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Biomedical subjects

L Chang

Publications and source records attributed to L Chang.

At least 109 records · Page 6Linked to original sources
PubMed2001

[A randomized clinical study of preoperative chemotherapy for esophageal carcinoma].

OBJECTIVE: To evaluate the effect of preoperative chemotherapy on the prognosis of stage II or III patients with esophageal carcinoma. METHODS: From February 1991 to June 1994, 50 patients with stage II, III esophageal carcinoma were treated with preoperative combination (CDDP) chemotherapy and compared with 50 patients received operation alone. RESULTS: The 5-year survival rate of the operation group and preoperative chemotherapy group was 32% and 46%, respectively. The difference was statistically significant. CONCLUSION: Preoperative chemotherapy improves survival of surgically treated esophageal cancer patients.

Aged↗
PubMed2001

[Isolation, purification and identification of metallothionein from strain BD102 of Hansenula anomala].

Metallothionein (MTs) in Cu and Cd resistant strain BD102 of Hansenula anomala were induced by administration of Cu2+ and Cd2+. These proteins were isolated and purified by Sephadex G-50 and subsequent DEAE-Sepharose CL-6B, then Sephadex G-25 for desalation. There were two isoform MTs by Cu(Cu-MTs), one form induced by Cd (Cd-MT). The molecular weights of the Cu-MTs and the Cd-MT were about 7 kD and 7.5 kD respectively. Exposure of Hansenula anomala to copper salts stimulated formation of two isoform Cu-MTs with a cysteine content of 6.6-6.8% and had 60 amino acids. Exposure of Hansenula anomala to cadmium, stimulated formation of Cd-MT with a cystein content of 10% was synthesized and had 61 amino acids. 4 atom Cu or Cd/mole MTs.

Amino Acids↗
PubMed2000

A novel pharmacological approach to treating cardiac ischemia. Binary conjugates of A1 and A3 adenosine receptor agonists.

Adenosine released during cardiac ischemia exerts a potent, protective effect in the heart via activation of A(1) or A(3) receptors. However, the interaction between the two cardioprotective adenosine receptors and the question of which receptor is the more important anti-ischemic receptor remain largely unexplored. The objective of this study was to test the hypothesis that activation of both receptors exerted a cardioprotective effect that was significantly greater than activation of either receptor individually. This was accomplished by using a novel design in which new binary conjugates of adenosine A(1) and A(3) receptor agonists were synthesized and tested in a novel cardiac myocyte model of adenosine-elicited cardioprotection. Binary drugs having mixed selectivity for both A(1) and A(3) receptors were created through the covalent linking of functionalized congeners of adenosine agonists, each being selective for either the A(1) or A(3) receptor subtype. MRS 1740 and MRS 1741, thiourea-linked, regioisomers of a binary conjugate, were highly potent and selective in radioligand binding assays for A(1) and A(3) receptors (K(i) values of 0.7-3.5 nm) versus A(2A) receptors. The myocyte models utilized cultured chick embryo cells, either ventricular cells expressing native adenosine A(1) and A(3) receptors, or engineered atrial cells, in which either human A(3) receptors alone or both human A(1) and A(3) receptors were expressed. The binary agonist MRS 1741 coactivated A(1) and A(3) receptors simultaneously, with full cardioprotection (EC(50) approximately 0.1 nm) dependent on expression of both receptors. Thus, co-activation of both adenosine A(1) and A(3) receptors by the binary A(1)/A(3) agonists represents a novel general cardioprotective approach for the treatment of myocardial ischemia.

Adenosine↗
PubMed2000

Cerebral perfusion abnormalities in abstinent cocaine abusers: a perfusion MRI and SPECT study.

