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Biomedical subjects

M H Lee

Publications and source records attributed to M H Lee.

At least 55 records · Page 3Linked to original sources
PubMed2002

Conditional loss of TGF-beta signalling leads to increased susceptibility to gastrointestinal carcinogenesis in mice.

BACKGROUND: Downregulation of TGF-beta receptors is implicated in colon cancer development. Inactivation of either of the two transmembrane serine/threonine kinases, TGF-beta1 types I/II receptors, is now implicated in carcinogenesis, especially gastrointestinal carcinogenesis. METHODS: We generated transgenic mice, called pS2-dnRII or ITF-dnRII, of which the dominant negative mutant of the TGF-beta type II receptor was expressed under the control of tissue-specific promoters, the pS2 promoter for stomach and ITF for intestine. They were either infected with H.pylori (ATCC 43504 strain, CagA+ and VacA+) or administered with azoxymethane to determine the significance of loss of TGF-beta signalling in gastrointestinal carcinogenesis. RESULTS: Gastric adenocarcinoma developed in pS2-dnRII mice, whereas only chronic active gastritis was noted in wild-type littermates after 36 weeks of H.pylori infection. Mice lacking in TGF-beta signalling specifically in the stomach showed a significantly higher proliferation cell nuclear antigen-labelling index when infected with H.pylori than wild-type littermates (P < 0.01). Development of colonic aberrant crypt foci was provoked in mice by intraperitoneal injections of azoxymethane, and ITF-dnRII mice showed significantly higher incidences of ACF and colon cancers than wild-type littermates. CONCLUSIONS: Maintaining normal TGF-beta signalling in the gastrointestinal tract seems to be important either for preventing abnormal mucosal proliferation, or for suppressing or retarding carcinogenesis.

Animals↗
PubMed2002

Hydroquinone, a reactive metabolite of benzene, enhances interleukin-4 production in CD4+ T cells and increases immunoglobulin E levels in antigen-primed mice.

Exposure to cigarette smoke is known to increase the risk of the development of allergic disease. The mechanism is not well understood. In this study, we determined the effect of hydroquinone (HQ), a major metabolite of benzene present in large quantities in cigarette tar, on interleukin-4 (IL-4) production by CD4+ T cells. HQ significantly enhanced IL-4 production by keyhole limpet haemocyanin (KLH)-primed CD4+ T cells in a dose-dependent manner. The enhancing effect of HQ on IL-4 production was maximal at a concentration of 50 micro m. It increased the level of IL-4 production approximately 10-fold. HQ enhanced IL-4 mRNA expression and also IL-4 gene promoter activity, suggesting that the enhancing effect of HQ on IL-4 production may occur at the transcriptional level. Furthermore, the injection of KLH-primed mice with HQ resulted in a significant increase in the levels of IL-4 and immunoglobulin E. These findings provide evidence that HQ, a major component of cigarette tar, may enhance allergic immune responses by inducing the production of IL-4 in CD4+ T cells.

Animals↗
PubMed2002

Evaluation of endoscopic hemostasis in upper gastrointestinal bleeding related to Mallory-Weiss syndrome.

BACKGROUND AND STUDY AIMS: The endoscopic hemostatic method has been introduced as a safe and effective mechanical approach to hemostasis for upper gastrointestinal bleeding related to Mallory-Weiss syndrome (MWS). However, the indications for when to use endoscopic treatment are debatable because many patients need only medical observation. The study was designed to evaluate the necessity and efficacy of endoscopic hemostasis in upper gastrointestinal bleeding related to MWS. PATIENTS AND METHODS: From July 1994 to May 2000, we conducted a clinical trial in 76 patients who were found by endoscopy to have active bleeding (I, spurting; II, oozing), protruding visible vessels (III), and/or adherent clots (IV). Two study periods can be differentiated: in the first 3 years endoscopic treatment (n = 30) was prospectively analyzed and in the final 3 years medical treatment (n = 46) was analyzed in both cases to compare the outcome in MWS bleeding II-IV. In the first study period, in addition, endoscopic treatment was randomised to an injection method, using a mixture of hypertonic saline and epinephrine (HSE) (n = 14) and a hemoclipping or band ligation method (n = 16). RESULTS: Rebleeding was observed in four of 14 patients who had received endoscopic hemostasis with HSE injection and one of 46 patients who had been managed with medical treatment. No rebleeding was found following hemoclipping or band ligation. While all rebleeding was in bleeding stigmata of the I (1) and II (4) grades, there was no rebleeding in protruding visible vessels (III) or in adherent clots (IV), regardless of treatment methods. CONCLUSIONS: Our results suggested that endoscopic hemostasis is not necessary in patients without active bleeding stigmata, and the mechanical hemostatic method is more effective than HSE injection in patients with active bleeding stigmata.

