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Objective: To use the spatiotemporal distribution model and INLA algorithm to study the spatiotemporal characteristics and influencing factors of tuberculosis in Shanghai and to provide a theoretical basis for formulating regional tuberculosis epidemic prevention and control measures. Methods: Based on the data of registered pulmonary tuberculosis cases in Shanghai during 2013-2020 derived from the tuberculosis management information system of China Disease Control and Prevention Information System, the hierarchical Bayesian model was adopted to fit the tuberculosis case data, identify the spatiotemporal variation characteristics of tuberculosis, and explore the potential socioeconomic characteristics and other factors related to health services and spatiotemporal characteristics. Results: From 2013 to 2020, 29 281 registered tuberculosis cases were reported in Shanghai, with an average annual incidence of 25.224/100 000. From 2013 to 2020, the incidence trend increased first and then decreased, the highest incidence was reported in 2014 (27.991/100 000). The incidence of tuberculosis in Shanghai is characterized by spatial clustering. Through the spatial characteristics and risk analysis of the reported incidence of tuberculosis, it is found that the high-risk area of tuberculosis in Shanghai is the suburban communities, whereas downtown communities are the low-risk areas. The incidence risk of pulmonary tuberculosis is associated with the gross domestic product per capita ( RR =0.48), the number of beds per 10 000 persons ( RR =0.56), the normalized vegetation index ( RR =0.50), and the night light index ( RR =0.80). Conclusions: With the steady progress of tuberculosis prevention and control in the central urban area of Shanghai, special attention should be paid to the prevention and control in the suburbs further to improve the social and economic level in the suburbs and increase the coverage rate of urban green space, to reduce the incidence of tuberculosis and reduce the disease burden of tuberculosis in Shanghai.

Objective: To analyze the spatiotemporal characteristics of hand,foot and mouth disease (HFMD) in China, explore the association of socioeconomic, population and health services factors with the incidence of HFMD in China, and provide information for the prevention and control of HFMD. Methods: Bayesian spatiotemporal model was used to fit the data of HFMD, evaluate the spatiotemporal variation of HFMD, and identify the potential association between the risk of HFMD and social, economic, population and health services. Results: From 2011 to 2018, a total of 17 118 050 HFMD cases, including 2 283 deaths, were reported in China. The reported incidence showed a fluctuating increase trend from 2011 to 2014, and a fluctuating decrease trend from 2014 to 2018. Meanwhile, there was a fluctuating decrease trend of mortality rate. The incidence of HFMD had spatial clustering, with the highest incidence in southern China with hot spot and high risk areas, and the lowest incidence in northwestern China where cold spot and low risk areas were found. The risk for HFMD was associated with GDP per capita ( RR =3.54), number of industrial enterprises above designated size of 10 000 people ( RR =1.61), urbanization rate ( RR =3.00), birth rate ( RR =2.36), number of beds in medical institutions per 10 000 people ( RR =3.40), and green area in parks per capita ( RR =0.57). Conclusions: The hotspot area for HFMD prevention and control in China was in the southeast coastal provinces from 2011 to 2018. In order to reduce the incidence of HFMD, it is necessary to increase the green area in parks per capita while accelerating urbanization process.

Objective: To evaluate the short-term efficacy and perioperative safety of catheter-based intervention in patients with pulmonary vein stenosis caused by fibrosing mediastinitis (FM). Methods: It was a case series study. Consecutive patients with pulmonary vein stenosis caused by FM, who underwent percutaneous pulmonary vein angioplasty in Gansu Provincial Hospital from January 2018 to June 2020, were retrospective enrolled. The baseline characteristics, comorbidities, exercise capacity and hemodynamic data before and after treatment were compared, and the procedural related complications were evaluated. Results: A total of 30 patients ((64.3±7.1) years, 15 males) were included. Sixty-three pulmonary vein stenosis were treated by 32 percutaneous pulmonary vein angioplasty procedures. Forty-four stents were implanted in 41 pulmonary veins after balloon angioplasty, and the diameter of implanted stents was (8.3±1.2)mm. Balloon angioplasty was performed on 22 pulmonary vein stenosis, the mean balloon diameter was (4.2±2.1)mm. The pulmonary vein diameter increased from (2.6±1.3) to (6.6±2.6) mm ( P <0.001) and the pressure gradient across the pulmonary vein stenotic segment reduced from 19 (12, 29) to 2 (0, 4) mmHg (1 mmHg=0.133 kPa) ( P <0.001) immediately post procedure. The pulmonary vein flow grade was significantly improved compared with baseline ( P <0.001). The most common operation related complications were lung injury (44.0% (11/25)) and hemoptysis (18.8% (6/32)), which did not need special treatment. During the 2.0 (1.3, 3.2) months follow-up, the WHO functional class was significantly improved ( P <0.05), the 6-minute walking distance increased from (254.8±114.5) m to (342.8±72.4)m ( P <0.05), the mean pulmonary arterial pressure decreased from (40.9±8.3) mmHg to (35.4±7.7) mmHg ( P <0.01), 17 out of 19 patients with refractory pleural effusion experienced total remission during the follow-up period ( P <0.001). CT pulmonary venography was repeated in 17 patients. The incidence of in-stent restenosis of pulmonary vein was 24.0% (6/25). Conclusions: Percutaneous pulmonary vein angioplasty is effective for the treatment of pulmonary vein stenosis caused by fibrosing mediastinitis. However, it ' s not so safe, procedural related complication should be paid attention to and the rate of in-stent restenosis is relative high during the short-term follow-up.

