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Biomedical subjects

J Y Wei

Publications and source records attributed to J Y Wei.

At least 19 recordsLinked to original sources
PubMed2005

Desloratadine prevents compound 48/80-induced mast cell degranulation: visualization using a vital fluorescent dye technique.

BACKGROUND: Desloratadine is a selective H1-antihistamine used in the treatment of allergic rhinitis and chronic idiopathic urticaria. Desloratadine inhibits the release of allergic inflammatory mediators in vitro. We studied the impact of desloratadine on mast cell degranulation due to activation and re-activation by the secretagogue, compound 48/80. METHODS: Rat peritoneal eluate containing 5-6% mast cells were activated by a low concentration of compound 48/80 in a medium containing the vital fluorescent dye, Sulforhodamine-B (SFRM-B, 200 microg/ml), which is engulfed by activated mast cells. The fluorescent image of activated mast cells was captured digitally and the total fluorescent area was analyzed when desloratadine was applied before or after compound 48/80. RESULTS: Mast cells were not activated by desloratadine (10(-4) M), SFRM-B (200 microg/ml), or diluent alone. A low concentration of compound 48/80 (0.125 microg/ml) induced fluorescence, while mast cells lost fluorescent images due to further degranulation on re-exposure to compound 48/80. Desloratadine (10(-8)-10(-4) M), inhibited compound 48/80-induced mast cell degranulation in a concentration-dependent manner. Desloratadine also reduced the loss of fluorescent images due to re-exposure to compound 48/80. CONCLUSIONS: Desloratadine may have a mast cell stabilizing effect at low concentrations in response to repeated mast cell activation in vitro.

Animals↗
PubMed2001

Early postnatal cardiac changes and premature death in transgenic mice overexpressing a mutant form of serum response factor.

Serum response factor (SRF) is a key regulator of a number of extracellular signal-regulated genes important for cell growth and differentiation. A form of the SRF gene with a double mutation (dmSRF) was generated. This mutation reduced the binding activity of SRF protein to the serum response element and reduced the capability of SRF to activate the atrial natriuretic factor promoter that contains the serum response element. Cardiac-specific overexpression of dmSRF attenuated the total SRF binding activity and resulted in remarkable morphologic changes in the heart of the transgenic mice. These mice had dilated atrial and ventricular chambers, and their ventricular wall thicknesses were only 1/2 to 1/3 the thickness of that of nontransgenic mice. Also these mice had smaller cardiac myocytes and had less myofibrils in their myocytes relative to nontransgenic mice. Altered gene expression and slight interstitial fibrosis were observed in the myocardium of the transgenic mice. All the transgenic mice died within the first 12 days after birth, because of the early onset of severe, dilated cardiomyopathy. These results indicate that dmSRF overexpression in the heart apparently alters cardiac gene expression and blocks normal postnatal cardiac growth and development.

Age of Onset↗
PubMed2001

Miniature postsynaptic currents depend on Ca2+ released from internal stores via PLC/IP3 pathway.

Miniature postsynaptic currents (mPSCs) were examined on autaptic innervation of single rat retinal ganglion cells in low density cultures. Removal of Ca2+ from bath solution or blocking of Ca2+ channels by Cd2+ had no detectable effect on mPSC frequency or amplitude. Thapsigargin, an agent for mobilization of Ca2+ from internal stores, increased mPSC frequency 3-5-fold in control, Ca2+-free or Cd2+-containing solutions. The inositol 1,4,5-triphosphate (IP3) receptor antago- nist, heparin; the phospholipase C (PLC) inhibitor, U73122; and caffeine abolished mPSC or decreased mPSCs frequency. Calcium imaging showed that cytosolic Ca2+ was increased by thapsigargin and decreased by caffeine. These data demonstrate that internal store-released Ca2+ regulated by the PLC/IP3/IP3-receptor pathway has critical contribution to generation and control of miniature release in retinal ganglion cells.

Animals↗
PubMed2001

Quantification and sequencing of somatic deleted mtDNA in single cells: evidence for partially duplicated mtDNA in aged human tissues.

