The expression of ferroptosis-related genes in osteoporosis based on GEO.

OBJECTIVE: The aim of this study was to screen the differential genes related to ferroptosis in osteoporosis patients. MATERIALS AND METHODS: GEO2R was used to screen the differential genes related to ferroptosis in osteoporosis patients by searching the relevant chips in the GEO database, and Spearman's correlation analysis was used to describe the correlation between quantitative variables without normal distribution. p-values lower than 0.05 were considered statistically significant. Another group of osteoporosis patients was selected in the GEO database to verify the significantly differentially expressed genes. RESULTS: The results showed that 10 samples in chip GSE35956 were identified as research objects, and a total of 5 ferroptosis differential genes were screened out: ATP5MC3, CDKN1A, MT1G, NCOA4, SLC1A5, of which 3 up-regulated genes (CDKN1A, MT1G, SLC1A5), 2 down-regulated genes (ATP5MC3, NCOA4). The above differential genes were placed in 19 samples of chip GSE35959 for verification, and the same expression trend was obtained, but only the MT1G difference was statistically significant. CONCLUSIONS: The gene correlation test found that MT1G and ATP5MC3 had a strong negative correlation.

[Evaluation of demand of resources for laboratory testing and prevention and control of COVID-19 in the context of global pandemic].

Objective: To rapidly evaluate the level of healthcare resource demand for laboratory testing and prevention and control of corona virus disease 2019 (COVID-19) in different epidemic situation, and prepare for the capacity planning, stockpile distribution, and funding raising for infectious disease epidemic response. Methods: An susceptible, exposed, infectious, removed infectious disease dynamics model with confirmed asymptomatic infection cases and symptomatic hospitalized patients was introduced to simulate different COVID-19 epidemic situation and predict the numbers of hospitalized or isolated patients, and based on the current COVID-19 prevention and control measures in China, the demands of resources for laboratory testing and prevention and control of COVID-19 were evaluated. Results: When community or local transmission or outbreaks occur and total population nucleic acid testing is implemented, the need for human resources is 3.3-89.1 times higher than the reserved, and the current resources of medical personal protective equipment and instruments can meet the need. The surge in asymptomatic infections can also increase the human resource demand for laboratory testing and pose challenge to the prevention and control of the disease. When vaccine protection coverage reach ≥50%, appropriate adjustment of the prevention and control measures can reduce the need for laboratory and human resources. Conclusions: There is a great need in our country to reserve the human resources for laboratory testing and disease prevention and control for the response of the possible epidemic of COVID-19. Challenges to human resources resulted from total population nucleic acid testing and its necessity need to be considered. Conducting non-pharmaceutical interventions and encouraging more people to be vaccinated can mitigate the shock on healthcare resource demand in COVID-19 prevention and control.

[Summary and prospect of early warning models and systems for infectious disease outbreaks].

This paper summarizes the basic principles and models of early warning for infectious disease outbreaks, introduces the early warning systems for infectious disease based on different data sources and their applications, and discusses the application potential of big data and their analysing techniques, which have been studied and used in the prevention and control of COVID-19 pandemic, including internet inquiry, social media, mobile positioning, in the early warning of infectious diseases in order to provide reference for the establishment of an intelligent early warning mechanism and platform for infectious diseases based on multi-source big data.

[Development of a quality of life questionnaire for adults with anisometropic amblyopia].

