Biomedical subjects
Publications and source records attributed to S J Chen.
Arsenic has recently been identified as an effective drug in the treatment of newly diagnosed and relapsed acute promyelocytic leukemia. Indeed, arsenic trioxide combined with all-trans retinoic acid shows a synergistic effect. Mechanistically, arsenic targets the key leukemogenic protein PML-RARalpha, setting up a new example of molecular target-based cancer therapy.
A truncated mutant alpha-amylase, Xa-S2, was obtained from Xanthomonas campestris wild type alpha-amylases (Xa-WT) through random mutagenesis that contained 167 amino acid residues (approx 65% shorter than that of Xa-WT). Secondary structure prediction implied that Xa-S2, would be unable to form the whole (beta/alpha)(8)-barrel catalytic domain and did not have the three conserved catalytic residues of wild type alpha-amylase, but it still displays the starch-hydrolyzing activity. Xa-S2 was prepared, characterized and compared to the recombinant wild-type enzymes. The K (m) for starch was 32 mg/ml; activity was optimal at pH 6.2 and 30 degrees C. In contrast, the K (m) for starch of Xa-WT was 8 mg/ml and optimal enzyme activity was at pH 6.0-6.2 and 45-50 degrees C. Our results suggested that Xa-S2 is a new amylase with a minimal catalytic domain for hydrolyzing substrates with of alpha-1,4-glucosidic bonds.
Rearrangement of the mixed lineage leukaemia (MLL) gene with extra eleven nineteen (EEN) was previously identified in an infant with acute myeloid leukaemia. Using homologous recombination, we have created a mouse equivalent of the human MLL-EEN allele and showed that when Mll(Een/+) embryonic stem (ES) cells were induced to differentiate in vitro into haemopoietic cells, there was increased proliferation of myeloid progenitors with self-renewal property. We also generated Mll(Een/+) chimeric mice, which developed leukaemia displaying enlarged livers, spleens, thymuses and lymph nodes owing to infiltration of Mll(Een/+)-expressing leukemic cells. Immunophenotyping of cells from enlarged organs and bone marrow (BM) of the Mll(Een/+) chimeras revealed an accumulation of Mac-1+/Gr-1- immature myeloid cells and a reduction in normal B- and T-cell populations. We observed differential regulation of Hox genes between myeloid cells derived from Mll(Een/+) ES cells and mouse BM leukemic cells which suggested different waves of Hox expression may be activated by MLL fusion proteins for initiation (in ES cells) and maintenance (in leukemic cells) of the disease. We believe studies of MLL fusion proteins in ES cells combined with in vivo animal models offer new approaches to the dissection of molecular events in multistep pathogenesis of leukaemia.
Non-invasive prediction of tachycardia mechanism is becoming clinically important in the era of catheter ablation for curing supraventricular tachycardia. Twelve-lead electrocardiograms (ECGs) during sinus rhythm and atrioventricular node re-entrant tachycardia (AVNRT) or atrioventricular reciprocating tachycardia (AVRT) with a narrow QRS complex were obtained from 154 consecutive adult patients who had received successful radiofrequency catheter ablation. The ECGs of initial 104 patients were analysed by three observers without knowledge of the electrophysiological diagnosis. The two arrhythmias were accurately diagnosed in 68% of cases. Three criteria were found to be discriminators of tachycardia mechanism by univariable analysis. Pseudo r/Q/S waves predicated AVNRT in 92% of cases (sensitivity 71%; specificity 95%). Retrograde P wave predicated AVRT in 86% of cases (sensitivity 75%; specificity 85%), RP interval > or =100 ms in 93% (sensitivity 71%; specificity 94%) and ST-segment elevation in lead aVR in 83% (sensitivity 71%; specficity 83%). According to the initial results, we proposed a modified stepwise ECG algorithm which used pseudo r/S/Q waves, RP interval and ST-segment elevation in lead aVR during tachycardia. Two observers assessed the modified algorithm in the remaining 50 patients. The algorithm was able to correctly diagnose the tachycardia mechanism in 84% and 87%, respectively. Using the modified algorithm can improve the accuracy and simplify the differential diagnosis between typical AVNRT and AVRT via concealed accessory pathway in adult patients.