Objective: Some circular RNAs (circRNAs) have been testified to play crucial roles in the regulation of skin melanoma, including circRNA&#95;0016418 (circ0016418). However, the regulatory mechanism of circ0016418 in skin melanoma is undiscovered., Materials and Methods: The RNA expression was examined through quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and associated-proteins levels were measured via Western blot. Cell counting kit-8 (CCK-8) assay was used for detecting cell proliferation. Transwell assay was conducted to assess the abilities of migration and invasion. The target relation was analyzed by Dual-Luciferase reporter assay., Results: The levels of circ0016418 and Yin Yang 1 (YY1) were up-regulated in skin melanoma tissues and cells. Knockdown of both circ0016418 and YY1 had suppressive effects on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of skin melanoma cells. YY1 overexpression reverted the inhibitory effects on skin melanoma cells caused by circ0016418 knockdown. Circ0016418 negatively modulated microRNA-625 (miR-625) expression and miR-625 directly targeted YY1. Circ0016418 functioned as a competitive endogenous RNA (ceRNA) of miR-625 to regulate YY1 expression., Conclusions: Circ0016418 regulated proliferation, migration, invasion, and EMT of skin melanoma cells through miR-625/YY1 axis. Circ0016418 might be a useful indicator of the therapeutic strategies of skin melanoma.

Objective: To evaluate the feasibility and safety percutaneous pulmonary vein intervention in patients with severe pulmonary vein stenosis (PVS) caused by fibrosing mediastinitis(FM). Methods: This retrospective analysis included 5 FM patients (2 male, 3 female, 54-77 years old) confirmed by clinical presentation and chest computed tomography (CT) scan from January to June 2018 who were from Gansu Provincial Hospital and Shanghai Chest Hospital. CT pulmonary angiography (CTPA) further revealed severe PVS caused by fibrotic tissue compression in mediastinum. After selective pulmonary vein angiography, gradually balloon angioplasty was used to expand the pulmonary vein and then stents were implanted in the pre-dilated stenotic pulmonary veins. Evaluation of therapeutic effect was made at 6 months after the procedure. Results: All of 11 serious compression PVS were treated with stent implantation (diameter: 7-10 mm, length: 17-27 mm). After stenting, degree of pulmonary vein stenosis decreased from (83±16)% to (12±4)% ( P< 0.01). The minimal diameter of the stenotic pulmonary vein was significantly increased from (0.8±0.5)mm to (7.5±0.8)mm ( P< 0.01). Trans-stenotic gradient decreased from (27.0±15.1)mmHg (1 mmHg=0.133 kPa) to (2.50±0.58)mmHg ( P< 0.05). Mean pulmonary pressure measured by cardiac catheter decreased from (45.0±9.0)mmHg to (38.7±8.4)mmHg ( P< 0.05). One patient experienced cardiac arrest due to vagal nerve reflex during big sizing balloon stent dilation and recovered after cardiopulmonary resuscitation. There were no other serious procedure related complications. During the follow-up, severe stenosis at end of proximal stent was evidenced in 1 patient due to fibrotic compression, and another patient developed in-stent thrombosis due to discontinuation of prescribed anticoagulant. Conclusion: Percutaneous intervention for severe pulmonary vein stenosis caused by FM is feasible and safe, and can improve hemodynamic caused by the compression of mediastinal vascular structures in these carefully selected patients.

