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Biomedical subjects

M C Lin

Publications and source records attributed to M C Lin.

At least 55 records · Page 3Linked to original sources
PubMed2001

Inhibition of proteasome function induced apoptosis in gastric cancer.

The ubiquitin-proteasome pathway plays a critical role in the degradation of cellular proteins and cell cycle control. Dysregulating the degradation of such proteins should have profound effects on tumor growth and causes cells to undergo apoptosis. The aims of this study are to evaluate the ubiquitin-proteasome pathway in gastric cancer and the potential role of pharmacological inhibition of proteasome on induction of apoptosis in gastric cancer cells. Gastric cancer cell lines AGS (p53 wild-type) and MKN-28 (p53 mutant) were treated with proteasome inhibitor MG132. The results showed that MG132 inhibited cell proliferation in AGS and MKN-28 cells in a time- and dose-dependent manner. The inhibition of cell proliferation was caused by apoptosis which was also time- and dose-dependent. AGS cells were more responsive to MG132 than MKN-28 cells. Induction of apoptosis was preceded by the activation of caspase-3, as measured by a colorimetric caspase-3 cellular activity and Western blotting of the cleavage of caspase-3 and its substrate PARP. Activation of caspase-7 was also exhibited. In addition, z-VAD-fmk, a broad spectrum caspase inhibitor, reversed apoptosis induced by MG132 in AGS and MKN28 cells. Although z-DEVD-fmk, a specific caspase-3 inhibitor, suppressed MG132-induced apoptosis in MKN28 cells, it only partially rescued the apoptotic effect in AGS cells. Caspase-3 activation was the result of release of cytochrome c from mitochondria into the cytosol, as a consequence of upregulation of bax. There were overexpressions of all the proteasome-related proteins p53, p21(waf1) and p27(kip1) at 4 hr after proteasome inhibition which was identified by the accumulation of ubiquitin-tagged proteins. This was accompanied by accumulation of cells at G(1) phase. Our present study suggests that inhibition of proteasome function in gastric cancer cells induces apoptosis and proteasomal inhibitors have potential use as novel anticancer drugs in gastric cancer.

Adenocarcinoma↗
PubMed2001

State of complementary and alternative medicine in cardiovascular, lung, and blood research: executive summary of a workshop.

The National Heart, Lung, and Blood Institute and the National Center for Complementary and Alternative Medicine recently cosponsored a workshop on the use of complementary and alternative medicine (CAM) in cardiovascular, lung, and blood research. In view of the increasing use of CAM by the general public, it is imperative to promote credible research by the established biomedical community. The goal of this workshop was to enhance the exchange of information and ideas between alternative medicine practitioners and scientists in cardiovascular, lung, and blood research and to foster collaborative research among these researchers. The workshop focused on 5 areas of research, including a historical and cultural perspective of CAM, methodological issues in clinical trials, herbal medicine, chelation therapy, mind/body (meditation) therapy, and acupuncture. CAM has become widely used without rigorously proven efficacy and safety. To protect the public, it was recommended that the fundamental mechanistic research for these CAM approaches be vigorously pursued and that any large-scale clinical trial be carefully executed to avoid any waste of resources and any unnecessary risk. It was felt that standardization of botanical products and procedure-based CAM intervention, such as acupuncture and meditation, is essential for meaningful basic and clinical research. Although botanical products properly consumed are perceived as generally safe, potential herb-drug interactions are a major safety concern. Clearly, many challenges need to be addressed by the scientific community before the public can be assured of the proper use of CAM.

Acupuncture↗
PubMed2001

Embryonic XMab21l2 expression is required for gastrulation and subsequent neural development.

Cell fate determining gene mab-21 regulates the proper establishment of neural cell fate and sensory organ identity in nematode. Mammalian homologs of mab-21 have also been implicated to play critical roles in mid-, hindbrain and craniofacial differentiation. We report here the isolation of a mab-21 homolog, XMab21l2, from Xenopus. We showed that its expression in Xenopus was initiated at gastrulation and prominent signal was detected in neurulating embryos at the neural tube, the optic tissue, the developing midbrain, and the pharyngeal pouches. We demonstrated by RNA interference (RNAi), together with other antisense approaches, that XMab21l2 expression is required for the completion of gastrulation and subsequent neural development.