Single-cell PCR of the whole mitochondrial genome provides detailed information about intracellular clonal expansions of deleted mitochondrial DNA (DeltamtDNA), which contribute to aging of the muscle and possibly other tissues. Analysis of approximately 1400 cells from heart, diaphragm and skeletal muscle from 20 individuals without mitochondrial disease revealed that up to 25% of cells in a tissue sample may bear clonally expanded DeltamtDNA. Sequence analysis of >50 clonal DeltamtDNA reveals that about half of them lack the light strand origin of replication. This observation is puzzling since these molecules must have retained the ability to replicate in order to be able to undergo clonal expansion. We present evidence that such DeltamtDNA molecules may in fact exist in the cell as partially duplicated mtDNA (pdmtDNA) previously described in certain mtDNA disorders. In contrast to the 'originless' DeltamtDNA, the corresponding pdmtDNA do possess a light strand origin required for their propagation. Most pdmtDNA also possess an extra heavy strand origin, which may result in higher replication rate and thus provide a mechanism for expansion. Importantly, pdmtDNA are indistinguishable from DeltamtDNA in PCR assays routinely used to detect somatic mtDNA deletions in tissues of normally aged individuals. These results indicate that a substantial proportion of age-related mtDNA deletions reported in the literature may exist as or be derived from pdmtDNA.

Adolescent↗
PubMed2001

Disparate effects of socioeconomic status on physical function and emotional well-being in older adults.

We tested the hypothesis that among community living older adults with relatively low and high socioeconomic status (SES), low SES is associated with both poorer emotional well-being and physical function. Ambulatory, community living older men and women (70-89 years of age) were recruited from outpatient geriatric assessment clinics in relatively high socioeconomic areas of greater Boston (High SES, N=47), and from an urban senior center in the inner city (Low SES, N=66). We assessed health status, mental health, upper and lower extremity strength and physical function. We found that health status was not significantly different in the two groups. Quadriceps strength (Low SES: 199+/-57 N; High SES: 190+/-56 N; p=0.531) and Up and Go times (Low SES: 14.3+/-3.1 sec; High SES: 16.7+/-9.5 sec; p=0.068) were not significantly different in the two groups, while grip strength was slightly higher in the Low SES group (Low SES: 22.8+/-6.45 kg; High SES: 20.07+/-7.55 kg; p=0.049). In contrast, subjects with Low SES tended to have an increased tendency towards depression. Scores on the Geriatric Depression Scale were 3.8+/-3.0 in Low SES, and 1.8+/-2.8 in High SES (p<0.001). We conclude that while health status and physical function were not worse in subjects with low SES, emotional well-being was markedly less compared to seniors with high SES. SES may have disparate effects on physical function and mental health, perhaps due to different compensatory mechanisms.

Activities of Daily Living↗
PubMed2001

Differential vulnerability to oxidative stress in rat cardiac myocytes versus fibroblasts.

OBJECTIVES: This study was designed to test the hypothesis that cardiac myocytes have greater vulnerability to oxidative stress compared with cardiac fibroblasts. BACKGROUND: The function of cardiac myocytes differs from that of fibroblasts in the heart, but differences in their response to oxidative stress have not been extensively studied. METHODS: Cardiomyocytes and fibroblasts from F344 neonatal rat hearts were cultured and exposed to different concentrations of hydrogen peroxide (H(2)O(2)) and menadione (superoxide generator). The mitogen-activated protein kinase (MAPK) proteins were assayed after oxidative stress; cell death was determined by trypan blue staining and deoxyribonucleic acid (DNA) ladder electrophoresis. RESULTS: The cardiac myocytes were significantly more vulnerable than the fibroblasts to oxidative damage, showing substantial DNA fragmentation and consistently poor cell survival after exposure to H(2)O(2) (100 to 800 microM), while the cardiac fibroblasts demonstrated little or no DNA fragmentation, and superior cell survival rates both over time (from 1 to 72 h after 100 microM) and across increasing doses of H(2)O(2) (100 to 800 microM). The p42/44 extracellular signal-regulated kinases were phosphorylated in both cell types after exposure to H(2)O(2), but significantly more in cardiac fibroblasts. However, p38 MAPK and c-jun NH(2)-terminal kinase were phosphorylated more in the cardiac myocytes compared to cardiac fibroblasts. This was also the case after exposure to menadione. CONCLUSION: Taken together, these results suggest that oxidative stress causes greater injury and cell death in cardiac myocytes compared with cardiac fibroblasts. It is possible that the signaling differences via the MAPK family may partly mediate the observed differences in vulnerability and functional outcomes of the respective cell types.

