[Spatiotemporal distribution of measles in China, 2001-2016].

Objective: To understand the spatial-temporal distribution and spatial clusters of measles cases in China. Methods: Measles incidence data was collected from the National Notifiable Disease Reporting System of Chinese Center for Disease Control and Prevention. The global and local spatial autocorrelation analyses were conducted by using software ArcGIS 10.2 and spatial-temporal scan was conducted by using software SaTScan 9.6. Results: A total of 1 012 537 cases of measles were reported in China from 2001 to 2016 and the annual incidence showed a sharp downward trend. There was global spatial clustering of measles cases during 2001-2004, 2005-2008, and 2009-2012, and their Moran's I coefficients were 0.29, 0.26, and 0.31, respectively. The results of local spatial autocorrelation analysis showed that there were high- high clustering areas of measles at all time periods, especially in western China. Guangdong province was detected as a separate high-low scattered area from 2005 to 2008 and no low-low clustering area was detected. The spatial-temporal scan statistics showed that there was a wide clustering area covering western, central and northern China, and Shanxi province and Guangxi Zhuang Autonomous Region from 2001-2008. Conclusion: The incidence of measles in China has a certain clustering in both space and time during 2001-2016, the results provide evidence for the development of future strategy of measles prevention and control in China.

[A study on measles and rubella antibody level in 319 pairs of mothers and infants in Songjiang District of Shanghai].

Objective: To explore serum levels of measles and rubella IgG antibodies among mothers and infants. Methods: According to the inclusion and exclusion criteria, we selected 319 puerperae and their infants in maternal hospitals of Songjiang district November 2016 to February 2017, venous blood were collected and serum measles and rubella IgG antibodies were measured using ELISA. To study the correlation between the level of measles and rubella antibodies in infants and mothers' by using the Spearman's correlation analysis. Results: The age at delivery was (29.71±4.25) years old; and the gestational age at delivery was (39.06±1.30) weeks. The positive rate and protection rate of measles antibody in puerperae were 82.5% (243/319) and 43.3% (135/319), the GMC [M (QR)] was 655.74 (251.21-1 299.02) mIU/ml. The positive rate of rubella antibody in puerperae was 61.1% (195/319), the GMC [M (QR)] was 31.34 (11.65-73.61) IU/ml. The positive rate and protection rate of measles antibody in infants were 84.1% (270/321) and 46.1% (148/321), the GMC [M (QR)] was 665.07 (279.63-1 544.07) mIU/ml. The positive rate of rubella antibody in infants was 69.5% (223/321), the GMC [M (QR)] was 40.30 (16.12-98.48) IU/ml. There was statistical difference in measles (Z=-14.64, P<0.001) and rubella (Z=-8.66, P<0.001) antibody levels between mothers and infants. There was positive correlation in measles (r=0.76, P<0.001) and rubella (r=0.86, P<0.001) antibody level between mothers and infants. Conclusion: The maternal antibody of measles and rubella had a concentration effect. The level of measles and rubella antibodies in the infants was higher than that in the mothers' and increased with the increase of the level of measles and rubella antibodies in the mothers.

A three-dimensional reconstruction plate for displaced midshaft fractures of the clavicle.

This randomised study compared outcomes in patients with displaced fractures of the clavicle treated by open reduction and fixation by a reconstruction plate which was placed either superiorly or three-dimensionally. Between 2003 and 2006, 133 consecutive patients with a mean age of 44.2 years (18 to 60) with displaced midshaft fractures of the clavicle were allocated randomly to a three-dimensional (3D) (67 patients) or superior group (66). Outcome measures included the peri-operative outcome index, delayed union, revision surgery and symptoms beyond 16 weeks. CT was used to reconstruct an image of each affected clavicle and Photoshop 7.0 software employed to calculate the percentage of the clavicular cortical area in the sagittal plane. The patients were reviewed clinically and radiographically at four and 12 months after the operation. The superior plate group had a higher rate of delayed union and had more symptomatic patients than the 3D group (p < 0.05). The percentage comparisons of cortical bone area showed that cortical bone in the superior distal segment is thicker than in the inferior segment, it is also thicker in the anterior mid-section than in the posterior (p < 0.05). If fixation of midshaft fractures of the clavicle with a plate is indicated, a 3D reconstruction plate is better than one placed superiorly, because it is consistent with the stress distribution and shape of the clavicle.

