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Biomedical subjects

J Chen

Publications and source records attributed to J Chen.

At least 271 records · Page 15Linked to original sources
PubMed2002

Hematopoietic stem cell functional failure in interleukin-2-deficient mice.

The effects of interleukin-2 (IL-2) deficiency on hematopoiesis were tested by measuring cellular compositions in peripheral blood, spleen, thymus, and bone marrow of 3- to 5-month-old gene-targeted Il2 null (Il2(-/-)) mice using the Advia 120 Hematology system and fluorescence-activated cell staining (FACS). Il2(-/-) mice developed hematological failure and autoimmune responses, showing variable but significant degrees of anemia, lymphocytopenia, thrombocytopenia, splenomegaly, thymus involution, and weight loss. Surprisingly, Il2(-/-) mice had normal numbers of bone marrow cells (BMCs) with increased numbers of Lin(-)Kit(+)Sca1(+)CD34(-) and Lin(-)Kit(+)Sca1(+)CD34(+) cells that are normally associated with hematopoietic stem cells (HSCs) and progenitor cells. Day-12 colony-forming units-spleen cells were slightly reduced in Il2(-/-) mice. When Il2(-/-) and Il2(+/+) mice were compared for long-term HSC function in vivo in the competitive repopulation assay, BMCs from Il2(-/-) donors had 10- to 20-fold less HSC repopulating ability, which affected both myeloid and lymphoid cell lineages. Thus, HSCs from Il2(-/-) mice can proliferate normally but are functionally defective for reconstituting lethally irradiated recipients.

Animals↗
PubMed2002

Can motivational signs prompt increases in incidental physical activity in an Australian health-care facility?

This study aimed to evaluate whether a stair-promoting signed intervention could increase the use of the stairs over the elevator in a health-care facility. A time-series design was conducted over 12 weeks. Data were collected before, during and after displaying a signed intervention during weeks 4-5 and 8-9. Evaluation included anonymous counts recorded by an objective unobtrusive motion-sensing device of people entering the elevator or the stairs. Self-report data on stair use by hospital staff were also collected. Stair use significantly increased after the first intervention phase (P = 0.02), but after the intervention was removed stair use decreased back towards baseline levels. Moreover, stair use did not significantly change after the re-introduction of the intervention. Lastly, stair use decreased below the initial baseline level during the final weeks of evaluation. Furthermore, there was no significant change in self-reported stair use by hospital staff. Therefore, the signed intervention aimed at promoting an increase in incidental physical activity produced small brief effects, which were not maintained. Further research is required to find more effective 'point of choice' interventions to increase incidental physical activity participation with more sustainable impact.

Adult↗
PubMed2002

Molecular wires, switches, and memories.

Design and measurements of molecular wires, switches, and memories offer an increased device capability with reduced elements. We report: Measurements on through-bond electronic transport properties of nanoscale metal-1,4-phenylene diisocyanide-metal junctions are reported, where nonohmic thermionic emission is the dominant process, with isocyanide-Pd showing the lowest thermionic barrier of 0.22 eV; robust and large reversible switching behavior in an electronic device that utilizes molecules containing redox centers as the active component, exhibiting negative differential resistance (NDR) and large on-off peak-to-valley ratio (PVR) are realized; erasable storage of higher conductivity states in these redox-center-containing molecular devices are observed; and a two-terminal electronically programmable and erasable molecular memory cell with long bit retention time is demonstrated.

Cyanides↗
PubMed2002

Clinical and genetic studies of Birt-Hogg-Dubé syndrome.

Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant cancer syndrome characterised by benign skin tumours, renal tumours, and spontaneous pneumothorax. The gene has been mapped to chromosome 17p11.2 and recently identified, expressing a novel protein called folliculin. We report the clinical and genetic studies of four sporadic BHD cases and four families with a total of 23 affected subjects. Haplotype analysis of these families using BHD linked markers showed they did not share the same affected alleles, excluding common ancestry. Mutation analysis of the BHD gene identified two germline mutations on exon 11 (c.1733insC and c.1733delC) in three of four families as well as two of four sporadic cases. A novel somatic mutation, c.1732delTCinsAC, was detected in a BHD related chromophobe renal carcinoma. Our results confirmed the (C)8 tract in exon 11 as a mutational hot spot in BHD and should always be considered for future genetic testing. Our observation also indicated that the second hit (of Knudson's two hit theory) in some BHD related tumours is in the form of somatic mutation rather than LOH. In a large French family in which eight affected subjects carry the c.1733delC mutation, a phenocopy who has multiple episodes of spontaneous pneumothorax was identified. A total of five mutation carriers (aged between 37 to 66) did not have any evidence of BHD features, suggesting either reduced penetrance or late age of onset of the disease. In addition, six out of eight affected subjects who have positive germline mutation have confirmed neoplastic colonic polyps, indicating that colorectal neoplasia is an associated feature of BHD in some families. Our studies have observed several interesting genetic features in BHD: (1) the poly (C) tract in exon 11 as a mutational hot spot; (2) the existence of phenocopy; (3) reduced penetrance or late age of onset of disease; (4) association with colorectal neoplasia in some families; and (5) somatic mutation instead of LOH as the second hit in BHD tumours.

Adult↗
PubMed2002

Nested case-control study of lung cancer in four Chinese tin mines.

OBJECTIVES: To evaluate the relation between occupational dust exposure and lung cancer in tin mines. This is an update of a previous study of miners with high exposure to dust at four tin mines in southern China. METHODS: A nested case-control study of 130 male lung cancer cases and 627 controls was initiated from a cohort study of 7855 subjects employed at least 1 year between 1972 and 1974 in four tin mines in China. Three of the tin mines were in Dachang and one was in Limu. Cumulative total exposure to dust and cumulative exposure to arsenic were calculated for each person based on industrial hygiene records. Measurements of arsenic, polycyclic aromatic hydrocarbons (PAHs), and radon in the work sites were also evaluated. Odds ratios (ORs), standard statistic analysis and logistic regression were used for analyses. RESULTS: Increased risk of lung cancer was related to cumulative exposure to dust, duration of exposure, cumulative exposure to arsenic, and tobacco smoking. The risk ratios for low, medium, and high cumulative exposure to dust were 2.1 (95% confidence interval (95% CI) 1.1 to 3.8), 1.7 (95% CI 0.9 to 3.1), and 2.8 (95% CI 1.6 to 5.0) respectively after adjustment for smoking. The risk for lung cancer among workers with short, medium, and long exposure to dust were 1.9 (95% CI 1.0 to 3.5), 2.3 (95% CI 1.3 to 4.1), and 2.3 (95% CI 1.2 to 4.2) respectively after adjusting for smoking. Several sets of risk factors for lung cancer were compared, and the best predictive model included tobacco smoking (OR=1.6, 95% CI 1.1 to 2.4) and cumulative exposure to arsenic (ORs for different groups from low to high exposure were 2.1 (95% CI 1.1 to 3.9); 2.1 (95% CI 1.1 to 3.9); 1.8 (95% CI 1.0 to 3.6); and 3.6 (95% CI 1.8 5 to 7.3)). No excess of lung cancer was found among silicotic subjects in the Limu tin mine although there was a high prevalence of silicosis. Exposures to radon were low in the four tin mines and no carcinogenic PAHs were detected. CONCLUSIONS: These findings provide little support for the hypothesis that respirable crystalline silica induces lung cancer. Ore dust in work sites acts as a carrier, the exposure to arsenic and tobacco smoking play a more important part in carcinogenesis of lung cancer in tin miners. Silicosis seems not to be related to the increased risk of lung cancer.

Adult↗
PubMed2002

Characteristics of carotid body chemosensitivity in NADPH oxidase-deficient mice.