Animals↗
PubMed2001

Endogenous anticholinergic substances may exist during acute illness in elderly medical patients.

BACKGROUND: The purpose of this study was to determine if serum anticholinergic activity (SACA) arises from endogenous substances produced during illness. METHODS: Elderly medical inpatients (N = 612) were screened for anticholinergic medication use in the week prior to the study by interviews of subjects and proxies and review of emergency room, hospital, and nursing home medication administration records. Of 24 subjects without a recent anticholinergic medication history, 15 were recruited and 10 completed the study. Serum samples were obtained on Day 2 of hospital admission. SACA was measured using a radionuclide displacement assay. Medications taken by subjects were assayed for central muscarinic receptor binding at therapeutic concentrations. Results. Eight of the ten subjects had SACA detectable in the serum. No medication used by these subjects had anticholinergic activity at usual therapeutic concentrations. CONCLUSIONS: Endogenous anticholinergic substances may exist during acute illness. Characterization of such substances may increase the depth of our understanding of delirium and lead to useful intervention strategies.

Acute Disease↗
PubMed2001

Cardiomyopathy in transgenic mice with cardiac-specific overexpression of serum response factor.

Serum response factor (SRF), a member of the MCM1, agamous, deficiens, SRF (MADS) family of transcriptional activators, has been implicated in the transcriptional control of a number of cardiac muscle genes, including cardiac alpha-actin, skeletal alpha-actin, alpha-myosin heavy chain (alpha-MHC), and beta-MHC. To better understand the in vivo role of SRF in regulating genes responsible for maintenance of cardiac function, we sought to test the hypothesis that increased cardiac-specific SRF expression might be associated with altered cardiac morphology and function. We generated transgenic mice with cardiac-specific overexpression of the human SRF gene. The transgenic mice developed cardiomyopathy and exhibited increased heart weight-to-body weight ratio, increased heart weight, and four-chamber dilation. Histological examination revealed cardiomyocyte hypertrophy, collagen deposition, and interstitial fibrosis. SRF overexpression altered the expression of SRF-regulated genes and resulted in cardiac muscle dysfunction. Our results demonstrate that sustained overexpression of SRF, in the absence of other stimuli, is sufficient to induce cardiac change and suggest that SRF is likely to be one of the downstream effectors of the signaling pathways involved in mediating cardiac hypertrophy.

Actins↗
PubMed2001

Clinical implications of physiological changes in the aging heart.

