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Biomedical subjects

L Chang

Publications and source records attributed to L Chang.

At least 163 records · Page 9Linked to original sources

Review article: gender-related differences in functional gastrointestinal disorders.

Many functional gastrointestinal disorders and other chronic visceral pain disorders such as interstitial cystitis and chronic pelvic pain are more common in women than in men. In irritable bowel syndrome (IBS) there is a 2:1 female to male ratio in prevalence of symptoms in community samples. Female irritable bowel syndrome patients are more likely to be constipated, complain of abdominal distension and of certain extracolonic symptoms. While animal studies have clearly demonstrated gender-related differences in pain perception and antinociceptive mechanisms, unequivocal evidence for gender-related differences in human pain perception or modulation has only been provided recently. Gender-related differences may be related to constant differences in the physiology of pain perception, such as structural or functional differences in the visceral afferent pathways involved in pain transmission or modulation, and/or they may be related to fluctuations in female sex hormones. Preliminary evidence suggests that female irritable bowel syndrome patients show specific perceptual alterations in regards to rectosigmoid balloon distension and that they show differences in regional brain activation measured by positron emission tomography. This preliminary evidence suggests that gender-related differences in symptoms and in the perceptual responses to visceral stimuli exist in IBS patients and can be detected using specific stimulation paradigms and neuroimaging techniques.

Animals↗

Impact of advertisement and clinic populations in symptoms and perception of irritable bowel syndrome.

BACKGROUND: This study assessed the impact of recruitment on irritable bowel syndrome clinical trials, by determining whether irritable bowel syndrome patients recruited from advertisement or a specialty clinic differ in clinical and physiologic measures. METHODS: We prospectively surveyed 657 irritable bowel syndrome patients who either: (i) were referred from a functional bowel disease clinic (52%); or (ii) responded to advertisement for clinical trials (48%), using questionnaires about bowel and psychological symptoms, and quality of life. In a subset of 42 irritable bowel syndrome patients (29 advertisement and 15 clinic patients), rectal discomfort thresholds were measured before and after repetitive sigmoid stimulation. RESULTS: While the advertisement population more commonly consulted primary care physicians, the clinic population more commonly consulted gastroenterologists. The clinic population reported more prevalent and severe abdominal pain, and higher psychological symptom scores, while the advertisement population had greater quality of life. In the visceral perception studies, both subgroups were hypersensitive to rectal distension. CONCLUSION: Compared to the clinic population, the advertisement population had less severe abdominal pain and psychological symptoms, better quality of life but similar visceral perception. The differences in clinical self-reports may have consequences for enrolment of these different patient populations into clinical trials.

Adult↗

Expression of the Escherichia coli NRZ nitrate reductase is highly growth phase dependent and is controlled by RpoS, the alternative vegetative sigma factor.

In the absence of oxygen, many bacteria preferentially use nitrate as a terminal electron acceptor for anaerobic respiration. In Escherichia coli, there are two membrane-bound, differentially regulated nitrate reductases. While the physiological basis for this metabolic redundancy is not completely understood, during exponential growth, synthesis of NRA is greatly induced by anaerobiosis plus nitrate, whereas NRZ is expressed at a low level that is not influenced by anaerobiosis or nitrate. In the course of identifying genes controlled by the stationary phase regulatory factor RpoS (sigmas), we found that the expression of NRZ is induced during entry into stationary phase and highly dependent on this alternative sigma factor. Expression studies, using operon fusions and nitrate reductase assays, revealed that the NRZ operon is controlled mainly at the level of transcription and is induced 10-fold at the onset of stationary phase in rich media. Consistent with previous reports of RpoS expression, the RpoS dependency of NRZ in minimal media was very high (several hundredfold). We also observed a fivefold stationary phase induction of NRZ in an rpoS background, indicating that other regulatory factors, besides RpoS, are probably involved in transcriptional control of NRZ. The RpoS dependence of NRZ expression was confirmed by Northern analyses using RNA extracted from wild-type and rpoS- strains sampled in exponential and stationary phase. In toto, these data indicate that RpoS-mediated regulation of NRZ may be an important physiological adaptation that allows the cell to use nitrate under stress-associated conditions.

Aerobiosis↗

Evolution of thyroid hormone binding by transthyretins in birds and mammals.