Adult↗
PubMed2002

Colourfast pigments in silicone hand and maxillofacial prostheses.

This study addresses the clinical problem of long-term discolouration of silicone hand and maxillofacial prostheses. Seven (7) pigment hues, considered essential for achieving a suitable tissue colour-matched prosthesis, were compared for their colourfast property, across three selected proprietary formulations. In all, a series of 21 pigments, were tested for colourfastness. The pigments, presenting as suspensions (PS), pastes (PP) and dry pigments (PD), were exposed, over nine months, to ultraviolet light, elevated temperatures and varying concentrations of salinity. Colour change of the pigments was measured and expressed as Commission International de l'Eclairage (CIE) (L*, a*, b*) units. Pigment discoloration was significantly attributed to ultraviolet light. Pigmented and clear silicone samples showed a "yellowing" (+delta b*) effect. Lighter pigments became darker (-delta L*) in shade. Pigment samples at the elevated temperature of 50 degrees C showed significant but small colour change (delta E, 0.77 to 3.63). Only the master blue pigment (PS-4) recorded a higher delta E, 6.26 at 50 degrees C. At a moderate temperature of 35 degrees C, both pigmented and clear silicone test samples remained relatively colourfast. Comparison was made to control samples, stored in darkness, at 26 degrees C. The pigments were generally colourfast (deltaE<6 units) to saline solutions of 0.15 M and 5.0 M concentrations. Only the monastral red (PD-3) pigment recorded a delta E of 9.33, in 0.15 M normal saline, simulating the vulnerability of this pigment to the salinity of human sweat. Pigment hues were systematically ranked according to colourfastness. Pigment suspensions were more colourfast than pigment pastes.

Artificial Limbs↗
PubMed2001

Tandem translocation of chromosomes 22 and 15 with two preserved satellite stalk regions and deletion 22q13.3-qter.

We describe here a case of a tandem 22/15 translocation with deletion of the 22q13.3-qter region and retention of the NOR of chromosome 15. A 2(1/2)-year-old Korean girl was referred for chromosome analysis after a clinical evaluation for developmental delay. Physical examination revealed hypotonia, developmental delay, delay of gross motor milestones and speech delay. No dysmorphic features of face, hands or feet were evident in the patient. G-banded peripheral blood lymphocyte chromosomes showed a tandem translocation between chromosomes 22 and 15, with the satellite stalks of chromosome 15 apparently being retained. All-telomere FISH analysis using a TTAGGG repeat probe showed absent signals at the junction of the translocation. Sequential G-banding and FISH analysis using a beta satellite probe showed positive signals close to the junction of the translocation, an indication that the short arms of the chromosome 15 involved in the translocation are retained. FISH with a probe for arylsulfatase, mapped to 22q13.3 region, was negative on the translocation chromosome. Therefore, the 22q13.3 region is deleted.

Abnormalities, Multiple↗
PubMed2001

Ergodic theory, infinite products, and long time behavior in Hermitian models.

Ergodic theory has been approached from the side of the time averages with correlation functions from many-body models. The condition for ergodic behavior is formulated in terms of infinite products of certain numbers associated with time evolution. Physical properties that make a model ergodic are identified.

Journal Article↗
PubMed2001

Tumor apoptosis in cervical cancer: its role as a prognostic factor in 42 radiotherapy patients.

To investigate tumor apoptosis as a prognostic factor for outcome following radiation therapy, comparisons were made of apoptotic index (AI) as a predictor of short- vs. long-term response and pretreatment vs. radiation-induced apoptosis. Forty-two patients with proven squamous cell carcinoma of the uterine cervix were treated by radiation alone. Apoptosis was measured by light microscopic observation of hematoxylin and eosin-stained sections from biopsies taken before treatment and 4 and 24 hr after 2 Gy. Patients were evaluated at the end of the external radiation for determination of short-term response and for long-term outcome as well (median follow-up of 27 months). Patients with high spontaneous AI showed poor short-term response, local control, and survival. The significance of AI as a predictor of short-term response was lost after allowing for differences in tumor size. The positive predictive value of AI for local control and survival was independent of tumor size and stage. High AI was associated with poor local control and long-term prognosis in advanced squamous cell carcinoma of the cervix. The in vivo radiation-induced AI after 4 or 24 hr did not predict radiation therapy outcome.