Elderly individuals experience a disproportionate burden from cardiovascular disease. Global changes in aging will have a significant impact on the future of medical practice. However, most physicians have little formal training in geriatric medicine and sometimes fail to distinguish disease states from normal aging. Increasingly, it is recognised that a sedentary lifestyle may be responsible for a large fraction of the so-called 'age-related' changes in the cardiovascular system. Nonetheless, well characterised changes do occur in most individuals with aging. Loss of myocytes with subsequent hypertrophy of the remaining cells is usually observed. Calcification involving the conduction and valvular apparatus is seen in most elderly individuals and may predispose to the common arrhythmias of old age. Age-related loss of arterial compliance contributes to isolated systolic hypertension and left ventricular hypertrophy. Despite these changes, for the majority of healthy older adults, cardiac output is well maintained in the basal state through use of the Frank-Starling principle, in the setting of reduced early diastolic filling. Myocardial relaxation is slowed in part due to age-related changes in the sarcoplasmic reticulum Ca2+ ATPase pump. Elevated blood levels of catecholamines contribute to desensitisation to noradrenergic stimulation and this is associated with an age-related decline in maximum achievable heart rate. Changes in the baroreceptor reflex function and decreased sodium conservation may predispose some individuals to orthostatic and postprandial hypotension. The aetiology of cardiovascular aging is under intense study. The most likely mechanisms involve the result of cumulative damage mediated through a variety of insults. Oxidative stress, non-enzymatic glycation, inflammation and changes in cardiovascular gene expression all seem to influence cardiovascular aging. The benefits of exercise continue to be discovered. Endurance-type training has been shown to have a dramatic impact on parameters of cardiovascular aging. Favourable effects are seen in maximum oxygen consumption, diastolic filling, relaxation and arterial stiffness. Some changes such as the maximum heart rate response do not appear to change with conditioning. Pharmacotherapy may afford the opportunity to influence the aging process. Drugs that can reduce age-associated arterial stiffness, cardiac fibrosis and ventricular hypertrophy should prove useful. Antioxidants continue to be a topic of great interest and require more study. Despite some well described changes with aging, most elderly individuals maintain the opportunity for improved cardiovascular function through conditioning. Early recognition and treatment of diseases that are distinguishable from normal aging, including hypertension and atherosclerosis, together with preventive efforts, should reduce the predicted trends in cardiovascular morbidity and mortality among the aged.

Aging↗
PubMed2001

[Function of the leaky UGA codon in ssRNA plant virus genomes].

The opal mutation (UGA) at nucleotide 2670-2672 in the replicase gene of the attenuated tomato mosaic virus K (ToMV-K) mainly contributes to the virus attenuation based on a series of studies on the viral attenuation mechanism. From analysis and comparison between the replicase gene mutation point of ToMV-K and the related regions of all plant viruses containing the leaky UGA, we have found that some characters, including the CGG motif, alpha-helix structure and some specific amino acids, are, presumably, able to helpfully confer the readthrough mechanism. Finally, some other ssRNA plant viruses like PVX, PVY, CMV have been analyzed. We found that their genomic modifications and viral attenuations could be explored according to the mutation mode of the ToMV-K replicase.

Amino Acid Sequence↗
PubMed2000

Suppression of stress kinase JNK is involved in HSP72-mediated protection of myogenic cells from transient energy deprivation. HSP72 alleviates the stewss-induced inhibition of JNK dephosphorylation.

Since protection of cells from stress-induced apoptosis by the heat shock protein Hsp72 involves suppression of stress kinase JNK, we suggested that Hsp72-mediated JNK inhibition might also be critical for myocardial protection from ischemia/reperfusion. Transient energy deprivation of H9c2 myogenic cells, used as an in vitro model of myocardial ischemia, led to cell death that had morphological features of apoptosis and necrosis and was independent of caspases. Surprisingly, this unusual type of cell death was regulated by JNK and ERK kinases. In fact, specific inhibition of JNK increased cell survival; specific inhibition of ERKs enhanced deleterious consequences of energy deprivation, whereas inhibition of p38 kinase had no effect. Hsp72 suppressed activation of JNK and did not increase ERK activity, suggesting that inhibition of JNK is the important component of Hsp72-mediated protection. Upon transient energy deprivation, activation of JNK proceeds via two distinct pathways, stimulation of JNK phosphorylation by a protein kinase SEK1 and inhibition of JNK dephosphorylation. Remarkably, in cells exposed to transient energy deprivation, Hsp72 enhanced the rate of JNK dephosphorylation but did not affect SEK1 activity. Therefore, it appears that Hsp72 specifically down-regulates JNK by accelerating its dephosphorylation, which reduces the susceptibility of cardiac cells to simulated ischemia/reperfusion.

Adenosine Triphosphate↗
PubMed2000

Synergistic interaction between CCK and leptin to regulate food intake.