Transthyretin, a protein synthesized and secreted by the choroid plexus and liver, binds thyroid hormones in extracellular compartments. This binding prevents accumulation of thyroid hormones in the lipids of membranes, establishing extracellular thyroid hormone pools for the distribution of the hormones throughout the body and brain. The N-termini of the transthyretin subunits are longer and more hydrophobic in chicken than in eutherian transthyretins. Here, we show that this is a general structural feature of avian transthyretins. Systematic changes of protein structure during evolution result from selection pressure leading to changes in function. The evolution of transthyretin function, namely, the binding of thyroid hormones, was studied in nine vertebrate species. The affinity of thyroxine binding to transthyretin is lowest in avians (mean Kd of about 30 nm), intermediate in metatherians (mean Kd of about 17 nm) and highest in eutherians (mean Kd of about 11 nm). The affinity for 3,5,3'-triiodothyronine shows an opposite trend, being four times higher for avian transthyretins than for mammalian transthyretins.

Amino Acid Sequence↗

Symptom differences in moderate to severe IBS patients based on predominant bowel habit.

OBJECTIVE: We sought to determine if irritable bowel syndrome (IBS) patients with different bowel habit predominance differ in self-reported viscerosensory symptoms related to the upper and lower gastrointestinal (GI) tract, somatosensory symptoms, and constitutional functions. METHODS: Six hundred and twenty-five Rome criteria-positive IBS patients completed a bowel symptom questionnaire (BSQ), psychological symptom checklist (SCL-90), and health status (SF-36). Bowel habit predominance for IBS patients was determined using the Rome criteria for functional constipation (IBS-C; n = 140) and functional diarrhea (IBS-D; n = 216). The BSQ included questions about viscerosensory symptoms of the upper (chest pressure, bloating, fullness, early satiety, nausea) and lower GI tract (bloating, pain, incomplete evacuation), somatosensory symptoms related to the musculoskeletal system (pain in neck/shoulders, lower back/hip, muscles/joints), and constitutional functions (sleep, appetite, libido). Analysis was further conducted between the IBS-C and IBS-D patients, controlling for gender and quality of sleep, and using the Bonferroni correction to control for multiple comparisons. RESULTS: Female gender was more prevalent among IBS-C than IBS-D (77% vs 56.1%, p < 0.01), whereas age did not differ (40.2 +/- 1.2 yr vs 39.5 +/- 1.0 yr). Symptoms referred to the upper GI were more prevalent in IBS-C than IBS-D: early satiety (56.7% vs 33.9%, p < 0.004), fullness (63.2% vs 38.5%, p < 0.05), and a trend for upper bloating (80.3 vs 62.6%). IBS-C patients reported higher severity ratings for lower GI bloating (p < 0.001). IBS-C more commonly reported musculoskeletal symptoms (92.2% vs 75.4%, p < 0.001), as well as impairment in sleep (31.3 vs 17.5%, p < 0.009), appetite (35.0% vs 18.4%, p < 0.015) and sexual function (45.2% vs 33.1%, p < 0.0021). There were no differences in SCL-90 and SF-36 scores. CONCLUSIONS: Compared with the IBS-D group, the IBS-C patients show greater prevalence of a wide range of symptoms referred to the upper and lower abdomen, musculoskeletal, and constitutional functions. These findings may be related to differences in autonomic or perceptual responses to visceral and somatic stimuli, and are likely to have implications for treatment responses in the two subgroups.

Adult↗

Progressive multifocal leukoencephalopathy and human immunodeficiency virus-associated white matter lesions in AIDS: magnetization transfer MR imaging.

PURPOSE: To determine the magnetization transfer features of progressive multifocal leukoencephalopathy (PML) and human immunodeficiency virus (HIV)-associated white matter lesions (WML) (hereafter, HIV-WML) on magnetic resonance (MR) images obtained in patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Conventional MR imaging and magnetization transfer MR imaging were performed in 21 AIDS patients with 42 areas of white matter hyperintensity on MR images (13 patients had 25 PML lesions, eight patients had 17 WML). The magnetization transfer ratio was calculated for each lesion. RESULTS: Compared with normal-appearing white matter (magnetization transfer ratio = 47.9%), both PML and HIV-WML showed reduced magnetization transfer ratio. The magnetization transfer ratio was significantly lower in PML lesions (magnetization transfer ratio = 26.1%) than in HIV-WML (magnetization transfer ratio = 38.0%, P < .0001), and there was no overlap in the magnetization transfer ratio between PML lesions and HIV-WML. The separation in magnetization transfer ratio between the two lesion types was valid for lesion as small as 0.5 cm2. CONCLUSION: The larger reduction in magnetization transfer ratio for PML lesions is most likely due to demyelination, whereas the reduction in HIV-WML may be associated primarily with gliosis. PML lesions appear to cause strong reductions in magnetization transfer ratio early in the course of disease. Magnetization transfer MR imaging is a noninvasive tool that improves the differentiation between PML and HIV-WML in patients with AIDS.

