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Biomedical subjects

L Chang

Publications and source records attributed to L Chang.

At least 199 records · Page 11Linked to original sources

The association of functional gastrointestinal disorders and fibromyalgia.

Previous epidemiological studies have confirmed the clinical impression that functional gastrointestinal disorders typically overlap with fibromyalgia (FM) in the same patient, suggesting a common etiology. FM syndrome occurs in up to 60% of patients with functional bowel disorders. Up to 50% of patients with a diagnosis of FM syndrome complain of symptoms characteristic of functional dyspepsia and 70% have symptoms of IBS. These two conditions have common clinical characteristics: (1) the majority of patients associate stressful life events with the initiation or exacerbation of symptoms, (2) the majority of patients complain of disturbed sleep and fatigue, (3) psychotherapy and behavioral therapies are efficacious in treating symptoms, and (4) low-dose tricyclic antidepressant medication can improve symptoms. Despite these similarities, their perceptual responses to both somatic and visceral stimuli differ. While FM patients characteristically exhibit somatic hyperalgesia, IBS patients without coexistent FM have somatic hypoalgesia to mechanical stimuli. Visceral distention studies have also demonstrated perceptual alterations in patients with IBS and FM although these findings appear to differ in the two conditions. Further studies will help explore the mechanisms which are responsible for the similarities and differences in clinical symptoms and physiologic parameters seen in IBS and FM.

Brain↗

Brain-gut interactions: implications for newer therapy.

Despite their high prevalence and significant economic impact on the healthcare system, functional GI 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, thus not permitting to draw any conclusions about true efficacy of any particular treatment. The past several years have seen the rapid evolution of a new, comprehensive disease model, based on alterations in brain-gut interactions. Even though the precise mechanisms and sites underlying these alterations remain incompletely understood, plausible targets for the development of effective pharmacologic treatment are receptors on peripheral terminals of visceral afferent nerves (opioids, serotonin), ion channels and receptors on dorsal horn neurons within the spinal cord (opioids, glutamate, CGRP, NK-1) and supraspinal targets in the brainstem, within the limbic system and in the prefrontal cortex (serotonin, catecholamines, dopamine, acetylcholine). Regardless of the primary pathophysiology underlying functional GI disorders (i.e. central vs. peripheral), different pharmacological strategies targeted at different sites in the periphery or within the central nervous system may be effective.

Brain↗

Isolation and characterization of new fission yeast cytokinesis mutants.

Schizosaccharomyces pombe is an excellent organism in which to study cytokinesis as it divides by medial fission using an F-actin contractile ring. To enhance our understanding of the cell division process, a large genetic screen was carried out in which 17 genetic loci essential for cytokinesis were identified, 5 of which are novel. Mutants identifying three genes, rng3(+), rng4(+), and rng5(+), were defective in organizing an actin contractile ring. Four mutants defective in septum deposition, septum initiation defective (sid)1, sid2, sid3, and sid4, were also identified and characterized. Genetic analyses revealed that the sid mutants display strong negative interactions with the previously described septation mutants cdc7-24, cdc11-123, and cdc14-118. The rng5(+), sid2(+), and sid3(+) genes were cloned and shown to encode Myo2p (a myosin heavy chain), a protein kinase related to budding yeast Dbf2p, and Spg1p, a GTP binding protein that is a member of the ras superfamily of GTPases, respectively. The ability of Spg1p to promote septum formation from any point in the cell cycle depends on the activity of Sid4p. In addition, we have characterized a phenotype that has not been described previously in cytokinesis mutants, namely the failure to reorganize actin patches to the medial region of the cell in preparation for septum formation.

Actins↗

Study on Haemophilus influenzae type b diseases in China: the past, present and future.

