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Biomedical subjects

C Ling

Publications and source records attributed to C Ling.

At least 19 recordsLinked to original sources
PubMed2006

Enhanced mitochondrial metabolism may account for the adaptation to insulin resistance in islets from C57BL/6J mice fed a high-fat diet.

AIM/HYPOTHESIS: Hyperinsulinaemia maintains euglycaemia in insulin-resistant states. The precise cellular mechanisms by which the beta cells adapt are still unresolved. A peripherally derived cue, such as increased circulating fatty acids, may instruct the beta cell to initiate an adaptive programme to maintain glucose homeostasis. When this fails, type 2 diabetes ensues. Because mitochondria play a key role in beta cell pathophysiology, we tested the hypothesis that mitochondrial metabolism is critical for beta cell adaptation to insulin resistance. METHODS: C57BL/6J mice were given high-fat (HF) diet for 12 weeks. We then analysed islet hormone secretion, metabolism in vivo and in vitro, and beta cell morphology. RESULTS: HF diet resulted in insulin resistance and glucose intolerance but not frank diabetes. Basal insulin secretion was elevated in isolated islets from HF mice with almost no additional response provoked by high glucose. In contrast, a strong secretory response was seen when islets from HF mice were stimulated with fuels that require mitochondrial metabolism, such as glutamate, glutamine, alpha-ketoisocaproic acid and succinate. Moreover, while glucose oxidation was impaired in islets from HF mice, oxidation of glutamine and palmitate was enhanced. Ultrastructural analysis of islets in HF mice revealed an accumulation of lipid droplets in beta cells and a twofold increase in mitochondrial area. CONCLUSIONS/INTERPRETATION: We propose that beta cells exposed to increased lipid flux in insulin resistance respond by increasing mitochondrial volume. This expansion is associated with enhanced mitochondrial metabolism as a means of beta cell compensation.

Adaptation, Physiological↗
PubMed2006

Influence of solid phase and formulation processing on stability of Abbott-232 tablet formulations.

Abbott-232 is a chemically stable, highly water soluble non-hygroscopic compound selected for development as a potent uroselective alpha(1A) agonist. An anhydrate, a monohydrate, and an amorphous phase were isolated. The anhydrate was chosen for formulation development based on solid-state characterization. Excipients for immediate release (IR) tablet formulations were selected according to compatibility studies. However, the prototype IR tablets designed for clinical trials were found to be chemically unstable. Thus, process-induced phase transformation was investigated as the likely cause of the observed instability. Since the drug loading in the formulations was low (1%), model granulations containing 30% drug were evaluated to test this hypothesis. Investigation using a variety of analytical techniques indicated that the observed degradation was, indeed, a result of a solution-mediated phase transformation from anhydrate to amorphous Abbott-232 during wet granulation. A new direct compression formulation was, therefore, developed to prevent the solution-mediated process induced phase transition. Since the drug loading was low, a polarized light microscope (PLM) method was used to evaluate the solid phase in the new formulation. PLM confirmed that the original anhydrate form remained unchanged in tablets manufactured by the dry process. Stability studies confirmed that both IR and extended release (ER) tablets of Abbott-232 were successfully developed for clinical trials using direct compression.

Adrenergic alpha-Agonists↗
PubMed2005

Aetiological role of viral and bacterial infections in acute adult lower respiratory tract infection (LRTI) in primary care.