Objective: To develop and validate the health-related quality of life (HRQOL) questionnaire for adult patients with anisometropic amblyopia. Methods: Cross-sectional study. A total of 170 adult patients with anisometropic amblyopia, 100 adult patients with other eye diseases and 80 healthy adults with normal vision were recruited at the First Affiliated Hospital of Nanjing Medical University, and 20 healthy adults with normal vision were recruited at Qinhuai Medical District of Easter Theater General Hospital of PLA from December 2019 to February 2020. Individual interviews of 30 adult patients with anisometropic amblyopia generated 80 questionnaire items. For item reduction, 40 adult patients with anisometropic amblyopia were asked to complete the 80-item questionnaire and responses were analyzed. Then factor analyses were performed to identify prominent factors (subscales). The reliability of the questionnaire was evaluated by Cronbach's α coefficient. The overall and sub-scale scores were the average scores of all included items, ranging from 0 (worst HRQOL) to 100 (best HRQOL). The final 20-item questionnaire was administered to additional 100 adult patients with anisometropic amblyopia, 100 adult patients with other eye diseases and 100 visually normal adults. Mean overall and subscale scores were compared across groups using one-way analysis of variance. Results: The final adult anisometropic amblyopia questionnaire (AAAQ) consisted of a function subscale and a psychosocial subscale, each containing 10 items. The Cronbach's α coefficients of the overall, function subscale and psychosocial subscale were 0.88, 0.78 and 0.78. There were 55 males and 45 females in 100 adult anisometropic amblyopia patients, with a median age of 26 years (range, 18 to 43 years). The age and gender distribution were matched with 100 adult patients with other eye diseases and 100 healthy adults with normal vision (all P>0.05). The mean overall score (28.63±9.18), function subscale score (27.69±9.88) and psychosocial subscale score (29.53±9.90) for adult patients with anisometropic amblyopia were significantly lower compared to adult patients with other eye diseases (71.28±8.14, P<0.01; 65.56±7.81, P<0.01; 76.85±10.76, P<0.01) and visually normal adults (84.54±9.13, P<0.01; 81.70±9.27, P<0.01; 87.38±10.06, P<0.01). Conclusion: The AAAQ meets the requirements for validity and reliability of a HRQOL questionnaire, and can be used to assess the HRQOL of adult patients with anisometropic amblyopia. (Chin J Ophthalmol, 2021, 57: 341-347).

[Establishment of multi-point trigger and multi-channel surveillance mechanism for intelligent early warning of infectious diseases in China].

This paper reviews the limitations of current infectious disease surveillance and early warning system in China, analyzes the concepts and countermeasures of the establishment of an intelligent early warning platform of infectious diseases based on multi-point trigger mechanism and multi-channel surveillance mechanism and proposes the realization routes for the purpose of facilitating capacity building and improvement of surveillance and early warning of infectious diseases in China.

[Utilization of Quality-of-life assessment Questionnaires for Intermittent Exotropia in China].

OBJECTIVE: To evaluate the reliability and validity of Chinese version of Quality-of-life assessment Questionnaires for Intermittent Exotropia (CIXTQ). METHODS: Cross-sectional study. The original English version of the IXTQ was translated into Chinese. The final Chinese version of the IXTQ (CIXTQ) consists of 3 parts: the 12-item child CIXTQ (for children ≥5 and<8 years old and ≥8 and<18 years old, respectively, to assess their health quality of life (HRQoL)), the 12-item proxy CIXTQ (for parents to assess children's HRQoL), and the 17-item parent CIXTQ (containing functional, psychosocial, and surgery subscales; for parents to assess their HRQoL). 175 IXT children and 151 control children along with one of their parents were recruited to answer the CIXTQ. Cronbach's α coefficient and split-half reliability were used to test the internal consistency reliability of the CIXTQ. Kappa coefficient was used to assess the test-retest reliability. Scale-level content validity index/average (S-CVI/Ave) was used to evaluate the content validity of the CIXTQ. Principal component analysis (PCA) was used to verify the construct validity of the parent CIXTQ. Comparison of different CIXTQ scores in IXT patients with controls was conducted by independent-samples t test to evaluate the discriminate validity of the CIXTQ. RESULTS: For all scales and subscales of the CIXTQ in different age groups, the Cronbach's α ranged from 0.804 to 0.963; the split-half reliability ranged from 0.658 to 0.963 and was higher than 0.7 except for the proxy CIXTQ for children aged ≥5 and<8 years old; the test-retest reliability ranged from 0.569 to 0.944. The S-CVI/Ave of the child, proxy and parent CIXTQ was 0.988, 0.988 and 0.966, respectively. Principal factors identified by PCA for the parent CIXTQ could be regrouped into the originally described 3 subscales which was functional, social psychology and surgery in different age groups. The mean scores of all the scales and subscales among IXT children and their parents (8.0±12.5-81.6 ±15.1) were significantly lower than these among control children and their parents (83.1±11.3-99.6±1.2) (t values range from -50.36 to -6.93, P<0.001). CONCLUSIONS: The CIXTQ are useful tools to evaluate the influence of IXT on HRQoL among Chinese children and their parents. (Chin J Ophthalmol, 2016, 52: 596-603).