Meningitis caused by Haemophilus influenzae type b (Hib) is a common and serious disease for which there now are WHO-certified vaccines that are recommended for universal infant immunization in North America and European countries. If these vaccines are to be recommended in Asia, it is necessary to know the incidence, age distribution and clinical outcome of Hib meningitis and other systemic infections in this region. Data on Hib disease in China are scanty. Hib meningitis was common during the 1950s in China, accounting for up to 16% of all of pyogenic meningitis (up to 38% of cases were caused by unknown pathogens), despite severe epidemics of meningococcal meningitis during that period. Since 1989 we have conducted hospital- and community-based etiologic and epidemiologic studies of bacterial meningitis. Hib accounts for 30 to 50% of bacterial meningitis in China. The incidence of Hib meningitis in Hefei City was 10.4 per 100000 children <5 years, a result relatively lower than in the West but higher than the rate of 2.7 found in a retrospective study in Hong Kong. Pneumonia is the primary cause of death for Chinese children. From 1991 to 1993 the average mortality of children<5 years because of pneumonia was 1563.2 per 100000. To achieve the goal of reducing the death rate of children by one-third by the year 2000, greater efforts should be made to reduce the mortality of children with pneumonia. Our preliminary study showed that about one-fourth to one-third of cases of pneumonia in Chinese children might be caused by Hib. Therefore Hib vaccination for infants and children in China might be an effective and valuable procedure to achieve the goal.

Child, Preschool↗

Silicone in nasal augmentation rhinoplasty: a decade of clinical experience.

A number of materials, both biologic and alloplastic, have been used for nasal augmentation. Although biologic bone and cartilage grafts are associated with lower infection rates, they are also associated with long-term resorption and donor-site morbidity. Alloplastic materials, in particular silicone, have been associated in the literature with extrusion and infection but have the advantages of being affordable and easy to reshape with no requirement for harvesting autografts. A 10-year experience with silicone nasal augmentation documenting clinical experience, acute and long-term complications, and patient satisfaction was reviewed. All patients undergoing silicone augmentation rhinoplasty between July of 1985 and December of 1995 were reviewed. Preoperative nasal phenotype, operative data, and postoperative outcome were recorded. Long-term follow-up was undertaken using a telephone survey. There were 422 patients who underwent silicone nasal augmentation from July of 1985 to December of 1995. Only nine were men. The indications were for aesthetic nasal augmentation in 98 percent, and the majority (98 percent) were of South East Asian origin. Mean age was 26 (range 17 to 36), and 41 of the 422 patients had had previous nasal augmentation performed before presentation. Twenty-three patients (5.5 percent) had complications requiring removal of the implant within 30 days of surgery. These included displacement, prominence, hemorrhage, and excessive pressure in addition to obvious supratip deformity. On late follow-up, a further 18 patients (4.3 percent) had subsequent removal of the prosthesis. The most common reason for this was either displacement or over-prominence, more often judged by the surgeon than the patient. There were only two patients (0.5 percent) who had extrusion of the prosthesis. A total of 266 patients (63 percent) were contacted for a telephone interview. The majority of patients (84.2 percent) were satisfied with their nasal shape. Of the 42 patients (15.8 percent) who were not satisfied, 21 patients still wanted further augmentation of their nose. Photographic analysis of 198 patients showed a mean augmentation of 16.5 percent (range 4.0 to 27.5). Amount of augmentation correlated with preoperative nasal phenotype. Silicone nasal augmentation is a safe and effective procedure when used for moderate increases in nasal height. Contrary to previous reports, this series showed no associated infection. If the implant is shaped appropriately to the patient's nasal phenotype, the risk of extrusion may be reduced.

Adolescent↗

Evolution of thyroid hormone distribution.