Nuclear medicine studies found decreased regional cerebral blood flow (rCBF) in the cortex and deep gray matter of cocaine users. Perfusion magnetic resonance imaging (MRI), a non-radioactive technique, has not been applied to evaluate persistent rCBF abnormalities. Twenty-five abstinent cocaine users and 15 healthy subjects without a history of drug use were examined with perfusion MRI, using dynamic bolus-tracking, and single photon emission computed tomography (SPECT), using 133Xe-calibrated 99mTc-HMPAO. After coregistration of SPECT with MRI, the relative rCBF (from perfusion MRI and SPECT) and absolute rCBF (from SPECT) were determined in 10 brain regions in each hemisphere. There was a statistically significant interaction between drug use and brain region on SPECT alone (relative and absolute rCBF), and on SPECT and perfusion MRI combined, but not on perfusion MRI alone. There also was a significant interaction among gender, drug use, and brain region. Compared to the control subjects, cocaine users showed increased rCBF in the frontal white matter (+8.6%, P=0.02) and in the globus pallidus (+6.3%, P=0.05), and decreased rCBF in the putamen (-3.9%, P=0.04) and the temporal cortex (-2.4%, P=0.02). SPECT and perfusion MRI detect a regional pattern of rCBF abnormalities in cocaine users that is consistent across the two methods. The hypoperfusion in the cortex and deep gray matter of the cocaine users is consistent with previous results. The increased rCBF in the white matter of cocaine users may be due to the presence of reactive glia.

Adolescent↗
PubMed2000

Gender differences in the functional organization of the brain for working memory.

Gender differences in brain activation during working memory tasks were examined with fMRI. Seventeen right-handed subjects (nine males, eight females) were studied with four different verbal working memory tasks of varying difficulty using whole brain echo-planar fMRI. Consistent with prior studies, we observed activation of the lateral prefrontal cortices (LPFC), the parietal cortices (PC), and additionally, caudate activation in both sexes. The volume of activated brain tissue increased with increasing task difficulty. For all four tasks, the male subjects showed bilateral activation or right-sided dominance (LPFC, PC and caudate), whereas females showed activation predominantly in the left hemisphere. The task performance data demonstrated higher accuracy and slightly slower reaction times for the female subjects. Our results show a highly significant (p < 0.001) gender differences in the functional organization of the brain for working memory. These gender-specific differences in functional organization of the brain may be due to gender-differences in problem solving strategies or the neurodevelopment. Therefore, gender matching or stratification is required for studies of brain function using imaging techniques.

Adult↗
PubMed2000

Structure-function studies on Taiwan cobra long neurotoxin homolog.

A novel long neurotoxin homolog was purified from Naja naja atra (Taiwan cobra) venom using the combination of ion exchange chromatography and reverse phase high performance liquid chromatography. The determined protein sequence was essentially the same as that deduced from the cDNA amplified by reverse transcriptase-polymerase chain reaction. The long neurotoxin homolog exhibited an activity that inhibited acetylcholine-induced muscle contractions, as with N. naja atra cobrotoxin. The degree of inhibition caused by the addition of long neurotoxin homolog was approximately 70% of that observed with the addition of cobrotoxin. Unlike the well-known short and long neurotoxins, this neurotoxin homolog contained two additional cysteine residues forming a disulfide linkage in the N-terminal region. Circular dichroism measurement and computer models of the neurotoxin reveal that its secondary structure was not abundant in beta-sheet as noted with short and long neurotoxins. This less ordered structure may be associated with the lower activity noted with the long neurotoxin homolog. Together with the finding that the known long neurotoxin homologs exclusively appear in the venoms of the Naja and Bungarus genera, the long neurotoxin homologs should represent an evolutionary branch from the long and short neurotoxins in the Elapidae family.

Amino Acid Sequence↗
PubMed2000

Sid4p is required to localize components of the septation initiation pathway to the spindle pole body in fission yeast.

