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Biomedical subjects

S Ling

Publications and source records attributed to S Ling.

At least 37 records · Page 2Linked to original sources
PubMed1999

Modulation of mitochondrial Ca(2+) homeostasis by Bcl-2.

We have investigated the role of mitochondrial Ca(2+) (Ca(m)) homeostasis in cell survival. Disruption of Ca(m) homeostasis via depletion of the mitochondrial Ca(2+) store was the earliest event that occurred during staurosporine-induced apoptosis in neuroblastoma cells (SH-SY5Y). The decrease of Ca(m) preceded activation of the caspase cascade and DNA fragmentation. Overexpression of the anti-apoptosis protein Bcl-2 led to increased Ca(m) load, increased mitochondrial membrane potential (DeltaPsi(m)), and inhibition of staurosporine-induced apoptosis. On the other hand, ectopic expression of the pro-apoptotic protein Bik led to decreased Ca(m) load and decreased DeltaPsi(m). Inhibition of calcium uptake into mitochondria by ruthenium red induced a dose-dependent apoptosis as determined by nuclear staining and DNA ladder assay. Similarly, reducing the Ca(m) load by lowering the extracellular calcium concentration also led to apoptosis. We suggest that the anti-apoptotic effect of Bcl-2 is related to its ability to maintain a threshold level of Ca(m) and DeltaPsi(m) while the pro-apoptotic protein Bik has the opposite effect. Furthermore, both ER and mitochondrial Ca(2+) stores are important, and the depletion of either one will result in apoptosis. Thus, our results, for the first time, provide evidence that the maintenance of Ca(m) homeostasis is essential for cell survival.

Calcium↗
PubMed1999

External beam radiotherapy in retinoblastoma: tumor control and comparison of 2 techniques.

OBJECTIVE: To investigate eye conservation, local control, and complication rates among children with retinoblastoma treated with 2 different external beam radiotherapy (EBR) techniques. METHODS: Fifty-eight eyes in 42 patients received EBR as the primary treatment modality for retinoblastoma (median follow-up, 37 months). The EBR technique was relative lens-sparing (RLS) in 26 eyes and modified lateral beam (MLB) in 32 eyes. Both groups were comparable in Reese-Ellsworth retinoblastoma classification. If necessary, patients received focal salvage therapy. RESULTS: At 24 months, eye conservation rates were 88.5% and 89.1% among eyes treated with RLS and MLB, respectively (P = .40); tumor control rates without salvage therapy were 84.6% and 53.3% (P = .02), respectively. Among eyes with Reese-Ellsworth stage IV and V disease, eye conservation rates were 88%+/-8% and 83%+/-9% at 36 months in the RLS and MLB groups, respectively, and local tumor control rates were 81%+/-10% and 51%+/-12%. Percentages of eyes without cataract at 36 months were 83.1% and 63.0%, respectively (P = .40). Among patients observed for at least 18 months, midfacial hypoplasia developed in 38.5% and 29.4%, respectively (P = .70). CONCLUSIONS: The EBR technique was associated with high eye conservation and local control rates. Salvage therapy was performed significantly less frequently in the RLS group compared with the MLB group, and complication rates in both groups were similar.

Child, Preschool↗
PubMed1999

Severity of hand osteoarthritis and its association with upper extremity impairment in a population of disabled older women: the Women's Health and Aging Study.

Most severity indices of osteoarthritis (OA) include measures of physical function which render them unsuitable for assessing the impact of OA on disability. Data from 1002 moderate to severely disabled community-dwelling women > or = 65 years were used to develop hand OA severity indices which are independent of functional status. Baseline exams and strength tests were conducted by trained nurse examiners. Each distal and proximal interphalangeal joint, and first carpometacarpal joint (20 joints in all) was scored for the presence of a) bony enlargement or deformity, and b) pain on motion or tenderness on palpation. Severity indices were then created: Deformity index (DEF) = sum of joints with bony changes (0-20); Pain/Tenderness index (PT) = sum of joints with pain or tenderness (0-20); and Combined Deformity/Pain index = sum of DEF and PT (0-40). These indices were then validated against grip and pinch strength. All three indices showed a significant trend for weaker grip strength as severity index scores increased. When the 25th, 50th and 75th percentiles were used to divide each severity index into levels of involvement, a threshold effect was observed with significantly poorer grip strength performance above the 75th percentile for each index. Similar results were seen for pinch strength. In conclusion, these hand OA severity indices, based on examination findings alone, help distinguish disease status, and may provide a valuable research tool for investigating the role of hand OA in impairment and disability.