Towards a table-top microscope for nanoscale magnetic imaging using picosecond thermal gradients.

Research advancement in magnetoelectronics is challenged by the lack of a table-top magnetic measurement technique with the simultaneous temporal and spatial resolution necessary for characterizing magnetization dynamics in devices of interest, such as magnetic memory and spin torque oscillators. Although magneto-optical microscopy provides superb temporal resolution, its spatial resolution is fundamentally limited by optical diffraction. To address this challenge, we study heat rather than light as a vehicle to stroboscopically transduce a local magnetic moment into an electrical signal while retaining picosecond temporal resolution. Using this concept, we demonstrate spatiotemporal magnetic microscopy using the time-resolved anomalous Nernst effect (TRANE). Experimentally and with supporting numerical calculations, we find that TRANE microscopy has temporal resolution below 30 ps and spatial resolution determined by the area of thermal excitation. Based on these findings, we suggest a route to exceed the limits imposed by far-field optical diffraction.

Effects of heat treatment of soy protein isolate on the growth performance and immune function of broiler chickens.

This study was conducted to evaluate the effects of oxidative modification of soy protein isolate (SPI) after exposure to heat on the growth performance and immune function of broilers. The SPI was heated in an oven at 100°C for 1, 4, and 8 h, respectively, and resultant oxidative status was evaluated. A total of 320 one-day-old Arbor Acres chickens were randomly divided into 4 treatment groups with 8 replicates of 10 birds, and fed diets supplemented with the native SPI or 1 of the 3 heat-treated SPI for 21 d. The results showed that heat exposure of SPI for 4 and 8 h caused an increase in protein carbonyl (P < 0.05), and a simultaneous decrease in sulfhydryl and free amine groups (P < 0.05) compared with native SPI. The BW of broilers fed diets supplemented with SPI heated for 8 h were significantly lower than that of broilers fed diets supplemented with native SPI (P < 0.05). Compared with native SPI, heat-treated SPI (heated for 8 h) diminished liver weight at 14 d (P = 0.01), spleen (P < 0.01) and bursa (P < 0.05) weights at 21 d; and the content of IgG in serum and duodenal mucosa of broilers (at 14 d) was decreased when diets supplemented with heat-treated SPI (heated for 8 h; P < 0.01). No significant differences were observed in the mucosa secretory IgA contents of broilers among the treatment groups (P > 0.05). Compared with native SPI, a significant increases were observed in the content of adrenocorticotropic hormone and cortisol in serum of broilers fed the heat-treated SPI (heated for 8 h) at 21 d (P < 0.05); and the myeloperoxidase activities in serum (at 14 d) and mucosa of broilers were increased when diets supplemented with heat-treated SPI (heated for 8 h; P < 0.05). The present study suggests that protein oxidation of SPI is induced by heating, and oxidized protein may negatively affect the immune function of broilers.

Mobile elements carrying ermF and tetQ genes in gram-positive and gram-negative bacteria.

Bacteroides spp. conjugative transposon Tn5030 is 150 kb which includes a 43 kb characterized region containing a number of defined genes and an open reading frame (ORF). The 43 kb region is organized with the ORF1 immediately upstream from the ermF gene, coding for an rRNA methylase, then an unknown 20 kb region downstream followed by the tetQ gene (coding for a ribosomal protection protein) then the rteA and rteB genes. The role of ORF1 is unclear; rteA is a putative sensor and rteB a regulator. Thirty-seven (62%) of 60 isolates, representing one gram-positive anaerobic and 13 gram-negative anaerobic species, co-transferred the ermFand tetQ genes to an unrelated Enterococcus faecalis recipient. We used the polymerase chain reaction to show the linkage between ORF1, ermF, tetQ, rteA and rteB. Our data suggest that the ORF1 gene product may participate in the transfer of the ermF gene with or without the ORF1-rteB region and has homology to bacterial transposases. Isolates that co-transferred the ermF and tetQ genes carried and transferred the rteB gene, suggesting that the rteB gene product may be important in transfer of the 43 kb ORF1-rteB region to E. faecalis. The rteB gene product is not required when ermF is transferred independently of tetQ.