Alternative definition of acute kidney injury following liver transplantation: based on serum creatinine and cystatin C levels.

OBJECTIVE: The aim of this study was to verify the estimation and the predictive abilities of serum creatinine (Cr), serum cystatin C (Cys C), and related formulas for acute kidney injury (AKI). PATIENTS AND METHODS: Thirty patients who underwent cadaveric donor liver transplantation were enrolled in this prospective study. Glomerular filtration rate (GFR) was assessed by the 99mTc DTPA clearance method and estimated by Cr-predicted clearances (Cockcroft-Gault method [CG] and abbreviated Modification of Diet in Renal Disease equation [MDRD]) as well as by 3 other Cys C-based formulas (Hoek, Filler, and Larsson). AKI was confirmed as GFR<80 mL/min/1.73 m2 in the first posttransplantation week. RESULTS: GFR was significantly correlated with reciprocal Cr, reciprocal Cys C, and the 5 formulas (P<.001 for all). The receiver operating characteristic (ROC) area of Cys C was larger than that of Cr (.937 vs .794, P<.05). ROC area of Hoek, or Filler or Larsson was also larger than that of CG or MDRD (.937, .935, .937 vs .802, .849, P<.05 for all). ROC analysis showed the cutoff values were 1.0 mg/dL for Cr and 1.57 mg/L for Cys C. Hoek, Filler, and Larsson equations all underestimated AKI; their optimal cutoff values should be adjusted to 47, 56, and 44 mL/min/1.73 m2, respectively. CONCLUSION: Cys C is a better predictor of AKI than Cr. A value of more than 1.57 mg/L might be considered a new definition of AKI.

The 170-kDa glucose-regulated stress protein is an endoplasmic reticulum protein that binds immunoglobulin.

Anoxia, glucose starvation, calcium ionophore A23187, EDTA, glucosamine, and several other conditions that adversely affect the function of the endoplasmic reticulum (ER) induce the synthesis of the glucose-regulated class of stress proteins (GRPs). The primary GRPs induced by these stresses migrate at 78 and 94 kDa (GRP78 and GRP94). In addition, another protein of approximately 150-170 kDa (GRP170) has been previously observed and is coordinately induced with GRP78 and GRP94. To characterize this novel stress protein, we have prepared an antisera against purified GRP170. Immunofluorescence, Endoglycosidase H sensitivity, and protease resistance of this protein in microsomes indicates that GRP170 is an ER lumenal glycoprotein retained in a pre-Golgi compartment. Immunoprecipitation of GRP170 with our antibody coprecipitates the GRP78 (also referred to as the B cell immunoglobulin-binding protein) and GRP94 members of this stress protein family in Chinese hamster ovary cells under stress conditions. ATP depletion, by immunoprecipitation in the presence of apyrase, does not affect the interaction between GRP78 and GRP170 but results in the coprecipitation of an unidentified 60-kDa protein. In addition, GRP170 is found to be coprecipitated with immunoglobulin (Ig) in four different B cell hybridomas expressing surface IgM, cytoplasmic Ig light chain only, cytoplasmic Ig heavy chain only, or an antigen specific secreted IgG. In addition, in IgM surface expressing WEHI-231 B cells, anti-IgM coprecipitates GRP78, GRP94, as well as GRP170; antibodies against GRP170 and GRP94 reciprocally coprecipitate GRP94/GRP170 as well as GRP78. Results suggest that this 170-kDa GRP is a retained ER lumenal glycoprotein that is constitutively present and that may play a role in immunoglobulin folding and assembly in conjunction or consecutively with GRP78 and GRP94.