BACKGROUND: Lower respiratory tract infections (LRTI) are a common reason for consulting general practitioners (GPs). In most cases the aetiology is unknown, yet most result in an antibiotic prescription. The aetiology of LRTI was investigated in a prospective controlled study. METHODS: Eighty adults presenting to GPs with acute LRTI were recruited together with 49 controls over 12 months. Throat swabs, nasal aspirates (patients and controls), and sputum (patients) were obtained and polymerase chain reaction (PCR) and reverse transcriptase polymerase chain reaction (RT-PCR) assays were used to detect Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, influenza viruses (AH1, AH3 and B), parainfluenza viruses 1-3, coronaviruses, respiratory syncytial virus, adenoviruses, rhinoviruses, and enteroviruses. Standard sputum bacteriology was also performed. Outcome was recorded at a follow up visit. RESULTS: Potential pathogens were identified in 55 patients with LRTI (69%) and seven controls (14%; p<0.0001). The identification rate was 63% (viruses) and 26% (bacteria) for patients and 12% (p<0.0001) and 6% (p = 0.013), respectively, for controls. The most common organisms identified in the patients were rhinoviruses (33%), influenza viruses (24%), and Streptococcus pneumoniae (19%) compared with 2% (p<0.001), 6% (p = 0.013), and 4% (p = 0.034), respectively, in controls. Multiple pathogens were identified in 18 of the 80 LRTI patients (22.5%) and in two of the 49 controls (4%; p = 0.011). Atypical organisms were rarely identified. Cases with bacterial aetiology were clinically indistinguishable from those with viral aetiology. CONCLUSION: Patients presenting to GPs with acute adult LRTI predominantly have a viral illness which is most commonly caused by rhinoviruses and influenza viruses.

Acute Disease↗
PubMed2005

Mycoplasma amphoriforme sp. nov., isolated from a patient with chronic bronchopneumonia.

A mycoplasma was isolated from the sputum of an immunodeficient patient with recurrent bronchitis. The isolate designated strain A39T was very fastidious and atypical for a mycoplasma in its colonial appearance. Classical biochemical tests for mycoplasma speciation could not differentiate the isolate from the pathogens Mycoplasma pneumoniae and Mycoplasma genitalium and serological identification as a recognized Mycoplasma species was lacking. Specific PCR detection for these two species was negative. Subsequently, other strains were isolated from human patients that appeared to be similar to strain A39T in their physiological and genetic characteristics. Analysis of the 16S rRNA gene placed strain A39T and other isolates in the pneumoniae group of mycoplasmas, with the highest sequence similarity to Mycoplasma testudinis (96.8 %), but with only 93.0 % similarity to M. pneumoniae and M. genitalium. Examination of the 16S-23S rRNA internally transcribed spacer sequence, protein electrophoresis profile, genome size and serological reactions indicated that this organism represents a novel species, for which the name Mycoplasma amphoriforme sp. nov. is proposed, with strain A39T (=NCTC 11740T=ATCC BAA-992T) as the type strain.

Bronchopneumonia↗
PubMed2003

Chronic bronchitis in immunocompromised patients: association with a novel Mycoplasma species.

Patients with primary antibody deficiency are prone to recurrent bronchitis, often caused by nonencapsulated Haemophilus influenzae and streptococcal infection. Productive cough often persists even after elimination of these organisms with antibiotics. During an investigation into the cause of unexplained chronic bronchitis in these patients, a novel Mycoplasma species (designated A39) was first isolated from the sputum of a man with X-linked agammaglobulinaemia. Screening of sputa from a further 45 patients with primary antibody deficiency showed that 10 were positive for a similar organism using culture and/or a polymerase chain reaction based on sequences within the 16S ribosomal RNA gene. A comparison of the sequence data showed that the organism was distinct from but similar to Mycoplasma pneumoniae and other closely related mycoplasmas found in humans and animals. Electron microscopy showed some unique morphological characteristics. Although respiratory symptoms improved after elimination of A39 from the sputum of the patient with X-linked agammaglobulinaemia, further work is needed to establish the organism as a pathogen.

Adult↗
PubMed2001

Increased resistin expression in the adipose tissue of male prolactin transgenic mice and in male mice with elevated androgen levels.

The aim of this study was to investigate the regulation of resistin, a recently identified adipocyte-secreted peptide, in the adipose tissue of prolactin (PRL)-transgenic (tg) mice using ribonuclease protection assay. The level of resistin mRNA increased 3.5-fold in the adipose tissue of untreated male PRL-tg mice compared to controls. However, there was no difference in resistin expression in the adipose tissue of female PRL-tg mice compared to control mice. PRL-tg male mice have elevated serum testosterone levels and we therefore analyzed the effects of testosterone alone on resistin mRNA expression. Furthermore, the effects of elevated androgen levels on PRL receptor (PRLR) mRNA expression in the adipose tissue were investigated. Resistin mRNA increased 2.6-fold in the adipose tissue of control male mice with elevated serum androgen levels. In addition, PRLR mRNA expression was increased in the adipose tissue of male mice with elevated testosterone. These results suggest testosterone to be a regulator of resistin and PRLR mRNA expression in the adipose tissue of male mice.

