[Clinicopathological features of gastric alpha-fetoprotein-producing adenocarcinoma with SWI/SNF complex deletion].

Objective: To investigate the clinicopathological features and treatment of gastric alpha-fetoprotein (AFP)-producing adenocarcinoma with SWI/SNF complex deletion. Methods: Four cases of gastric AFP-producing adenocarcinoma with SWI/SNF complex deletion diagnosed in Zhongshan Hospital of Fudan University from January 2021 to December 2022 were collected, and their histomorphological characteristics, immunohistochemical (IHC), in situ hybridization of Epstein-Barr virus-encoded RNA (EBER), next-generation sequencing results, clinicopathological features and treatment were summarized, and literature review was conducted. Results: Among the 4 patients, there were three males and one female. They presented with abdominal pain, belching and melena. Serum AFP was significantly elevated in three patients, and endoscopy showed ulcerative lesions. Microscopically, the tumor cells showed mainly diffuse flaky or nest-like growth and typical characteristics of hepatoid adenocarcinoma. In two cases there were adenoid growth, and the tumor cells in these areas possessed clear cytoplasm, suggesting enteroblastic differentiation. The tumor cell nuclei were pleomorphic with large nucleoli and brisk mitoses. The IHC results showed that the tumor cells expressed AFP, GPC3 and SALL4, and there was retained expression of broad-spectrum keratin (CKpan) and E-cadherin. IHC detection of SWI/SNF complex subunits, namely INI1 (SMARCB1), BRG1 (SMARCA4), BRM (SMARCA2), ARID1A protein was performed. In all four cases the hepatoid adenocarcinoma region and enteroblastic differentiation region showed SMARCA2 deletion, and one case with enteroblastic differentiation also showed ARID1A deletion. SMARCB1 and SMARCA4 deletions were not seen. All the four cases were diffusely positive for p53 protein, and the Ki-67 proliferation index was 80%-90%. There were no mismatch repair deletion detected; one cases showed HER2 was strongly positive (3+), and EBER was negative. None of the four cases had mutations in the SWI/SNF complex-related subunits detected by next-generation sequencing. Among the four patients, two underwent palliative surgery due to distant metastasis at the time of surgery, two underwent radical resection. Postoperative adjuvant chemotherapy was given to three patients. Conclusions: AFP-producing adenocarcinoma is a rare subtype of gastric cancer, which can be combined with SWI/SNF complex deletion, and the pathomorphological manifestations are different from the classical SWI/SNF complex deletion of undifferentiated carcinoma with rhabdoid phenotype.

[Gastrointestinal tumors with SWI/SNF complex deficiency: a clinicopathological analysis of 36 cases].

Objective: To investigate the clinicopathological characteristics of gastrointestinal tumors with SWI/SNF complex deficiency and to perform a prognostic analysis of the patients. Methods: Gastrointestinal tumor cases with SWI/SNF complex deficiency expression diagnosed at the Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China from August 2021 to May 2023 were collected. Hematoxylin and eosin (HE) stained slides were reviewed, and immunohistochemical results were analyzed. Clinical and pathological information was recorded, and relevant literature was reviewed. Results: A total of 36 cases of gastrointestinal tumor with loss of SWI/SNF complex expression were identified, including 28 males (77.8%) and 8 females (22.2%). The average age at diagnosis was 70 years (range 48-85 years). Clinical staging showed 3 cases in stage Ⅰ (8.3%), 12 cases in stage Ⅱ (33.3%), 19 cases in stage Ⅲ (52.8%), and 2 cases in stage Ⅳ (5.6%). Complete or partial loss of ARID1A expression was observed in 20 cases (55.6%); complete or partial loss of SMARCA2 expression was observed in 24 cases (66.7%). SMARCA4 exhibited complete loss of expression in 4 cases (11.1%). Eleven cases (30.6%) showed concurrent complete or partial losses of both ARID1A and SMARCA2 expression. Twelve cases (33.3%) had mismatch repair protein deficiency, all of which were characterized by MLH1/PMS2 absence. Mismatch repair protein deficiency was associated with loss of ARID1A expression (P<0.01). Patients with mismatch repair protein deficiency were also associated with earlier clinical stage and a lower risk of lymph node metastasis compared to the ones with intact mismatch repair proteins (P<0.05). Conclusions: SWI/SNF complex deficiency in gastrointestinal tumors is associated with dedifferentiation and often accompanied by mismatch repair protein deficiency. Compared to the cases with intact mismatch repair proteins, the cases with defective mismatch repair protein have an earlier clinical stage and a lower risk of lymph node metastasis.