Various heme-containing proteins have been proposed as primary molecular O(2) sensors for hypoxia-sensitive type I cells in the mammalian carotid body. One set of data in particular supports the involvement of a cytochrome b NADPH oxidase that is commonly found in neutrophils. Subunits of this enzyme have been immunocytochemically localized in type I cells, and diphenyleneiodonium, an inhibitor of the oxidase, increases carotid body chemoreceptor activity. The present study evaluated immunocytochemical and functional properties of carotid bodies from normal mice and from mice with a disrupted gp91 phagocytic oxidase (gp91(phox)) DNA sequence gene knockout (KO), a gene that codes for a subunit of the neutrophilic form of NADPH oxidase. Immunostaining for tyrosine hydroxylase, a signature marker antigen for type I cells, was found in groups or lobules of cells displaying morphological features typical of the O(2)-sensitive cells in other species, and the incidence of tyrosine hydroxylase-immunopositive cells was similar in carotid bodies from both strains of mice. Studies of whole cell K(+) currents also revealed identical current-voltage relationships and current depression by hypoxia in type I cells dissociated from normal vs. KO animals. Likewise, hypoxia-evoked increases in intracellular Ca(2+) concentration were not significantly different for normal and KO type I cells. The whole organ response to hypoxia was evaluated in recordings of carotid sinus nerve activity in vitro. In these experiments, responses elicited by hypoxia and by the classic chemoreceptor stimulant nicotine were also indistinguishable in normal vs. KO preparations. Our data demonstrate that carotid body function remains intact after sequence disruption of the gp91(phox) gene. These findings are not in accord with the hypothesis that the phagocytic form of NADPH oxidase acts as a primary O(2) sensor in arterial chemoreception.

Animals↗
PubMed2002

Role of endothelin and endothelin A-type receptor in adaptation of the carotid body to chronic hypoxia.

Chronic exposure in a low-PO(2) environment (i.e., chronic hypoxia, CH) elicits an elevated hypoxic ventilatory response and increased hypoxic chemosensitivity in arterial chemoreceptors in the carotid body. In the present study, we examine the hypothesis that changes in chemosensitivity are mediated by endothelin (ET), a 21-amino-acid peptide, and ET(A) receptors, both of which are normally expressed by O(2)-sensitive type I cells. Immunocytochemical staining showed incremental increases in ET and ET(A) expression in type I cells after 3, 7, and 14 days of CH (380 Torr). Peptide and receptor upregulation was confirmed in quantitative RT-PCR assays conducted after 14 days of CH. In vitro recordings of carotid sinus nerve activity after in vivo exposure to CH for 1-16 days demonstrated a time-dependent increase in chemoreceptor activity evoked by acute hypoxia. In normal carotid body, the specific ET(A) antagonist BQ-123 (5 microM) inhibited 11% of the nerve discharge elicited by hypoxia, and after 3 days of CH the drug diminished the hypoxia-evoked discharge by 20% (P < 0.01). This inhibitory effect progressed to 45% at day 9 of CH and to nearly 50% after 12, 14, and 16 days of CH. Furthermore, in the presence of BQ-123, the magnitude of the activity evoked by hypoxia did not differ in normal vs. CH preparations, indicating that the increased activity was the result of endogenous ET acting on an increasing number of ET(A). Collectively, our data suggest that ET and ET(A) autoreceptors on O(2)-sensitive type I cells play a critical role in CH-induced increased chemosensitivity in the rat carotid body.

Adaptation, Physiological↗
PubMed2002

Chronic hypoxia upregulates connexin43 expression in rat carotid body and petrosal ganglion.

Recent studies have demonstrated that oxygen-sensitive type I cells in the carotid body express the gap junction-forming protein connexin43 (Cx43). In the present study, we examined the hypothesis that chronic exposure to hypoxia increases Cx43 expression in type I cells as well as in chemoafferent neurons in the petrosal ganglion. Immunocytochemical studies in tissues from normal rats revealed diffuse and granular Cx43-like immunoreactivity in the cytoplasm of type I cells and dense punctate spots of immunoreactive product at the margins of type I cells and near the borders of chemosensory cell lobules. Cx43-like immunoreactivity was not detectable in petrosal ganglion neurons from normal animals. After a 2-wk exposure to hypobaric (380 Torr) hypoxia, Cx43 immunostaining was substantially enhanced in and around type I cells. Moreover, chronic hypoxia elicited the expression of Cx43-like immunoreactivity in the cytoplasm of afferent neurons throughout the petrosal ganglion. Quantitative RT-PCR studies indicate that chronic hypoxia evokes a substantial increase in Cx43 mRNA levels in the carotid body, along with a marked elevation of Cx43 expression in the petrosal ganglion. Increased Cx43 expression and gap junction formation in type I cells and sensory neurons may contribute to carotid body adaptation during sustained stimulation in extreme physiological conditions.

Actins↗
PubMed2002

Application of spontaneous suction phase-dispersing (SSPD) extractors in the extraction of penicillin G.