Adipose Tissue↗
PubMed2001

Microtubule reconfiguration during axogenesis.

When cultured on polylysine, rat sympathetic neurons extend modest lamellae which contain a mass of relatively short non-aligned microtubules. Microtubules display movements, but these movements do not result in any obvious alterations in the overall configuration of the array. Application of a mixture of growth factors called matrigel results in a rapid expansion of the lamellae followed by the outgrowth of axons. Microtubules undergo rapid behavioral changes that result in dramatic alterations in the microtubule array. Microtubules become significantly longer, and extend to the periphery of the lamellae where they invade newly-forming axons. The microtubules align with one another and relative to the cell cortex, and draw together into bundles. Microtubules within a bundle move apart as well, particularly at the tips of developing axons. These observations demonstrate a complexity of microtubule behaviors, some of which can be explained by interactions with actin and/or by forces generated by molecular motor proteins.

Actin Cytoskeleton↗
PubMed2001

PRL receptor-mediated effects in female mouse adipocytes: PRL induces suppressors of cytokine signaling expression and suppresses insulin-induced leptin production in adipocytes in vitro.

PRL has been reported to regulate fat metabolism in several species. We recently reported PRL receptor (PRLR) expression in mouse adipocytes and increased levels of PRLR expression in the adipose tissue of lactating and PRL-transgenic mice compared with controls. These results suggest PRLR-mediated effects in adipose tissue. However, to date most studies have been performed in vivo, and it is unclear whether PRL has direct effects on adipocytes. The PRLR belongs to the cytokine receptor family, and a family of suppressors of cytokine signaling (SOCS) was recently identified. The present study was performed to investigate whether PRL has direct effects on adipocytes. The expression of cytokine-inducible SH2-domain-containing protein (CIS), SOCS-3, and SOCS-2 mRNA and protein was analyzed using ribonuclease protection assay and immunoblotting, respectively. Ovine PRL induced CIS mRNA expression and a combination of oPRL and insulin induced SOCS-3 mRNA expression in adipocytes cultured in vitro for 0-240 min, demonstrating PRLR-mediated direct effects in these cells. Furthermore, CIS, SOCS-3, and SOCS-2 mRNA and protein were all transiently expressed in adipose tissue obtained from female mice stimulated with oPRL (1 microg/g BW) for 0-24 h. In adipose tissue of female mice with endogenously high PRL levels, PRL-transgenic mice, only SOCS-2 expression was increased. The level of SOCS-2 mRNA was also increased in adipose tissue during pregnancy and lactation compared with that in wild-type virgin female mice. A possible reason for increased SOCS-2 expression after prolonged PRL exposure during lactation and in the PRL transgenes could be to restore the sensitivity of adipose tissue to PRL. In addition, the direct effect of PRL on leptin production was investigated in adipocytes cultured in vitro for 6 h. PRL inhibited insulin-induced leptin production in vitro. However, PRL had no effect on leptin production in the absence of insulin. In contrast, serum leptin concentrations were increased in PRL-transgenic females compared with control mice. In conclusion, our results demonstrate functional PRLRs in mouse adipocytes and suggest a role for CIS, SOCS-3, and SOCS-2 in regulating PRL signal transduction in adipose tissue.

Adipocytes↗
PubMed2000

Zn2+ current is mediated by voltage-gated Ca2+ channels and enhanced by extracellular acidity in mouse cortical neurones.