Aged↗
PubMed1999

Disability, physical activity, and muscle strength in older women: the Women's Health and Aging Study.

OBJECTIVE: To study associations of motor disability, physical activity, and muscle strength in older women, in particular to investigate whether model of spiraling decrease is expressed in the data. DESIGN: Cross-sectional analysis using data from the baseline measurements of The Women's Health and Aging Study (WHAS). SETTING: Participants' homes. PARTICIPANTS: A total of 1,002 disabled women aged 65 years and older living in the community. OUTCOME MEASURES: Motor disability was measured by the number of self-reported difficulties in grasping, lifting 101b, walking across a small room, walking 1/4 mile, climbing 10 steps, and doing heavy housework. Level of physical activity was determined from response to a series of questions on the frequency and amount of common activities and physical exercise. Hand grip and knee extension forces were measured using portable hand-held dynamometers. RESULTS: Disability and physical activity were inversely associated, with inactivity being most common among the most disabled women. Those with poorer strength reported more difficulties in motor activities. Greater strength was found among the physically more active. In stratified analyses, the positive association of physical activity on knee extension strength was consistent across disability levels. Multiple regression analysis showed that both physical activity and muscle strength were significant predictors for severity of disability. Structural equation model (LISREL) showed that muscle strength had a mediating role between physical activity and disability; disability was associated with physical inactivity, which correlated with lower muscle strength, which was associated with greater degree of disability. CONCLUSION: Even though causality cannot be confirmed in this cross-sectional analysis, our findings suggested a spiraling model of decline in which muscle strength has a significant role.

Activities of Daily Living↗
PubMed1999

Low back pain and disability in older women: independent association with difficulty but not inability to perform daily activities.

BACKGROUND: Low back pain is a highly prevalent chronic condition, yet little is known about the disabling effects of this common problem in older adults. This study examines the relationship between the presence and severity of low back pain and disability in older women. METHODS: The study population was 1,002 disabled older women participating in a population-based prospective study of disablement. Key outcome measures of disability included level of difficulty and inability to perform the following daily activities: light housework, shopping, walking one-quarter mile, climbing stairs, lifting, and activities of daily living (ADLs). RESULTS: Forty-two percent of participants reported they had low back pain for at least one month in the year before baseline. The prevalence of severe back pain decreased markedly with age (10% of those > or = 85 yr versus 23% in each of the two younger 10 yr age groups). After multivariate adjustments, women with severe back pain were 3 to 4 times more likely than other women to have a lot of difficulty with light housework or shopping. There was also an increased likelihood of difficulty with mobility tasks and basic ADLs among those with severe back pain. No associations were found between back pain and being unable to perform any of the daily activities studied, indicating possible differences in disablement processes leading to functional difficulties versus functional incapacity. CONCLUSIONS: There was a strong association between back pain and functional difficulties in older women, pointing to the need for further research using longitudinal methods.

Activities of Daily Living↗
PubMed1999

Matrix-dependent gene expression of egr-1 and PDGF A regulate angiotensin II-induced proliferation in human vascular smooth muscle cells.

We have previously shown, in a neonatal rat cell line, that angiotensin II (Ang II)-induced proliferation in vascular smooth muscle cells is extracellular matrix (ECM) dependent. We hypothesized that such an effect might be mediated via differences in Ang II-induced increases in the transcriptional factor early growth response-1 (Egr-1) gene and, consequently, in platelet-derived growth factor (PDGF). Cultured human newborn aortic smooth muscle cells were studied on 4 different surfaces: (1) plastic, (2) laminin, (3) collagen, and (4) fibronectin. Ang II-induced increases in DNA synthesis were significantly greater on collagen (2.0+/-0.3-fold) and fibronectin (1.9+/-0.3-fold) than on laminin (1.0+/-0.2-fold) or plastic (1.4+/-0.2-fold). As with DNA synthesis, at 48 and 72 hours, Ang II-induced increases in cell numbers occurred only in cells grown on collagen and fibronectin culture plates and were blocked by an antagonist to the angiotensin type 1 (losartan, 10 micromol/L) but not the angiotensin type 2 (PD 123319, 10 micromol/L) receptor. Anti-PDGF AA antibody (6 microg/mL) blocked the increase in DNA synthesis by 60% to 64% in cells on collagen or fibronectin cultures but not on plastic cultures. When PDGF-AA (10 ng/mL) and Ang II were added together, DNA synthesis increased 2-fold and did not differ on the various ECM proteins. Increases in PDGF A-chain mRNA were observed only in cells grown on collagen (3.21+/-0.65-fold) and fibronectin (2.86+/-0.49-fold) plates 2 to 8 hours after the addition of Ang II and were blocked by losartan but not PD 123319. Expression of Egr-1, an early growth response gene, increased at 15 minutes, peaked at 30 minutes, and returned to normal after 2 hours with Ang II treatment. Ang II-induced increases in Egr-1 mRNA were greater on collagen (4. 82+/-0.66-fold at maximum) and fibronectin (4.01+/-0.56-fold) than on laminin (2.74+/-0.45-fold) or plastic (2.53+/-0.40-fold) and were blocked by losartan but not PD 123319. Thus, in human vascular smooth muscle cells in culture, Ang II-induced proliferation is mediated via the angiotensin type 1 receptor, dependent on ECM proteins, and regulated by differential gene expression of Egr-1 and PDGF-1.