The extraction of penicillin G from an aqueous solution with butyl acetate (BA) and tributyl phosphate (TBP) as extractants was carried out at pH 4 with spontaneous suction phase-dispersing (SSPD) extractors under various operating conditions. Four kinds of SSPD extractors were tested with results compared to those obtained by using an extractor with mechanical stirrers. Rotation speed and different extraction systems were found to influence the penicillin recovery and the stability of emulsion formed during extraction. The percentage of extraction under optimum conditions was 91% without formation of emulsion. The laser particle size measurement instrument combined with SSPD can be used to measure the emulsion droplet size in situ.

Biochemistry↗
PubMed2002

Differential dimerization and association among resistin family proteins with implications for functional specificity.

Secreted by white adipose tissue as a hormone, resistin was identified as a possible link between obesity and insulin resistance. High circulating resistin levels were observed to correlate with obesity. Administration of resistin lowered the glucose tolerance threshold and impaired insulin activity; whereas anti-resistin antibodies had the opposite effects. However, contradictory data were subsequently reported in regard to the correlation between resistin expression level and obesity or type 2 diabetes. Two additional proteins that share a highly homologous C-terminus with resistin have been identified in mouse, and one in human, forming a resistin-related protein family. Resistin was shown to dimerize through a disulfide bond formed by the N-terminal-most cysteine (Cys26). Here we demonstrate that while Cys26 is both necessary and sufficient for homodimer formation, all three resistin family members can also interact with one another regardless of the presence of Cys26 through non-covalent interactions. Furthermore, protein crosslinking analysis indicated that resistin and resistin beta, but not resistin alpha, exist as multimers, probably with a dimer as the subunit. The multiple protein complex formation is obviously at a level higher than the Cys26 disulfide bonding. These results suggest the potential importance of considering intermolecular interactions among resistin family members in studying their functions.

Animals↗
PubMed2002

Erythropoietin-mediated decrease of the redox-sensitive transcription factor NF-kappaB is inversely correlated with the hemoglobin level.

The aim of this study was to determine the effect of rh-EPO on the redox-sensitive transcription factor (NF-kappaB) in vivo and in vitro. Ten patients (7 female, 3 male), mean age 69.2 +/- 11 years, with end-stage renal failure and anemia prior to initiation of regular hemodialysis were enrolled and divided into 2 groups (group A "good responder", 7 patients and group B "poor responder", 3 patients) in accordance to the response to rh-EPO therapy. Nuclear binding activity of NF-kappaB was determined in ex vivo isolated mononuclear cells before, 4 and 8 weeks after onset of regular hemodialysis and rh-EPO therapy by electrophoretic mobility shift assays (EMSA). In group A, a reduction of NF-KB binding activity from 100% to 56 +/- 6% was observed within the first four weeks of rh-EPO treatment, while mean hemoglobin rose from 8.2 +/- 0.4 g/dl to 11.1 +/- 0.2 g/dl. However, this effect was abrogated after another 4 weeks of treatment when NF-kappaB signal increased back to 85.2 +/- 10.6% despite consistent mean hemoglobin level of 11.3 +/- 0.4 g/dl. Group B demonstrated a slight increase of NF-kappaB signal from 100% to 129 +/- 18.5%, while mean hemoglobin only moderately rose from 7.6 +/- 0.3 g/dl to 8.3 +/- 0.1 g/dl within the first 4 weeks, and it further rose to 180 +/- 45% after 8 weeks of treatment, while mean hemoglobin (9.5 +/- 0.1 g/dl) remained low. The NF-kappaB binding activity differed significantly when comparing both groups (p = 0.007). Binding activity of Oct-1, serving as control, did not change notably in either group (p = 0.34). In vitro studies showed that rh-EPO did not directly affect NF-KB binding activity in THP-1 cells. However, coincubation of THP-1 cells with erythrocytes led to a reduction of NF-kappaB binding activity only in THP-1 cells with a hemoglobin level adjusted to 11 g/dl compared to 8 g/dl in the presence of rh-EPO. In vivo and in vitro data implicate a complex interaction between rh-EPO, stimulated RBC and the redox-sensitive transcription factor NF-kappaB in mononuclear cells.