A coupled waveguide-surface plasmon resonance (CWSPR) biosensor based on the Kretschmann configuration is developed. The CWSPR couples the surface plasmon resonance (SPR) mode and the waveguide mode and generates two sharp resonance dips in the reflectivity spectrum. The proposed biosensor not only retains the same sensing sensitivity as that of a conventional SPR device but also yields sharper dips in the reflectivity spectrum and therefore provides an improved measurement precision. The two reflectivity spectrum dips enable the refractive indices and thicknesses of both the self-assembled monolayer and a layer of human serum albumin absorbed dynamically on the sensing surface to be determined directly on a real-time basis. The CWSPR biosensor provides the capability to detect the biomolecular conformational changes that occur in biomolecular kinetic interactions.
The maize inbred lines 1145 (resistant) and Y331 (susceptible), and the F(1), F(2) and BC(1)F(1) populations derived from them were inoculated with the pathogen Pythium inflatum Matthews, which causes stalk rot in Zea mays. Field data revealed that the ratio of resistant to susceptible plants was 3:1 in the F(2) population, and 1:1 in the BC(1)F(1)population, indicating that the resistance to P. inflatum Matthews was controlled by a single dominant gene in the 1145xY331 cross. The gene that confers resistance to P. inflatum Matthews was designated Rpi1 for resistance to P. inflatum) according to the standard nomenclature for plant disease resistance genes. Fifty SSR markers from 10 chromosomes were first screened in the F(2) population to find markers linked to the Rpi1 gene. The results indicated that umc1702 and mmc0371 were both linked to Rpi1, placing the resistance gene on chromosome 4. RAPD (randomly amplified polymorphic DNA) markers were then tested in the F(2)population using bulked segregant analysis (BSA). Four RAPD products were found to show linkage to the Rpi1 gene. Then 27 SSR markers and 8 RFLP markers in the region encompassing Rpi1 were used for fine-scale mapping of the resistance gene. Two SSR markers and four RFLP markers were linked to the Rpi1 gene. Finally, the Rpi1 gene was mapped between the SSR markers bnlg1937 and agrr286 on chromosome 4, 1.6 cM away from the former and 4.1 cM distant from the latter. This is the first time that a dominant gene for resistance to maize stalk rot caused by P. inflatum Matthews has been mapped with molecular marker techniques.
Surface plasmon resonance (SPR) and common-path phase-shift interferometry (PSI) techniques are integrated in a biosensing imaging system for measuring the two-dimensional spatial phase variation caused by biomolecular interactions on a sensing chip without the need for additional labeling. The common-path PSI technique has the advantage of long-term stability, even when it is subjected to external disturbances. Hence the system meets the requirements of the real-time kinetic studies involved in biomolecular interaction analysis. The proposed SPR-PSI imaging system demonstrates a detection limit of a 2 x 10(-7) refractive-index change, a long-term phase stability of 2.5 x 10(-4) pi rms for 4 h, and a spatial phase resolution of 10(-3) pi with a lateral resolution of 100 microm.
An antisense strategy by targeting both bcr3/abl2 and VEGF was designed to suppress the growth of Philadephia1 leukemia cells in vitro and in vivo in mice. In vitro, although bcr3/abl2 or VEGF antisense oligodeoxyribonucleotides (AS-ODNs) alone was able to inhibit the proliferation of K562 cells, the combination of bcr3/abl2 and VEGF AS-ODNs produced an additive inhibitory effect on the growth of K562 cells and significantly enhanced the sensibility of K562 cells to apoptosis-inducing stimuli including STI571. In vivo, the nude mice xenografted with K562 cells received intratumoral injections of bcr3/abl2 and VEGF AS-ODNs showed a significant reduction in leukemia tumor size and microvessel density and an increase of apoptosis in the tumors when compared to the mice that received an individual agent. These results demonstrate that targeting both bcr3/abl2 and VEGF can result in an additive tumor-suppressive action and may represent an excellent strategy to augment the efficacy of chemotherapy in CML.