[Application and comparison of three occupational health risk assessment methods in an automobile manufacturing industry].

Objective: Three occupational health risk assessment methods were used to assess the occupational health risk of noise exposed posts in an automobile manufacturing enterprise. According to the results, the selection of risk assessment methods and risk management of such occupational noise enterprises were provided. Methods: Form April to November 2021, The occupational health field survey was carried out in an automobile manufacturing industry in Tianjin. The occupational health MES risk assessment method, occupational health risk index risk assessment method and Australian occupational hazard risk assessment method were used to evaluate the occupational health risk of noise-exposed posts in this enterprise, and the evaluation results of different methods were analyzed and compared. Results: The average value of L(Aeq, 8 h) in the four workshops of automobile manufacturing industry was 82.95 dB (A) , and the noise detection exceeding rate was 22.41% (26/116) . The LAeq, 8h and exceeding rate noise of welding workshop were higher than those of other workshops (χ(2)=23.56, 32.94, P<0.01) . The three occupational health risk assessment methods have the same risk assessment results for the four major workshops. The assembly and painting workshops are level 4 risk (possible risk) , and the stamping and welding workshops are level 3 risk (significant risk) . Conclusion: Occupational noise has certain potential hazards to workers in automobile manufacturing enterprises. Therefore, in the future work, corresponding organizational management measures should be taken to improve the working environment and reduce the actual exposure level of workers in order to protect the health of occupational workers.

[The 486th case: chronic diarrhea and orthostatic hypotension].

A 57-year-old man was admitted to hospital with diarrhea for 10 months and dizziness for 4 months. The patient had 1-2 liters watery stool per day, without pyogenic blood or abnormality in gastroenteroscopy examination. The level of hemoglobin and albumin was generally normal, and fasting test was positive. At the same time, he was accompanied with hyperalgesia of lower limbs and orthostatic hypotension. After the discussion of multiple disciplinary teams, the patient was diagnosed with amyloidosis by sural nerve biopsy, myocardial MRI, and the assays of urine immunoelectrophoresis and serum free light chain. Light chain amyloidosis was confirmed after excluded the diagnosis of familial amyloidosis. The patient was improved after courses of chemotherapy with melphalan and dexamethasone.

[Research on the short-term effects of welding fumes on workers' lung function: a panel study].

Objective: To explore the short-term effects of welding fumes on workers' lung function in the welding environment preliminarily, and provide reference for future research. Methods: In October 2020, the lung function of the subjects was repeatedly measured before and after the working shift with a panel study. The paired t test was used to compare the lung function before and after the shift, and the linear mixed effects model was used to analyze the short-term changes of lung function. Results: 36 male welders were included, and the average age was (30.72±5.21) years, average employed year was (4.36±2.17) years. And the average concentration of welding fume was (1.27±0.49) mg/m(3). The forced vital capacity (FVC) , forced expiratory volume in the first second (FEV1) and peak expiratory flow (PEF) of welders after the shift were significantly lower than those before the shift (t=19.52, 48.13, 62.03, P<0.05) . After adjusting the workers' age, BMI and employed years, the changes of FVC% and FEV1% with the concentration of welding fume were statistically significant (ß=-1.02, 95%CI: -1.54--0.52; ß=-1.56, 95%CI: -1.95--1.16; P<0.01) . In another word, for the 1 mg/m(3) increase of welding fume in the working environment, compared with the baseline, the FVC decreases by 1.02%, and FEV1 decreases by 1.56%. Conclusion: Short-term exposure to welding fumes in workplace can reduce the lung function of welders.

[Correlation between intestinal mucosal permeability and prognosis in patients with liver cirrhosis].