Aims: Parkinson disease (PD) is a common neurodegenerative disease. The aim of this study was to evaluate the risk of PD in patients with organophosphate (OP) or carbamate (CM) poisoning by using the Taiwan National Health Insurance Research Database., Methods: We conducted a retrospective study involving a cohort of 45 594 patients (9128 patients with a history of OP or CM poisoning and 36 466 control patients) who were selected from the Taiwan National Health Insurance Research Database. The patients were observed for a maximum of 12 years to determine the rates of new-onset PD, and a Poisson regression model was used to identify the predictors of PD. The cumulative incidence of PD between the two cohorts was plotted through Kaplan-Meier analysis., Results: During the study period, the incidence rate ratio (IRR) of PD in the OP or CM poisoning patients was 1.36-fold [95% confidence interval (CI)=1.26-1.47] higher than that in the control patients in the multivariable model. The absolute incidence of PD was the highest for the group aged ≥75 years in both cohorts (77.4 vs 43.7 per 10 000 person-years). However, the age-specific relative risk was higher for the group aged <50 years (adjusted IRR=3.88; 95% CI=3.44-4.39)., Conclusion: Our results suggest that the likelihood of developing PD is greater in patients with OP or CM poisoning than in those without poisoning. OP or CM poisoning may be an independent risk factor for PD., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To investigate the prevalence of latent tuberculosis infection(LTBI) and associated risk factors among the tuberculosis(TB) contacts in Minhang District of Shanghai. Methods: A self-designed questionnaire was used to acquire socio-demographic information and to assess the degree of exposure to index cases. LTBI screening was performed by T-SPOT.TB assay. Pearson chi-square test and Logistic regression analyses were used to identify the risk factors associated with LTBI among the TB contacts. Results: A total of 137 contacts from 59 mycobacterial (culture) positive pulmonary TB patients were enrolled in this study. In these contacts, there were 54 men and 83 women, with the average age of 42. LTBI was identified in 20% (27/137) of these contacts. Several risk factors were found by logistic analyses in this study. The worse the ventilation in the exposure location was, the more likely to develop LTBI. Contacts aged more than 60 (42.1%) were 3.9 times more likely to develop LTBI than those aged less than 60 (16.1%). Individuals in contact with TB patients for more than 40 h/week(25.8%) had a 4.2 times risk of LTBI as compared to those for less than 40 h/week(6.8%). Conclusion: The prevalence of LTBI was 20% among the TB contacts in this study, highlighting the need of TB screening and intervention among TB contacts.

In the near future, the inactivated enterovirus 71 (EV71) vaccine is expected to become available on the market in China. Since EV71 is a major cause of hand, foot and mouth disease (HFMD), the vaccine is expected to significantly reduce the number of cases, as well as the detrimental economic effect of the disease. However, for a national vaccination strategy to be developed, policy-makers need more information on the socioeconomic burden of EV71 HFMD infection. Based on the 2011 population data, we estimated the clinical and economic effect of EV71 HFMD infection in children aged 0-9 years in Shanghai, China. The annual cost related to HFMD is >US$7.66 million for a population of 1·42 million children aged 0-9 years with an average cost of US$208.2/case. The extrapolated cost for EV71 HFMD infection was US$3.53 million, comprising 46·1% of the overall cost associated with HFMD. Around 97% of all of the HFMD-related expenses were paid for by the families creating a considerable economic burden. Our findings could provide the necessary recommendations on the most effective national EV71 vaccine implementation, as well as a baseline data for assessing the cost-effectiveness of the vaccine in China.

We examined the expression of angiopoietin-2 in serum samples from patients diagnosed with colorectal cancer and healthy volunteers and investigated the feasibility of using angiopoietin-2 as a potential diagnostic colorectal cancer biomarker. Enzyme-linked immunosorbent assays were used to measure the levels of angiopoietin-2 in patients with colorectal cancer and healthy control subjects. Correlations between serum angiopoietin-2 levels and clinicopathological factors were investigated. A receiver operating characteristic curve was used to predict cut-off values of the markers. Serum concentrations of angiopoietin-2 were significantly higher in patients with colorectal cancer than in controls (2896 ± 1273 vs 1554 ± 991 pg/mL, P = 0.004). Serum angiopoietin-2 expression levels were significantly positively correlated with TNM stage (P = 0.003), lymph node involvement (P = 0.04), and distant metastases (P = 0.005). Receiver operating characteristic curve analysis revealed that serum level of angiopoietin-2 was a potential biomarker for differentiating colorectal cancer patients from controls and had a receiver operating characteristic area under the curve of 0.859 (95% confidence interval = 0.740-0.978). At a cut-off value of 2710 pg/mL, the sensitivity was 79.3% and the specificity was 82.4%. Our results suggest that angiopoietin-2 can be used as a diagnostic biomarker for colorectal cancer in clinical practice. Additional studies are needed to clarify the detailed mechanism of angiopoietin-2 in the carcinogenesis and metastasis of colorectal cancer.

Two outbreaks of sheeppox in sheep have occurred in Gansu Province, China. The P32, GPCR, and RPO30 genes were used as markers for differential diagnosis. We confirmed that the outbreaks were caused by sheeppox virus. Sequence and phylogenetic analysis of the P32, GPCR, and RPO30 genes revealed a close relationship between the 2 isolates and Chinese sheeppox viruses. Because ill sheep were imported from Jingyuan, another county of Gansu Province, our results strongly suggest the importance of veterinary surveillance prior to transportation.

Ketamine, an N-methyl-D-aspartate receptor (NMDAR) channel blocker, has been found to induce rapid and robust antidepressant-like effects in rodent models and in treatment-refractory depressed patients. However, the marked acute psychological side effects of ketamine complicate the interpretation of both preclinical and clinical data. Moreover, the lack of controlled data demonstrating the ability of ketamine to sustain the antidepressant response with repeated administration leaves the potential clinical utility of this class of drugs in question. Using quantitative electroencephalography (qEEG) to objectively align doses of a low-trapping NMDA channel blocker, AZD6765 (lanicemine), to that of ketamine, we demonstrate the potential for NMDA channel blockers to produce antidepressant efficacy without psychotomimetic and dissociative side effects. Furthermore, using placebo-controlled data, we show that the antidepressant response to NMDA channel blockers can be maintained with repeated and intermittent drug administration. Together, these data provide a path for the development of novel glutamatergic-based therapeutics for treatment-refractory mood disorders.