Characterization of ciliary activity in distal Fallopian tube biopsies of women with obstructive tubal infertility.

Biopsy specimens were obtained from the distal end of the Fallopian tubes of 62 women with tubal infertility and examined by light and electron microscopy. Ciliary beat frequency (CBF) measurements were obtained using laser light spectroscopy. Neither demographic nor behavioural characteristics nor serological evidence of past chlamydial infection were associated with CBF measurements. In contrast, CBF were significantly lower (P < 0.05) in tissues with oedema compared to tissues without oedema (6.7 versus 12.9) and in tissues with erythema compared to tissues without erythema (9.2 versus 13.7). Furthermore, CBF measurements did vary by chlamydial serotype pattern, with lower values observed among the tissues of women with antibodies to serotype C or E (without D) as compared to the tissues of women with other serotypes (P < 0.04). However, these data must be interpreted with caution as the numbers of subjects with chlamydial antibodies to serotype C (n = 3) or E without D (n = 5) were few in number and serotyping of IgG antibodies in blood is not as accurate as it is in bacterial isolates. Confirmation of the suggested association between chlamydial serotype and risk of adverse sequelae could indicate potential new avenues for vaccine research.

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

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

[Pediatric Haemophilus influenzae type b meninngitis in Hefei city: an epidemiologic study].

OBJECTIVE: To obtain epidemiologic information about Hib meningitis from Hefei. METHODS: Data were collected from 1990 to 1992 by a coordinative group including 13 hospitals. All children with a clinical diagnosis of acute bacterial meningitis were enrolled and specimens were taken for etiologic studies. CSF and blood were tested by standard bacteriologic technique. CSF, blood and concentrated urine were tested directly for detecting antigen by CIE. The data were analysed by epidemiologic methods. RESULTS: Of 60 cases of bacterial meningitis clinically diagnosed, 31 (51.7%) were CIE positive for Hib antigen. Only 3 cases of CSF culture were positive for Hib. The annual incidence of Hib meningitis in Hefei was culculated as 4.81/100,000 children younger than 15 years and 10.66/100,000 children younger than 5 years. The case fatality rate was 9.7%. 21.4% of survivors suffered from neurological or psychological problems. CONCLUSIONS: Using antigen detection combined with bacterial culture, we could make etiologic diagnosis in 90% of the cases. Hib is the most common cause of bacterial meningitis, but the incidence is much lower than in most parts of the world.

[Study of adsorptive voltammetry for adrenaline on carbon paste electrode].

Adrenaline is determined by adsorptive voltammetry using a carbon paste electrode in a base solution of 0.5 mol.L-1 H2SO4. The peak potential of anode is 0.58 V (vs. SCE). There is a good linear relationship between the peak current and the concentration of adrenaline in the range of 5.0 x 10(-9)-1.0 x 10(-4) mol.L-1. The detection limit of the method is 2.5 x 10(-9) mol.L-1. The recovery is 93.75%-103.33%, and the relative standard deviation is 3.1% (n = 12). The adrenaline hydrochloride injection has been determined with good results by this method. The possible reaction mechanism is discussed. The electrode reaction of adrenaline is irreversible process with two electrons and two protons on the carbon paste electrode.

Distribution and mobility of the tetracycline resistance determinant tetQ.