BACKGROUND: Psychogenic factors have been considered to be important in the exacerbation and possibly the onset of rosacea. However, there are very few studies that have reported conclusive findings. OBJECTIVES: To examine the association between rosacea and major depressive disease, a common and usually treatable psychiatric disorder. METHODS: Data from 1995 to 2002, collected by the National Ambulatory Medical Care Survey and the outpatient component of the National Hospital Ambulatory Care Survey, which are both nationally representative surveys of healthcare visits in the U.S.A., were studied. The basic sampling unit in both surveys is the patient visit or encounter. A "Rosacea" variable was created by grouping all rosacea (ICD-9-CM code 695.3) visits and a "Depression" variable was created by grouping the patient visits related to major depressive disorder (ICD-9-CM codes 296.2, 296.3 and 311). As alcohol abuse has been implicated in rosacea, and alcohol can confound symptoms of depression, an "Alcohol" variable was created by grouping all ICD-9-CM codes related to alcohol dependence and abuse (codes 303, 303.0, 303.9 and 305.0). All analyses were conducted using the Complex Samples module of SPSS version 13, to account for the multistage probability sampling design used to collect the data. RESULTS: The weighted data were representative of over 608 million dermatology visits between 1995 and 2002. Logistic regression analysis using "Rosacea" as the dependent variable and age, sex, "Alcohol" and "Depression" as independent variables revealed that the odds ratio for depressive disease in the rosacea group was 4.81 (95% confidence interval 1.39-16.62). The association between "Alcohol" and "Rosacea" was not significant. CONCLUSIONS: The comorbidity between major depressive disease and rosacea may have important clinical implications. Alcohol abuse does not appear to play a significant role in this association.
A new resolution-enhanced surface plasmon resonance (SPR) biosensor offers a tenfold improvement in resolution compared with conventional SPR biosensors in the detection of the surface coverage of biomaterials. The proposed optical biosensor, based on the attenuated total-reflection method, excites both the surface plasmons and particle plasmons to enhance the local electromagnetic field by control of the size and volume fraction of embedded Au nanoparticles to increase the resolution of the device. The SPR biosensor design is based on the Maxwell-Garnett model and the Fresnel equations, and the device is fabricated with a cosputtering deposition system.
1 Smooth muscle membrane potential and tension measurements were made in isolated mesenteric resistance arteries from rats exposed to bacterial endotoxin (lipopolysaccharide, LPS; 10 mg kg(-1), i.p.) for 3 h to mimic septic shock syndrome. 2 Over this period, rats developed an endotoxaemic response, assessed in vivo as a 41+/-4 mmHg drop in mean blood pressure, vascular hyporeactivity to noradrenaline (1 microg kg(-1), i.v.) and a significant increase in core body temperature. 3 In mesenteric small resistance arteries from these rats (o.d. 180 - 240 microm), phenylephrine (0.01-3 microm)-evoked contraction was not altered when compared with arteries from sham-operated animals, but the concentration-relaxation curve to acetylcholine (ACh; 0.01 - 3 microm) displayed a small, but significant, shift to the right. 4 The smooth muscle resting membrane potential (-70.3+/-1.6 mV) in arteries from LPS-treated rats was significantly greater than in control arteries (-55.4+/-1.2 mV), but in both cases the smooth muscle was depolarized to a similar potential by the application of N(omega)-nitro-L-arginine methyl ester (L-NAME; 0.3 mm; -54.1+/-2.3 vs -52.4+/-2.5 mV) or glibenclamide (10 microm; -55.0+/-2.1 vs -50.4+/-2.0 mV). 5 ACh (1 microm) elicited a maximal hyperpolarization, which ranged from -14.7+/-3.2 mV (in arteries from LPS-treated rats) to -20.6+/-2.4 mV (in arteries from sham-operated rats), and was not altered by the presence of L-NAME. Levcromakalim (1 microm) increased the smooth muscle membrane potential by around -24 mV in arteries from both sets of experimental animals. 6 These results indicate that at the level of the resistance vasculature, endotoxaemia is associated with pronounced smooth muscle hyperpolarization reflecting the action of NO on KATP channels. These changes were not associated with vascular hyporeactivity or depressed endothelial cell function in vitro, suggesting that mesenteric resistance arteries may not contribute to equivalent changes in vivo.