Adult↗
PubMed2001

Identification of in vivo mRNA targets of GLD-1, a maxi-KH motif containing protein required for C. elegans germ cell development.

Caenorhabditis elegans GLD-1, a KH motif containing RNA-binding protein of the GSG/STAR subfamily, controls diverse aspects of germ line development, suggesting that it may have multiple mRNA targets. We used an immunoprecipitation/subtractive hybridization/cloning strategy to identify 15 mRNAs that are putative targets of GLD-1 binding and regulation. For one target, the rme-2 yolk receptor mRNA, GLD-1 acts as a translational repressor to spatially restrict RME-2 accumulation, and thus yolk uptake, to late-stage oocytes. We found that GLD-1 binds sequences in both 5' coding and the 3' untranslated region of rme-2 mRNA. Initial characterization of the other 14 targets shows that (1) they are coexpressed with GLD-1; (2) they can have mutant/RNA-mediated interference depletion phenotypes indicating functions in germ line development or as maternal products necessary for early embryogenesis; and (3) GLD-1 may coregulate mRNAs corresponding to functionally redundant subsets of genes within two gene families. Thus, a diverse set of genes have come under GLD-1-mediated regulation to achieve normal germ line development. Previous work identified tra-2 as a GLD-1 target for germ line sex determination. Comparisons of GLD-1-mediated translational control of rme-2 and tra-2 suggests that the mechanisms may differ for distinct target mRNA species.

Animals↗
PubMed2001

Observation of Cabibbo suppressed B --> D(*)K- decays at Belle.

We report observations of the Cabibbo suppressed decays B-->D((*))K- using a 10.4 fb(-1) data sample accumulated at the Upsilon(4S) resonance with the Belle detector at the KEKB e(+)e(-) storage ring. We find that the ratios of Cabibbo suppressed to Cabibbo favored branching fractions are B(B--->D0K-)/B(B--->D0pi(-)) = 0.079+/-0.009+/-0.006, B(B(0)-->D+K-)/B(B(0)-->D+pi(-)) = 0.068+/-0.015+/-0.007, B(B--->D(*0)K-)/B(B--->D(*0)pi(-)) = 0.078+/-0.019+/-0.009, and B(B(0)-->D(*+)K-)/B(B(0)-->D(*+)pi(-)) = 0.074+/-0.015+/-0.006. These are the first observations of the B-->D+K-, D(*0)K-, and D(*+)K- decay processes.

Journal Article↗
PubMed2001

Expression of Helicobacter pylori urease subunit B gene in Lactococcus lactis MG1363 and its use as a vaccine delivery system against H. pylori infection in mice.

The use of Lactococcus lactis as an antigen delivery vehicle for mucosal immunisation has been proposed. To determine whether L. lactis could effectively deliver Helicobacter pylori antigens to the immune system, a recombinant L. lactis expressing H. pylori urease subunit B (UreB) was constructed. Constitutive expression of UreB by a pTREX1 vector resulted in the intracellular accumulation of UreB to approximately 6.25% of soluble cellular protein. Five different oral regimens were used to vaccinate C57BL/6 mice and the immune response measured. One regimen, which consisted of four weekly doses of 10(10) bacteria, followed after an interval of approximately 4 weeks by three successive daily doses, was able to elicit a systemic antibody response to UreB in the mice, although subsequently, a similar regimen produced a significant antibody response in only one out of six mice. The other three regimes, in which mice were vaccinated with two or three sets of three consecutive daily doses of recombinant bacteria over 30 days, failed to elicit significant anti-UreB serum antibody responses. In three regimens, the immunised mice were then challenged by H. pylori strain SS1 and no protective effect was observed. These findings suggest that any adjuvant effects of L. lactis are unlikely to be sufficient to produce an effective immune response and to protect against H. pylori challenge, when used to deliver a weak immunogen, such as UreB.

Animals↗
PubMed2001

Optical mapping of ventricular defibrillation in isolated swine right ventricles: demonstration of a postshock isoelectric window after near-threshold defibrillation shocks.