Objective: To investigate the correlation between changes in intestinal mucosal permeability and prognosis of patients with liver cirrhosis. Methods: Data of 89 cases with liver cirrhosis who were hospitalized in the Hepatology Department of Shanxi Provincial Hospital of Traditional Chinese Medicine from January 2017 to August 2017 were collected as the liver cirrhosis experimental group, and 40 healthy subjects were randomly selected as the healthy control group. JY-DLT, the Intestinal Mucosal Barrier Biochemical Index Analysis System was used to measure the levels of serum diamine oxidase (DAO), D-lactic acid, and endotoxin (ETX) in two groups to evaluate intestinal mucosal barrier function. Spearman's rank correlation test was used to evaluate the correlation between liver cirrhosis prognosis and intestinal mucosal permeability. The results of the two groups were compared by Mann-Whitney H test of two independent samples. One-way Anova was used for intergroup comparison. The pairwise comparison between groups was performed using the LSD or SNK test. Results: The level of ETX in patients with decompensated cirrhosis was significantly higher than that in the compensated phase, and the difference was statistically significant (P < 0.05). The levels of DAO, D-lactic acid and ETX in the liver cirrhosis group were significantly higher than those in the healthy control group, and the differences were statistically significant (P < 0.01). The plasma levels of DAO, D-lactic acid and ETX in the Child-Pugh grade groups of patients with liver cirrhosis were significantly higher than those in the healthy control group, and the differences were statistically significant (P < 0.05). The results of intergroup comparison showed that there were statistically significant differences in DAO, D-lactic acid and ETX levels between Child-Pugh grade A and grade B groups (t = -4.255, 2.527, -2.179, P < 0.05). Furthermore, there were statistically significant differences in the levels of D-lactic acid and ETX between the Child-Pugh grade A and grade C groups (t = -2.693, -4.248, P < 0.01).The plasma levels of DAO, D-lactic acid and ETX levels were positively correlated (r = 0.205, 0.372, 0.342, P < 0.01). D-lactic acid and ETX levels were positively correlated with CTP score, Forns' index, RPR index, APRI score, FIB-4 index and FibroScan score(P < 0.01). Conclusion: The three indices (plasma DAO, D-lactic acid, and ETX) can accurately detect the changes in intestinal mucosal permeability. Moreover, the higher index of intestinal mucosal permeability causes the more severe degree of liver cirrhosis and the correlation between the intestinal mucosal permeability and the prognosis score of liver cirrhosis provides a reference for a new evaluation system and new ideas for the treatment of liver cirrhosis.

[Analysis of silicosis surveillance data in Tianjin in 2017].

Objective: Analyzes of the monitoring results of silicosis in key occupational disease monitoring in Tianjin in 2017, providing reference for continuous monitoring, and prevention and control work of silicosis. Methods: Monitor and analyze the current state of silica dust hazard enterprises, the health status of silica dust workers, and the characteristics of newly developed silicosis cases in accordance with the national 2017 work plan for key occupational disease monitoring and occupational health risk assessment. Results: In 2017, 210 enterprises have silica dust hazard in Tianjin, silica dust workplaces exceed the standard rate is 34.73%, 5 695 workers' health examination who contact with silica dust were collected. 2 were detected occupational contraindication, the abnormal detection rate of chest examination is 3.60%, the abnormal index of lung function mainly is FVC, the abnormal rate is 15.8%. The abnormal rate increases with working years. In 2017, 193 new cases of silicosis were reported most cases were developed after years of decontamination. Most enterprises with cases had already out of market, only 7 were still producing. Conclusion: The key prevention and control in Tianjin was enterprises with silica dust excess of standard, as well as older and longer working years workers, adopting effective measures to reduce the concentration of silica dust in workplace is a fundamental measure to reduce the risk of silicosis.

[Analysis of the quality of life and the influencing factors in patients with diabetic retinopathy before and after receiving pan-retinal photocoagulation].

