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Biomedical subjects

H Lin

Publications and source records attributed to H Lin.

At least 19 recordsLinked to original sources
PubMed2003

Cariporide enhances lactate clearance upon reperfusion but does not alter lactate accumulation during global ischaemia.

Cariporide (HOE 642) inhibits the Na+/H+ exchanger and would be expected to reduce lactate accumulation during ischaemia and stimulate lactate/H+ co-transporter upon reperfusion. The aim of this study was to determine the effect of cariporide on lactate production during global ischaemia and release during reperfusion. Guinea-pig hearts perfused in the Langendorff mode were exposed to 45 min global ischaemia and 30 min reperfusion with or without cariporide (5 or 10 micromol/l). Cardiac function was assessed by measurement of left ventricular developed pressure (LVDP). Lactate and pH were measured in coronary effluent before ischaemia and throughout reperfusion. Tissue metabolites (lactate, adenine nucleotides, guanine nucleotides and purine) were measured in ventricular biopsy samples collected at the beginning and end of ischaemia. Cariporide significantly improved recovery of LVDP (from 66% for control to 88% and 93% for 5 and 10 micromol/l cariporide, respectively). During ischaemia, only 10 micromol/l cariporide produced a small (10%) but significant preservation of ATP and GTP compared to control. This was associated with significant reduction (25%) in ischaemic contracture. Cariporide did not influence lactate accumulation during ischaemia but significantly increased lactate efflux (18%) during the first 60 s of reperfusion. In conclusion, cariporide does not alter lactate accumulation during ischaemia but enhances lactate efflux upon reperfusion, which may have implications for its cardioprotective action.

Animals↗
PubMed2003

Genetic evidence for a role of phospholipase C at the budding yeast kinetochore.

Chromosome segregation during mitosis requires kinetochores, specialized organelles that mediate chromosome attachment to spindle microtubules. We have shown previously that in budding yeast, Plc1p (phosphoinositide-specific phospholipase C) localizes to centromeric loci, associates with the kinetochore proteins Ndc10p and Cep3p, and affects the function of kinetochores. Deletion of PLC1 results in nocodazole sensitivity, mitotic delay, and a higher frequency of chromosome loss. We report here that despite the nocodazole sensitivity of plc1Delta cells, Plc1p is not required for the spindle checkpoint. However, plc1Delta cells require a functional BUB1/BUB3-dependent spindle checkpoint for viability. PLC1 displays strong genetic interactions with genes encoding components of the inner kinetochore, including NDC10, SKP1, MIF2, CEP1, CEP3, and CTF13. Furthermore, plc1Delta cells display alterations in chromatin structure in the core centromere. Chromatin immunoprecipitation experiments indicate that Plc1p localizes to centromeric loci independently of microtubules, and accumulates at the centromeres during G(2)/M stage of cell cycle. These results are consistent with the view that Plc1p affects kinetochore function, possibly by modulating the structure of centromeric chromatin.

Cell Nucleus↗
PubMed2003

Kinematics of the human pelvis following open book injury.

The objective of this study is to determine the three dimensional kinematics of the human pelvis including both sacroiliac joints following a simulated open book injury induced on cadavers by applying anterior-posterior compressive loads to the pelvis. An electromagnetic digitizing and motion tracking system was utilized to measure the morphology of the pelvis and the relative movements of its bones during this simulated open book fracture. The screw displacement axis method was used to describe the relative motion between the sacrum and each hipbone. Morphologically, it was found that the articular surfaces forming the sacroiliac joints could be approximated with planar surfaces directed from proximal and lateral to distal and medial and from posteromedial to anterolateral. The kinematic data obtained from this study indicate that there is a direct correlation between the opening of the symphysis pubis and the opening of the sacroiliac joint (SIJ) during open book injury. This suggests that the extent of injury of the SIJ maybe estimated from the degree of opening of the symphysis pubis as demonstrated on anteroposterior (A-P) x-rays. The results obtained from this study also indicate that the motion of the hipbone with respect to the sacrum on the side of the sacroiliac joint opening is almost a pure rotation, which translates clinically on the A-P x-rays as pure opening of the SIJ without vertical displacement. The average axis of rotation was found to be almost parallel to the SIJ planar articular surface. Furthermore, the pubic bone on the side of SIJ opening was found to displace inferiorly and posteriorly. One can thus conclude that in open book pelvic injuries, the pubic bone on the side of injury displaces inferiorly on the outlet projection x-rays with no vertical displacement of the SIJ. This is important since the initial assessment of the open book injury in the emergency room includes outlet projection x-rays. From this study, the relative vertical positions of the pubic bones on these x-rays can help the surgeon in differentiating open book fracture injury from other pelvic injuries.