Amino Acid Sequence↗
PubMed2001

Transcriptional regulation of the Drosophila gene zen by competing Smad and Brinker inputs.

The establishment of expression domains of developmentally regulated genes depends on cues provided by different concentrations of transcriptional activators and repressors. Here we analyze the regulation of the Drosophila gene zen, which is a target of the Decapentaplegic (Dpp) signaling pathway during cellular blastoderm formation. We show that low levels of the Dpp signal transducer p-Mad (phosphorylated Mad), together with the recently discovered negative regulator Brinker (Brk), define the spatial limits of zen transcription in a broad dorsal-on/ventral-off domain. The subsequent refinement of this pattern to the dorsal-most cells, however, correlates with high levels of p-Mad that accumulate in the same region during late blastoderm. Examination of the zen regulatory sequences revealed the presence of multiple Mad and Brk binding sites, and our results indicate that a full occupancy of the Mad sites due to high concentrations of nuclear Mad is the primary mechanism for refinement of zen. Interestingly, several Mad and Brk binding sites overlap, and we show that Mad and Brk cannot bind simultaneously to such sites. We propose a model whereby competition between Mad and Brk determines spatially restricted domains of expression of Dpp target genes.

Animals↗
PubMed2001

Arsenic trioxide induces apoptosis in human gastric cancer cells through up-regulation of p53 and activation of caspase-3.

Arsenic trioxide (As(2)O(3)) can induce clinical remission in patients suffering from acute promyelocytic leukemia, through induction of apoptosis and activation of caspases. We investigated the potential use of As(2)O(3) in human gastric cancer and its possible mechanisms. Human gastric cancer cell lines AGS and MKN-28 were treated with various concentrations (0.1 to 100 microM) of As(2)O(3) for 24 to 72 hr. Apoptosis was determined by acridine orange staining, flow cytometry and DNA fragmentation. Protein levels of p53, p21(waf1/cip1), c-myc, bcl-2 and bax were detected by Western blotting. Effects of As(2)O(3) on caspase-3 protease activity, its protein concentration and cleavage of poly(ADP)-ribose polymerase (PARP) were also studied. As(2)O(3) inhibited cell growth and induced apoptosis in both cell lines, though AGS cells were more sensitive. As(2)O(3) induced apoptosis in AGS cells in a concentration- and time-dependent manner. Treatment resulted in a marked increase in p53 protein levels as early as 4 hr. Co-incubation with p53 anti-sense oligo-nucleotide suppressed As(2)O(3)-induced intracellular p53 over-expression and apoptosis. As(2)O(3) increased the activity of caspase-3, with appearance of its 17 kDa peptide fragment, and cleavage of PARP, with appearance of the 85 kDa cleavage product, both in parallel with the induction of apoptosis. Both the tripeptide caspase inhibitor zVAD-fmk and the specific caspase-3 inhibitor DEVD-fmk partially suppressed As(2)O(3)-induced caspase-3 activation and apoptosis. As(2)O(3) inhibits cell growth and induces apoptosis in gastric cancer cells, involving p53 over-expression and activation of caspase-3. The potential use of this compound in the treatment of gastric cancer is worth further investigation.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Acute toxicity modeling of rainbow trout and silver sea bream exposed to waterborne metals.