Leptin administered (either intracerebroventricularly, icv, or intraperitoneally, ip) acts in synergy with CCK to suppress food intake and body weight in lean mice or rats. The potentiating effect induced by the co-injection of ip CCK and leptin to inhibit food consumption in mice is mediated by the CCK-A receptor and capsaicin sensitive afferents. In vitro, studies in rats showed that a subset of gastric vagal afferent fibers responded to leptin injected directly into the gastric artery only after a prior intra-arterial CCK injection. Moreover, the tonic activity of gastric-related neurons in the nucleus tractus solitarius (NTS) increased when leptin was delivered into the gastric chamber of an in vitro stomach-brainstem preparation. CCK co-injected with leptin potentiated Fos expression selectively in the area postrema, NTS and paraventricular nucleus of the hypothalamus (PVN), which points to the PVN as part of the afferent and efferent limbs of the circuitry involved in the synergistic interaction between leptin and CCK. The dampening of CCK or leptin inhibitory action on ingestive behavior when either factor is not present or their receptors are non functional supports the notion that such leptin-CCK interaction may have a physiological relevance. These observations provide a mean through which leptin and CCK integrate short- and mid-term meal-related input signals into long-term control of energy balance.

Animals↗
PubMed2000

Neutrophilia and congestive heart failure after acute myocardial infarction.

BACKGROUND: Inflammation associated with acute myocardial infarction (AMI) is frequently marked by a peripheral leukocytosis and relative neutrophilia. Whether this process may contribute to the development of postinfarction congestive heart failure (CHF) is not established. The objective of this study was to examine the association between hospital admission peripheral total leukocyte count and the neutrophil percentage and the subsequent development of CHF in patients with AMI. The study was designed as a retrospective cohort study in the setting of a tertiary referral hospital. Participants included 185 patients discharged with a diagnosis of AMI between May 1 and Sept 30, 1996. METHODS AND RESULTS: Outcome measures included clinical episodes of CHF with confirmatory chest roentgenogram findings and/or echocardiographic evidence of contractile dysfunction. Multivariable logistic regression analyses were performed to examine the relation between the total leukocyte count, neutrophil percentage, and the development of CHF in the first 4 days after AMI while controlling for baseline characteristics and early therapeutic interventions. Thirty-one percent of the cohort had a leukocyte count >11.0 x10(9)/L on admission to the hospital; 65% had a neutrophil percentage >65%, and 61% had a lymphocyte percentage </=25%. CHF developed in 43% of the cohort. Of these, 92. 5% had relative neutrophilia (neutrophil percentage >65%) compared with 45% of those in whom CHF did not develop. Multivariable analysis revealed a highly significant association between relative neutrophilia and the subsequent development of CHF (odds ratio 14.3; 95% confidence interval 5.2 to 39.3). CONCLUSIONS: Relative neutrophilia on admission to the hospital in patients with AMI is significantly associated with the early development of CHF. This association may help in the identification of individuals at high risk who might benefit from more aggressive interventions to prevent or reduce the risk of CHF.

Adult↗
PubMed2000

Peripheral corticotropin-releasing factor and stress-stimulated colonic motor activity involve type 1 receptor in rats.

BACKGROUND & AIMS: Corticotropin-releasing factor (CRF) exerts its action through CRF receptors 1 and 2 (CRF-R1 and CRF-R2). CRF has preferential affinity for CRF-R1, whereas urocortin displays high affinity for both. We investigated changes in colonic motor function after intraperitoneal (IP) injection of CRF-related peptides. METHODS: Colonic motility was recorded in vivo in conscious rats equipped with electrodes chronically implanted in the cecum and proximal colon or in vitro in distal colon; fecal output was monitored in naive rats. RESULTS: Rat CRF, rat urocortin, and amphibian sauvagine (10 microg/kg, IP) induced a new pattern of cecocolonic myoelectric activity characterized by clustered spike bursts of long duration; the percentage of occurrence was highest after CRF. The rank order of potency to increase fecal pellet output after IP peptide injection (0.3-10 microg/kg, IP) was CRF > urocortin = sauvagine. The CRF-R1/R2 antagonist astressin (33 microg/kg, IP) and the CRF-R1 antagonist CP-154,526 (20 mg/kg, subcutaneously) inhibited IP CRF-induced changes in cecocolonic myoelectric activity and IP CRF- and water avoidance stress-induced fecal output. In vitro, CRF injected into the inferior mesenteric artery increased distal colonic myoelectric activity compared with saline injection. CONCLUSIONS: These results demonstrate that CRF acts peripherally to stimulate colonic motility and that CRF-R1 is primarily involved in mediating IP CRF/urocortin- and water avoidance stress-induced colonic motor response.