1. Appropriate distribution of thyroxine between the lipid-soluble compartments of cells and tissues and the extracellular aqueous space is established by binding to extracellular proteins. Among these proteins, transthyretin is of particular interest because it is the only one synthesized in the brain. 2. The evolutionary onset of transthyretin synthesis in cells of the blood-brain barrier precedes that in the liver, with the exception of a very short period of transthyretin synthesis in the liver of tadpoles, just prior to the climax of metamorphosis. In adult liver, transthyretin is only synthesized in endothermic vertebrates. 3. The affinity of transthyretin for thyroxine increases and that for 3,5,3'-triiodothyronine decreases during the evolution of eutherians from reptile/bird-like common ancestors. 4. A systematic change of the N-terminal region of transthyretin occurred during evolution, leading to shorter and more hydrophilic transthyretin N termini in eutherians compared with those in reptiles and birds. 5. The molecular mechanism of the evolution of the transthyretin N termini is a stepwise shift of the splice site at the intron 1/exon 2 border in the 3' direction. The most probable cause for this shift is a series of single base mutations. 6. As the N termini are located on the surface of transthyretin near the entrance to its central channel leading to the thyroxine binding sites, it is possible that a change in the structure of this region could influence the access of thyroxine to the binding sites. The increase in affinity for thyroxine could then be a driving force in the natural selection during evolution of transthyretins with shorter and more hydrophilic N termini.

Amino Acid Sequence↗

Gallstone pancreatitis: a prospective study on the incidence of cholangitis and clinical predictors of retained common bile duct stones.

OBJECTIVE: The aim of this study was to define the incidence of cholangitis in gallstone pancreatitis, in the absence of cholangitis, to identify the clinical predictors of persistent common bile duct (CBD) stones at endoscopic retrograde cholangiography (ERCP) or at intraoperative cholangiography (IOC). METHODS: A total of 122 consecutive patients with acute gallstone pancreatitis were prospectively evaluated for the presence of CBD stones as determined by elective ERCP or IOC. Urgent ERCP was restricted to patients with concomitant cholangitis. APACHE II scores and serial laboratory data were obtained. RESULTS: Four (3%) patients had cholangitis and all underwent urgent ERCP successfully. Eighteen (15%) patients without cholangiogram were excluded. The remaining 100 patients underwent elective ERCP or IOC on a mean of hospital day 6.8. Twenty-one (21%) patients had persistent CBD stones. Univariate analysis detected significant differences in serum total bilirubin, ALT, and alkaline phosphatase levels between patients with and without persistent CBD stones. On multivariate analysis, serum total bilirubin on hospital day 2 was the best predictor of CBD stones. A serum total bilirubin level > 1.35 mg/dl had a sensitivity of 90.5% and specificity of 63%. Age, gender, mean APACHE II score, amylase, and presence of CBD dilation on ultrasound were not predictive of CBD stones. CONCLUSION: In patients with gallstone pancreatitis, 1) cholangitis is uncommon, and 2) the best clinical predictor of persistent CBD stones is serum total bilirubin on hospital day 2.

APACHE↗

Identification of conserved, RpoS-dependent stationary-phase genes of Escherichia coli.

During entry into stationary phase, many free-living, gram-negative bacteria express genes that impart cellular resistance to environmental stresses, such as oxidative stress and osmotic stress. Many genes that are required for stationary-phase adaptation are controlled by RpoS, a conserved alternative sigma factor, whose expression is, in turn, controlled by many factors. To better understand the numbers and types of genes dependent upon RpoS, we employed a genetic screen to isolate more than 100 independent RpoS-dependent gene fusions from a bank of several thousand mutants harboring random, independent promoter-lacZ operon fusion mutations. Dependence on RpoS varied from 2-fold to over 100-fold. The expression of all fusion mutations was normal in an rpoS/rpoS+ merodiploid (rpoS background transformed with an rpoS-containing plasmid). Surprisingly, the expression of many RpoS-dependent genes was growth phase dependent, albeit at lower levels, even in an rpoS background, suggesting that other growth-phase-dependent regulatory mechanisms, in addition to RpoS, may control postexponential gene expression. These results are consistent with the idea that many growth-phase-regulated functions in Escherichia coli do not require RpoS for expression. The identities of the 10 most highly RpoS-dependent fusions identified in this study were determined by DNA sequence analysis. Three of the mutations mapped to otsA, katE, ecnB, and osmY-genes that have been previously shown by others to be highly RpoS dependent. The six remaining highly-RpoS-dependent fusion mutations were located in other genes, namely, gabP, yhiUV, o371, o381, f186, and o215.