One single pathogen Fusarium graminearum Schw. was inoculated to maize inbred lines 1,145 (Resistant) and Y331 (Susceptive), and their progenies of F(1), F(2) and BC(1)F(1) populations. Field statistical data revealed that all of the F(1) individuals were resistant to the disease and that the ratio of resistant plants to susceptive plants was 3:1 in the F(2) population, and 1:1 in the BC(1)F(1 )population. The results revealed that a single dominant gene controls the resistance to F. graminearum Schw. The resistant gene to F. graminearum Schw. was denominated as Rfg1 according to the standard principle of the nomenclature of the plant disease resistant genes. RAPD (randomly amplified polymorphic DNA) combined with BSA (bulked segregant analysis) analysis was carried out in the developed F(2) and BC(1)F(1 )populations, respectively. Three RAPD products screened from the RAPD analysis with 820 Operon 10-mer primers showed the linkage relation with the resistant gene Rfg1. The three RAPD amplification products (OPD-20(1000), OPA-04(1100) and OPY-04(900)) were cloned and their copy numbers were determined. The results indicated that only OPY-04(900) was a single-copy sequence. Then, OPY-04(900) was used as a probe to map the Rfg1 gene with a RIL F(7) mapping population provided by Henry Nguyen, which was developed from the cross "S3xMo17". Rfg1 was primarily mapped on chromosome 6 between the two linked markers OPY-04(900) and umc21 (Bin 6.04-6.05). In order to confirm the primary mapping result, 25 SSR (simple sequence repeat) markers and six RFLP (restriction fragment length polymorphism) markers in the Rfg1 gene-encompassing region were selected, and their linkage relation with Rfg1 was analyzed in our F(2) population. Results indicated that SSR marker mmc0241 and RFLP marker bnl3.03 are flanking the Rfg1 gene with a genetic distance of 3.0 cM and 2.0 cM, respectively. This is the first time to name and to map a single resistant gene of maize stalk rot through a single pathogen inoculation and molecular marker analysis.
OBJECTIVE: To discuss special behavioural problems shown by a patient with Asperger's disorder from adolescence onward. METHOD: The case and treatment of a 21-year-old male patient is described. RESULTS: A 21-year-old male developed obstinate stealing behaviours when he was 17 years old. He was regarded as a schizophrenic at first, and was suspected of kleptomania later. Asperger's disorder was diagnosed after we reconsidered the relationship between the schizoid psychopathy in childhood and the stealing behaviours which occurred in adolescence. CONCLUSION: A wide variety of bizarre behaviours and so-called borderline behaviours occur in late adolescence and adult life of patients with Asperger's disorder. But classic schizophrenia is very rare. Psychiatrists unacquainted with the clinical diagnosis/context may find it difficult to evaluate 'concrete', 'childish', or 'bizarre' symptoms in patients with Asperger's disorder, and thus are prone to misdiagnose them as having schizophrenia disorders or other similar disorders.
Cervical arch is a rare congenital anomaly presumed to result from persistence of the third aortic arch and regression of the normal fourth arch. Rather rare is cervical aortic arch associated with aneurysm and obstruction, with eight known cases reported. Definitive diagnosis with a noninvasive imaging modality is desirable and very important to prevent the need for disaster intervention. We present two cases of a pulsatile mass in the left supraclavicular region. Three-dimensional computed tomographic angiography and magnetic resonance angiography clearly showed a left-sided cervical aortic arch (Haughton type D) with arch aneurysm and coarctation (pseudocoarctation).
A six-year-old boy was diagnosed with beta-thalassaemia major during infancy. Since then, he required monthly blood transfusion and irregular iron chelation therapy. He had hepatosplenomegaly and elevated liver enzymes; the serum ferritin was up to 3800 ng/mL. An echocardiogram showed left-ventricular enlargement. His one-antigen-mismatched mother was chosen as a bone marrow donor. He was pretreated with intensive red blood cell transfusion and hydroxyurea for 6 weeks prior to conditioning. The conditioning included total body irradiation (300 cGy), busulfan (14 mg/kg), cyclophosphamide (160 mg/kg) and anti-thymocyte globulin (rabbit; 90 mg/kg). Marrow cell dose was 5.4 x 108/kg. Graft versus host disease (GVHD) prophylaxis included cyclosporine A (CSA) and methylprednisolone. Neutrophil engraftment occurred on day 23. Grade II acute GVHD occurred on day 45. The patient developed complications including septicaemia, haemorrhagic cystitis, intracranial haemorrhage and heart failure. He subsequently recovered from the complications without sequelae. The patient remained transfusion-independent at a follow-up examination after 18 months. This case suggested that a mismatched family member may be considered as a bone marrow donor for beta-thalassaemia major. In places where conventional treatment is not feasible, for example, in China, this approach may be an alternative option. A more intensive immunosuppressive regimen and a higher marrow cell dose may be important for successful engraftment. High-dose anti-thymocyte globulin may also prevent severe GVHD.