We tested 34 American Type Culture Collection (ATCC) and 168 clinical bacterial isolates, from the human urogenital and oral tracts and streptococci isolated from cows with mastitis, for the presence of the tetQ gene using a polymerase chain reaction (PCR) assay and DNA-DNA hybridization. The identities of PCR products were confirmed by Southern blot hybridization of whole-cell DNA. Eleven of the ATCC strains were positive for tetQ, including five Bacteroides spp., five Prevotella spp. and a single isolate of Mitsuokella multiacidus. Twenty-eight (29%) of the 95 clinical Gram-negative isolates carried the tetQ gene, while eight (11%) of the 73 clinical Gram-positive isolates carried the tetQ gene. This is the first description of tetQ in Gram-positive species. All isolates except one Peptostreptococcus sp. carried tetQ integrated into the chromosome. The tetQ gene could be transferred from Prevotella bivia, Bacteroides ovatus, Bacteroides fragilis, Bacteroides vulgatus and Bacteroides distasonis into an Enterococcus faecalis recipient at frequencies of 10(-7)-10(-9) per recipient. In contrast, tetQ failed to transfer from two isolates of Prevotella intermedia, two isolates of Porphyromonas gingivalis, one isolate of Mobiluncus curtisii and one isolate of Peptostreptococcus sp. The latter two are Gram-positive species. The PCR assay was used to screen 198 proteinase K-treated biopsies of prostate, periprostate and bladder from 84 men with prostatitis. Thirty-four (40%) of the patients had one or more positive samples, suggesting that the PCR assay could be of value in screening patient material directly for the presence of bacteria.

Acute bacterial meningitis in children in Hefei, China 1990-1992.

OBJECTIVE: To obtain etiologic and epidemiologic information about bacterial meningitis, especially the H influenza type B (Hib), from a medium-sized city, Hefei, China. METHODS: Data were collected prospectively over 3 years, from 1990 to 1992 by a well-organized group including 13 hospitals. All children with a clinical diagnosis of acute bacterial meningitis were enrolled and the specimens were taken for the etiologic studies. CSF and blood were tested by standard bacteriologic technique. CSF, blood and concentrated urine were tested directly for detection of antigen by countercurrent immuno-electrophoresis (CIE). Data were analyzed by epidemiologic methods. RESULTS: Bacterial culture and CSF Gram's staining were positive only in 13.3% and 11.7%, respectively. Bacterial antigen detection was positive in up to 90% by CIE which was more sensitive than bacterial culture (chi 2 = 67.7, P < 0.005). The annual incidence of acute bacterial meningitis in the city is calculated as 9.3 cases/100,000 children from 1 month to 15 years of age and 19.2 cases/100,000 children from 1 month to 5 years of age. Hib meningitis accounted for 51.7%, N. meningitis (Nm) for 38.3%, and S. pneumoniae (Sp) for 8.3%. There was no significant seasonal variation. Of the patients, 76.7% were children under 5 years of age, and 51.7% under 1 year of age. The case fatality rate was 11.7% for all bacterial meningitis, 9.7% for Hib, 17.4% for Nm and 20% for Sp. A total of 22.6% of survivors suffered from neurological or psychological problems. CONCLUSIONS: Using antigen detection combined with bacterial culture, we could make an etiologic diagnosis in up to 90% of the patients in this group. Hib, Nm and Sp were the predominant pathogens, which was similar to the findings in other countries. Hib was the most common cause of bacterial meningitis, but the incidence was much lower than in most parts of the world.

Evaluation of the detection limits of PCR for identification of Mycoplasma pneumoniae in clinical samples.

The detection limits of the polymerase chain reaction (PCR) for Mycoplasma pneumoniae were determined using specimens from persons known to have had M. pneumoniae pneumonia. Four primers were selected from the known sequence of the P1 gene. The primer pair (P1-178 and P1-809) which generates a 631 fragment gave the lowest detection limit. Nineteen of 21 throat swabs, which contained between 0.06 and 2 colony-forming units (CFU) per microlitre, from culture positive patients, were positive by PCR. The fact that M. pneumoniae grows in broth culture in spherules causes problems for determining the number of CFU detected in PCR. Filtering broth cultures through a 0.6 micron polycarbonate filter increased the number of CFUs two-to-ten-fold compared to unfiltered cultures. The lysis method needed to assay throat swabs differed from that necessary for broth cultures in that proteinase K treatment for 18 h increased the detection limit 10- to 100-fold when compared to NaOH digestion.

