal mucosa from both bladder-cancer groups, compared with histologically normal bladder mucosa of prostatic carcinoma patients (p < 0.05). CONCLUSIONS: The results suggest the existence of early malignantly transformed cells in the benign-looking and morphologically normal bladder mucosa of superficial bladder carcinoma patients, which possibly is the source of recurrent bladder cancer. This approach models the mapping of histopathologic premalignant lesions of the bladder to predict risk.

Aged↗

PubMed1997

A family medicine teaching program for obstetrics-gynecology residents.

BACKGROUND AND OBJECTIVES: The Harbor-UCLA Family Practice Residency Program has offered a year-long primary care continuity clinic experience to first-year obstetrics-gynecology (OB-GYN) residents since July 1994. This paper describes the teaching programs and compares the experience of the OB-GYN residents to that of family practice (FP) residents in the same clinic site. METHODS: OB-GYN residents worked in the family medicine teaching clinic for a half day each week for the entire year. The teaching program was evaluated with a questionnaire and interviews of OB-GYN residents to obtain their opinions on the value of this teaching modality. A review of clinic schedules and medical records compared the practice profiles of six OB-GYN residents with six matched FP residents. RESULTS: Five out of six OB-GYN residents felt that the educational objective of improving primary care skills was achieved. Half of them were pleased about their relationships with the family medicine faculty; the remainder reported being treated as second-class citizens. Patient volume and the diagnosis encountered were similar between the OB-GYN residents and the FP residents. CONCLUSIONS: Evaluation of the primary care continuity clinic experience for OB-GYN residents through questionnaires, interviews, and medical records analysis revealed the acceptability, feasibility, and appropriateness of this teaching program for OB-GYN residents. However, not all OB-GYN residents were happy about their relationships with the family medicine faculty. The long-term effectiveness of the experience needs further study.

Adult↗

PubMed1996

Structure of the GDP-Pi complex of Gly203-->Ala gialpha1: a mimic of the ternary product complex of galpha-catalyzed GTP hydrolysis.

BACKGROUND: G proteins play a vital role in transmembrane signalling events. In their inactive form G proteins exist as heterotrimers consisting of an alpha subunit, complexed with GDP and a dimer of betagamma subunits. Upon stimulation by receptors, G protein alpha subunits exchange GDP for GTP and dissociate from betagamma . Thus activated, alphasubunits stimulate or inhibit downstream effectors. The duration of the activated state corresponds to the single turnover rate of GTP hydrolysis, which is typically in the range of seconds. In Gialpha1, the Gly203-->Ala mutation reduces the affinity of the substrate for Mg2+, inhibits a key conformational step that occurs upon GTP binding and consequently inhibits the release of betagamma subunits from the GTP complex. The structure of the Gly203-->Ala mutant of Gialpha1 (G203AGialpha1) bound to the slowly hydrolyzing analog of GTP (GTPgammaS) has been determined in order to elucidate the structural changes that take place during hydrolysis. RESULTS: We have determined the three dimensional structure of a Gly203-->Ala mutant of Gialpha1 at 2.6 A resolution. Although crystals were grown in the presence of GTPgammaS and Mg2+, the catalytic site contains a molecule of GDP and a phosphate ion, but no Mg2+. The phosphate ion is bound to a site near that occupied by the gamma-phosphate of GTPgammaS in the activated wild-type alpha subunit. A region of the protein, termed the Switch II helix, twists and bends to adopt a conformation that is radically different from that observed in other Gialpha1 subunit complexes. CONCLUSIONS: Under the conditions of crystallization, the Gly203-->Ala mutation appears to stabilize a conformation that may be similar, although perhaps not identical, to the transient ternary product complex of Gialpha1-catalyzed GTP hydrolysis. The rearrangement of the Switch II helix avoids a potential steric conflict caused by the mutation. However, it appears that dissociation of the gamma-phosphate from the pentacoordinate intermediate also requires a conformational change in Switch II. Thus, a conformational rearrangement of the Switch II helix may be required in Galpha-catalyzed GTP hydrolysis.