Animals↗
PubMed2000

One-year follow-up of medication management capacity in highly functioning older adults.

BACKGROUND: We tested the hypothesis that impairment in the ability to take medication independently predicts early functional decline. METHODS: A 12-month, prospective cohort study was performed at two continuing-care retirement facilities using the Drug Regimen Unassisted Grading Scale (DRUGS). This geriatric screening tool utilizes a stepwise progression of four tasks: (i) identification, (ii) access. (iii) dosage, and (iv) timing. RESULTS: Forty-seven (86%) of the eligible participants completed the 12-month follow-up assessment; three were transferred to skilled nursing facilities. The mean age at study entry was 84.2+/-5.1 years; 72% of the participants were women, and 68% were college educated. At 12 months there was a decline in the Mini-Mental State Examination (MMSE) score (p = .029), an increase in the timed "Up and Go" test (p = .023), and a decline in the DRUGS score (p .029). Nine (18%) of the participants resided in assisted- versus independent-living situations compared with three participants (5%) at study entry (p = .031). Both 12-month DRUGS score and 12-month self-reported medication management capacity were associated with 12-month MMSE (p = .0001 and p = .019, respectively). Baseline DRUGS score was associated with 12-month MMSE and Geriatric Depression Scale scores (p = .0002 and p = .002, respectively). Both baseline DRUGS score and self-reported medication management capacity were also associated with residence in assisted-living communities at 6 months (p = .029 and p = .040, respectively). MMSE was not associated with any of the clinical outcomes.

Activities of Daily Living↗
PubMed2000

Reducing cardiovascular stress with positive self-stereotypes of aging.

We examined whether aging self-stereotypes, or older individuals' beliefs about elderly people, can influence cardiovascular function. Older individuals were subliminally exposed to either positive or negative aging stereotypes. Then all participants faced mathematical and verbal challenges. Those exposed to the negative aging stereotypes demonstrated a heightened cardiovascular response to stress, measured by systolic blood pressure, diastolic blood pressure, and heart rate, compared with those exposed to positive aging stereotypes. The aging stereotypes appeared to influence the outcome variable of skin conductance in the same way. It appears that the negative aging stereotypes acted as direct stressors, whereas the positive aging stereotypes reduced cardiovascular stress. These findings indicate that negative aging stereotypes may contribute to adverse health outcomes in elderly persons without their awareness. The results also suggest that positive aging stereotypes could be used in interventions to reduce cardiovascular stress.

Aged↗
PubMed2000

Physician perceptions of HMO care for older persons. Health Maintenance Organization.

OBJECTIVE: Physician attitudes may be a key factor in effective managed care for older patients. We sought to explore physicians' views of the influence of health maintenance organization (HMO) policies on the care of their older patients. DESIGN: A self-administered one-page questionnaire consisting of questions about physician demographics, the impact of HMOs on physician practice, patient care, HMO policies, and respondents' personal use of managed health care plans. PARTICIPANTS: The survey was mailed to 838 randomly selected primary care physicians affiliated with two large, nonprofit, academically-oriented, Medicare HMOs in Massachusetts. RESULTS: Completed surveys were received from 516 of 797 eligible primary care physicians, affiliated with either Secure Horizons (Tufts Associated Health Plan) or First Seniority (Harvard Pilgrim Health Care). About half (55%) of the physician respondents reported they had sufficient time to spend with their older patients. Most (81%) respondents indicated that overall, patients aged 65 and older received either better care or no change in care after joining an HMO. The majority of physicians reported that HMO affiliation had increased the frequency with which they addressed geriatric issues with their older patients. There were several patterns of response that emerged with respect to beliefs about key HMO policies. CONCLUSIONS: The majority of physicians working in two nonprofit, academically oriented Medicare HMOs in Massachusetts believed that the overall quality of care that older patients received after joining an HMO either did not change or improved.

Aged↗