A mutation in the Schizosaccharomyces pombe sid4(+) (septation initiation defective) gene was isolated in a screen for mutants defective in cytokinesis. We have cloned sid4(+) and have found that sid4(+) encodes a previously unknown 76.4-kDa protein that localizes to the spindle pole body (SPB) throughout the cell cycle. Sid4p is required for SPB localization of key regulators of septation initiation, including the GTPase Spg1p, the protein kinase Cdc7p, and the GTPase-activating protein Byr4p. An N-terminally truncated Sid4p mutant does not localize to SPBs and when overproduced acts as a dominant-negative mutant by titrating endogenous Sid4p and Spg1p from the SPB. Conversely, the Sid4p N-terminal 153 amino acids are sufficient for SPB localization. Biochemical studies demonstrate that Sid4p interacts with itself, and yeast two-hybrid analysis shows that its self-interaction domain lies within the C-terminal half of the protein. Our data indicate that Sid4p SPB localization is a prerequisite for the execution of the Spg1p signaling cascade.

Cell Cycle↗
PubMed2000

Effects of intestinal ischemia/reperfusion injury on gastric acid secretion.

BACKGROUND: The mechanism responsible for gastric colonization in critically injured ICU patients remains to be fully elucidated. Moreover, the effects of gut ischemia/reperfusion (I/R) injury on gastric function are unclear. It was our hypothesis that gut I/R injury would cause gastric dysfunction. MATERIALS AND METHODS: Rats were anesthetized and, via laparotomy, the superior mesenteric artery (SMA) was clamped at its aortic origin for 45 min followed by clamp removal. Rats were allowed to awaken and then killed after 6 h of reperfusion. Control rats underwent laparotomy with SMA isolation. Stomachs were removed, gastric fluid was aspirated, and the volume, pH, and protein, bicarbonate, and glucose contents were determined. Serum and antral mucosa were prepared for gastrin radioimmunoassay and the glandular mucosa was assessed for morphologic injury. RESULTS: SMA I/R injury caused significant accumulation of gastric luminal fluid that was alkaline and rich in protein, glucose, and bicarbonate content when compared with sham controls. SMA I/R injury also caused gastric surface epithelial cell injury and significantly increased serum and antral gastrin levels. In additional rats, gut I/R injury inhibited basal acid secretion and blunted the acid secretory response to pentagastrin. CONCLUSIONS: This study demonstrated for the first time that small intestinal I/R injury causes significant gastric dysfunction. The findings suggest that this type of injury, a frequent occurrence in critically injured ICU patients, may predispose patients to gastric colonization due to stasis and loss of the natural bactericidal effects of gastric acid.

Animals↗
PubMed2000

The role of the sid1p kinase and cdc14p in regulating the onset of cytokinesis in fission yeast.

Coordination of mitosis and cytokinesis is crucial for ensuring proper chromosome segregation and genomic stability. In Schizosaccharomyces pombe, the sid genes (cdc7, cdc11, cdc14, spg1, sid1, sid2 and sid4) define a signaling pathway that regulates septation and cytokinesis. Here we describe the characterization of a novel protein kinase, Sid1p. Sid1p localizes asymmetrically to one spindle pole body (SPB) in anaphase. Sid1p localization is maintained during medial ring constriction and septum synthesis and disappears prior to cell separation. Additionally, we found that Cdc14p is in a complex with Sid1p. Epistasis analysis places Sid1p-Cdc14p downstream of Spg1p-Cdc7p but upstream of Sid2p. Finally, we show that cyclin proteolysis during mitosis is unaffected by inactivating the sid pathway; in fact, loss of Cdc2-cyclin activity promotes Sid1p-Cdc14p association with the SPB, possibly providing a mechanism that couples cytokinesis with mitotic exit.

Amino Acid Sequence↗
PubMed2000

Evidence for long-term neurotoxicity associated with methamphetamine abuse: A 1H MRS study.