Objective: To study the mechanism of 5-aza-2-deoxycytidine (DAC; a methylation inhibitor) on growth of the human cholangiocarcinoma QBC939 cell line., Methods: A colourimetric assay was used to detect growth of QBC939 cells treated with DAC (0.1-100 μmol/l) over 24 h, 48 h and 72 h. Cell morphology was observed by transmission electron microscopy (TEM). The cell cycle and apoptosis were analysed by flow cytometry. Hypermethylation of the promoters of the p53-BAX mitochondrial apoptosis genes cyclin-dependent kinase inhibitor 2A (CDKN2A), death-associated protein kinase 1 (DAPK1) and PYD and CARD domain containing (PYCARD) was detected by methylation-specific polymerase chain reaction, with and without DAC treatment., Results: DAC inhibited QBC939 cell growth with a half maximal inhibitory concentration of 5 μmol/l at 72 h. After DAC treatment, apoptosis was observed by TEM. Flow cytometric analysis of propidium iodide-positive cells demonstrated increased apoptosis of DAC-treated QBC939 cells (43.04%) compared with untreated cells (4.31%). DAC treatment resulted in demethylation of the gene promoters of CDKN2A and DAPK1 in QBC939 cells., Conclusions: DAC induces apoptosis of QBC939 cells by reactivation of hypermethylated p53-BAX mitchondrial apoptosis genes in cholangiocarcinoma cells.

Thromboembolic complications commonly occur in patients with multiple myeloma (MM). The risk of such complications may be elevated by the use of immunomodulatory agents such as thalidomide and lenalidomide as initial therapy for MM. However, arterial thrombosis after treatment with bortezomib is rare. Herein we report a case of a 70-year-old Chinese male patient with extramedullary relapse of MM. After treatment with bortezomib and dexamethasone he developed a nonfatal thrombotic stroke. Administration of bortezomib and dexamethasone was then discontinued and he obtained partial remission.

Objective: The clinical differentiation between early Parkinson's disease (PD) and essential tremor (ET) could be difficult, therefore, the aim of this study was to investigate 99mTc-TRODAT-1 SPECT as an applicable tool in this field., Methods: 99mTc-TRODAT-1 single photon emission computed tomography (SPECT) was performed in 10 healthy volunteers, 27 patients with idiopathic PD (Hoehn and Yahr 1-1.5) and 12 patients with ET. The ratio of striatal (99m)Tc-TRODAT-1 binding was calculated as the index of (striatum - occipital cortex)/occipital cortex., Results: Compared with the striatal 99mTc-TRODAT-1 uptake in the ET group (0.49 +/- 0.07) or healthy controls (0.54 +/- 0.18), there was a significant decrease in the bilateral striatums of early PD, with a greater reduction in the contralateral striatum (0.27 +/- 0.08) than ipsilateral one (0.36 +/- 0.10, P < 0.01). Its sensitivity and specificity of differentiating early PD from ET was 96.4% and 91.7% respectively., Conclusion: 99mTc-TRODAT-1 SPECT can detect the dysfunction of nigrostriatal system in patients with early PD and provided a feasible tool to help differentiate early PD from ET.

A simple two-step hydrogen reduction method was used to synthesize FePt/Fe composite nanotubes. As the first step, L1(0) FePt nanotubes were prepared by heating a porous alumina template loaded with an alcohol solution of a Fe chloride and Pt chloride mixture in flowing hydrogen at 670 degrees C. Then, FePt/Fe composite nanotubes were obtained by reducing the alcohol solution of the Fe chloride within the formed FePt nanotubes at a lower temperature, namely 470 degrees C. Through changing the concentrations of initial alcohol solutions, the FePt:Fe atomic ratios of the composite nanotubes were easily adjusted and the magnetic properties were tuned accordingly. For (FePt)(100-x)/Fe(x) composite nanotubes with x ranging between 0 and 26 at.%, the hard and soft phases were well coupled and the coercivity was tunable over a large range (1.27-2.73 T). Furthermore, the marked interdiffusion between Fe and FePt, which usually exists in FePt-based composites fabricated by using conventional methods, was not observed in the formed composite nanotubes. This indicates the two-step hydrogen reduction method to be a promising route for synthesizing nanocomposites which are difficult to fabricate by using conventional methods due to the interdiffusion between different phases.