Cadaver↗
PubMed2003

High prevalence of left ventricular systolic and diastolic asynchrony in patients with congestive heart failure and normal QRS duration.

OBJECTIVE: To study the possible occurrence of left ventricular (LV) systolic and diastolic asynchrony in patients with systolic heart failure (HF) and narrow QRS complexes. DESIGN: Prospective study. SETTING: University teaching hospital. PATIENTS: 200 subjects were studied by echocardiography. 67 patients had HF and narrow QRS complexes (< or = 120 ms), 45 patients had HF and wide QRS complexes (> 120 ms), and 88 served as normal controls. INTERVENTIONS: Echocardiography with tissue Doppler imaging was performed using a six basal, six mid-segmental model. MAIN OUTCOME MEASURES: Severity and prevalence of systolic and diastolic asynchrony, as assessed by the maximal difference in time to peak myocardial systolic contraction (T(S)) and early diastolic relaxation (T(E)), and the standard deviation of T(S) (T(S)-SD) and of T(E) (T(E)-SD) of the 12 LV segments. RESULTS: The mean (SD) maximal difference in T(S) (controls 53 (23) ms v narrow QRS 107 (54) ms v wide QRS 130 (51) ms, both p < 0.001 v controls) and in T(S)-SD (controls 17.0 (7.8) ms v narrow QRS 33.8 (16.9) ms v wide QRS 42.0 (16.5) ms, both p < 0.001 v controls) was prolonged in the narrow QRS group compared with normal controls. Similarly, the maximal difference in T(E) (controls 59 (19) ms v narrow QRS 104 (71) ms v wide QRS 148 (87) ms, both p < 0.001 v controls) and in T(E)-SD (controls 18.5 (5.8) ms v narrow QRS 33.3 (27.7) ms v wide QRS 48.6 (30.2) ms, both p < 0.001 v controls) was prolonged in the narrow QRS group. The prevalence of systolic and diastolic asynchrony was 51% and 46%, respectively, in the narrow QRS group, and 73% and 69%, respectively, in the wide QRS group. Stepwise multiple regression analysis showed that a low mean myocardial systolic velocity from the six basal LV segments and a large LV end systolic diameter were independent predictors of systolic asynchrony, while a low mean myocardial early diastolic velocity and QRS complex duration were independent predictors of diastolic asynchrony. CONCLUSIONS: LV systolic and diastolic mechanical asynchrony is common in patients with HF with narrow QRS complexes. As QRS complex duration is not a determinant of systolic asynchrony, it implies that assessment of intraventricular synchronicity is probably more important than QRS duration in considering cardiac resynchronisation treatment.

Aged↗
PubMed2002

Phospholipase C interacts with Sgd1p and is required for expression of GPD1 and osmoresistance in Saccharomyces cerevisiae.