BACKGROUND: Investigators who studied ventricular defibrillation by use of optical mapping techniques failed to observe an initial defibrillation event (isoelectric window or quiescent period) shown by electrode mapping studies. This discrepancy has important implications for the mechanisms of defibrillation. The purpose of the present study was to demonstrate an optical equivalent of an isoelectric window after a near-threshold defibrillation shock. Methods and Results-- We studied 10 isolated, perfused swine right ventricles. Upper limit of vulnerability was determined by shocks on T waves. A 50% probability of successful defibrillation (DFT50) was determined with an up-down algorithm. Immediately after unsuccessful defibrillation shock, new wavefronts were generated. When the shock strength was low, immediate reinitiation of reentry and ventricular fibrillation might occur without a postshock isoelectric window. However, if the shock strength was within 50 V of DFT50 (near-threshold), a synchronized activation occurred, followed by organized repolarization that ended 64+/-18 ms after shock. After a period of quiescence (18+/-24 ms), activation recurred 83+/-33 ms after shock and reinitiated ventricular fibrillation. Similar patterns of activation, including a quiescent period, were observed after shock was applied on the T wave of the paced beat that induced ventricular fibrillation. Upper limit of vulnerability correlated well with DFT50. CONCLUSIONS: In isolated swine right ventricles, an optical equivalent of an isoelectric window exists after near-threshold defibrillation shocks. These findings support the idea that a near-threshold defibrillation shock terminates all activation wavefronts but fails to halt ventricular fibrillation because the same shock reinitiates ventricular fibrillation after an isoelectric window.

Action Potentials↗
PubMed2001

Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively.

Sitosterolemia is a rare autosomal recessive disorder characterized by (a) intestinal hyperabsorption of all sterols, including cholesterol and plant and shellfish sterols, and (b) impaired ability to excrete sterols into bile. Patients with this disease have expanded body pools of cholesterol and very elevated plasma plant-sterol species and frequently develop tendon and tuberous xanthomas, accelerated atherosclerosis, and premature coronary artery disease. In previous studies, we have mapped the STSL locus to human chromosome 2p21. Recently, we reported that a novel member of the ABC-transporter family, named "sterolin-1" and encoded by ABCG5, is mutated in 9 unrelated families with sitosterolemia; in the remaining 25 families, no mutations in sterolin-1 could be identified. We identified another ABC transporter, located <400 bp upstream of sterolin-1, in the opposite orientation. Mutational analyses revealed that this highly homologous protein, termed "sterolin-2" and encoded by ABCG8, is mutated in the remaining pedigrees. Thus, two highly homologous genes, located in a head-to-head configuration on chromosome 2p21, are involved as causes of sitosterolemia. These studies indicate that both sterolin-1 and sterolin-2 are indispensable for the regulation of sterol absorption and excretion. Identification of sterolin-1 and sterolin-2 as critical players in the regulation of dietary-sterol absorption and excretion identifies a new pathway of sterol transport.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2001

p27 Kip1 inhibits HER2/neu-mediated cell growth and tumorigenesis.

HER2/neu, a receptor tyrosine kinase oncogene, promotes mitogenic growth and transformation of cancer cells. We previously identified that its oncogenic signals down-regulate the cyclin-dependent kinase inhibitor p27 Kip1, which is defined as a haplo-insufficient tumor suppressor. Here, we applied the human p27 gene as a novel anticancer agent for HER2/neu-overexpressing cells under the control of a tetracycline (tet)-regulated gene expression system. Overexpression of p27 inhibits HER2/neu-activated CDK2 activity, cell proliferation, and transformation. Most significantly for clinical application, p27 expression in HER2/neu-overexpressing cells can be regulated in vivo and reduce the tumor volume in a tumor model. The findings demonstrate the applicability of employing p27 in HER2/neu-associated cancer gene therapy.

3T3 Cells↗
PubMed2001

Induction of human promyelocytic leukemia HL-60 cell differentiation into monocytes by silibinin: involvement of protein kinase C.

The effect of silibinin, an active component of Silybum marianum, on cellular differentiation was investigated in the human promyelocytic leukemia HL-60 cell culture system. Treatment of HL-60 cells with silibinin inhibited cellular proliferation and induced cellular differentiation in a dose-dependent manner. Cytofluorometric analysis and morphologic studies indicated that silibinin induced differentiation of HL-60 cells predominantly into monocytes. Importantly, strongly synergistic induction of differentiation into monocytes was observed when silibinin was combined with 5 nM 1alpha,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], a well-known differentiation inducer of HL-60 cells into the monocytic lineage. Silibinin enhanced protein kinase C (PKC) activity and increased protein levels of both PKCalpha and PKCbeta in 1,25-(OH)(2)D(3)-treated HL-60 cells. PKC and extracellular signal-regulated kinase (ERK) inhibitors significantly inhibited HL-60 cell differentiation induced by silibinin alone or in combination with 1,25-(OH)(2)D(3), indicating that PKC and ERK may be involved in silibinin-induced HL-60 cell differentiation.

Antioxidants↗
PubMed2001

A case-control study of unilateral and bilateral breast carcinoma patients.