Of three proposed acute toxicity models, the uptake-depuration (UD) model, the time-integrated concentration (TIC) model, and the concentration-time (CT) model are derived and verified with acute toxicity data to estimate the internal residues of waterborne metals in fish as a function of a few constants and variables. The main factors are the exposure time, the external exposure concentration, the bioconcentration factor (BCF), and the depuration rate constant (k2). The UD model is based on the concept of residue levels at the cell membrane well correlating with the whole-body concentrations, whereas the TIC and the CT models are based on the idea of irreversible inhibition of the enzyme acetylcholinesterase (AChE) governing the metal acute toxicity in that metals in the entire fish or in the aqueous phase can be described by the critical area under the time-concentration curve that is associated with a critical TIC of toxicant in the target tissue. A highly significant correlation (r2 > 0.9) was found between predictions and LC50(t) data for both the TIC and the CT models, indicating successfully describe 4- to 18-d LC50(t) data of arsenic (As), cobalt (Co), copper (Cu), and Co/Cu mixture in rainbow trout (Oncorhyuchus mykiss) and of Cu in fingerlings and subadults of silver sea bream (Sparus sarba). The time-dependent lethal internal concentration at the site of action that causes 50% mortality is also predicted for a given compound and species. It concludes that the TIC and the CT models can be applied to regulate the acute toxicity and to estimate incipient LC50 values and internal residues of waterborne metals in fish.

Animals↗
PubMed2001

Tamoxifen-induced Ca2+ mobilization in bladder female transitional carcinoma cells.

This study examined the effect of tamoxifen, an anti-breast cancer drug, on Ca2+ handling in bladder female transitional cancer cells. Changes in cytosolic free Ca2+ levels were recorded by using the Ca2+-sensitive dye fura-2. In a dose-dependent manner, tamoxifen induced intracellular free Ca2+ concentrations ([Ca2+]i) increases between 5 and 20 microM with an EC50 of 10 microM. External Ca2+ removal reduced the response by 60+/-6%. Addition of 3 mM Ca2+ caused a [Ca2+]i increase after pretreatment with 10 microM tamoxifen in Ca2+-free medium. In Ca2+-free medium, pretreatment with 10 microM tamoxifen abolished the [Ca2+]i increase induced by 1 microM thapsigargin, an endoplasmic reticulum Ca2+ pump inhibitor. Conversely, pretreatment with 1 microM thapsigargin prevented tamoxifen from releasing more Ca2+. Inhibition of phospholipase C-dependent inositol 1,4,5-tris-phosphate formation with 2 microM U73122 did not alter 10 microM tamoxifen-induced Ca2+ release. The [Ca2+]i increase induced by 5 microM tamoxifen was not altered by 10 microM La3+, nifedipine, verapamil, and diltiazem. Collectively, it was found that tamoxifen increased [Ca2+]i in bladder cancer cells by releasing Ca2+ from the endoplasmic reticulum Ca2+ stores in a manner independent of phospholipase C activity, and by inducing Ca2+ entry from external medium.

Anticarcinogenic Agents↗
PubMed2001

Adsorption of acid dye onto activated carbons prepared from agricultural waste bagasse by ZnCl2 activation.

A series of activated carbons were prepared from agricultural waste sugarcane bagasse by chemical activation with zinc chloride (ZnCl2) as an activating agent at 500 degrees C and 0.5 h soaking time. The Langmuir surface area and total pore volume were used to estimate the average pore diameter of the carbon products. The values of the surface area and pore volume increased linearly with increase in the impregnation ratio (IR) up to 100 wt%. The adsorption capacities of the derived adsorbents for Acid Orange 10 were measured at 20 degrees C and 40 degrees C to gain further insights into the acidic surface oxides of the adsorbent from the results of Fourier transform infrared (FTIR) spectroscopy analysis and pH measurement. Adsorption isotherms of the acid dye on adsorbents prepared were determined and correlated with common isotherm equations. It was found that the Langmuir model appears to fit the isotherm data better than the Freundlich model. The physical properties of these adsorbents were consistent with the parameters obtained from the isotherm equations.

Adsorption↗
PubMed2001

The Berkeley Contact Lens Extended Wear Study. Part II : Clinical results.