The Saccharomyces cerevisiae PLC1 gene encodes a homolog of the delta isoform of mammalian phosphoinositide-specific phospholipase C. Cells deleted for PLC1 ( plc1Delta) are viable, but display several phenotypes, including osmotic, temperature, and nocodazole sensitivity. We have used a two-hybrid screen to identify Plc1p-interacting proteins. One of the interacting proteins found was Sgd1p, a recently identified, essential, nuclear protein. The SGD1 gene was originally cloned by complementation of an osmostress-sensitive mutant. The Plc1p-Sgd1p interaction was confirmed biochemically by affinity chromatography. SGD1 interacts genetically with both PLC1 and HOG1 (which encodes an osmosensing mitogen-activated protein kinase). Overexpression of Sgd1p suppresses the temperature sensitivity of cells bearing the plc1-4 allele, and the double mutant strain plc1Delta sgd1-1 displays enhanced temperature and nocodazole sensitivity. The plc1Delta hog1Delta strain displays increased osmosensitivity, and has a synthetic defect in glycerol synthesis and the expression of GPD1 (which encodes the enzyme glycerol 3-phosphate dehydrogenase that is involved in glycerol biosynthesis), suggesting that Plc1p and Hog1p function in independent pathways. The hog1Delta sgd1-1 double mutant displays enhanced osmosensitivity relative to that of either single mutant. The triple mutant plc1Delta hog1Delta sgd1-1 is inviable, while the plc1Delta hog1Delta sgd1-2 strain grows extremely slowly and is more osmosensitive than the plc1Delta hog1Delta or hog1Delta sgd1-2 strain. These results are consistent with a model in which Plc1p and Hog1p function in parallel pathways affecting osmoregulation, and signals from both these pathways converge, at least partly, on Sgd1p.

Glycerolphosphate Dehydrogenase↗
PubMed2002

Discovering subpopulation structure with latent class mixed models.

The linear mixed model is a well-known method for incorporating heterogeneity (for example, subject-to-subject variation) into a statistical analysis for continuous responses. However heterogeneity cannot always be fully captured by the usual assumptions of normally distributed random effects. Latent class mixed models offer a way of incorporating additional heterogeneity which can be used to uncover distinct subpopulations, to incorporate correlated non-normally distributed outcomes and to classify individuals. The methodology is motivated with examples in health care studies and a detailed illustration is drawn from the Nutritional Prevention of Cancer trials. Latent class models are used with longitudinal data on prostate specific antigen (PSA) as well as incidence of prostate cancer. The models are extended to accommodate prostate cancer as a survival endpoint; this is compared to treating it as a binary endpoint. Four subpopulations are identified which differ both with regard to their PSA trajectories and their incidence rates of prostate cancer.

Adolescent↗
PubMed2002

Change in demographic picture and increase of drug resistance in pulmonarytuberculosis in a 10-year interval in Taiwan.

BACKGROUND: This study was designed to compare the change in demographics, medical characteristics and drug resistance of patients with active pulmonary tuberculosis (TB) between two time periods within a 10-year interval. PATIENTS AND METHODS: We retrospectively reviewed the clinical records and chest radiographs of 1,826 patients with active pulmonary TB for two time periods from 1992-1996 (n = 884) and 1982-1986 (n = 942). RESULTS: The mean age was significantly higher and there were significantly more female patients in the 1992-1996 period than in the 1982-1986 period. In the 1992-1996 period, there were significantly fewer patients with the main complaints of cough, fever and body weight loss at the time of diagnosis but significantly more patients who had diabetes mellitus, obstructive airway disease, cancer other than lung cancer or who were on corticosteroid therapy. During the 1992-1996 period, single drug resistance against isoniazid (INH), rifampin (RIF) and streptomycin increased by 0.5%, 3% and 0.7%, respectively. Multiple drug resistance against both INH and RIF increased by 2% in the 1992-1996 period. A history of pulmonary TB and extensive pulmonary involvement were two significant factors for drug resistance against INH, RIF or ethambutol (EMB). CONCLUSION: In the 1992-1996 period, the mean age of patients and number of female patients significantly increased. There were more patients with diabetes mellitus, obstructive airway diseases, cancer other than lung cancer and prior steroid therapy but fewer patients presenting with classic clinical symptoms of TB. In consideration of the high prevalence and increasing rate of single and multiple drug resistance, we recommend an initial four-drug regimen (INH, RIF, EMB, pyrazinamide) for the treatment of pulmonary TB in Taiwan.

Adolescent↗
PubMed2002

Comparison of competitive-nested PCR and real-time PCR in detecting BCR-ABL fusion transcripts in chronic myeloid leukemia patients.