Aged↗
PubMed2002

Hyaluronan metabolism in rat tail skin following blockage of the lymphatic circulation.

This study was undertaken to explore the effects of lymphatic blockage on the metabolism of hyaluronan in the skin. In initial experiments, [3H] hyaluronan was injected subcutaneously into the tail skin of rats that either had no surgical intervention (control) or into those that had their lymphatic drainage blocked two hours earlier (acute lymphedema) or after the lymphatics had been blocked for three months (chronic lymphedema). The removal of tritiated hyaluronan from the injection sites was determined by the appearance of [3H] in the plasma. The results showed that the clearance of injected hyaluronan was delayed in rats with lymphatic blockage. The half- life of injected hyaluronan in the controls was approximately 70-75 hr, compared with approximately 105-110 hr in the lymph blocking rats. The levels of radioactivity in the plasma from rats with both acute and chronically blocked lymphatics were lower than that of control rats during the entire follow up period. In addition, biochemical analysis revealed that there was a significant increased amount of hyaluronan in the tail skin three months after lymphatic blocking. These results suggest that lymph absorption is an important factor in the transport of hyaluronan from the interstitium. Blockage of regional draining lymphatics likely impairs the catabolism of hyaluronan, which stagnates in skin tissue.

Animals↗
PubMed2001

Packing is a key selection factor in the evolution of protein hydrophobic cores.

The energy derived from optimized van der Waals interactions in closely packed, folded proteins has been proposed to be of similar energetic magnitude to hydrophobicity in stabilizing the native state. If packing is this energetically important, it should influence the evolution of protein core sequences. To test this hypothesis, the occurrence of various amino acid side chains in the major hydrophobic core of staphylococcal nuclease and 42 homologous proteins was determined. Most such positions in this protein family are usually isoleucine, leucine, or valine. Previously we have constructed and measured the stabilities of 12 single, 44 double, 64 triple, and 32 quadruple mutants, representing all possible permutations of these three side chains at two overlapping sets of four positions in the core of staphylococcal nuclease. The stabilities and interaction energies of those mutants with various combinations of the most common, or consensus, sequence were compared to the stabilities of all other mutants. Mutants which had the consensus side-chain combinations were not necessarily the most stable, but usually were found to have the best interaction energies. In other words, these proteins were far more stable than would be predicted from simply summing the observed energetic effects of the component single mutations, apparently reflecting particularly favorable packing interactions that are possible for the most common side chains. An additional 12 mutants which tested possible alternate explanations of the results were constructed. The stabilities and interaction energies of these mutants also support the conclusion that packing is a crucial determinant guiding the sequence evolution of protein cores.

Amino Acid Sequence↗
PubMed2001

Sex differences in cardiac catheterization: the role of physician gender.

CONTEXT: Many studies indicate that women are less likely than men to undergo cardiac procedures after an acute myocardial infarction (AMI), raising concerns of sexual bias in clinical care. However, no data exist regarding the relationship between patient sex, physician sex, and use of cardiac procedures. OBJECTIVE: To determine whether sex differences in cardiac catheterization after AMI were greater when patients were treated by male attending physicians compared with female attending physicians. DESIGN, SETTING, AND PATIENTS: Analysis of data from the Cooperative Cardiovascular Project, a retrospective medical record review. A total of 104 >231 Medicare fee-for-service beneficiaries who were hospitalized in US acute care hospitals for an AMI between January 1994 and February 1995. MAIN OUTCOME MEASURE: Use of cardiac catheterization within 60 days of admission, compared between the 4 groups of patient sex-physician sex combinations. RESULTS: Women underwent fewer cardiac catheterizations than men when treated by either male physicians (38.6% vs 50.8%; P =.001) or female physicians (34.8% vs 45.8%; P =.001). Sex differences in procedure use were not greater when a patient and physician were of different sexes (P for interaction =.85). After potential confounders in multivariable analysis were accounted for, women were less likely to undergo cardiac catheterization (risk ratio, 0.90 [95% confidence interval (CI), 0.88-0.92]), regardless of the treating physician's sex. Patients treated by male physicians were more likely to undergo cardiac catheterization (risk ratio, 1.06 [95%CI, 1.02-1.10]) than those treated by female physicians, regardless of patient sex. CONCLUSIONS: Women who have had an AMI undergo a cardiac catheterization less often than men, whether treated by a male or female physician. These results suggest that factors other than sexual bias by male physicians toward women account for sex differences in cardiac procedure use.