The glutathione S-transferase mu polymorphism as a marker for susceptibility to lung carcinoma.

Glutathione S-transferase (GST) enzymes detoxify carcinogens in tobacco smoke. Interindividual variation in GST function may be related to differences in risk for smoking-related cancer. Leukocytes from 50% of Caucasians lack GST activity toward trans-stilbene oxide (TSO), due to a deletion of the gene for the GST-mu enzyme. Presence of GST-TSO activity in leukocytes has been associated with low risk for lung cancer among cigarette smokers. We sought to determine whether GST activity in lung tissue is determined by the same gene polymorphism and whether it is associated with risk for lung cancer. Subjects were cigarette smokers, identified at the time of lung resection or autopsy in Seattle hospitals. Uninvolved lung tissue was obtained from 35 patients with lung carcinoma and 43 control patients and assayed for GST-mu activity with TSO, for the presence of the GST-mu gene product with an immunological assay, and for the GST-mu gene with Southern blotting. Mailed questionnaires were used to collect information on subjects' smoking histories and exposures which might alter enzyme activity. Interindividual results from the three assays correlated well. Smokers with high GST-TSO enzyme activity present in their lung tissue had a lower risk for lung carcinoma than did smokers with no or low activity (relative risk = 0.30; 95% confidence interval, 0.11-0.79), as did smokers with GST-mu antigen identified in lung tissue versus those with no antigen (relative risk = 0.30; 95% confidence interval, 0.11-0.79). Smokers with both maternal and paternal copies of GST-mu DNA (n = 7) had a lower cancer risk than smokers lacking GST-mu DNA (n = 30; relative risk = 0.35; 95% confidence interval, 0.06-2.10). High GST-mu activity appeared to be associated with a greater decrease in lung cancer risk among 38 heavy cigarette smokers (relative risk = 0.15; 95% confidence interval, 0.03-0.64) than among 38 light smokers (relative risk = 0.61; 95% confidence interval, 0.14-2.60). Presence or absence and number of copies of the GST-mu gene appear to determine activity of the GST-mu enzyme in lung. Smokers with the GST-mu enzyme have approximately one-third of the risk for lung carcinoma of smokers without the enzyme.

Cytoplasmic and nuclear signaling pathways of V1-vascular vasopressin receptors.

We studied the cytoplasmic and nuclear signaling pathways of V1-vascular AVP receptors of human platelets, primary cultures of renal glomerular mesangial cells, and established cultures of the A7r5 aortic smooth muscle cell line. The immediate transmembrane signals are triggered by the formation of ligand-receptor complexes as illustrated by binding experiments with [3H]AVP (Kd = 2.50 nM), d(CH2)5Tyr(Me)AVP (Kd = 0.62 nM), the linear V1 antagonist phenylacetyl-D-Tyr(Et)-Phe-Val-Asn-Lys-Pro-[125I]Tyr-NH2 (Kd = 1.42 nM) or by fluorescence experiments with linear antagonists like phenylacetyl-D-Tyr(Et)-Phe-Gln-Asn-Lys-Pro-Arg-NH2 coupled to biotin and made fluorescent by labeling with tetramethylrhodamine-avidin. We used several approaches (radioreceptor binding, radioactive labeling, autoradiographic, enzymatic, photoaffinity labeling, and immunoblotting procedures) to identify the guanine nucleotide regulatory protein coupled to V1-vascular vasopressin receptors. AVP-stimulated GTPase activity of human platelet membranes was blocked by pretreatment with antibodies specific for the C-terminal of the newly described Gq alpha protein. In the presence of MgCl2, AVP increased labeling by the photoreactive GTP analog [alpha-32P]azidoanilido GTP of a platelet membrane protein of apparent molecular mass of 42 kDa. AVP effect was reversed by the specific V1-vascular antagonist d(CH2)5Tyr(Me)AVP and labeling was completely abolished by GTP gamma s.(ABSTRACT TRUNCATED AT 250 WORDS)