Induction of glucose regulated proteins during growth of a murine tumor.

Chronic anoxia, glucose starvation, low pH, and numerous other conditions induce the glucose-regulated system of stress proteins (GRPs), whose principal members are observed at 78, 94, and 170 kDa. These stresses may be expected to occur during growth in untreated tumors. To examine the possibility that GRPs are correspondingly induced, we have examined the protein profiles of small (< 0.1 g), intermediate (0.2-0.8 g), and large (> 1.8 g) radiation-induced fibrosarcoma (RIF) tumors grown on C3H mice. One and two-dimensional gel electrophoresis indicate that the principal GRPs at 78 and 94 are coordinately and substantially increased in large tumor masses, relative to the small, and may be partially increased in the intermediate tumors. Necrotic material removed from large tumors exhibited an identical pattern of GRP induction with no visible indication of protein degradation and also contained a significant fraction of viable cells. Western blot analysis using rabbit antisera raised against the 78 and 170 kDa GRPs also demonstrated the enhanced accumulation of these proteins in the large tumors. The antibody against the 170 kDa GRP was also capable of detecting the induction of this stress protein in large tumors by indirect immunofluorescence analysis. Northern blot studies using a probe for the GRP 78 gene also showed an increase in GRP 78 message in large tumors as well as in RIF cells exposed to anoxic stress in vitro. Two-dimensional gel electrophoresis indicated that the major heat shock proteins at 70 and 90 kDa were not increased in the larger tumors, and the amount of the 90 kDa species was reduced. Finally, the quantity of vimentin and its degradation products is significantly diminished in large tumors and in anoxic cells. This study demonstrates that RIF tumor cells undergo a glucose regulated stress response in situ during tumor growth.

Induction of heat-shock proteins by glutamine. The 'feeding effect'.

Subconfluent, log-phase Chinese hamster ovary cells induced the major heat-shock proteins (hsp) when cells were refed, 40 hours after seeding. This method of inducing heat-shock proteins was also obtained by refeeding with fresh serum-free media, but not with media with a long shelf life or with media prepared without glutamine. It was observed that addition of glutamine alone to cultures at 40 hours post-seeding induced heat-shock proteins. Addition of ammonium chloride, however, had no discernible effect on heat-shock protein synthesis. Northern blot analysis indicated that this phenomenon reflected an increase in the levels of message for the constitutive/inducible member of the hsp 70 family, but not the non-constitutive member. To determine the effect of this induction on heat sensitivity, unfed and 'heat-shock-induced' refed cultures were heated at 45 degrees C. No significant difference in cell survival was observed. Therefore glutamine is the necessary ingredient required for the induction of heat-shock proteins and this method of inducing heat-shock proteins does not alter heat sensitivity.

Resistance to etoposide induced by three glucose-regulated stresses in Chinese hamster ovary cells.

The induction of glucose-regulated proteins by a variety of specific inducers leads to an increase in resistance to Adriamycin (Shen et al., Proc. Natl., Acad. Sci. USA, 84: 3278, 1987). In this study we examine several additional agents for cross-resistance induced during a glucose-regulated response in an attempt to better define the mechanism through which this phenomenon occurs. When anoxia, calcium ionophore A23187, or 2-deoxyglucose are used, a substantial resistance is obtained against the topoisomerase II-targeted agent, etoposide. Partial resistance is induced against vincristine and actinomycin D. Glucose-regulated protein inducers do not substantially alter cellular response to either bleomycin or radiation. In the case of mitomycin C there is a cellular sensitization with anoxia and 2-deoxyglucose while calcium ionophore A23187 had no effect on survival. This study suggests that the resistance obtained during a glucose-regulated response against etoposide and Adriamycin may involve topoisomerase II.