Objective: Quality of life and the influencing factors in patients with diabetic retinopathy before and after receiving treatment of pan-retinal photocoagulation (PRP) were studied. Methods: Prospective study. A total of 55 diabetic retinopathy patients were collected at Beijing Friendship Hospital, Capital Medical University from November 2016 to August 2017 and were surveyed using Vision Function Questionaire (VFQ-25) to evaluate their quality of life before and 3 months after treatment with PRP. According to diagnostic criteria, the patients were divided into two groups: severe nonproliferative diabetic retinopathy(NPDR) and proliferative diabetic retinopathy group(PDR). SPSS was used for statistical analysis. Results: The score of VFO-25 general health before PRP treatment was 62.73±14.20, obviously lower the other sub scale scores of VFO-25. The results of variance analysis there was significant statistical difference between the composite score and the different educational levels (F=2.94, P<0.05), but there was no statistical difference for diabetes duration (F=3.01, P<0.05). The composite score was significantly significance between the severe NPDR and PDR group(t=8.95, P<0.05). The patients with hyperlipidemia (t=-3.21, P<0.05), hypertension(t=-2.32, P<0.05) and renal insufficiency(t=-2.05, P=0.045) has lower composite score. There was high relationship for age among the factors of worse logMAR vision, better logMAR vision and age (r=-0.47, P<0.05; r=-0.38, P<0.05; r=-0.26, P<0.05). The scores of VFQ-25 subscale of social function (t=-2.07, P<0.05) , role limitations (t=-2.38, P<0.05) , dependency (t=-2.99, P<0.05) and mental health (t=-2.26, P<0.05) was significantly increased after treatment of PRP. The score of ocular pain was obviously decreased (t=4.19, P<0.001) ; there were no significance in other sub scale scores. Conclusions: This study showed that the degree of visual acuity, the severity of DR and age were an important factor affecting the quality of life in DR patients. PRP therapy could improve the mental health and social field of DR patients, but failed to improve the scores of other visual functions in the patients. (Chin J Ophthalmol, 2018, 54:611-616).

[Evaluation uncertainty of power frequency electric field for a Power Project in inner Mongolia].

Objective: With the measurement and uncertainty analysis of the power frequency electric field of the main transformer in the power station, the source of uncertainty, its quantitative calculation, the synthetic assessment method and the reporting method of the measurement results are described to ensure the reliability of the power frequency electric field measurement data. Methods: Referring to the "Measurement of power frequency electric field in the workplace" (GBZ/T189.3-2007) , "Labour environment monitoring technological specification of electric power industry Partt7: Monitoring of power frequency electromagnetic fields" (DL/T 799.7-2010) and "Evaluation and Expression of Uncertainty in Measurement" (JJF 1059.1-2012) , the uncertainty of power frequency electric field measurement data of the main transformer of a power plant was analyzed and the extended uncertainty was obtained. Results: The main source of the uncertainty of power frequency electric field measurement was the measurement of repetitive operation, and the expanded uncertainty of power frequency electric field was 0.09 kV/m. Conclusion: When reporting the results of power frequency electric field measurement, the measurement uncertainty should be used simultaneously to quantify the quality of the measurement results. This method has strong practicability and operability, which can meet the requirements of uncertainty evaluation of power frequency electric field measurement results.

[Study on the mechanism of resistance to cypermethrin in Culex pipiens pallens using proteomics].

OBJECTIVE: To compare the differentially expressed proteins between cypermethrin-resistant and -sensitive Culex pipiens pallens, so as to unravel the mechanism underlying the resistance to cypermethrin in Cx. p. pallens. METHODS: A quantitative proteomic analysis was performed among cypermethrin-sensitive and -resistant isolates of Cx. p. pallens using isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with liquid chromatography with tandem mass spectrometry (LC-MS/MS). RESULTS: A total of 164 differentially expressed proteins were identified between cypermethrin-sensitive and -resistant isolates of Cx. p. pallens, including 54 up-regulated proteins and 110 down-regulated proteins. A large number of cuticular proteins, larval cuticular proteins, pupal cuticular proteins and cuticular structural constituent proteins, which are associated with cytoskeletal structure and components, were differentially expressed between cypermethrin-sensitive and -resistant isolates of Cx. p. pallens. Thirteen proteins, which were involved in energy production and conversion, translation, ribosomal structure and biogenesis, lipid transport and metabolism, post-translational modification, protein turnover, chaperones, cytoskeleton and intracellular transportation, were validated to be differentially expressed between cypermethrin-sensitive and -resistant isolates of Cx. p. pallens, which may serve as potential markers of cypermethrin resistance. CONCLUSIONS: Multiple insecticide resistance mechanisms contribute to the resistance to cypermethrin in Cx. p. pallens, including cuticular resistance and metabolic resistance, and the cuticular protein genes and cytochrome P450 enzymes may play an important role in the resistance of Cx. p. pallens to cypermethrin.