Artificial Gene Fusion↗

Cerebral toxoplasmosis and lymphoma in AIDS: perfusion MR imaging experience in 13 patients.

PURPOSE: To evaluate the perfusion magnetic resonance (MR) imaging characteristics of cerebral toxoplasmosis and lymphoma in patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Perfusion MR imaging was performed prospectively in 13 patients with AIDS who had contrast material-enhancing focal brain lesions (six with active lymphoma, five with toxoplasmosis, one with treated lymphoma in remission, and one with toxoplasmosis plus lymphomatoid granulomatosis). Regional cerebral blood volume (rCBV) was determined by using dynamic echo-planar MR imaging during bolus injection of a gadolinium chelate. RESULTS: The rCBV was decreased (44% +/- 24 [standard deviation] of rCBV in the contralateral regions) throughout the toxoplasmosis lesions and in the surrounding edema of both lesion types, whereas all active lymphomas displayed areas of increased rCBV (258% +/- 99). These differences were significant (P < .005). CONCLUSION: Reduced rCBV i toxoplasmosis lesions is probably due to a lack of vasculature within the abscess; increased rCBV in lymphomas is probably due to hypervascularity in foci of active tumor growth; and decreased rCBV in the edema is probably due to vasoconstriction associated with increased interstitial pressure. Perfusion MR imaging is a rapid, noninvasive tool that may allow differentiation between cerebral lymphoma and toxoplasmosis in patients with AIDS.

AIDS-Related Opportunistic Infections↗

Effects of endotoxin on gastric injury from luminal irritants in rats: potential roles of nitric oxide.

The expression and function of inducible nitric oxide synthase (iNOS) in the stomach is unclear. This study assessed the effects of endotoxin on rat gastric iNOS expression and its role in gastric injury from luminal irritants. In conscious rats, a 5-h treatment with intraperitoneal lipopolysaccharide (LPS; 1-20 mg/kg) dose dependently increased gastric mucosal iNOS immunoreactivity and increased gastric luminal nitrate and nitrite accumulation (Griess reaction). LPS also increased gastric luminal fluid accumulation and reduced macroscopic gastric injury from orogastric acidified ethanol. Aminoguanidine (45 mg/kg) did not prevent LPS-induced gastroprotection or gastric fluid accumulation. NG-nitro-L-arginine methyl ester increased gastric luminal fluid and caused macroscopic gastric injury when given with LPS. Using an anesthetized preparation followed by removal of luminal fluid, LPS reduced gastric mucosal blood flow and exacerbated gastric injury from either acidified ethanol or acidified taurocholate, an effect that was negated by aminoguanidine. These data indicate that in conscious rats, the gastroprotective effect of endotoxin is dependent on constitutive NOS but not iNOS activity. However, the inducible isoform participates in the ability of endotoxin to exacerbate gastric injury from luminal irritants in the anesthetized rat.

Animals↗

Physiologic MRI of a tumefactive multiple sclerosis lesion.

Structural and physiologic MRI were performed after subacute onset of left hemiparesis in a patient with MS. MRI showed a large ring-enhancing lesion with surrounding edema and mass effect; differential diagnosis included a neoplasm or a large MS plaque. Physiologic MRI showed reduced blood flow and magnetization transfer, as well as increased diffusion, in the large lesion. Because these findings suggested a tumefactive MS plaque rather than a neoplasm, the patient received steroid treatment for acute MS exacerbation. Three months later the patient improved clinically and on MRI.

Adult↗

Enhancement of apoptotic susceptibility by interleukin-1 beta in human endometrial epithelial cells.