Depletion of topoisomerase II in isolated nuclei during a glucose-regulated stress response.

Conditions, such as anoxia or glucose starvation, which induce the glucose-regulated set of stress proteins also lead to resistance to adriamycin (J. Shen, C. Hughes, C. Chao, J. Cai, C. Bartels, T. Gessner, and J. Subjeck, Proc. Natl. Acad. Sci. USA 84:3278-3282, 1987) and etoposide. We report here that chronic anoxia, glucose starvation, 2-deoxyglucose, the calcium ionophore A23187, glucosamine, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), and tunicamycin (all specific inducers of the glucose regulated system) lead to a rapid and selective depletion of topoisomerase II from isolated nuclei of Chinese hamster ovary cells. This effect precedes a decline in tritiated thymidine incorporation and a redistribution of cells from S into G1/G0. The depletion of the enzyme is not accompanied by a decline in mRNA levels. We have also examined the mutant Chinese hamster K12 cell line which is temperature sensitive for expression of glucose-regulated proteins. When nuclei were isolated from K12 cells incubated at the nonpermissive temperature, a loss of topoisomerase II was again observed in congruence with the expression of stress proteins and cellular resistance to etoposide. These changes were not obtained in parental Wg1A cells incubated at the same temperature. These studies indicate that topoisomerase II is highly sensitive to glucose-regulated stresses and that its depletion from the nucleus, with the associated changes in cell cycle parameters, may represent general characteristics of the glucose-regulated state. Since anoxia and glucose starvation can occur during tumor development, this pathway for expression of drug resistance may have clinical ramifications.

Multiparameter evaluation of the expression in situ of normal and tumor-associated antigens in human colorectal carcinoma.

The immunoreactivity of a panel of monoclonal antibodies (MoAb) was studied in a series of patients with colorectal carcinomas to test the association of antigen expression with other parameters such as histopathologic stage, differentiation, and clinical outcome. Low-level binding to normal tissue and high-level binding to malignant tissue were observed with MoAb defining, respectively, a gastrointestinal cancer antigen (GICA), Leb (distal colon only), A, H type 2 antigen, X-like antigen, and the 200-kilodalton (Kd) protein of carcinoembryonic antigen (CEA). The degree of histologic differentiation correlated with the expression of Lea antigen, A, and Y haptens, whereas a progressive loss of these antigens coincided with loss of differentiation. Two undifferentiated carcinomas expressed only two, H type 2 antigen and a highly glycosylated protein of 20-50 Kd, of the 14 antigens investigated. An interesting, but not significant, association between Leb antigen expression and more extensive disease was found: Whereas 71% of Dukes C tumors were positive for Leb, only 48% of patients with Dukes A and B2 tumors showed the presence of Leb antigen. On the other hand, the presence of B72.3-defined antigen is significantly associated with an earlier stage of disease. Chi-square tests to assess the association of antigen positivity with disease recurrence indicated a significant binding association with tumor recurrence over a broad range of percent positive cells for two MoAb defining different determinants of GICA. Similar associations, but over a narrow range of positive cells, were found for H type 2 antigen and the 200-Kd protein of CEA.

The infrahyoid myocutaneous flap for reconstruction after resection of head and neck cancer.

From May 1979 to August 1984, 112 infrahyoid myocutaneous flaps (IHMCFs) were used for reconstruction of the tongue after resection of lingual carcinoma (67 flaps in 63 consecutive cases) and for repair of defects after resection of carcinomas of buccal mucosa (23 cases), floor of mouth (8 cases), parotid gland (7 cases), and other malignancies (7 cases). Ten IHMCFs were extended to Ludwig's angle for repairing the open defect of the cheek or combined defect in the buccal mucosa and hard palate. The donor sites of 76 IHMCFs could be sutured primarily. The flap was successful in 90% of the cases (101 of 112 cases). Postoperatively, 94% of the cases (60 of 64 cases) of reconstructed tongue had good deglutition and 78% of the cases (50 of 64 cases) gave satisfactory enunciation. IHMCF is a new, versatile, reliable, and convenient flap suitable for repairing the defects in and around the oral cavity, particularly in the tongue, even in aged and weak patients.