OBJECTIVE: To describe the principal clinical outcomes associated with 12 months use of rigid gas-permeable (RGP) extended wear contact lenses and address two primary study questions: (1) does extended wear (EW) of high oxygen transmissibility (Dk/t) RGP lenses reduce the incidence of ocular complications, and (2) does the wearing of high-Dk/t lenses reduce the rate of failure to maintain 6-night RGPEW over 12 months? DESIGN: A randomized, concurrently controlled clinical trial. INTERVENTION: Subjects who adapted to EW with high Dk (oxygen permeability) RGP lenses were randomized to either high Dk or medium-Dk RGP lenses for 12 months of 6-night EW. MAIN OUTCOME MEASURES: Contact lens-associated keratopathies (CLAK), changes in refractive error and corneal curvature, and survival in EW. RESULTS: Two hundred one subjects were randomized to medium or high-Dk lenses for 12 months of EW. Sixty-two percent of the subjects in each group completed 12 months of EW; however, the probability of failure was significantly greater for the medium-Dk group. Although the risk of complications was similar for the two groups, the number of CLAK events that led to termination were 16 versus 5 for the medium-Dk and high-Dk groups, respectively. This suggests that the type of adverse response or the inability to reverse an adverse event was different for the group being exposed to the lower oxygen dose. CONCLUSIONS: The level of oxygen available to the cornea has a significant impact on maintaining successful RGP extended contact lens wear, but not on the initial onset of CLAK. The number of clinical events leading to termination was substantially higher for the medium Dk group, which suggests that corneal hypoxia is an important factor in the development of CLAK. Although overnight contact lens wear should be recommended with caution and carefully monitored for early detection of ocular complications, it appears that high-Dk RGP lenses can be a safe and effective treatment for correction of refractive error for most individuals who can adapt to EW.

Adult↗
PubMed2001

The Berkeley Contact Lens Extended Wear Study. Part I : Study design and conduct.

OBJECTIVE: The primary aim of the Berkeley Contact Lens Extended Wear Study (CLEWS) was to test the hypotheses that extended wear of rigid gas-permeable (RGP) contact lenses with greater oxygen permeability (Dk) reduces the incidence of contact lens-associated keratopathy (CLAK) and increases the survival rate in RGP extended wear (EW). In this article we describe the clinical trial design in detail, present the results of subject recruitment and retention, and provide the baseline demographic and ocular characteristics of the CLEWS subjects, whose data will be analyzed to address the study aims in a companion article. DESIGN: A randomized, concurrently controlled clinical trial. INTERVENTION: Subjects were fitted with day wear (DW) high-Dk RGP lenses and then adapted to EW. Subjects who adapted to EW were then randomly assigned to either high- or medium-Dk RGP lenses for 12 months of 6-nights/week EW. MAIN OUTCOME MEASURES: Slit-lamp assessment and grading of 17 possible keratopathies, measurement of refractive error and corneal curvature, and symptoms. Follow-up data were collected every 3 months. RESULTS: From 545 subjects entering the DW adaptation phase, 201 adapted to EW and were randomly assigned to medium- or high-Dk lenses for 12 months of EW. The baseline characteristics of the two study groups were similar and did not differ from the 344 DW subjects who failed to adapt to EW. The distributions of oxygen transmissibility for the two study groups were disjoint, indicating that each group received distinctly different levels of hypoxia. CONCLUSIONS: We show that CLEWS was appropriately designed to address the study hypotheses, was conducted with regard for the safety of the subjects, and adhered to rigorous protocols designed to control for bias and ensure the integrity of study data. We establish the internal validity of between-group statistical comparisons and characterize our study population to permit informed evaluation of the applicability of our results to the contact lens-wearing population in general.

Adult↗
PubMed2001

Risk factors for pneumothorax and bleeding after CT-guided percutaneous coaxial cutting needle biopsy of lung lesions.