Alanine↗

PubMed1996

Delayed maturation of CD4- CD8- Fc gamma RII/III+ T and natural killer cell precursors in Fc epsilon RI gamma transgenic mice.

Fc epsilon RI gamma (gamma) is a member of a group of related proteins (the zeta-family dimers) that function as signal-transducing components of both Fc receptors and the T cell antigen receptor (TCR). Analysis of gamma expression during fetal thymus ontogeny revealed that it is expressed in early thymocytes, before the initiation of clonotypic TCR-alpha and TCR-beta gene rearrangement but is down-regulated in most adult thymocytes. To explore a possible role for gamma in thymocyte development, we generated transgenic mice in which this protein was overexpressed at all stages of ontogeny. Overexpression of gamma inhibited the maturation of T cells as well as natural killer (NK) cells. The developmental effects were transgene dose related and correlated with markedly delayed maturation of fetal CD4-CD8- FcRII/III+ thymocytes, cells thought to include the progenitors of both T and NK cells. These results suggest that the zeta and gamma chains serve distinctive functions in thymocyte development and indicate that Fc receptor(s) may play an important role in regulating the differentiation of early progenitor cells within the thymus.

Animals↗

PubMed1996

Involvement of histone hyperacetylation in triggering DNA fragmentation of rat thymocytes undergoing apoptosis.

The treatment of rat thymocytes with trichostatin A and sodium butyrate, which are inhibitors of histone deacetylase, resulted in an increase in DNA fragmentation in a concentration-dependent manner. A significant increase in DNA fragmentation induced by these compounds was observed after a lag time of 2 h. Analysis of the fragmented DNA revealed the production of approximately 50 kb DNA fragments and DNA ladders, the biochemical hallmarks of apoptotic cell death. Judging from a laser scanning microscopic analysis, the inhibitors of histone deacetylase induced nuclear condensation, the morphological feature of apoptosis. Biochemical and morphological analyses demonstrated that trichostatin A and sodium butyrate induced thymocyte apoptosis. Furthermore, hyperacetylation of nuclear histones was observed in thymocytes treated with the inhibitors of histone deacetylase. These effects of sodium butyrate and trichostatin A were seen 0.5 and 1 h, respectively, after incubation of the cells. These results thus indicate that hyperacetylation of nucleosomal histones precedes DNA fragmentation in thymocytes undergoing apoptosis induced by trichostatin A and sodium butyrate.

Acetylation↗

PubMed1996

Vitamin E potentiates arachidonate release and phospholipase A2 activity in rat heart myoblastic cells.

Cytosolic phospholipase A2 (cPLA2) selectively catalyses the release of arachidonic acid from the sn-2 position of glycero-phospholipids to produce prostaglandins and leukotrienes. In this study, vitamin E enrichment of rat heart myoblastic H9c2 cells caused an increase in the release of arachidonate during ionophore (A23187) stimulation. PLA2 activity in the cytosolic fraction was also enhanced but enzyme activity in the particulate fraction was not affected by this treatment. Immunoblotting analysis with a polyclonal anti-cPLA2 antibody showed an increased level of the enzyme in vitamin E-treated cells. Direct incorporation of vitamin E into lipid vesicles in the assay mixture resulted in modulation of enzyme activity in a biphasic manner. Pretreatment of cells with phorbol 12-myristate 13-acetate, a known activator of protein kinase C, synergistically potentiated the ionophore-induced arachidonate release in both the control and vitamin E-treated cells. However, vitamin E treatment by itself did not affect the protein kinase C activity, indicating that the vitamin E-induced activation of cPLA2 was independent of the protein kinase C cascade. Collectively, these results suggest that vitamin E potentiates arachidonate release through the direct and/or indirect modulation of cPLA2 activity.

Animals↗

PubMed1996

Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function.