AIDS Dementia Complex↗

Safety and antitumor activity of recombinant soluble Apo2 ligand.

TNF and Fas ligand induce apoptosis in tumor cells; however, their severe toxicity toward normal tissues hampers their application to cancer therapy. Apo2 ligand (Apo2L, or TRAIL) is a related molecule that triggers tumor cell apoptosis. Apo2L mRNA is expressed in many tissues, suggesting that the ligand may be nontoxic to normal cells. To investigate Apo2L's therapeutic potential, we generated in bacteria a potently active soluble version of the native human protein. Several normal cell types were resistant in vitro to apoptosis induction by Apo2L. Repeated intravenous injections of Apo2L in nonhuman primates did not cause detectable toxicity to tissues and organs examined. Apo2L exerted cytostatic or cytotoxic effects in vitro on 32 of 39 cell lines from colon, lung, breast, kidney, brain, and skin cancer. Treatment of athymic mice with Apo2L shortly after tumor xenograft injection markedly reduced tumor incidence. Apo2L treatment of mice bearing solid tumors induced tumor cell apoptosis, suppressed tumor progression, and improved survival. Apo2L cooperated synergistically with the chemotherapeutic drugs 5-fluorouracil or CPT-11, causing substantial tumor regression or complete tumor ablation. Thus, Apo2L may have potent anticancer activity without significant toxicity toward normal tissues.

Animals↗

Gender effects on persistent cerebral metabolite changes in the frontal lobes of abstinent cocaine users.

OBJECTIVE: Previous studies found functional changes in the frontal brain region and regions with projections to the frontal lobe in cocaine users. The aim of this study was to investigate persistent neurochemical changes in the frontal lobes of subjects with a history of crack cocaine dependence and to determine whether these changes are different in male and female users. METHOD: The frontal gray and white matter of 64 young asymptomatic and abstinent (> 5 months) cocaine users (34 male and 30 female) and 58 healthy comparison subjects without a history of drug abuse was evaluated with localized proton magnetic resonance spectroscopy (1H-MRS). RESULTS: Two-way analysis of variance showed significant cocaine effects on the concentration of frontal gray matter N-acetyl compounds, on the ratio of frontal white matter N-acetyl compounds to creatine levels, on frontal gray and white matter myoinositol levels, and on the ratio of myoinositol to creatine. Significant gender effects were observed for frontal gray matter choline-containing compounds, the ratio of choline-containing compounds to creatine, and the percentage of CSF in both gray and white matter. Interaction effects of cocaine and gender were observed for creatine, N-acetyl/creatine ratio, and myoinositol/creatine ratio in frontal white matter. CONCLUSIONS: Cocaine use is associated with neuronal injury (with decreased N-acetyl compounds) in the frontal cortex and glial activation (with increased myoinositol) in both frontal gray and white matter. In the frontal lobe, cocaine affects male users differently than female users. Future studies on the effects of cocaine abuse should control for the effects of gender-specific neurotoxicity.

Adult↗

Characterization of antibody response to porcine reproductive and respiratory syndrome virus ORF5 product following infection and evaluation of its diagnostic use in pigs.

The sensitivity and specificity of recombinant open reading frame 5 products used in the Western blotting assay for confirmation of porcine reproductive and respiratory syndrome virus (PRRSV) serologic status were evaluated. The recombinant antigen-based assays were specifically compared with a commercial enzyme-linked immunosorbent assay (ELISA) for PRRSV antibodies using 1) PRRSV antibody-negative reference sera (n = 30), 2) naturally infected pig sera (n = 40), 3) sequential sera obtained from 24 experimentally infected pigs, and 4) sera submitted to 3 state diagnostic laboratories (n = 200). The recombinant antigen assay yielded an average increased sensitivity of 10% over the commercial PRRSV ELISA. The negative controls (group 1 sera) showed no difference between the 2 assays. This comparison confirmed that the recombinant antigen-specific assay was more sensitive than the commercial ELISA and is well suited for routine confirmation of the presence of PRRSV antibodies.

Animals↗

Approaches to the modulation of abdominal pain.

Despite their high prevalence and significant economic impact on the health care system, functional gastrointestinal disorders have evaded successful therapy. Conventional medical therapies are based on inadequate disease models, and the great majority of published treatment trials are flawed in their design, permitting no conclusions to be drawn about the true efficacy of any particular treatment. During the past several years, a new, comprehensive disease model based on alterations in brain-gut interactions has rapidly evolved. Even though the precise mechanisms and sites underlying these alterations remain incompletely understood, plausible targets for the development of effective pharmacological treatments are receptors on peripheral terminals of visceral afferent nerves (opioids and serotonin), ion channels and receptors on dorsal horn neurons within the spinal cord (opioids, glutamate, calcitonin gene-related peptide and neurokinin-1), and supraspinal targets in the brainstem within the limbic system and in the prefrontal cortex (serotonin, catecholamines, dopamine and acetylcholine). Regardless of the primary pathophysiology underlying functional gastrointestinal disorders (ie, central versus peripheral), different pharmacological strategies targeted at different sites in the periphery or within the central nervous system may become effective therapies in the future.