A 14.5-year-old male dog was presented with stranguria and hematuria of 1-month duration. Hematology and blood chemistry revealed a neutrophilia, mild azotemia and a mild decrease in the packed cell volume. Urinalysis showed high specific gravity (> 1.040 g/mL), hematuria, proteinuria and mild bilirubinuria. On physical examination, a firm oval mass located caudal to the distended urinary bladder, was palpated. Differential diagnoses included prostatitis, prostatic neoplasm, prostatic hyperplasia, and abscess. The enlarged prostate was suspected to be the cause of hematuria, and a total prostatectomy was performed. Histologically, the prostate was affected by a prostatitis with cystic papillary hyperplasia of the epithelium. The dog's condition continued to deteriorate, and death occurred 1 week later. Necropsy showed a tumor mass, approximately 5 x 4 x 3 cm in size, between the abdominal aorta and the left kidney, where the adrenal glands were embedded. Lesions were found in the kidneys, adrenal gland, lungs, heart, liver, intestine, and serosa of viscera, while the spleen was spared. This hemangiosarcoma most likely arose from the renal arteries, resulting in diffuse lesions in the kidneys thought to be the cause of hematuria.

Infection of dengue viruses (DENs) can cause human dengue fever, hemorrhagic fever, or shock syndrome. Although DEN-induced apoptosis has been implicated in pathogenesis of the DEN-related diseases, the underlying mechanism remains largely unexplored. In this study, we investigated the effect of ectopic expression of human bcl-2 and bcl-X genes on DEN-induced apoptosis in cultured cells. We employed a human isolate of DEN serotype 2 (DEN-2), PL046, which not only caused cell-cycle arrest in the G1 phase but also induced apoptosis in infected baby hamster kidney (BHK-21) cells, murine neuroblastoma N18 cells, and human neuronal NT-2 cells. Our results reveal that overexpression of bcl-2 in fibroblast-like BHK-21 cells, although not inhibiting virus yields, delayed the process of DEN-induced apoptosis, thereby permitting surviving cells to become persistently infected. In contrast, stable bcl-2 expression in neuronal N18 cells failed to block DEN-induced apoptosis. On the other hand, Bcl-X(L), expressed predominantly in the nervous system, appeared to delay DEN's killing effect in neuronal N18 cells but not in fibroblast-like BHK-21 cells. In addition, inducible expression bcl-X(s), despite its proapoptotic property in other reported system, was found to merely accelerate cell death in DEN-infected N18 but not in infected BHK-21 cells. Thus, through studying the effect of human bcl-2-related genes, our results suggest that DEN infection may trigger target cells to undergo morphologically similar but biochemically distinct apoptotic pathways in a cell-specific manner., (Copyright 2001 Academic Press.)

Background and Objectives: Interferons (IFNs) exhibit anti-tumor activities through either immune modulation or direct anti-tumor effects. We have investigated the activity and mechanisms of IFN-alpha and IFN-gamma on the growth of TSGH9201, TMK-1 and AGS gastric cancer cells in vitro., Methods: Activities of IFNs on cell growth were analyzed by measuring total cellular DNA. Effects of IFNs on apoptosis was evaluated by formation of in situ DNA breakage and DNA ladders. Effects of IFNs on cells cycle phase distribution were analyzed using flow cytometry. Levels of Bcl-2 family proteins after treatment with IFNs were analyzed using Western blot., Results: Both IFN-alpha and IFN-gamma were active in suppressing the growth of TSGH9201 and TMK-1 cells, while AGS cells were resistant to treatment with IFNs. The IC(50)s of IFN-alpha for TSGH9201 and TMK-1 cells were 300 and 500 U/ml, respectively, and the IC(50)s of IFN-gamma were 40 and 2.0 U/ml, respectively. Both IFN-alpha- and IFN-gamma-induced cell cycle arrest in sensitive cells. IFN-gamma also increased cellular apoptosis, demonstrated by increasing in situ DNA damage and DNA fragmentation. IFN-gamma increased BAK protein levels and decreased Bcl-2 and Bcl-X(S) protein levels in TSGH9201 cells., Conclusions: IFN-alpha suppressed growth of gastric cancer cells through induction of cell cycle arrest. IFN-gamma suppressed cell growth through induction of both cell cycle arrest and apoptosis. IFN-gamma-mediated apoptosis was associated with the alteration in protein levels of Bcl-2, Bcl-X(S) and BAK., (Copyright 2000 Wiley-Liss, Inc.)

Upon infection of Japanese encephalitis virus (JEV), baby hamster kidney (BHK-21) and Chinese hamster ovary (CHO) cells were killed by a mechanism involved in apoptosis. While readily established in a variety of cell lines, JEV persistence has never been successfully instituted in BHK-21 and CHO cells. Since stable expression of human bcl-2 in BHK-21 cells has been shown to delay JEV-induced apoptosis, in this study we investigated whether JEV persistence could be established in such cells. When constitutively expressing bcl-2, but not its closest homolog, bcl-XL, following a primary lytic infection, approximately 5 to 10% of BHK-21 and CHO cells became persistently JEV infected during a long-term culture. From the persistent bulks, several independent clones were selected and expanded to form stable cell lines that continuously produced infectious virus without marked cytopathic effects (CPE). Among these stable cell lines, the truncated nonstructural protein 1 (NS1) was also detected and was indistinguishable from the NS1 truncations previously observed in JEV-persistent murine neuroblastoma N18 cells. However, the stable expression of NS1 alone, regardless of whether it was truncated or full length, failed to render the engineered cells persistently infected by JEV, implying that aberrant NS1 proteins were likely a consequence of, rather than a cause for, the viral persistence. Enforced bcl-2 expression, which did not affect virus replication and spread during the early phase of cytolytic infection, appeared to attain JEV persistence by restriction of virus-induced CPE. Our results suggest that it is the antiapoptotic, rather than the antiviral, effect of cellular bcl-2 which plays a role in the establishment of JEV persistence.