Targeted gene disruption in the mouse shows that the Sonic hedgehog (Shh) gene plays a critical role in patterning of vertebrate embryonic tissues, including the brain and spinal cord, the axial skeleton and the limbs. Early defects are observed in the establishment or maintenance of midline structures, such as the notochord and the floorplate, and later defects include absence of distal limb structures, cyclopia, absence of ventral cell types within the neural tube, and absence of the spinal column and most of the ribs. Defects in all tissues extend beyond the normal sites of Shh transcription, confirming the proposed role of Shh proteins as an extracellular signal required for the tissue-organizing properties of several vertebrate patterning centres.

Animals↗

PubMed1996

Efficient in vivo manipulation of mouse genomic sequences at the zygote stage.

We describe a transgenic mouse line carrying the cre transgene under the control of the adenovirus EIIa promoter that targets expression of the Cre recombinase to the early mouse embryo. To assess the ability of this recombinase to excise loxP-flanked DNA sequences at early stages of development, we bred EIIa-cre transgenic mice to two different mouse lines carrying loxP-flanked target sequences: (i) a strain with a single gene-targeted neomycin resistance gene flanked by 1oxP sites and (ii) a transgenic line carrying multiple transgene copies with internal loxP sites. Mating either of these loxP-carrying mouse lines to EIIa-cre mice resulted in first generation progeny in which the loxP-flanked sequences had been efficiently deleted from all tissues tested, including the germ cells. Interbreeding of these first generation progeny resulted in efficient germ-line transmission of the deletion to subsequent generations. These results demonstrate a method by which loxP-flanked DNA sequences can be efficiently deleted in the early mouse embryo. Potential applications of this approach are discussed, including reduction of multicopy transgene loci to produce single-copy transgenic lines and introduction of a variety of subtle mutations into the line.

Animals↗

PubMed1996

Evaluation of monoclonal antibody-mediated anti-acute myeloid leukemia immunotherapy in a SCID/hu model.

The therapeutic potential of the IgM complement-fixing murine monoclonal antibody (mAb) PM-81 (anti-CD15) against acute myeloid leukemia (AML) was assessed in a SCID/hu leukemia model. Intraperitoneal (i.p.) injection of NB4 leukemia cells resulted in aggressive growth of leukemia cells in the peritoneal cavity of irradiated SCID/CB-17 mice. Flow cytometric analysis of human CD15, 33 and 45 expression, as well as cytologic examination, revealed that leukemia cells disseminated into the peripheral blood and multiple tissues of the mice. The approximately linear relationship between the injected leukemia cells and the subsequent leukemia cell proliferation provided a reliable model for monitoring the therapeutic effects of immunotherapy. Intraperitoneal injection of the mAb PM-81 markedly suppressed leukemia cell growth in this SCID/leukemia model. Most of the untreated mice died within 35-50 days of leukemia cell inoculation. Four weeks after inoculation of NB4 cells, five of nine mAb PM-81 treated mice had no solid tumor growth and six of nine had no detectable peritoneal exudate leukemia cells as determined by flow cytometry. In contrast, 100% of the mice in the untreated or control mAb groups were found to have both solid and peritoneal leukemia growth. In further experiments designed to evaluate the effects of therapy on survival, 50% (4/8) of PM-81 treated mice survived to 150 days, and had no detectable solid or suspension leukemia cells detectable at necropsy. In contrast, the median survival of untreated or negative control antibody-treated mice was 40 days (comparison to PM-81 treated; p = 0.006 and p = 0.03, respectively). The mechanism of leukemia cell suppression is not likely due to complement fixation since we could not demonstrate in vitro any cytotoxicity mediated by SCID mouse plasma. Further study is required to understand the mechanism of the antileukemia effect of PM-81 in this model.

Animals↗

PubMed1996

Fatality due to acute fluoride poisoning following dermal contact with hydrofluoric acid in a palynology laboratory.

A fatal accident involving concentrated hydrofluoric acid in a palynological laboratory is described. Similar deaths due to dermal exposure to concentrated hydrofluoric acid have been reported in the literature. It is evident that rigorous control measures including proper personal protective equipment and first aid are of utmost importance in the prevention of death and injury when handling hydrofluoric acid. Possible factors that may have contributed to the accident are reviewed.

Accidents, Occupational↗