Interleukin-1 (IL-1) is considered to be an essential cytokine for embryonic implantation. Expression of the IL-1 receptor in endometrial luminal epithelium increases maximally in the peri-implantation period, and embryonic implantation in mice is blocked by the IL-1 receptor antagonist. However, the function of IL-1 alone in implantation is still unclear. It has been reported that endometrial epithelial cells undergo apoptosis at the implantation site. In this study we have investigated the regulatory function of IL-1 in endometrial epithelial apoptosis, using the human endometrial epithelial cell line HHUA, which is susceptible to Fas-mediated apoptosis. The enhancement of endometrial apoptosis by IL-1 beta was not accompanied by any increase in cell-surface expression of Fas, which suggested that IL-1 beta enhanced the postreceptor apoptotic signals in the activated cells. IL-1 may be a regulator of apoptotic susceptibility in endometrial epithelium in the peri-implantation period.

Adenocarcinoma↗

Differential apoptotic susceptibility to anti-Fas IgM and anticancer drugs in a human endometrial adenocarcinoma cell line HHUA on laminin and type I collagen.

Apoptotic susceptibility of epithelial cells is known to be regulated by cell adhesions to basement membranes. In this study differences in anticancer drug-sensitivities of early and advanced endometrial adenocarcinomas were examined by using highly-differentiated human endometrial adenocarcinoma cell line, HHUA, whose apoptotic susceptibility was hypothesized to be modulated by extracellular matrices. The cells express high levels of laminin receptors and laminin suppressed Fas-mediated apoptosis of the cells. However laminin did not show any effect on apoptotic susceptibility to 4 anticancer drugs. These results suggest that there is little variation in drug-sensitivity associated with disruption of endometrial stromal tissue, and that pathological staging of endometrial carcinoma is not likely to have any relation to drug sensitivity.

Adenocarcinoma↗

[Isolation, purification and identification of metallthionein from strain BD 101 of Saccharomyces cerevisiae].

Selection of Saccharomyces cerevisiae BD101 having resistance to metal ions and producing metallothionein by inducer from Saccharomyces. These proteins were isolated and purified by Sephadex G-50 and subsequent DEAE Sepharose CL-4B, then Sephadex G-25 for desalination. There were two iso-MTs for Cu-induced. The, molecular weights were 7 kD and had 60 amino acids. Both Cu-MTs were rich in Cysteine (10%). 4 atom Cu/6 mole Cys/mole Cu-MTs.

Amino Acids↗

Neurochemical alterations in asymptomatic abstinent cocaine users: a proton magnetic resonance spectroscopy study.

Cocaine can cause a variety of neuropsychiatric and neurobehavioral complications; however, it is uncertain whether cocaine causes persistent cerebral structural and neurochemical abnormalities in asymptomatic users. We studied 52 African-American men (26 human immunodeficiency virus-negative asymptomatic heavy cocaine users and 26 normal subjects). Ventricle-to-brain ratio (VBR) and white matter lesions (WML) were quantified on magnetic resonance imaging. N-acetyl-containing compounds (NA), total creatine, choline-containing compounds, myo-inositol, and glutamate + glutamine were measured with in vivo proton magnetic resonance spectroscopy, VBR and WML were not significantly different in the cocaine users compared to the normal controls. Elevated creatine (+7%; p = .05) and myo-inositol (+18%; p = .01) in the white matter were associated with cocaine use. NA, primarily a measure of N-acetyl aspartate and neuronal content, was normal. Normal NA suggest no neuronal loss or damage in the brain regions examined in these cocaine users. Therefore, we conclude that neurochemical abnormalities observed might result from alterations in nonneuronal brain tissue.

Adolescent↗

The orphan nuclear receptor TR2 suppresses a DR4 hormone response element of the mouse CRABP-I gene promoter.