OBJECTIVE: To determine whether proton MRS (1H MRS) can detect long-term metabolite abnormalities in abstinent methamphetamine users. BACKGROUND: Methamphetamine is toxic to dopaminergic and serotonergic neurons in rodents; however, little data are available on the toxic effects of methamphetamine on the human brain. METHODS: 1H MRS was performed in 26 abstinent methamphetamine abusers with a history of methamphetamine dependence (median total cumulative lifetime exposure, 3,640 g; median recency of last methamphetamine use, 4.25 months) and 24 healthy subjects without a history of drug abuse. Cerebral metabolite concentrations on 1H MRS were measured in the frontal cortex, frontal white matter, and basal ganglia. RESULTS: The concentration of N-acetylaspartate ([NA]), a neuronal marker, was reduced significantly (-5 to -6%) in the basal ganglia and frontal white matter of methamphetamine users compared with control subjects. The frontal white matter [NA] correlated inversely with the logarithm of the lifetime methamphetamine use. The methamphetamine users also showed significantly reduced total creatine in the basal ganglia (-8%), and increased choline-containing compounds ([CHO], +13%) and myo-inositol ([MI], +11%) in the frontal grey matter. CONCLUSIONS: The reduced [NA] on 1H MRS provides evidence for long-term neuronal damage in abstinent methamphetamine users.

Adult↗
PubMed2000

Effect of ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] on cerebral blood flow: a co-registered SPECT and MRI study.

3,4-methylenedioxymethamphetamine (MDMA), an illicit recreational drug, damages serotonergic nerve endings. Since the cerebrovasculature is regulated partly by the serotonergic system, MDMA may affect cerebral blood flow (CBF) in humans. We evaluated 21 abstinent recreational MDMA users and 21 age- and gender-matched healthy subjects with brain SPECT and MRI. Ten of the MDMA subjects also had repeat SPECT and MRI after receiving two doses of MDMA. Abstinent MDMA users showed no significantly different global or regional CBF (rCBF) compared to the control subjects. However, within 3 weeks after MDMA administration, rCBF remained decreased in the visual cortex, the caudate, the superior parietal and dorsolateral frontal regions compared to baseline rCBF. The decreased rCBF tended to be more pronounced in subjects who received the higher dosage of MDMA. Two subjects who were scanned at 2-3 months after MDMA administration showed increased rather than decreased rCBF. Low-dose recreational MDMA use does not cause detectable persistent rCBF changes in humans. The lack of long-term rCBF changes may be due to a non-significant effect of serotonergic deficits on rCBF, or regeneration of serotonergic nerve terminals. The subacute decrease in rCBF after MDMA administration may be due to the direct effect of MDMA on the serotonergic system or the indirect effects of its metabolites on the dopaminergic system; the preliminary data suggest these effects may be transient.

Adult↗
PubMed2000

Perfusion MRI detects rCBF abnormalities in early stages of HIV-cognitive motor complex.

OBJECTIVE: To evaluate patients with early HIV-cognitive motor complex (HIV-CMC) for possible regional cerebral blood flow (rCBF) abnormalities on perfusion MRI (pMRI). BACKGROUND: Nuclear medicine techniques have demonstrated global and focal cerebral perfusion abnormalities in patients with HIV dementia. Ultrafast pMRI enables the measurement of rCBF throughout the brain without the need to apply radioactive tracers or ionizing radiation. METHODS: pMRI was used to measure the rCBF in 19 patients with early stages of HIV-CMC and 15 healthy seronegative control subjects. The rCBF maps were registered to high-resolution anatomic MRI scans and transformed into Talairach space. Statistical analysis of the rCBF maps was performed with SPM96. RESULTS: Compared with the control subjects, the patients with HIV had statistically significantly decreased rCBF bilaterally in the inferior lateral frontal cortices (right: -15%, p < 0.002; left: -12%, p < 0.005) and in the inferior medial parietal brain region (-15%, p < 0.0009). In contrast, rCBF was increased bilaterally in the posterior inferior parietal white matter (right: +19%, p < 0.0001; left: + 17%, p < 0.001). Furthermore, rCBF abnormalities correlated significantly with clinical disease severity as measured by CD4 count, plasma viral load, Karnofsky score, and HIV dementia scale. DISCUSSION: Our results are consistent with previous findings from PET and SPECT studies. Furthermore, pMRI can detect rCBF abnormalities that correlate with disease severity in HIV-CMC. Because pMRI is more cost-effective, faster, and safer than nuclear medicine techniques for monitoring rCBF changes, pMRI may be more feasible for monitoring the effects of therapy for HIV-CMC.