Real-time RT-PCR has great advantages for estimating transcript levels in a variety of situations. These include relative rapid assay times (hours), reliability and ease of performing replicate analyses. In contrast, competitive PCR is a very labor-intensive procedure requiring a few days to generate useful data. We compared the same samples from CML patients by both methods. Importantly, we used the Bcr-Abl junction plasmid DNA, which is used as a competitor in the manual competitive PCR assay, to generate a standard curve for the real-time assay. This permitted reporting the real-time data as the number of BCR-ABL transcripts per microg of total RNA, which is the same format used for the competitive PCR assay. In this study, a total of 435 peripheral blood and marrow samples from 285 CML patients were analyzed by RT-PCR; these patients were undergoing therapy by STI-571, interferon, and bone marrow transplantation treatment. Most samples also had assay values for the Philadelphia chromosome (Ph), FISH and Western blotting for the Bcr-Abl oncoprotein. Our findings indicated that the real-time assay was less sensitive than the manual competitive RT-PCR assay (t = 5.118; P < 0.001). Of interest, the transcript levels in cell line mixtures with various ratios of K562/KG-1 (BCR-ABL positive/negative) cells were also significantly higher with the competitive RT-PCR assays than real-time RT-PCR, except for levels of BCR-ABL below 200 transcripts per microg of RNA. In both patient and cell line experiments, dividing the BCR-ABL transcripts by the total ABL transcripts virtually eliminated the difference between real-time BCR-ABL transcript values and quantitative competitive BCR-ABL transcript values, indicating that both BCR-ABL and ABL transcripts were underestimated by the real-time assay. In addition, the increased sensitivity of the nested, competitive RT-PCR was readily apparent in patients with minimal residual disease, which by the real-time were negative in the majority of patients but were positive by nested, competitive RT-PCR in 44.6% (n = 29) of samples analyzed (n = 65). These findings indicate that real-time RT-PCR, when normalized for the total ABL transcripts, can be used to monitor CML patients during therapy, but we suggest that nested, competitive RT-PCR be used to determine BCR-ABL/ABL transcript ratios at low transcript values or especially when real-time analyses are negative.

Fusion Proteins, bcr-abl↗
PubMed2002

Effect of dietary supplemental levels of vitamin A on the egg production and immune responses of heat-stressed laying hens.

Two experiments were conducted to evaluate the effect of vitamin A supplementation of a commercial layer diet on the laying performance and immune function of heat-stressed hens. In Experiment 1, two different levels of vitamin A supplementation (3,000 and 9,000 IU/kg) were used to investigate the laying performance and antibody titer against Newcastle disease virus (NDV) of heat-stressed hens. Results showed that the high level of vitamin A supplementation (9,000 IU/kg) had a beneficial effect on the feed intake and laying rate of heat-stressed hens (P < 0.05), compared with the control group (3,000 IU/kg). The antibody titers were not influenced by the level of vitamin A (P > 0.05). In Experiment 2, the effect of four levels of vitamin A (3,000, 6,000, 9,000, and 12,000 IU/kg) on the antibody titer to NDV and T lymphocyte proportion was studied. The experimental birds were exposed to a high temperature (31.5 C) 15 d after NDV vaccination (Treatment 1) or immediately (Treatment 2). The results showed that the egg weight was increased (P < 0.01) by the high levels of vitamin A supplementation (6,000 and 9,000 IU/kg), but feed intake, laying rate, and body weight loss were not (P > 0.05). In Treatment 1, vitamin A had no significant effect on antibody titers against NDV in normal or hot environments but increased (P < 0.01) the proportion of alpha-naphthyl acetate esterase (ANAE)-positive cells. Vitamin A supplementation had a significant effect on NDV antibody titer and ANAE-positive cell proportion in Treatment 2 (P < 0.01). The results of the present study suggested that vitamin A supplementation in commercial layer diets to layer chickens under heat stress was beneficial to laying performance and immune function.

Animal Feed↗
PubMed2002

Localization of the single-stranded RNA-binding domains of bluetongue virus nonstructural protein NS2.

The S2 gene of bluetongue virus, serotype 17, has been cloned, and the nonstructural protein NS2 has been expressed. Synthetic peptides matching regions within the amino acid sequence of NS2 were used to map three single-stranded RNA (ssRNA)-binding regions within the protein. A prokaryotic expression system was then used to generate a series of deletion mutants with the ssRNA-binding domains of NS2 removed, singly and in different combinations. These truncated proteins were expressed on a large scale and purified to near homogeneity. The affinity of each truncated protein towards ssRNA was then assayed by electrophoretic mobility shift assays. As a result, the three ssRNA-binding domains of BTV nonstructural protein NS2 have been conclusively localized, and removal of these three domains completely abrogates the ability of NS2 to bind to ssRNA.