PURPOSE: To evaluate risk factors for pneumothorax and bleeding after computed tomography (CT)-guided percutaneous coaxial cutting needle biopsy of lung lesions. MATERIALS AND METHODS: This study involved 117 consecutive patients with 117 intrapulmonary lesions. Statistical analysis of factors related to patient characteristics, lung lesions, and biopsy technique was performed to determine possible contribution to the occurrence of pneumothorax and bleeding. Interactions between related factors were considered to prevent colinearity. RESULTS: Pneumothorax occurred in 12% (14 of 117) of patients. Needle aspiration of two moderate asymptomatic pneumothoraces were performed; there was no chest tube insertion. Lesion depth (P =.0097), measured from the pleural puncture site to the edge of the intrapulmonary lesion along the needle path, was the single significant predictor of pneumothorax. The highest risk of pneumothorax occurred in subpleural lesions 2 cm or shorter in depth (this represented 33% of lung lesions but caused 71% of all pneumothoraces; OR = 7.1; 95% CI, 1.3-50.8). Bleeding presented as lung parenchyma hemorrhage and hemoptysis in 30 patients (26%). Hemoptysis occurred in four patients (3%). Univariate analysis identified lesion depth (P <.0001), lesion size (P <.015), and pathology type (P =.007) as risk factors for bleeding. Multivariate logistic regression analysis identified lesion depth as the most important risk factor, with the highest bleeding risk for lesions more than 2 cm deep (14% of lesions caused 46% of all bleeding; OR = 17.3; 95% CI, 3.3-121.4). CONCLUSIONS: In CT-guided coaxial cutting needle biopsy, lesion depth is the single predictor for risk of pneumothorax, which occurs at the highest rate in subpleural lesions. Increased risk of bleeding occurs in lesions deeper than 2 cm.

Adolescent↗
PubMed2001

Low-energy paths for the unimolecular decomposition of CH3OH: a G2M/statistical theory study.

The potential energy surface (PES) of the CH3OH system has been characterized by ab initio molecular orbital theory calculations at the G2M level of theory. The mechanisms for the decomposition of CH3OH and the related bimolecular reactions, CH3 + OH and 1CH2 + H2O, have been elucidated. The rate constants for these processes have been calculated using variational RRKM theory and compared with available experimental data. The total decomposition rate constants of CH3OH at the high- and low-pressure limits can be represented by k infinity = 1.56 x 10(16) exp(-44,310/T) s-1 and kAr0 = 1.60 x 10(36) T-12.2 exp(-48,140/T) cm3 molecule-1 s-1, respectively, covering the temperature range 1000-3000 K, in reasonable agreement with the experimental values. Our results indicate that the product branching ratios are strongly pressure dependent, with the production of CH3 + OH and 1CH2 + H2O dominant under high (P > 10(3) Torr) and low (P < 1 atm) pressures, respectively. For the bimolecular reaction of CH3 and OH, the total rate constant and the yields of 1CH2 + H2O and H2 + HCOH at lower pressures (P < 5 Torr) could be reasonably accounted for by the theory. For the reaction of 1CH2 with H2O, both the yield of CH3 + OH and the total rate constant could also be satisfactorily predicted theoretically. The production of 3CH2 + H2O by the singlet to triplet surface crossing, predicted to occur at 4.3 kcal mol-1 above the H2C...OH2 van der Waals complex (which lies 82.7 kcal mol-1 above CH3OH), was neglected in our calculations.

Journal Article↗
PubMed2001

Improving operative safety for cirrhotic liver resection.

BACKGROUND: Liver resection in a patient with cirrhosis carries increased risk. The purposes of this study were to review the results of cirrhotic liver resection in the past decade and to propose safe strategies for cirrhotic liver resection. METHODS: Based on the date of operation, 359 cirrhotic liver resections in 329 patients were divided into two intervals: period 1, from September 1989 to December 1994, and period 2, from January 1995 to December 1999. The patient backgrounds, operative procedures and early postoperative results were compared between the two periods. The factors that influenced surgical morbidity were analysed. RESULTS: In period 2, patient age was higher and the amounts of blood loss and blood transfused were lower. Although postoperative morbidity rates were similar, blood transfusion requirement, postoperative hospital stay and mortality rate were significantly reduced in period 2. No death occurred in 154 consecutive cirrhotic liver resections in the last 38 months of the study. Prothrombin activity and operative time were independent factors that influenced postoperative morbidity. CONCLUSION: With improving perioperative assessment and operative techniques, most complications after cirrhotic liver resection can be treated with a low mortality rate. However, more care should be taken if prothrombin activity is low or there is a long operating time.