[Effects of low temperature on trehalose and trehalase contents in Culex pipiens pallens].

OBJECTIVE: To examine the effect of low temperature on trehalose and trehalase levels in Culex pipiens pallens. METHODS: The fourth instar larvae and female adult mosquitoes of Cx. pipiens pallens were exposed at 4 ℃ for 0, 1, 3, 6, 12, 18, 24 h and 0, 1, 3, 6, 12, 18, 24, 36, 48, 72 h, respectively. Then, the trehalose and trehalase contents were detected by enzyme-linked immunosorbent assay (ELISA) in mosquitoes. RESULTS: The contents of trehalose and trehalase significantly increased in the larval and female adult mosquitoes post-exposure to low temperature. The changing trend of trehalose levels was consistent in the larval and female adult mosquitoes, and the highest levels were (2.458 8 ± 0.379 2) mg/g and (2.825 7 ± 0.211 1) mg/g 3 h post-exposure to low temperature, respectively. The trehalose and trehalase levels fluctuated greatly within the first 6 h post-exposure to low temperature. Following adaptation for a period of time, the trehalose and trehalase levels remained at a relatively high level. CONCLUSIONS: Low temperature may induce the production of trehalose and trehalase in Cx. pipiens pallens, and the trehalose and trehalase may play an important role in the improvement of the cold resistance.

[Study on insecticide resistance of Culex pipiens pallens in southwest region of Shandong Province].

OBJECTIVE: To explore the sensitivity of Culex pipiens pallens to common chemical insecticides in the southwestern region of Shandong Province, so as to provide a theoretical basis for the development of reasonable and effective mosquito control measures. METHODS: The resistance of Cx. pipiens pallens larvae to 5 chemical insecticides, such as cypermethrin, deltamethrin, DDVP, propoxur, and acetofenate were tested by using the WHO biological test method in 2018, and the co-toxicity coefficients after compounding the above-mentioned insecticides were tested by using a drug compounding method. RESULTS: The resistance indexes of Cx. pipiens pallens to cypermethrin, deltamethrin, DDVP, propoxur, and acetofenate in 3 cities were 144.43-557.54, 118.17-445.33, 6.44-19.00, 2.37-8.10, and 0.88-2.98, respectively, and expect the difference between the DDVP resistances of Cx. pipiens pallens in Jining City and Heze City was not statistically significant (P > 0.05), all the other differences were statistically significant (all P < 0.05). The synergistic coefficients of cypermethrin + DDVP, cypermethrin + propoxur, DDVP + acetofenate, and propoxur + acetofenate were 199.58 - 456.95, 190.56 - 292.37, 123.32 - 319.24, and 192.31 - 367.32, respectively. The lower synergism was observed by using the mixture of DDVP + propoxur (synergistic coefficient: 99.87-108.36) . CONCLUSIONS: After decades of chemical control, Cx. pipiens pallens in the southwestern region of Shandong Province has produced different degrees of resistance to common chemical insecticides. Therefore, comprehensive control measures should be taken to control mosquito breeding and prevent the development of insecticide resistance.

Henry's law constants of phenol and mononitrophenols in water and aqueous sulfuric acid.