Angiotensin II↗
PubMed1999

Lower body osteoarticular pain and dose of analgesic medications in older disabled women: the Women's Health and Aging Study.

OBJECTIVES: This study assessed use and dosage of analgesic medications in relation to severity of osteoarticular pain. METHODS: The type and dose of analgesic medication and the severity of pain in the lower back, hips, knees, or feet of 1002 older disabled women were assessed. RESULTS: Severe pain and the use of analgesic medications were reported by 48.5% and 78.8% of women, respectively. Among those who had severe pain, 41.2% were using less than 20% of the maximum analgesic dose. Overall, 6.6% of women were using more than 100% of the maximum dose. CONCLUSIONS: Severe pain is common. Additional, more effective, and safe analgesic treatments are needed for controlling pain in older persons.

Activities of Daily Living↗
PubMed1998

The importance of postoperative radiation therapy in multimodality management of locally advanced breast cancer: a phase II trial of neoadjuvant MVAC, surgery, and radiation.

PURPOSE: To determine the impact of postoperative radiation on locoregional relapse and overall survival rate in a multimodality protocol for locally advanced breast cancer (LABC). MATERIAL AND METHODS: Of the patients entered in the protocol, 55 were evaluable. Treatment consisted of: neoadjuvant MVAC (methotrexate, vinblastine, adriamycin, and cisplatin) until a maximum response had been achieved; modified radical mastectomy; 6 courses of postoperative adjuvant MVAC chemotherapy, and chest wall irradiation (CWXRT). Multivariate analysis of locoregional response and overall survival was done. RESULTS: Of the total, 42 patients received chest wall radiation; 28 of these also received radiation to regional lymph nodes. Chest wall doses ranged from 45 Gy to 50.4 Gy to the whole chest wall, with 31 patients receiving an additional chest-wall boost. The incidence of locoregional relapse with and without radiation was 7% vs. 31%, respectively (p = 0.026). An overall survival benefit was seen in those receiving radiation, with a mean overall survival of 50 months vs. 20 months, and a 3-year overall survival of 88% vs. 46% with and without radiation, respectively (p = 0.003). Multivariate analysis showed that overall survival was affected by the presence of pathological CR (p = .047), the number of pre-operative chemotherapy cycles (p = .036) and whether or not they received radiation (p = 0.003). Neither the interval between surgery and radiation, technique of radiation, nor radiation modality significantly affected local control. CONCLUSION: The significant improvement in local regional control and overall survival with the addition of radiation suggests that radiation should be an integral part of multimodality management of locally advanced breast cancer.

Adult↗
PubMed1998

Stabilization of a channel's open state by a hydrophobic residue in the sixth membrane-spanning segment (S6) of rKv1.4.

We report the effects of mutating a threonine residue at position 529 (T529) in the middle of the S6 segment of rKv1.4 on the voltage-dependence and kinetics of activation and deactivation. Replacing T529 with glycine (no side chain) or with a residue that has a hydrophobic side chain (T529L, T529I, T529V, T529A, or T529F) caused a slowing of deactivation, along with a negative shift in the activation curve and a voltage-dependent slowing of activation. Numerical simulation showed that these effects could be reproduced by decreasing the rate constant for a transition from open to closed states. The degree of slowing of deactivation largely correlated with the degree of increase in 529 side-chain hydrophobicity. Specifically, the 529 mutation-induced alteration in free energy change accompanying deactivation per channel could be accounted for by the increase in free energy needed to transfer the 529 side chain of one subunit from a hydrophobic environment to an aqueous environment. We propose that in the open state, the 529 side chain faces a hydrophobic protein interior. The rate-limiting step in channel deactivation includes a conformational change in one subunit's S6 segment, moving its 529 side chain to face the aqueous lumen of the pore.

Amino Acid Sequence↗
PubMed1998

The use of a chimera HIV-1/HIV-2 envelope protein for immunodiagnosis of HIV infection: its expression and purification in E. coli by use of a translation initiation site within HIV-1 env gene.