Amino Acid Sequence↗
PubMed2001

Polyploids require Bik1 for kinetochore-microtubule attachment.

The attachment of kinetochores to spindle microtubules (MTs) is essential for maintaining constant ploidy in eukaryotic cells. Here, biochemical and imaging data is presented demonstrating that the budding yeast CLIP-170 orthologue Bik1is a component of the kinetochore-MT binding interface. Strikingly, Bik1 is not required for viability in haploid cells, but becomes essential in polyploids. The ploidy-specific requirement for BIK1 enabled us to characterize BIK1 without eliminating nonhomologous genes, providing a new approach to circumventing the overlapping function that is a common feature of the cytoskeleton. In polyploid cells, Bik1 is required before anaphase to maintain kinetochore separation and therefore contributes to the force that opposes the elastic recoil of attached sister chromatids. The role of Bik1 in kinetochore separation appears to be independent of the role of Bik1 in regulating MT dynamics. The finding that a protein involved in kinetochore-MT attachment is required for the viability of polyploids has potential implications for cancer therapeutics.

Binding Sites↗
PubMed2001

Disruption of cell cycle kinetics and cyclin-dependent kinase system by ethanol in cultured cerebellar granule progenitors.

An in vitro model of neuronal precursors, primary culture of cerebellar granule progenitors (CGPs), was used to investigate the mechanisms underlying ethanol-induced cell cycle damage. The CGP cultures were generated from 3-day-old rats. Ethanol significantly inhibited the proliferation of the CGPs in culture. Analysis of cell cycle kinetics by a cumulative 5-bromo-2'-deoxyuridine (BrdU) labeling technique demonstrated that ethanol exposure increased the duration of the cell cycle and decreased the growth fraction (the cycling population). The duration of the S-phase and total cell cycle was significantly prolonged by ethanol exposure by 220% and 135%, respectively, while the growth fraction was decreased from 44% in the control groups to 22% in the ethanol-exposed cultures. Cyclin-dependent kinase 2 (Cdk2) is a key protein that regulates both the passage from G1 into S, and the S phase progression. The results from in vitro phosphorylation assay and Western blot demonstrated that ethanol dramatically down-regulated both the activity and the expression of Cdk2. In addition, ethanol significantly decreased the expression of Cyclin A and Cyclin D(2). Further studies using in situ TUNEL assay and DNA fragmentation ELISA showed that ethanol caused a delayed apoptosis, i.e. the ethanol-induced apoptosis was evident only after chronic exposure. On the other hand, ethanol did not affect the necrotic index. In conclusion, ethanol decreases the cycling pool of CGPs by inducing cell cycle delay and promoting apoptosis. Ethanol-mediated disturbance of the cyclin-dependent kinase system may be an important mechanism to account for cell cycle arrest in neuronal precursor cells.

Animals↗
PubMed2001

The overall pattern of cardiac contraction depends on a spatial gradient of myosin regulatory light chain phosphorylation.

Evolution of the human heart has incorporated a variety of successful strategies for motion used throughout the animal kingdom. One such strategy is to add the efficiency of torsion to compression so that blood is wrung, as well as pumped, out of the heart. Models of cardiac torsion have assumed uniform contractile properties of muscle fibers throughout the heart. Here, we show how a spatial gradient of myosin light chain phosphorylation across the heart facilitates torsion by inversely altering tension production and the stretch activation response. To demonstrate the importance of cardiac light chain phosphorylation, we cloned a myosin light chain kinase from a human heart and have identified a gain-in-function mutation in two individuals with cardiac hypertrophy.

Animals↗
PubMed2001

A novel homozygous deletion at chromosomal band 6q27 in an ovarian cancer cell line delineates the position of a putative tumor suppressor gene.