AIDS Dementia Complex↗
PubMed2000

An integrated genetic linkage map with 1,137 markers constructed from five F2 crosses of autoimmune disease-prone and -resistant inbred rat strains.

The rat (Rattus norvegicus) is an important experimental model for many human diseases including arthritis, diabetes, and other autoimmune and chronic inflammatory diseases. The rat genetic linkage map, however, is less well developed than those of mouse and human. Integrated rat genetic linkage maps have been previously reported by Pravenec et al. (1996, Mamm. Genome 7: 117-127) (500 markers mapped in one cross), Bihoreau et al. (1997, Genome Res. 7: 434-440) (767 markers mapped in three crosses), Wei et al. (1998, Mamm. Genome 9: 1002-1007) (562 markers mapped in two crosses), Brown et al. (1998, Mamm. Genome 9: 521-530) (678 markers mapped in four crosses), and Nordquist et al. (1999, Rat Genome 5: 15-20) (330 markers mapped in two crosses). The densest linkage map combined with a radiation hybrid map, reported by Steen et al. (1999, Genome Res. 9: AP1-AP8), includes 4736 markers mapped in two crosses. Here, we present an integrated linkage map with 1137 markers. We have constructed this map by genotyping F2 progeny of five crosses: F344/NHsd x LEW/NHsd (673 markers), DA/Bkl x F344/NHsd (531 markers), BN/SsN x LEW/N (714 markers), DA/Bkl x BN/SsNHsd (194 markers), and DA/Bkl x ACI/SegHsd (245 markers). These inbred rat strains vary in susceptibility/resistance to multiple autoimmune diseases and are used extensively for many types of investigation. The integrated map includes 360 loci mapped in three or more crosses. The map contains 196 new SSLP markers developed by our group, as well as many SSLP markers developed by other groups. Two hundred forty genes are incorporated in the map. This integrated map should allow comparison of rat genetic maps from different groups and thereby facilitate genetic studies of rat autoimmune and related disease models.

Animals↗
PubMed2000

Simplified admission criterion for predicting severe complications of gallstone pancreatitis.

HYPOTHESIS: Simple admission criteria (white blood cell count, > or =14. 5 x 10(9)/L; blood urea nitrogen level, > or =4.3 mmol/L [> or =12 mg/dL]; heart rate, > or =100 beats per minute; and serum glucose level, > or =8.3 mmol/L [> or =150 mg/dL]) are better predictors of severe complications of gallstone pancreatitis than an Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 5 or greater, a modified Imrie (Glasgow) score of 3 or greater, and a biliary Ranson score of 3 or greater. DESIGN: A prospective consecutive case study. SETTING: A university-affiliated, urban, public hospital. PATIENTS: Ninety-two consecutive patients (77 women and 15 men, aged 18 to 76 years [mean age, 39 years]) with gallstone pancreatitis. Seventy-seven patients were Hispanic. MAIN OUTCOME MEASURES: Major local and systemic complications requiring intensive care unit care, and death. RESULTS: Fourteen patients (15%) had severe complications with a mortality of 2%. On univariate analysis, a white blood cell count of 14.5 x 10(9)/L or more (P =.03), a serum glucose level of 8. 3 mmol/L or more (> or =150 mg/dL) (P<.001), an APACHE II score of 5 or greater (P =.008), a modified Imrie score of 3 or greater (P<.001), and a biliary Ranson score of 3 or greater (P =.03) were statistically associated with the development of severe complications; whereas a blood urea nitrogen level of 4.3 mmol/L or more (> or =12 mg/dL) and a heart rate of 100 beats per minute or more were not. On multivariate analysis, only a serum glucose level of 8. 3 mmol/L or more (> or =150 mg/dL) was predictive of adverse events (P<. 001). CONCLUSIONS: Glucose level (> or =8.3 mmol/L [> or =150 mg/dL]) is the best single admission predictor of severe complications of gallstone pancreatitis and is superior to an APACHE II score of 5 or greater, a modified Imrie score of 3 or greater, and a biliary Ranson score of 3 or greater.