A chimera HIV-1/HIV-2 envelope sequence composed of multiple conserved immunodominant epitopes of HIV-1 envelope protein (HIV-1 IIIB: env482-518 + env548-675) and the HIV-2 gp36 immunodominant epitope (env592-603), was constructed and directly over-expressed in E. coli by using a prokaryotic translation initiation sequence contained within the gene of HIV-1 envelope. The recombinant product was purified and applied in antibody-screening assay. The purified chimera antigen reacted with all the thirty-eight HIV-1 positive serum samples, the two HIV-2 serum samples, and had no cross-reaction with all the eighty-eight normal healthy serum sample. The results indicated that this recombinant chimera HIV-1/HIV-2 envelope protein could be useful for diagnostic purposes of HIV infection.

AIDS Serodiagnosis↗
PubMed1998

Racial differences in muscle strength in disabled older women.

This study examines racial differences in muscle strength, and associations of muscle strength to level of physical activity and severity of disability, among a community sample of 254 black and 665 white, moderately to severely disabled women aged 65 and older. Potential confounders that were adjusted for in the models included age, body weight and height, joint pain, number of chronic conditions, and socioeconomic status. Hand grip, hip flexion, and knee extension forces were measured using portable hand-held dynamometers in the participants' homes. Hand grip strength was measured as the maximal isometric force. Hip flexion and knee extension forces were measured as the greatest force the tester had to apply to break the isometric contraction. A declining strength gradient was observed with increasing severity of disability and for decreasing level of physical activity in both races. At equal levels of disability or physical activity, blacks had better hand grip and hip flexion strength, but knee extension strength did not differ by race. The greater hand grip and hip flexion strength found in black women may be related to their greater muscle mass and known racial differences in body dimensions. No consistent racial differences were observed in the relationship between physical activity and muscle strength, or muscle strength and disability, suggesting that the role of muscle strength in the disablement process does not differ between races. Physical activity and exercise programs may be feasible ways to prevent worsening of disability in blacks and whites.

Aged↗
PubMed1997

Separate bisphosphatase domain of chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: the role of the C-terminal tail in modulating enzyme activity.

The separate bisphosphatase domain (amino acid residues 243-468) of the chicken liver bifunctional enzyme 6-phosphofructo-2-kinase-fructose-2,6-bisphosphatase was expressed in Escherichia coli and purified to homogeneity. The fructose-2, 6-bisphosphatase activity of the separate domain was 7-fold higher than that of the native bifunctional enzyme, and exhibited substrate inhibition characteristic of the native enzyme. The inhibition of the enzymes by fructose 2,6-bisphosphate could be overcome by Pi, glycerol 3-phosphate and GTP. Deletion of 30 amino acid residues from the C-terminus of the separate domain resulted in around a 5-fold increase in the Vmax of the bisphosphatase. Also, the truncated form was more accessible to chemical modification by diethyl pyrocarbonate and N-ethylmaleimide, suggesting a more open structure than the wild-type form. In addition, the mutation of cysteine-389 to alanine increased bisphosphatase activity by 20% and the Km value for fructose 2,6-bisphosphate by 3-fold, and both the point mutation at cysteine-389 and the deletional mutation led to the predominantly insoluble expression of the enzyme. The results indicated that the C-terminal tail plays a role in modulating the enzyme activity and suggested that the difference in the C-terminal tail sequence is responsible for the difference in activity of the chicken and rat liver fructose-2,6-bisphosphatases. It is postulated that an interaction between the C-terminal tail and the active site might be present.

Animals↗
PubMed1997

[Anoxia-induced c-fos expression of cultured rat hippocampal neurons and effect of recombinant human interleukin-1 beta].

Effects of recombinant human interleukin-1 beta (rhIL-1 beta) on the c-fos expression of cultured rat hippocampal neurons in vitro induced by anoxia were studied by using an immunohistochemical method. The results showed that the percentage and the mean optical density of the Fos-positive neuronal nuclei in cultured hippocampal neurons increased markedly as anoxia prolonged, while those in hippocampal neurons pretreated with rhIL-1 beta were significantly lower than those of control. The results indicate that anoxia can induce c-fos expression of cultured rat hippocampal neurons in vitro and this can be inhibited by rhIL-1 beta, suggesting that rhIL-1 beta may protect neurons from damage in a certain degree during anoxia.

Animals↗
PubMed1996

The inhibiting effect of aqueous Azadirachta indica (Neem) extract upon bacterial properties influencing in vitro plaque formation.