Abdominal Pain↗

Cell culture influenza vaccine: an Australian perspective.

The Australia Influenza Vaccine Committee makes independent decisions concerning the influenza vaccine formulation for Australia. Large-scale cell culture using MDCK cells would improve response time for vaccine production in the face of a new pandemic. There must be a consensus with respect to the use of MDCK or other cells before the next pandemic. It is unrealistic to expect any national regulatory authority to determine what safety requirements should be met before approving a cell substrate for vaccine production during an influenza pandemic. Regulatory issues seen as obstacles to the approval of MDCK cells as an accepted cell substrate for influenza vaccine production are identified.

Animals↗

Overdiagnosis of prostatic adenocarcinoma.

A wide variety of histopathologic mimics of prostatic adenocarcinoma have been recently described, which may cause overdiagnosis of malignancy. To our knowledge, the frequency and causes of overdiagnosis of prostate cancer have not been previously examined. Two pathologists evaluated the Mayo Clinic experience with small foci of stage T1a cancer diagnosed between 1960 and 1970 in an effort to identify cases that were overdiagnosed as cancer. Only cases with available diagnostic slides and blocks were re-evaluated, and immunohistochemical studies were obtained in select cases to confirm the amended diagnoses. Follow-up was obtained in all cases from patient medical records. We identified a total of 31 patients who were overdiagnosed with prostatic carcinoma from among a series of 150 cases initially diagnosed as well-differentiated stage T1a cancer (21% incidence). Patients ranged in age from 42 to 85 years, and the weight of the transurethral resections varied from 6 to 90 g. Findings misinterpreted as cancer included atypical adenomatous hyperplasia (8 cases), basal cell hyperplasia (8), atrophy (5), sclerosing adenosis (3), high-grade prostatic intraepithelial neoplasia (3), xanthogranulomatous prostatitis (2), florid cribriform hyperplasia (1), and post-atrophic hyperplasia (1). None of the patients received additional treatment for prostatic disease. Mean follow-up was 10.8 years; 14 patients were alive with no evidence of disease, 14 died of intercurrent disease without recurrent prostatic disease, and the status of 3 was unknown. We conclude that misinterpretation of prostate cancer in transurethral resection specimens results from overdiagnosis of small microscopic foci of hyperplasia, atrophy, prostatic intraepithelial neoplasia, and granulomatous inflammation. The incidence of overdiagnosis three decades ago was 21% of small foci in transurethral resections, usually resulting from the presence of undescribed pathological entities. Long-term follow-up revealed no evidence of recurrent prostatic disease.

Adenocarcinoma↗

[Variations of EGG in subjects under vestibular stimulation].

Objective. To investigate the patterns of electrogastrogram [correction of electrogastrogragm] (EGG) before, during and after vestibular stimulation. Method. 25 subjects were stimulated by Coriolis acceleration and 28 by Coriolis [correction of corolis] stimulation. Result. Dysrythmia of EGG and increase of tachygastria were recorded in all subjects during the stimulation. The period dominant frequency (PDF) of EGG shifted from 2.40-3.70 cpm to 3.70-10.00 cpm during Coriolis stimulus in subjects with nausea. Conclusion. It suggests that PDF could be a parameter in reflecting the level of motion sickness.

Acceleration↗

[Determination of total sulfite in wine by high performance liquid chromatography(HPLC) with fluorescence detection].

A highly sensitive fluorometric method for the determination of total sulfite in wine is reported. The strong fluorescent derivatives formed by the quantitative reaction of sulfite in wine and N-(9-acridinyl) maleimide(NAM) in aqueous solution under mild conditions was injected into the HPLC. Separation was performed on an ODS column(200 mm x 5 mm) with a mobile phase of V(CH3CN):V(0.1 mo/L NH4AC) = 25:75 at a flow rate of 1.0 mL/min and detected by fluorometry at 455 nm(excitation at 365 nm). There was a good linear calibration curve in the range from 0.25-4 mg/L(r = 0.9998), The limit of detection was 1 ng. Sulfite mass concentration in wine has been determined by this method with good results and recoveries. This method is simple, rapid and reliable, and a sample size of only 1 mL is required to complete an analysis.

Chromatography, High Pressure Liquid↗