1. Mammalian neuronal voltage-gated Ca2+ channels have been implicated as potential mediators of membrane permeability to Zn2+. We tested directly whether voltage-gated Ca2+ channels can flux Zn2+ in whole-cell voltage-clamp recordings from cultured murine cortical neurones. 2. In the presence of extracellular Zn2+ and no Na+, K+, or other divalent cations, a small, non-inactivating, voltage-gated inward current was observed exhibiting a current-voltage relationship characteristic of high-voltage activated (HVA) Ca2+ channels. Inward current was detectable at Zn2+ levels as low as 50 microM, and both the amplitude and voltage sensitivity of the current depended upon Zn2+ concentration. This Zn2+ current was sensitive to blockade by Gd3+ and nimodipine and, to a lesser extent, by omega-conotoxin GVIA. 3. Zn2+ could permeate Ca2+ channels in the presence of Ca2+ and other physiological cations. Inward currents recorded with 2 mM Ca2+ were attenuated by Zn2+ (IC50 = 210 microM), and currents recorded with Zn2+ were unaffected by up to equimolar Ca2+ concentrations. Furthermore, the Zn2+-selective fluorescent dye Newport Green revealed a depolarisation-activated, nimodipine-sensitive Zn2+ influx into cortical neurones that were bathed in a physiological extracellular solution plus 300 microM ZnCl2. 4. Surprisingly, while lowering extracellular pH suppressed HVA Ca2+ currents, Zn2+ current amplitude was affected oppositely, varying inversely with pH with an apparent pK of 7.4. The acidity-induced enhancement of Zn2+ current was associated with a positive shift in reversal potential but no change in the kinetics or voltage sensitivity of channel activation. 5. These results provide evidence that L- and N-type voltage-gated Ca2+ channels can mediate Zn2+ entry into cortical neurones and that this entry may be enhanced by extracellular acidity.

Acids↗
PubMed2000

Isolation of differentially expressed aldose reductase in ovaries after estrogen withdrawal from hypophysectomized diethylstilbestrol treated rats: increased expression during apoptosis.

More than 99% of the follicles are eliminated by apoptosis before reaching ovulation. Several growth factors and hormones inhibit apoptosis in the ovary, including estrogen. Using differential display of mRNA, aldose reductase was shown to increase in the ovary of diethylstilbestrol treated hypophysectomized rats after estrogen withdrawal, inducing apoptosis. The aldose reductase mRNA expression was confirmed to be 2.2 +/- 0.2-fold higher after estrogen withdrawal using northern blot analysis. In addition, untreated immature rats showed a 1.7 +/- 0.3-fold higher expression of ovarian aldose reductase mRNA compared to ovaries 24 h after pregnant mare's serum gonadotropin treatment, decreasing apoptosis in the ovary. In the prostate, the level of aldose reductase was increased 3.1 +/- 1.1-fold 2 days after castration induced apoptosis. Although the physiological role of aldose reductase in the ovary is not known, these data suggest that aldose reductase may be part of a hormonally regulated apoptotic pathway in the ovary and prostate.

Aldehyde Reductase↗
PubMed2000

Primary cutaneous B-cell lymphoma and Borrelia burgdorferi infection in patients from the Highlands of Scotland.

Although a link between primary cutaneous B-cell lymphoma (PCBCL) and Borrelia burgdorferi infection has long been suspected, previous studies have not demonstrated a significant association. The authors looked for evidence of B. burgdorferi in 20 cases of PCBCL from the Scottish Highlands, an area with endemic Lyme disease, and compared their findings with those in 40 control patients (20 undergoing wide reexcision at sites of malignant melanoma and 20 biopsies of inflammatory dermatoses). All studies were performed on formalin-fixed, paraffin-embedded tissues. The cases of PCBCL were classified according to criteria described by the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Project Group using a combination of morphology, immunohistochemistry, and seminested polymerase chain reaction (PCR) for immunoglobulin heavy chain gene rearrangement. A nested PCR was performed on deoxyribonucleic acid (DNA) extracts from the lymphoma and control cases using primers to a unique conserved region of the B. burgdorferi flagellin gene. B. burgdorferi-specific DNA was detected in seven of 20 lymphoma cases (five of 12 marginal zone lymphomas, one of five primary cutaneous follicle center cell lymphomas, one of three diffuse, large B-cell lymphomas of the leg) and in one melanoma reexcision patient of 40 control subjects. The relationship between B. burgdorferi and PCBCL was significant when compared with the control groups separately (p <0.05) or in combination (p <0.01). These results provide strong evidence to support the concept of B. burgdorferi-driven lymphomagenesis in the skin.