Chromosomal band 6q27 is believed to contain a tumor suppressor gene important in the development of several cancer types, including ovarian cancer. However, repeated efforts to identify a tumor suppressor gene in this region have been unsuccessful. Because homozygous deletions have been useful in the positional cloning of a number of tumor suppressor genes, we initiated a systematic search for such deletions in ovarian cancer cell lines using 6q microsatellite markers. One of the cell lines, OV167, was found to contain an 80 kb homozygous deletion encompassing marker D6S193 at 6q27 but excluding nearby marker D6S297. No known genes were present in the deleted region. Because the homozygous deletion might affect the expression of nearby genes, we analyzed the expression of the two closest known genes flanking the deletion, RNASE6PL and RSK-3. The expression of these genes were unaffected by the homozygous deletion, suggesting that the functional target of the deletion is located between these two genes. A search of the region against expressed sequence tag (EST) databases revealed that it contained four sets of expressed sequences. The first expressed sequences were derived from a LINE repetitive element and were considered unlikely to represent a tumor suppressor gene. The other expressed sequence tags identified did not show homology to known genes and are currently being investigated. This data may significantly reduce the magnitude of the search for the 6q tumor suppressor gene as it suggests a small area as a prime target for investigation.

Chromosome Mapping↗
PubMed2001

Nitrate relationships between stream baseflow, well water, and land use in the Tomorrow-Waupaca Watershed.

We examined the use of stream baseflow water quality as a representative measure of mean ground water quality in the Tomorrow-Waupaca Watershed in central Wisconsin and the relationship between agricultural land use and watershed water quality. From 1997 to 1999, 38 stream sites were sampled for nitrate during winter and summer baseflow conditions. Some sites have been sampled during winter baseflow conditions since 1994. The land area contributing ground water to each stream sampling site was delineated, resulting in 38 sub-basins. In addition, over 3500 test results from private wells in the watershed were compiled and mapped using a Geographic Information System (GIS). Nitrate concentrations in stream baseflow and well waters were found to have strong positive correlation in the sub-basins of second order or higher. This indicates that stream baseflow may be valid for monitoring mean ground water quality in watersheds predominantly fed by ground water, where much of the stream nitrate is believed to originate from ground water. Analysis of seasonal variation in the stream data showed that winter nitrate concentrations were higher than summer concentrations, implying that winter stream monitoring may be more critical for the assessment of overall ground water quality in the watershed. We also found that, as the amount of agricultural land increased in each sub-basin, average nitrate concentrations in the well and stream waters also increased, suggesting a connection between agricultural land use and nitrate contamination of water resources in the watershed.

Agriculture↗
PubMed2001

Chronic myelogenous leukemia blast cell proliferation is inhibited by peptides that disrupt Grb2-SoS complexes.

Chronic myelogenous leukemia (CML) is commonly characterized by the presence of the p210(Bcr-Abl) oncoprotein. Many downstream effectors of Bcr-Abl have been described, including activation of the Grb2-SoS-Ras-MAP kinase (Erk) pathway. The precise contributions of these signal-transduction proteins in CML blast cells in human patients are not yet well defined. To gain further insight into the importance of Grb2 for CML, peptides that disrupt Grb2-SoS complexes were tested. These high-affinity Grb2-binding peptides (HAGBPs) can autonomously shuttle into cells and function by binding to the N-terminal SH3 domain of Grb2. The HAGBPs were analyzed for their effects on Bcr-Abl-expressing cell lines and freshly isolated CML blast cells from patients. They induced a dramatic decrease in the proliferation of CML cell lines. This was not observed with point-mutated control peptides with abolished Grb2SH3(N) binding. As expected, Grb2-SoS complexes were greatly diminished in the HAGBP-treated cells, and MAP kinase activity was significantly reduced as determined by an activation-specific phospho-MAPK antibody. Furthermore, cell fractions that are enriched for blast cells from CML patients with active disease were also incubated with the Grb2 blocker peptides. The HAGBPs led to a significant proliferation reduction of these cells in the majority of the isolates, but not in all patients' cells. These results show that, in addition to the direct targeting of Bcr-Abl, selective inhibition of Grb2 protein complexes may be a therapeutic option for a significant number of CML patients.

3T3 Cells↗