Intranulear microinjection and electrical stimulation technique were employed to evaluate the effect of ventromedial hypothalamus (VMH) on the gastric inhibition elicited by basomedial amygdala nucleus (BMA) excitation. The results were as follows: (1) Microinjections of CCk-8 (50 ng/microliter) into bilateral BAM resulted in significant decrease in intragastric pressure (IGP) and gastric motility frequency (GMF) (P < 0.01). (2) Neither CCK-A receptor antagonist [L364, 718] nor CCK-8 receptor antagonist [L365, 260] induced effects on IGP or GMF when given alone. (3) If bilateral BMA were pretreated with [L364, 718], CCK-8 could no longer induce any inhibitory effects, whlie [L365, 260] had no similar suppressive effect. (4) The inhibitory effects were not found in other nuclei in the amygdaloid body, such as bed nucleus of the stria terminalis intramygdaloid (BSTIA) and amygdaloid nucleus medial (Me). (5) Electrical stimulation of unilateral VMH or BMA would result in the inhibition of IGP and GMF. (6) After electric coagulation of VMH unilateraly injection of CCK-8 to or stimulation of homolateral VMH could no longer inhibite IGP or GMF. The above results suggest that in BMA CCK-8 exerts inhibitory effect on both motility and intragastric pressure through CCK-A receptors.

The level of Gs alpha activity has been shown to modulate the rate of adipogenesis in mouse embryo fibroblast 3T3-L1 cells (H.-Y. Wang, D. C. Watkins, and C. C. Malbon. Nature Lond. 358: 334-337, 1992). For the current work the role of Gi alpha 2, a G protein mediator of inhibitory control of adenylyl cyclase, in regulating terminal differentiation of these cells was explored by stable transfection of fibroblasts expressing wild-type and a constitutively active mutant of Gi alpha 2 (Q205L). Under the influence of the cytomegalovirus promoter, the expression vector yielded a 1.7-fold (Q205L mutant Gi alpha 2) and 2.2-fold (wild-type Gi alpha 2) increase in steady-state levels of these G protein alpha-subunits. Elevation of Gi alpha 2 expression or expression of constitutively active Gi alpha 2 (Q205L) promoted lipid accumulation in these clones, the hallmark of terminal differentiation of 3T3-L1 fibroblasts to adipocytes. Increasing Gi alpha 2 activity promotes adipogenic conversion, as was previously observed by decreasing Gs alpha either by inducers of differentiation or by oligodeoxynucleotides antisense to Gs alpha. Thus Gs alpha and Gi alpha 2 are shown to be counterregulatory with respect to promoting differentiation of 3T3-L1 mouse embryo fibroblasts to adipocytes in the absence of exogenously added inducers of differentiation. This is the first report demonstrating the induction of terminal differentiation of cells by the overexpression of a G protein alpha-subunit, further implicating G proteins as regulators of complex biological responses such as adipogenesis.

The study clinically and radiographically evaluated the long-term success rate of pulpotomy treatment in pulp-exposed primary molars. Five clinicians participated in this study and four glutaraldehyde preparations included 2% buffered, 2% unbuffered, 5% buffered, and 5% unbuffered glutaraldehyde solutions were used. There were 201 children, 108 boys and 93 girls, ranging in age from 4 to 7 years with 258 primary molars treated. After 36 months, 150 teeth with complete clinical records and radiographs were available for evaluation. The treatment of 98% of the patients was clinically successful, but when evaluated radiographically the overall success rate was 78.7%. The group treated with 5% buffered glutaraldehyde showed the highest success rate (87.5%) and group treated with the 5% unbuffered solution the lowest (74.1%), but no significant difference was found among the four groups. Canal obliteration was noted in 22 teeth successfully treated. Four of the teeth that were not successfully treated had canal obliteration before other pathoses became evident. The relative high failure rate in this long-term follow-up indicated that clinicians should be cautious before extensively using glutaraldehyde as a pulpotomy agent.

The purpose of this study is to evaluate the comprehensive dental treatment for children under general anesthesia. From 1989 to 1991, 57 children with mean age of 3 years 2 months were treated, followed up with a minimal of 1 year. This procedure allows the dentition to be restored in one visit. Further care including preventive options and behavior shaping was provided on a 3-6 months recall schedule. The reasons for general anesthesia are that these children were either unable to accept treatment because of handicaps, extreme fear or young age. Their mean number of decayed tooth was 15 (Standard Deviation, SD = 5) and nearly three quarters of the children were under 6 years old. The most frequent treatment procedures were the extraction of teeth, composite resin restoration and Ni-Cr crown restoration. The Ni-Cr crown (1.7% failure rate) was more successful than the amalgam and composite resin restoration (9.7% failure rate). Pedo-strip crown had the highest failure rate (22%) for anterior teeth restoration. Nineteen children needed retreatment with conventional behavior guide. Six children had new caries and required further treatment. Thirty eight children returned for regular recall during the minimal 1 year follow-up period.