Adult↗
PubMed2000

Prolactin (PRL) receptor gene expression in mouse adipose tissue: increases during lactation and in PRL-transgenic mice.

There are indications that PRL may exert important metabolic actions on adipose tissue in different species. However, with the exception of birds, the receptor has not been identified in white adipose tissue. The present study was designed to examine the possible expression and regulation of the PRL receptor (PRLR) in mouse adipose tissue. The long PRLR messenger RNA (mRNA) splice form (L-PRLR) and two short splice forms (S2- and S3-PRLR) were detected in mouse adipose tissue by RT-PCR. Furthermore, L-PRLR mRNA was detected by ribonuclease protection assay. Immunoreactive PRLR with a relative molecular mass of 95,000 was revealed by immunoblotting. Furthermore, L-PRLR mRNA expression was demonstrated in primary isolated adipocytes. In mouse adipose tissue, the level of L-PRLR mRNA expression increased 2.3-fold during lactation compared with those in virgin and pregnant mice. In contrast, in the liver the expression of L-PRLR increased 3.4-fold during pregnancy compared with those in virgin and lactating mice. When comparing the levels of L-PRLR expression in virgin female and male mice, no difference was detected in adipose tissue. However, in virgin female liver the expression was 4.5-fold higher than that in male liver. As PRL up-regulates its own receptor in some tissues, we analyzed L-PRLR expression in PRL-transgenic female and male mice. In PRL-transgenic mice L-PRLR expression was significantly increased in both adipose tissue (1.4-fold in females and 2.4-fold in males) and liver (1.9-fold in females and 2.7-fold in males) compared with that in control mice. Furthermore, in female PRL-transgenic mice retroperitoneal adipose tissue was decreased in weight compared with that in control mice. However, no difference was detected when comparing the masses of parametrial adipose tissue. Our results suggest a direct role for PRL, mediated by PRLR, in modulating physiological events in adipose tissue.

Adipose Tissue↗
PubMed1999

Technology assessment of multileaf collimation: a North American users survey.

PURPOSE: The American Association of Physicists in Medicine (AAPM) initiated an Assessment of Technology Subcommittee (ATS) to help the radiotherapy community evaluate emerging technologies. The ATS decided to first address multileaf collimation (MLC) by means of a North American users survey. The survey attempted to address issues such as MLC utility, efficacy, cost-effectiveness, and customer satisfaction. METHODS AND MATERIALS: The survey was designed with 38 questions, with cross-tabulation set up to decipher a particular clinic's perception of MLC. The surveys were coded according to MLC types, which were narrowed to four: Elekta, Siemens, Varian 52-leaf, and Varian 80-leaf. A 40% return rate was desired. RESULTS: A 44% (108 of 250) return was achieved. On an MLC machine, 76.5% of photon patients are being treated with MLC. The main reasons for not using MLC were stair stepping, field size limitation, and physician objection. The most common sites in which MLC is being used are lung, pelvis, and prostate. The least used sites are head & neck and mantle fields. Of the facilities, 31% claimed an increase in number of patients being treated since MLC was installed, and 44% claimed an increase in the number of fields. Though the staffing for block cutting has decreased, therapist staffing has not. However, 91% of the facilities claimed a decreased workload for the therapists, despite the increase in daily treated patients and fields. Of the facilities that justified MLC purchase for more daily patients, 63% are actually treating more patients. Only 26% of the facilities that justified an MLC purchase for intensity-modulated radiotherapy (IMRT) are currently using it for that purpose. The satisfaction rating (1 = low to 5 = high) for department groups averaged 4.0. Therapists ranked MLC as 4.6. CONCLUSIONS: Our survey shows that most users have successfully introduced MLC into the clinic as a block replacement. Most have found MLC to be cost-effective and efficient. The use of MLC for IMRT has progressed slower, but users anticipate escalated use.

Consumer Behavior↗
PubMed1999

Scavenger receptor class B type I in the rat ovary: possible role in high density lipoprotein cholesterol uptake and in the recognition of apoptotic granulosa cells.