Phenols are widely present in the atmosphere and nitration probably in the aerosol phase leads to nitrophenols. Nitration by nitric acid in sulfuric acid can be rapid, but little is known of the process under atmospheric conditions. The Henry's law constants K(H)(dagger) of phenol and 2-, 3- and 4-nitrophenol were all measured by a bubble stripping method as: 2820mol kg(-1) atm(-1) (at 298K), 147mol kg(-1) atm(-1) (at 298K), 1.6x10(4)mol kg(-1)atm(-1) (at 308K) and 2.1x10(4)mol kg(-1) atm(-1) (at 308K), respectively. The Henry's law constant of phenol in sulfuric acid systems is lower by more than a factor of two at 1020mol kg(-1) atm(-1) (at 298K) in 40wt% sulfuric acid, which is in line with salting-out of oxygen-containing aromatic compounds in water-sulfuric acid systems. The Henry's law constants of 2- and 4-nitrophenol behave differently and are almost independent of sulfuric acid concentration. The variation of K(H)(dagger) with temperature (T) described in terms of -dln(K(H)(dagger))/d(1/T) does not to vary with sulfuric acid concentration, suggesting enthalpy of dissolution for phenol is independent of sulfuric acid. The series of Henry's law constants measured here can describe the equilibrium situation for phenols in careful determinations of phase partitioning in the atmosphere.

[CD(4+) T lymphocyte responses to anti-retroviral therapy, among HIV/AIDS patients aged 18 and over].

Objective: To compare the differences of CD(4) (+) T lymphocyte (CD(4)) counts between patients aged 18 and over, to explore the effect of age on treatment, 36 months after having received the China National Free AIDS Antiretroviral Treatment on HIV/AIDS. Methods: Through the National ART Information Ssystem, we selected those HIV/AIDS patients who initiated the ART 36 months after the ART, between January 1, 2010 and December 31, 2012 in Guangzhou, Liuzhou and Kunming. Patients were divided into age groups as 18-49, 50-59 and 60 or over year olds, at the baseline of treatment. Under different levels of baseline CD(4) counts, we chose the baseline and different time-point of CD(4) counts as dependent variables, applied mixed linear model to analyze the effects of age, viral suppression, gender, baseline CD(4)/CD(8) ratio and initial treatment regimen. Results: A total of 5 331 HIV/AIDS patients were recruited. No differences were found on age group ratios between different levels of baseline CD(4) counts. At the level of baseline CD(4)<200 cells/µl, both the 50-59 and 60 or above years old groups had lower CD(4) counts than the 18-49 year-old group, within 36 months after the initiation of ART. However, at the baseline CD(4) level of 200-350 cells/µl, no significant differences on CD(4) counts between the 50-59 year-old and 18-49 year-old groups were noticed. CD(4) counts seemed lower in the 60 and above year-old group than in the 18-49 year-old group. Conclusion: Age might serve as an influencing factor on CD(4) counts within 36 months after the initiation of ART, suggesting that earlier initiation of ART might be of help to the recovery of immune function in the 50-59 year-old group.

Cerebrospinal fluid IgG against TB-SA for diagnosis of tuberculous meningitis.

OBJECTIVE: A commercial enzyme linked immunosorbent assay (ELISA) detecting cerebrospinal fluid (CSF) IgG against TB-SA (CYPCO TB (IgG) ELISA assay) for diagnosing tuberculous meningitis (TBM) was evaluated retrospectively. Meanwhile, Pandy test was introduced to grade patients, improving its role in the detection of TBM. PATIENTS AND METHODS: 187 consecutive cases with determined diagnosis were enrolled and divided into TBM group and Non-TBM group. CSFs were collected and sent for Pandy test, cytology, routine biochemistry tests, acid-fast smear and mycobacterial culture. The diagnostic parameters of the ELISA assay were evaluated. Differences in sensitivity between groups were estimated using a McNemar's test. RESULTS: The overall sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of the ELISA assay were 31.6% (95% CI: 21.0-44.5%), 97.7% (95% CI: 93.4-99.2%), 85.8, 76.5, 13.7 and 0.7, respectively. McNemar's test showed the sensitivity of CYPCO TB (IgG) ELISA assay significantly positively correlated with the results of Pandy test (p < 0.05). The ten Pandy test "3+" patients were all TBM. Therefore, patients with "3+" Pandy test are highly suspected of TBM. CONCLUSIONS: The commercial CYPCO TB (IgG) ELISA assay is able to rapidly confirm a diagnosis of TBM. The sensitivity of the ELISA assay is significantly positively correlated with the results of Pandy test. Patients with "3+" Pandy test are highly suspected of TBM.

Transgenic mice overexpressing mutant PRKAG2 define the cause of Wolff-Parkinson-White syndrome in glycogen storage cardiomyopathy.