Previous study of lymphocyte proliferation in the presence of liver arginase has indicated that arginine-depletion in the culture medium plays an important role in inhibiting cell proliferation. The inhibitory effect of both liver arginase and arginine-free condition on DNA, RNA and protein syntheses in PHA-stimulated lymphocytes were studied in cultures by measuring the incorporation of labeled precursors. Simultaneously, their influence on DNA and RNA contents in cells stained by acridine orange was investigated by automated flow cytometry. With 3 micrograms/ml arginase, the syntheses of DNA, RNA and protein were markedly inhibited after 72 h of culture. The degrees of inhibition were close to that induced in an arginine-free condition. The DNA and RNA contents of the individual cell, either cultured with 3 micrograms/ml arginase or in arginine-free medium, were arrested in G0/G1 phase. The results of cell arrest in G0/G1 phase were similar whether the cells were cultured for 24, 48 or 72 h.

Five hundred and forty-three Chinese patients in the primary dentition stage were evaluated for mesiodens with maxillary, anterior occlusal films. Compared with other studies, a higher prevalence was found, using different age-groups and diagnostic methods. The distributions of mesiodens by sex, location, and direction were also studied. Because mesiodens could interfere with normal development of the occlusion, especially in the early mixed dentition stage, early diagnosis, using appropriate radiographs during the primary dentition stage, could lead to more comprehensive treatment planning.

This study was conducted to evaluate the effectiveness of electroacupuncture (EA) on the recovery of adrenocortical function from Iatrogenic Cushings Syndrome (ICS) in dogs. Experiment I: Selection of the most effective Acupuncture point to treat ICS--Six healthy adult female dogs were treated bilaterally with EA for 15 minutes at loci BL22 + BL23 + BL24, ST36, or a non-locus control point on M. brachialis. Each dog was tested at all three sites in rotation. Blood samples were collected before and 0, 15 and 60 minutes after EA, and the serum cortisol levels were measured by radioimmunoassay. The data showed that EA at ST36 resulted in the highest response of serum cortisol levels among the three treatments. Experiment II: Evaluation of the effectiveness of EA ST36 in the treatment of ICS in dogs--Eight healthy adult female dogs were given prednisolone acetate 2mg/kg/day IM for 3 weeks. They were then randomly divided into ST36 and control groups of 4 dogs each. In the ST36 group, ST36 was treated bilaterally with EA for 30 minutes, 3 times per week, for 3 consecutive weeks. For the control, a non-locus point on M. brachialis was treated bilaterally with the same protocol. After the first week of EA, the serum cortisol levels of the ST36 and control groups were 0.9 +/- 0.1 and 0.5 +/- 0.1 micrograms/dl (P less than 0.005) baseline and 2.5 +/- 0.2 and 1.4 +/- 0.4 micrograms/dl (p less than 0.05) and after ACTH stimulation test, respectively. After the third week of EA treatment, the results were 1.0 +/- 0.1 and 0.6 +/- 0.2 micrograms/dl (p less than 0.05) baseline and 4.0 +/- 0.5 and 1.7 +/- 0.5 micrograms/dl (p less than 0.001) after ACTH stimulation respectively. These data indicated that EA at ST36 could restore the adrenocortical hypofunction resulting from ICS in dogs.

Liver aqueous extract (LEx) can powerfully inhibit phytohaemagglutinin (PHA)-induced lymphocyte proliferation. The extracellular mechanism of inhibition by LEx was studied. There are three possibilities. (1) The possibility of extracellular inactivation of PHA by LEx was excluded by incubating cells with PHA first, followed by washing, and then incubating cells with LEx. The result was that LEx was still able to inhibit cell proliferation completely. (2) The possibility of competition for cell surface PHA receptors by LEx was excluded by the above experiments plus the use of N-acetyl-D-galactosamine to remove surface-bound PHA. Following this treatment, LEx was still able to inhibit cell proliferation completely. (3) The possibility of arginase-induced arginine depletion resulting in lymphocyte suppression was supported by the following experiments. Cells were incubated in media in which arginine was depleted either by reacting with LEx, and the media were afterwards bound with anti-arginase antibody, or by amino acid constituted media without arginine. The degrees of proliferation inhibition were similar in both treatments. These results indicate the important role of arginine-depletion by LEx, and may account for the LEx-induced lymphocyte inhibition.

The incorporation of labeled precursors into DNA, RNA and protein in phytohaemagglutinin (PHA)-prestimulated human lymphocytes was maximally inhibited by liver extract (LEx) or arginase at 24 h. The activities of DNA polymerase alpha, beta and gamma were less inhibitable by these agents than was [3H]thymidine incorporation. The inhibition of DNA, RNA and protein syntheses by either LEx or arginase is probably due to arginine depletion by arginase activity, since their syntheses were similarly inhibited when cultured in an arginine-free medium in the absence of arginase. These results indicate that arginase nonspecifically inhibits the activities of DNA polymerase. The inhibition is probably due to arginine depletion.