Adult↗
PubMed2001

Interleukin-1beta induces cyclo-oxygenase-2 expression in gastric cancer cells by the p38 and p44/42 mitogen-activated protein kinase signaling pathways.

BACKGROUND AND AIMS: Cyclo-oxygenase-2 (COX-2) is the inducible enzyme in the gastric mucosa responsible for prostaglandin production during inflammation and ulcer healing. The regulation of COX-2 gene expression in gastric epithelial cells is not well understood. In this study, we investigated the effect of interleukin (IL)-1beta on COX-2 expression in the human gastric cancer cell, and explored the signaling pathways involved. METHODS: Gastric cancer cell line AGS was treated with IL-1beta or the inhibitors of mitogen-activated protein-Erk kinase (MEK) and p38 mitogen-activated protein (MAP) kinase prior to the addition of IL-1beta. The COX-2 mRNA or protein levels were measured by using RT-PCR or western blot analysis, respectively. Prostaglandin E2 (PGE2) production/secretion was determined by using the prostaglandin E2 EIA assay. The phosphorylation/activation of p44/42 and p38 MAP kinases were determined by using western blot analysis and using phospho-specific antibodies. RESULTS: Interleukin-1beta treatment dose- and time-dependently increased COX-2 mRNA and protein expression levels, and enhanced PGE2 production/secretion in AGS cells. In contrast, IL-1beta had no effect on the level of the constitutively expressed COX-1. In parallel to the increase of COX-2, we showed that p44/42 and p38 MAP kinase activities were also upregulated by IL-1beta treatment. To demonstrate the cause-effect relationship, we showed that inhibition of MEK and p38 MAP kinase with specific inhibitors suppressed IL-1beta-mediated increases in COX-2 mRNA and protein levels, and the PGE2 production. CONCLUSIONS: Our results demonstrated that in human gastric cancer cells, IL-1beta upregulates the COX-2 gene expression through the activation of MEK/p44/42 and p38 MAP kinases pathway.

Adenocarcinoma↗
PubMed2001

Energy expenditure of wheeling and walking during prosthetic rehabilitation in a woman with bilateral transfemoral amputations.

OBJECTIVE: To compare the energy expenditure of locomotion by wheelchair with that required for prosthetic ambulation in a person with bilateral transfemoral (TF) amputations. DESIGN: Observational, single patient, descriptive. SETTING: An 80-meter long rectangular hallway in a rehabilitation unit. PATIENT: A 41-year-old woman with bilateral TF amputations that were performed 79 days before her admission to the rehabilitation unit. MAIN OUTCOME MEASURES: The oxygen uptake, oxygen cost, heart rate, speed, cadence, and stride length of walking measured during a 4-month course of prosthetic rehabilitation. Five locomotion conditions were evaluated: (1) wheelchair propulsion, (2) walking with short-leg prostheses (stubbies) and a walker, (3) long-leg prostheses and a walker, (4) long-leg prostheses without knee mechanism and axillary crutches, and (5) long-leg prostheses with right polycentric knee and left locked knee and axillary crutches. A portable and telemetric system was used to measure the metabolic parameters. An arm ergometry graded exercise test was performed at the end of rehabilitation. RESULTS: Oxygen cost (range, 466%--707% of that of wheeling) and heart rate (range, 106%--116% of that of wheeling) were higher during walking with various combinations of prostheses and walking aids. The speed of prosthetic walking was only 24% to 33% of that of wheeling. Our patient preferred using a wheelchair to prosthetic walking after discharge. CONCLUSIONS: People with bilateral TF amputations require very high cardiorespiratory endurance to fulfill the energy demand during prosthetic rehabilitation. The high energy cost of prosthetic walking will limit its application in daily activities.

Accidents, Traffic↗