The mouse orphan nuclear receptor TR2-11-f suppressed the expression of reporters fused to a hormone response element of the mouse cellular retinoic acid-binding protein I gene promoter. TR2-11-f was able to bind to a direct repeat with four nucleotides in the spacer (5'TGACCTTTGGGGACCT3') located within this hormone response element as homodimers. The specificity of protein-DNA interactions was demonstrated by competition in gel retardation and antibody-mediated supershift reactions. The residues critical for TR2-11-f binding were mapped to both repeated sequences, whereas the spacer and the flanking sequences were less important. The Kd and Bmax of TR2-11-f homodimer binding to this direct repeat were determined to be 2.6 nM and 0.012 nM, respectively. By using a yeast two-hybrid system, it was demonstrated that dimerization of TR2-11-f was mediated by its ligand-binding domain. The actions of TR2-11-f in regulating cellular retinoic acid-binding protein I gene will likely influence retinoic action and availability within the cells.

Animals↗

Structure-activity relationships of 4-(phenylethynyl)-6-phenyl-1,4-dihydropyridines as highly selective A3 adenosine receptor antagonists.

4-(Phenylethynyl)-6-phenyl-1,4-dihydropyridine derivatives are selective antagonists at human A3 adenosine receptors, with Ki values in a radioligand binding assay vs [125I]AB-MECA (N6-(4-amino-3-iodobenzyl)-5'-(N-methylcarbamoyl)adenosine) in the submicromolar range. In this study, structure-activity relationships at various positions of the dihydropyridine ring (the 3- and 5-acyl substituents, the 4-aryl substituent, and 1-methyl group) were probed synthetically. Using the combined protection of the 1-ethoxymethyl and the 5-[2-(trimethylsilyl)ethyl] ester groups, a free carboxylic acid was formed at the 5-position allowing various substitutions. Selectivity of the new analogues for cloned human A3 adenosine receptors was determined vs radioligand binding at rat brain A1 and A2A receptors. Structure-activity analysis at adenosine receptors indicated that pyridyl, furyl, benzofuryl, and thienyl groups at the 4-position resulted in, at most, only moderate selectivity for A3 adenosine receptors. Ring substitution (e.g., 4-nitro) of the 4-phenylethylnyl group did not provide enhanced selectivity, as it did for the 4-styryl-substituted dihydropyridines. At the 3-position of the dihydropyridine ring, esters were much more selective for A3 receptors than closely related thioester, amide, and ketone derivatives. A cyclic 3-keto derivative was 5-fold more potent at A3 receptors than a related open-ring analogue. At the 5-position, a homologous series of phenylalkyl esters and a series of substituted benzyl esters were prepared and tested. (Trifluoromethyl)-, nitro-, and other benzyl esters substituted with electron-withdrawing groups were specific for A3 receptors with nanomolar Ki values and selectivity as high as 37000-fold. A functionalized congener bearing an [(aminoethyl)amino]carbonyl group was also prepared as an intermediate in the synthesis of biologically active conjugates.

Adenosine↗

Novel SnoRNAs from Naja naja atra (Taiwan cobra) and Bungarus multicinctus (Taiwan banded krait), form extended sequence complementarity to 5S rRNA.

During the mapping and sequencing of Naja naja atra cobrotoxin and cardiotoxin 4 genes, we have found that novel small nucleolar RNAs (snoRNAs) are encoded in the first intron of the two genes. The snoRNAs in Naja naja atra were amplified from the venom glands cDNA mixtures of Naja naja atra by reverse transcription-polymerase chain reaction using the primers designed from the first intronic sequences of cobrotoxin and cardiotoxin 4 genes. Likewise, the snoRNAs in Bungarus multicinctus were also amplified by the same primers. Comparison of these snoRNA genes reveals that the regions involved in binding to 5S rRNA are highly conserved among these genes, and form 12-nt and 15-nt tracts of complementarity to phylogenetically invariant sequences in eukaryotic 5S rRNAs. The box C sequence in these snoRNAs is consensus, however, variations with the sequence of box D motif are observed. The present study is the first case of intron-encoded snoRNAs contain extended regions of perfect complementarity to mature 5S rRNA.

Animals↗