Knox reported that the short-term effects of the carcinogen methylnitrosourea (MNU) were due to the formation of its decomposition product, the cyanate ion. He showed that cell survival and DNA synthesis decreased as the concentration of MNU and the cyanate ion (NCO-) increased in the medium. Further, the product of MNU decomposition comigrated with NCO- when added to his chromatographic test system. However, Knox did not study the mutagenicity of MNU or its breakdown products. We compared the mutagenicity of MNU and potassium cyanate (KNCO) in mammalian cells. Our results demonstrate that, although it is toxic to cells, KNCO does not induce ouabain-resistant mutants in cultured Chinese hamster cells (V79).

Clinical and urodynamic findings in 167 women and 96 men, aged 65 years and older evaluated consecutively during a four-year period in an outpatient urodynamic laboratory, are presented and compared with findings from other studies of geriatric populations. Seventy-three percent of the patients (81% of the women and 60% of the men) presented with symptoms of incontinence, most commonly of the mixed type. Although pathological lesions such as tumors and stones were rare, urodynamic abnormalities were common. Urodynamic evidence of sphincter weakness in women and detrusor motor instability were the most common urodynamic findings among patients who presented with incontinence. Close to 20% of patients who presented without incontinence also had one or more of these findings. Approximately one-third of patients had multiple urodynamic findings, emphasizing the complexity of the pathophysiology, diagnosis, and treatment of genitourinary dysfunction in many geriatric patients. Despite the long duration of symptoms in most patients, the majority were substantially improved after diagnosis and treatment of the specific genitourinary and urodynamic abnormalities detected.

Experiments were carried out on 48 rabbits anaesthetized with urethane (1 g/kg). The animals were immobilized with gallamine triethiodide and ventilated artificially. Both intravenous injection of diazepam (0.5 mg/kg) and intracerebroventricular injection of flurazepam (2 mg in 50 microliters) or gamma-aminobutyric acid (GABA) (300 micrograms in 50 microliters) decreased the peak value of left ventricular pressure area of cardiac force loop and dp/dtmax. These suppressive effects of diazepam and flurazepam were prevented by intracerebroventricular injection of picrotoxin (15 micrograms in 50 microliters) or microinjection of bicuculline (3 micrograms in 0.5 microliter) into bilateral rostral ventrolateral medulla (gamma VLM). The results suggest that the inhibitory effects of diazepam on cardiac function may be mediated by activation of GABA receptor in gamma VLM.

The inhibitory effects of liver extract (LEx) on DNA, RNA, and protein synthesis in phytohaemagglutinin (PHA)-stimulated lymphocytes were studied by measuring the incorporation of labelled precursors. DNA, RNA, and protein synthesis were all inhibited by LEx in a dose-related manner. The inhibitory effect of LEx on protein synthesis was additive to the inhibitory effect of puromycin. The inhibitory effect of LEx on DNA synthesis was antagonistic to the inhibitory effect of mitomycin C. In the case of actinomycin D for RNA synthesis, its interactions with LEx were variable, but not additive. LEx may act as an inhibitor of protein synthesis through the mechanism of arginine-depletion.

The clinical presentation of incontinence was compared to diagnoses based on urological and urodynamic evaluation in 135 elderly women assessed consecutively in an outpatient clinic. Most patients (64 per cent) presented with mixed symptoms: 16 per cent presented with pure stress and 16 per cent with pure urge incontinence. After evaluation 46 per cent of the patients had stress incontinence with a stable bladder, 27 per cent had detrusor instability or hyperreflexia without sphincter weakness and 19 per cent had mixed urodynamic abnormalities. Presenting symptoms were predictive of urodynamic diagnosis in 64 per cent of the patients with pure stress incontinence and 55 per cent with pure urge incontinence. In general, symptoms in our patient population were less predictive of urodynamic findings than in previously reported series of younger incontinent women but they were more predictive than in other series of elderly women. Predictive values for some urodynamic findings were enhanced by combining a symptom with certain physical findings. Implications of these data for the evaluation and treatment of incontinence in the geriatric population are discussed.

Murine liver extract (LEx) purified by ammonium sulfate (45-70% saturation) possesses a strong inhibitory effect on human lymphocyte proliferation. We have shown that the inhibitory effect of LEx is not via a cytotoxic effect and that it is proportional to the length of incubation with LEx. Mitogen-prestimulated lymphocytes are more resistant to LEx inhibition than cells not prestimulated. B cells stimulated by PWM are more susceptible to LEx-induced inhibition than PHA- or Con A-stimulated T cells. In Con A cultures, there may be a population of cells more resistant to LEx inhibition. This population is not yet identified. The degree of reversibility of LEx inhibition was different in cells prestimulated by different mitogens. The inhibitory activity of LEx decreased in the presence of an increasing number of cells in the culture.