Acute Disease↗
PubMed2000

Perfusion MRI of the human brain with dynamic susceptibility contrast: gradient-echo versus spin-echo techniques.

In this study, spin-echo and gradient-echo-based perfusion magnetic resonance imaging (MRI) techniques are systematically compared with respect to their application in the human brain. Six healthy subjects were evaluated with both techniques consecutively and injected twice with a gadolinium-based contrast agent. In accordance with theoretical predictions and with previous animal experiments, the spin-echo-based technique shows a markedly reduced appearance of large vessels. The intersubject standard deviations of the two methods are similar but smaller for the spin-echo technique in small regions adjacent to large vessels. Therefore, the sensitivity of the two acquisition methods for evaluating pathologic abnormalities may be similar despite the higher contrast-to-noise ratio of the gradient-echo-based technique. The gray-to-white matter ratio of the regional cerebral blood flow of the spin-echo method is closer to previous nuclear medicine measurements than that of the gradient-echo method. Our measurements indicate that spin-echo-based perfusion MRI is more representative of capillary perfusion than gradient-echo measurements. J. Magn. Reson. Imaging 2000;12:381-387.

Adult↗
PubMed2000

Changes in cerebral metabolism are detected prior to perfusion changes in early HIV-CMC: A coregistered (1)H MRS and SPECT study.

Human immunodeficiency virus-cognitive motor complex (HIV-CMC), a common complication of the acquired immunodeficiency syndrome (AIDS), is characterized by progressive cognitive impairment and motor dysfunction. Functional imaging methods, such as single-photon emission computed tomography (SPECT) and proton magnetic resonance spectroscopy ((1)H-MRS), have been applied to assess the severity of brain injury. However, it is unclear which of these two methods is more sensitive in detecting brain abnormalities in patients with early HIV-CMC. Twenty-four HIV-CMC patients were compared with 34 healthy subjects; each had quantitative SPECT ((133)Xenon-calibrated (99m)Tc-HMPAO) and quantitative (1)H-MRS. Both modalities were co-registered in order to assess regional cerebral blood flow (rCBF) and metabolite concentrations within the same voxel of interest in four brain regions (midfrontal and midparietal gray matter, temporoparietal white matter, and basal ganglia). On SPECT, only the temporoparietal white matter showed a trend for decreased rCBF in HIV-CMC patients (-13%, P = 0.06). On MRS, HIV-CMC patients showed significantly reduced creatine concentration in the basal ganglia (-8%, P = 0.008), as well as increased myoinositol concentrations in the basal ganglia (+25%, P = 0.01) and the temporoparietal white matter (+18%, P = 0.08). There was no significant correlation between SPECT and MRS variables in the patients in any region. (1)H MRS showed abnormal neurochemistry in the basal ganglia, whereas rCBF on SPECT was normal in the same region. This finding suggests that metabolite concentrations on (1)H MRS are better surrogate markers than rCBF measurements with SPECT for the evaluation of brain injury in early HIV-CMC. J. Magn. Reson. Imaging 2000;12:859-865.

AIDS Dementia Complex↗
PubMed2000

Percutaneous cholecystostomy for acute cholecystitis in veteran patients.

BACKGROUND: Surgical cholecystostomy has been shown to carry a significantly higher mortality rate at Veterans Administration (VA) hospitals than at non-federal hospitals in the past. METHODS: A retrospective outcomes study was undertaken at a large VA medical center with a policy favoring radiologic over surgical cholecystostomy over the past 9 years. Records of 24 consecutive patients with acute cholecystitis were reviewed to evaluate the effectiveness of the procedure. RESULTS: Cholecystostomy was performed radiologically in 22 patients and surgically in 2 patients. Most (78%) of patients improved within 48 hours. The periprocedural mortality was 25%. The majority of these patients died from unrelated illnesses. Four patients developed complications, none of which required operative intervention. CONCLUSIONS: Comorbidities are the most important mortality factor for cholecystostomies in VA patients. Radiologic tube placement is effective and uncomplicated in most cases.

Acute Disease↗