Aged↗
PubMed2001

Purification and characterization of the 1.0 MDa CCR4-NOT complex identifies two novel components of the complex.

The CCR4-NOT complex is an evolutionarily conserved, transcriptional regulatory complex that is involved in controlling mRNA initiation, elongation and degradation. The CCR4-NOT proteins from Saccharomyces cerevisiae exist in two complexes, 1.9x10(6) Da and 1.0x10(6) Da (1.0 MDa) in size, and individual components of these complexes display such disparate functions as binding to and restricting TFIID functions, contacting SAGA and contributing to mRNA deadenylation. As a first step in characterizing the functional roles of the 1.0 MDa complex, we have purified it to near homogeneity. Mass spectrometric analysis was subsequently used to identify all the components of the complex. The 1.0 MDa complex was found to contain CCR4, CAF1, NOT1-5 and two new proteins, CAF40 and CAF130. CAF130 and CAF40 are two unique yeast proteins, with CAF40 displaying extensive homology to proteins from other eukaryotes. Immunoprecipitation and gel filtration experiments confirmed that CAF130 and CAF40 are components of both of the 1.9 MDa and 1.0 MDa CCR4-NOT complexes. Biochemical analysis indicated that the CAF40 and CAF130 proteins bind to the NOT1 protein and exist in a location separate from the two other subsets of proteins in the complex: the CCR4 and CAF1 proteins, and the NOT2, NOT4 and NOT5 proteins. Moreover, CAF40 was able to interact with human NOT1, suggesting that human CAF40 would also be a component of the recently identified human CCR4-NOT complex. Analysis of caf40 and caf130 deletions indicated that they elicited phenotypes shared by defects in other CCR4-NOT genes. The distinct location of CAF40 and CAF130 and the evolutionary conservation of CAF40 implicate them in novel roles in the function of the CCR4-NOT complex.

Binding Sites↗
PubMed2001

Exposure to flaxseed or its purified lignan during suckling only or continuously does not alter reproductive indices in male and female offspring.

Based on the reported health benefits of flaxseed, many Canadians are choosing to consume flaxseed or flaxseed-containing foods. However, the safety of exposure to flaxseed during early life such as the suckling period has not been studied, despite the fact that components in flaxseed with potential hormone-like effects can be transferred to nursing offspring via mother's milk. Previous investigations demonstrated that maternal feeding of a 10% flaxseed diet during pregnancy and lactation resulted in estrogenic effects on reproductive indices among male and female offspring. These effects were attributed to the potential estrogenic activity of enterodiol and enterolactone, the two major mammalian lignans that are converted from secoisolariciresinol diglycoside (SDG) in flaxseed by colonic bacteria; however, the effect of exposure to purified SDG at the level of a 10% flaxseed diet was not studied. The objective of this study was to determine whether maternal feeding of flaxseed during lactation altered reproductive indices in male and female offspring. Rat dams were fed basal diet (BD) or BD containing either 100% flaxseed (10F) or the equivalent quantity of SDG present in the 10% (10S) flaxseed diet from the start of lactation until pups were 21 d old. At the end of lactation (postnatal day IPND] 21), suckling pups either continued on the mother's diet or were switched to BD until adolescence (PND 50) or young adulthood (PND 132) to determine if continuous exposure to flaxseed or SDG altered reproductive indices. The reproductive indices that were measured included anogenital distance from birth through PND 21, age and body weight at puberty onset (females only), estrous cycle length, reproductive organ weights at PND 50 and 132, and histological analysis of reproductive organs (uterus, ovaries, prostate) at PND 132. There were no significant effects of exposing male or female offspring to flaxseed or SDG during suckling only or during suckling through the postsuckling period on any of the reproductive indices measured. These findings are in contrast to the estrogenic effects observed in male and female offspring exposed to flaxseed during fetal life through suckling and suggest that fetal life is a more hormone-sensitive period of development. Although maternal feeding of flaxseed during lactation appears to be safe with respect to reproductive indices among offspring, future investigation is required to elucidate whether there are any long-term implications with respect to fertility.

Age Factors↗