BACKGROUND: Women with unilateral breast carcinoma are at increased risk for developing contralateral disease. The clinical significance of bilateral breast carcinoma has not been fully defined, and the subset of patients who may benefit from medical or surgical risk-reduction intervention has not yet been characterized. The purpose of this study was to evaluate risk factors and outcomes for bilateral breast carcinoma. METHODS: A subject group of 70 bilateral breast carcinoma patients (62% metachronous) was matched by age and survival interval with a control group of 70 unilateral breast carcinoma patients. Median follow-up was 103 months. RESULTS: Eighty-two percent of the unilateral patients and 80% of the bilateral patients had Stage I or II disease at diagnosis. Median age at presentation was 53 years. In the bilateral group, the contralateral cancer was diagnosed at the same or earlier stage than the first cancer in 87% of cases. Bilateral patients were significantly more likely to have multicentric disease and to have a positive family history for breast carcinoma compared with the unilateral group. There were no significant differences regarding history of exogenous hormone exposure, lobular histology, hormone-receptor status, or HER-2/neu expression. Five-year disease-free survival was 94% for the unilateral breast carcinoma patients and 91% for the bilateral breast carcinoma patients (P = 0.16). CONCLUSIONS: Survival for patients with bilateral breast carcinoma is similar to that of patients with unilateral disease; however, prophylactic risk-reduction intervention for the contralateral breast should be considered in patients who have multicentric unilateral disease or a positive family history for breast carcinoma.

Adult↗
PubMed2001

Dynamics of intramural and transmural reentry during ventricular fibrillation in isolated swine ventricles.

The intramural dynamics of ventricular fibrillation (VF) remain poorly understood. Recent investigations have suggested that stable intramural reentry may underlie the mechanisms of VF. We performed optical mapping studies of VF in isolated swine right ventricles (RVs) and left ventricles (LVs). Nine RV walls were cut obliquely in their distal edge exposing the transmural surface. Six LV wedge preparations were also studied. Results showed that intramural reentry was present. In RV, 28 of 44 VF episodes showed reentry; 15% of the activation pathways were reentrant. Except for 4 episodes, reentry was transmural, involving subendocardial structures as the papillary muscle (PM) or trabeculae. In LV, reentry was observed in 27 of 27 VF episodes; 23% of the activations were part of reentrant pathways (P<0.05 compared with RV). All LV reentrant pathways were truly intramural (confined to the wall) and were frequently located at the PM insertion. In both ventricles, reentry was spatially and temporally unstable. Histological studies showed abrupt changes in fiber orientation at sites of reentry and wave splitting. Connexin 40 immunostaining demonstrated intramyocardial Purkinje fibers at sites of reentry in the PM root and around endocardial trabeculae. Our results confirm that reentry is frequent-but unstable-in the myocardial wall during VF. In RV, reentry is mostly transmural and requires participation of subendocardial structures. The LV has a greater incidence of reentry and is intramural. Anisotropic anatomic structures played key roles in the generation of wave splitting and in the maintenance of reentry.

Animals↗
PubMed2001

Interleukin 12 gene therapy of cancer by peritumoral injection of transduced autologous fibroblasts: outcome of a phase I study.

A phase I dose-escalation clinical trial of peritumoral injections of interleukin 12 (IL-12)-transduced autologous fibroblasts was performed in patients with disseminated cancer for whom effective treatment does not exist. The goals of this study were to assess the safety and toxicities as well as the efficacy, and ancillarily the immunomodulatory effects, of peritumoral IL-12 gene transfer. Primary dermal fibroblasts cultured from the patients were transduced with retroviral vector carrying human IL-12 genes (p35 and p40) as well as the neomycin phosphotransferase gene (TFG-hIL-12-Neo). Patients received four injections at intervals of 7 days. Nine patients were enrolled in this dose-escalation study, with secreted IL-12 doses ranging from 300 ng/24 hr for the first three patients to 1000, 3000, and 5000 ng/24 hr for two patients in each subsequent dosage level. Although a definite statement cannot be made, there appears to be perturbation of systemic immunity. Also, the locoregional effects mediated by tumor necrosis factor alpha (TNF-alpha) and CD8+ T cells were observed with tumor regression. Treatment-related adverse events were limited to mild to moderate pain at the injection site; clinically significant toxicities were not encountered. Transient but clear reductions of tumor sizes were observed at the injected sites in four of nine cases, and at noninjected distant sites in one melanoma patient. Hemorrhagic necrosis of tumors was observed in two melanoma patients. These data indicate that gene therapy by peritumoral injection of IL-12-producing autologous fibroblasts is feasible, and promising in patients with advanced cancer.

Adult↗