The purpose of this investigation was to examine the inhibitory effects of aqueous extracts derived from the bark-containing sticks (Neem stick) of Azadirachta indica upon bacterial aggregation, growth, adhesion to hydroxyapatite, and production of insoluble glucan, which may affect in vitro plaque formation. Neem stick extracts were screened for minimal bacterial growth inhibition (MIC) against a panel of streptococci by means of a broth dilution assay. Initial bacterial attachment was quantified by the measurement of the adhesion of 3H-labeled Streptococcus sanguis to saliva-conditioned synthetic hydroxyapatite. The effect of the Neem stick extract upon insoluble glucan synthesis was measured by the uptake of radiolabeled glucose from 14C-sucrose. Aggregating activity of the Neem stick extracts upon a panel of streptococci was also examined. No inhibition of bacterial growth was observed among the streptococcal strains tested in the presence of < or = 320 micrograms/mL of the Neem stick extract. The pre-treatment of S. sanguis with the Neem stick extract or the gallotannin-enriched extract from Melaphis chinensis at 250 micrograms/mL resulted in a significant inhibition of the bacterial adhesion to saliva-conditioned hydroxyapatite. Pre-treatment of saliva-conditioned hydroxyapatite with the Neem stick or gallotannin-rich extract prior to exposure to bacteria yielded significant reductions in bacterial adhesion. The Neem stick extract and the gallotannin-enriched extract from Melaphis chinensis inhibited insoluble glucan synthesis. Incubation of oral streptococci with the Neem stick extract resulted in a microscopically observable bacteria aggregation. These data suggest that Neem stick extract can reduce the ability of some streptococci to colonize tooth surfaces.

Alkaloids↗
PubMed1996

Quinidine enhances and suppresses Kv1.2 from outside and inside the cell, respectively.

We studied the effects of quinidine on two K channel clones expressed in Xenopus oocytes, Kv1.2 and Kv1.4. Quinidine had an agonist (enhancement) and a blocker (suppression) action on Kv1.2, whereas only the blocker action was seen with Kv1.4. For both, the blocker action was exerted from the intracellular side of the membrane due to quinidine binding in its protonated form to a site in the membrane electrical field. The agonist action on Kv1.2 was exerted from the extracellular side of the membrane. A quaternary analog of quinidine, Q+1C, that had a low membrane permeability allowed the agonist action to be separated from the blocker action. Experiments with Q+1C showed that the agonist action was caused by a parallel shift of the voltage dependence of Kv1.2 activation in the negative direction. There was no increase in channel conductance when channel activation reached a plateau. Q+1C had little or no effect on the rate of Kv1.2 activation, but significantly slowed Kv1.2 deactivation at voltages as negative as - 160 mV. These changes in channel gating could be largely reproduced by a simple kinetic model, assuming that the agonist action was caused by a decrease in the rate constants for transitions from the activated to the rested states. In oocytes coexpressing Kv1.2 and Kv1.4 at approximately a 1:1 ratio, the response to Q+1C was similar to that of oocytes expressing Kv1.2 alone, suggesting that heteromultimer channels of Kv1.2 and Kv1.4 subunits could respond to the agonist action of quinidine.

Animals↗
PubMed1995

Effects of n-dodecylguanidine on A-type potassium channels: role of external surface charges in channel gating.

n-Dodecylguanidine (C12-G) is an amphipathic compound with a guanidine moiety, which is positively charged at physiological pH, and a hydrophobic side chain. Its effects on an A-type K+ channel clone (rKv1.4) expressed in Xenopus oocytes were examined. C12-G caused a concentration-dependent (1-20 microM) positive shift in the voltage dependences of the following channel properties: activation, inactivation, rate of decay during depolarization, and rate of recovery from inactivation. C12-G was effective when added to the bath solution but was without effect when applied to the cytoplasm of oocytes, indicating an extracellular site of action. The effects of C12-G were antagonized by elevation of the extracellular Mg2+ concentration and by external guanidine ions but were augmented by lowering of the ionic strength of the external solution. C12-G did not affect the instantaneous current-voltage relationship for rKv1.4 or the time constant of decay during strong depolarizations, when the voltage dependence of channel activation approached a plateau. Our observations suggest that C12-G exerts its actions by causing a positive shift in the external surface potential around rKv1.4, without altering the ion permeation process or voltage-independent transition steps. In canine ventricular myocytes, C12-G caused changes in the function of a native A-type K+ channel similar to those seen with rKv1.4. However, C12-G had negligible effects on the voltage dependence of the slow delayed-rectifier K+ channel in the same cell type, suggesting that the actions of C12-G are not nonspecific.

Animals↗