Circulating tumor markers and assessment of response to intrahepatic chemotherapy of colon carcinoma.

To assess the change in concentrations of circulating gastrointestinal cancer-associated antigens in response to therapy, we analyzed the sera of patients with hepatic metastasis from colorectal carcinoma who were treated with intrahepatic arterial chemotherapy. Serial serum samples were assessed for the tumor-associated antigens, carcinoembryonic antigen (CEA) and the gastrointestinal cancer antigen CA 19-9. Computed axial tomographic (CAT) scans were made to assess the size of the hepatic metastasis. In 9/10 of these patients the CEA predicted tumor response within 2-6 weeks after initiation of treatment, and in 7/10 the information was supported or more dramatically demonstrated by the CA 19-9. Combining data from both tumor markers may provide a more accurate assessment of the clinical response than one antigen alone. Recurrence of hepatic metastatic growth or extrahepatic tumor also was identified by elevation of one or both circulating tumor-associated antigens prior to other laboratory or clinical evidence of tumor growth.

Binding of murine immunoglobulin to human tissues after immunotherapy with anticolorectal carcinoma monoclonal antibody.

An anticolorectal carcinoma antibody, 17-IA, that is of gamma 2a isotype and has been used in previous immunotherapy trials, binds to an antigen on most human colon tumors. This antigen is destroyed by the fixative and embedding procedures employed for routine histologic evaluation of tissues. It can be demonstrated by the avidin/biotin-labelled peroxidase complex (ABC) immunoperoxidase technique on briefly fixed, frozen sections of fresh human tissues. With this assay technique, the antibody is found to bind in vitro to both human colonic carcinoma and normal gastrointestinal epithelia. Tissues removed from patients having received the 17-IA antibody intravenously in an immunotherapy trial show bound antibody 1-2 after administration. This is no longer evident 3 weeks later though the antigen is present on the cell surface and is still capable of binding antibody in vitro.

Detection of a circulating gastrointestinal cancer antigen in sera of patients with gastrointestinal malignancies by a double determinant immunoassay with monoclonal antibodies against human blood group determinants.

Monoclonal antibodies (MoAbs) produced against determinants A and B of the human ABO blood group system and against the Lea and Leb determinants of the Lewis (Le) blood group system detected these determinants on molecules released by cultured cells of human colorectal, gastric and/or pancreatic carcinoma (Ca) but not by a variety of other cells maintained in culture. Circulating Le antigen could be demonstrated in sera of patients by inhibiting the binding of MoAbs to a target preparation. A double determinant radioimmunoassay (DDIA) was then developed to detect the association of blood group determinants with a previously defined gastrointestinal cancer antigen (GICA). The DDIA with the anti-blood group and anti-GICA antibody was in some cases more sensitive in detecting GICA in sera than using the anti-GICA MoAb alone. Of 55 sera from patients with primary and early recurrent colorectal carcinoma (CRC), 10 (18%) were scored positive in the DDIA using only anti-GICA MoAb. When MoAb binding to a determinant on Leb and on H, type I, was used as first antibody in DDIA followed by anti-GICA MoAb 11 additional sera were reactive, increasing the percentage of positive sera to 38. Using the same combinations of MoAbs, the sensitivity of detection of GICA was only slightly improved from 63 to 66% in sera of patients with advanced CRC. The number of false positive sera from patients with non-malignant gastrointestinal diseases or from healthy donors remained at low levels when anti-blood group determinant antibodies were used together with anti-GICA MoAb. The results indicate that DDIAs with MoAbs against different blood group determinants and tumour associated antigens can improve the detection of circulating antigens in patients with early stage cancer.