Scavenger receptor class B type I (SR-BI) mediates the selective uptake of high density lipoprotein cholesterol. SR-BI is expressed at high levels in the ovary, indicating that it plays a role in the delivery of cholesterol as substrate for steroid hormone production. However, SR-BI also binds anionic phospholipids with high affinity and could therefore be involved in the recognition of apoptotic cells. In this study we have characterized the expression of SR-BI in rat ovarian follicles undergoing atresia. Atretic follicles with cells undergoing apoptosis were identified by in situ DNA end labeling, and SR-BI expression was determined by in situ hybridization and immunohistochemistry. SR-BI was expressed in thecal cells at all stages of follicular development, including atretic follicles, and in corpus luteum. Isolated apoptotic granulosa cells (but not viable granulosa cells) bound annexin V, indicating that they display anionic phospholipids on the cell surface. Transfection of COS-7 cells with an expression vector carrying the rat SR-BI complementary DNA resulted in increased binding to apoptotic granulosa cells (46 +/- 2% of the SR-BI-expressing cells bound at least one granulosa cell compared with 24 +/- 3% for the mock-transfected cells; P < 0.0001), whereas the binding to viable granulosa cells was unchanged. Apoptotic granulosa cells also bound to isolated thecal shells. We conclude that thecal cells of both nonatretic and atretic follicles express SR-BI. The location of SR-BI expression in the ovary supports a role of this receptor in the uptake of high density lipoprotein cholesterol. In addition, our data suggest that SR-BI mediates the recognition of apoptotic granulosa cells by the surrounding thecal cells and that it therefore may play a role in the remodeling of atretic follicles to secondary interstitial cells.

Animals↗
PubMed1999

[Experimental study on protective effect of Chinese herbal medicine on glucocorticoid receptor].

OBJECTIVE: To probe the relationship of glucocorticoid receptor and some Chinese medicinal herbs. METHODS: The models of Qi-Yang exhaustion and Qi-Yin exhaustion were made with hemorrhagic rats and heat-stressed rats respectively. The effect of Shenfu Decoction (SFD) and Shengmai Powder (SMP) on plasma glucocorticoid (GC) and its receptor (GcR) in hepatic cytosol of the models were measured respectively. RESULTS: The activity of GcR decreased in both models, while their blood level of GC increased markedly. SFD and SMP showed no regulating effect on blood GC, but displayed obvious up-regulation on GcR level in both models. CONCLUSION: SFD and SMP could up-regulate the activity of GcR in Qi-Yang and Qi-Yin exhaustion models.

Animals↗
PubMed1998

[Effect of zinc on the cellular immunity and NK cell activity in acute heat exposed rats].

To study the effects of zinc on the cellular immunity and NK cell activity in acute heat-exposed rats. Rats were fed with dietary containing high, moderate and low zinc for 15 days. The concentrations of zinc in high, moderate and low zinc dietary are 92.20 mg/kg, 45.61 mg/kg and 21.70 mg/kg respectively. After exposed to acute heat (41.5 degrees C) for 5 min, 30 min and 60 min, the rats were killed and the cellular immunity and NK cell activity were measured. The proliferation of lymphocyte and the NK cell activity were higher in high zinc group than in moderate and low zinc groups no matter the rats were exposed to heat or not. Zinc can improve the cellular immunity and NK cell activity in acute heat exposed rats.

Animals↗
PubMed1998

[The long-term effect of double embolization of bronchial artery on patients with hemoptysis].

OBJECTIVE: To investigate the long-term effect of bronchial arterial embolization with different material and procedure on patients with hemoptysis. METHOD: Seventy two cases were divided into two groups, one received the double embolization of bronchial artery, the other group used single gelfoam embolization. In double embolization group, the mixture containing gelfoam microspheres (0.5 mm x 0.5 mm), erythromycin and high osmalality sodium chloride were firstly used to embolize the terminal vessels, the gelfoam particle (1 mm x 1 mm) was then used to embolize the main trunk of bronchial artery. RESULT: After 2-4.8 years following up, it turned out that the cure rate and general effectiveness were: the double embolization group 83%, 100% respectively, the single gelfoam embolization group 61%, 95%. By comparison, there were significant difference on cure rate between these two groups(P < 0.05). CONCLUSION: The bronchial arterial double embolization will increase the long-term effect obviously on patients with hemoptysis.

Adolescent↗