This study reports the clinical psychiatric presentations and post-traumatic symptoms among 525 survivors at Yu-Chyr District in Nantou County who sought psychiatric service in the first month following the devastating earthquake that struck the central area of Taiwan. All subjects received psychiatric interviews and assessments using the 12-item Chinese Health Questionnaire (CHQ-12) and a checklist for post-traumatic symptoms. The most common psychiatric symptoms reported were insomnia, palpitations, nervousness, and dizziness with headache. Eleven percent of the subjects reported having thought of death or having suicidal ideation. The mean score on the CHQ-12 was 6.43 (S.D.=2.89). The rate of probable psychiatric morbidity as defined by a CHQ-12 score > or =3 was 89.9%. Post-traumatic symptoms were very prevalent, particularly symptoms of re-experiencing the earthquake and hyper-arousal. Factors significantly associated with high psychiatric morbidity were being female, serious destruction of property and house, and personality characteristics of nervousness and obsessiveness. Findings of this study suggest that early psychiatric intervention, including pharmacological treatment for acute stress disorder, is indicated during the early stages following a disastrous earthquake.
Acute promyelocytic leukemia (APL) is an interesting model in cancer research, because it can respond to the differentiation/apoptosis induction therapy using all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)). Over the past 5 years, it has been well demonstrated that As(2)O(3) induces a high complete remission (CR) rate in both primary and relapsed APL patients (around 85 to 90%). The side effects are mild to moderate in relapsed patients, while severe hepatic lesions have been found in some primary cases. After CR obtained in relapsed patients, chemotherapy in combination with As(2)O(3) as post-remission therapy has given better survival than those treated with As(2)O(3) alone. The effect of As(2)O(3) has been shown to be related to the expression of APL-specific PML-RARalpha oncoprotein, and there is a synergistic effect between As(2)O(3) and ATRA in an APL mouse model. Cell biology studies have revealed that As(2)O(3) exerts dose-dependent dual effects on APL cells. Apoptosis is evident when cells are treated with 0.5 approximately 2.0 microM of As(2)O(3) while partial differentiation is observed using low concentrations (0.1 approximately 0.5 microM) of the drug. The apoptosis-inducing effect is associated with the collapse of mitochondrial transmembrane potentials in a thiol-dependent manner, whereas the mechanisms underlying APL cell differentiation induced by low dose arsenic remain to be explored. Interestingly, As(2)O(3) over a wide range of concentration (0.1 approximately 2.0 microM) induces degradation of a key leukemogenic protein, PML-RARalpha, as well as the wild-type PML, thus setting up a good example of targeting therapy for human cancers.
The effect of the estrogen diethylstilbestrol (DES) on cytosolic free Ca(2+) levels ([Ca(2+)](i)) in MG63 human osteoblasts was explored by using fura-2 as a Ca(2+) indicator. DES at concentrations between 5--20 microM induced an immediate increase in [Ca(2+)](i) in a concentration-dependent manner with an EC(50) of 10 microM. Removing extracellular Ca(2+) reduced the Ca(2+) signal by 70%. Pretreatment with 50 microM La(3+) or 10 microM of nifedipine, verapamil and diltiazem did not change 20 microM DES-induced [Ca(2+)](i) increases. Addition of 3 mM Ca(2+) increased [Ca(2+)](i) in cells pretreated with 20 microM DES in Ca(2+)-free medium. Pretreatment with 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) to deplete the endoplasmic reticulum Ca(2+) store partly inhibited 20 microM DES-induced Ca(2+) release, but addition of carbonylcyanide m-chlorophenylhydrazone (CCCP; a mitochondrial uncoupler) and thapsigargin together abolished DES-induced Ca(2+) release. Conversely, pretreatment with 20 microM DES abrogated CCCP- and thapsigargin-induced Ca(2+) release. Inhibition of phospholipase C activity with 2 microM U73122 did not alter 20 microM DES-induced Ca2+ release. Another estrogen 17beta-estradiol also increased [Ca(2+)](i) in a concentration-dependent manner with an EC50 of 7 microM. Together, the data indicate that in human osteoblasts, DES increased [Ca(2+)](i) via causing Ca(2+) release from both mitochondria and the endoplasmic reticulum in a phospholipase C-independent manner, and by causing Ca(2+) influx.