BACKGROUND: Mutations in the gamma2 subunit (PRKAG2) of AMP-activated protein kinase produce an unusual human cardiomyopathy characterized by ventricular hypertrophy and electrophysiological abnormalities: Wolff-Parkinson-White syndrome (WPW) and progressive degenerative conduction system disease. Pathological examinations of affected human hearts reveal vacuoles containing amylopectin, a glycogen-related substance. METHODS AND RESULTS: To elucidate the mechanism by which PRKAG2 mutations produce hypertrophy with electrophysiological abnormalities, we constructed transgenic mice overexpressing the PRKAG2 cDNA with or without a missense N488I human mutation. Transgenic mutant mice showed elevated AMP-activated protein kinase activity, accumulated large amounts of cardiac glycogen (30-fold above normal), developed dramatic left ventricular hypertrophy, and exhibited ventricular preexcitation and sinus node dysfunction. Electrophysiological testing demonstrated alternative atrioventricular conduction pathways consistent with WPW. Cardiac histopathology revealed that the annulus fibrosis, which normally insulates the ventricles from inappropriate excitation by the atria, was disrupted by glycogen-filled myocytes. These anomalous microscopic atrioventricular connections, rather than morphologically distinct bypass tracts, appeared to provide the anatomic substrate for ventricular preexcitation. CONCLUSIONS: Our data establish PRKAG2 mutations as a glycogen storage cardiomyopathy, provide an anatomic explanation for electrophysiological findings, and implicate disruption of the annulus fibrosis by glycogen-engorged myocytes as the cause of preexcitation in Pompe, Danon, and other glycogen storage diseases.

Tyrosine phosphorylation is involved in phosphatidylinositol 3-kinase activation in bovine rod outer segments.

PURPOSE: We have previously shown that phosphatidylinositol 3-kinase (PI 3-kinase) activity is present in bovine rod outer segments (ROS). The present study was undertaken to investigate the mechanism of PI 3-kinase activation in these membranes. METHODS: Tyrosine-phosphorylated ROS (PY-ROS) were obtained by incubating ROS with ATP, MgCl2, and orthovanadate (Na3VO4), a tyrosine phosphatase inhibitor. Non-phosphorylated ROS (N-ROS) were obtained by incubating ROS under the same conditions, but without ATP and orthovanadate. Both were subjected to immunoprecipitation using antibodies against the regulatory p85 (anti-p85) subunit of PI 3-kinase, the catalytic p110 (anti-p110) subunit of PI 3-kinase, or phosphotyrosine (anti-PY). The immunoprecipitates (IPs) were assayed for PI 3-kinase activity. Enzyme assay products were separated by thin-layer chromatography (TLC), deacylated, and identified by high performance liquid chromatography (HPLC). RESULTS: PI 3-kinase activity in anti-p85 and p110alpha IPs was significantly higher in PY-ROS than in N-ROS. No enzyme activity was recovered in anti-p110beta IPs. PI 3-kinase activity in anti-PY IPs from PY-ROS was six-fold greater than those from N-ROS. Immunoblot analysis showed that the amount of p85 in PY IPs from PY-ROS was significantly higher than those from N-ROS. However, tyrosine phosphorylation of p85 and p110alpha was not observed in anti-p85 and anti-p110alpha IPs that were probed with anti-PY. CONCLUSIONS: This study indicates that the p85/p110alpha complex of PI 3-kinase is present in ROS and tyrosine phosphorylation is involved in the regulation of its activity.

[Changes in type II alveolar epithelial cells in experimental allergic alveolitis].

Changes of type II alveolar epithelial cells (type II cells) were studied in experimental allergic alveolitis by using enzyme histochemical, electron microscopic and morphometric techniques. The results showed that the number of type II cells increased obviously after exposed to thermoactinomyces vulgaris (TV). The peak was on the 15th day and then decreased gradually till to normal on the 180th day. Type II cells could be divided into two populations in TV-treated rats, namely, the large type II cells and the small type II cells. The former ones bore a diameter larger than the value of mean + 2.58s and mean indicated the mean value of type II cells diameters of the controls. The large type II cells are known to be the hypertrophic cells.