Air Quality Response in China Linked to the 2019 Novel Coronavirus (COVID-19) Lockdown.

Efforts to stem the spread of COVID-19 in China hinged on severe restrictions to human movement starting 23 January 2020 in Wuhan and subsequently to other provinces. Here, we quantify the ancillary impacts on air pollution and human health using inverse emissions estimates based on multiple satellite observations. We find that Chinese NOx emissions were reduced by 36% from early January to mid-February, with more than 80% of reductions occurring after their respective lockdown in most provinces. The reduced precursor emissions increased surface ozone by up to 16 ppb over northern China but decreased PM2.5 by up to 23 µg m-3 nationwide. Changes in human exposure are associated with about 2,100 more ozone-related and at least 60,000 fewer PM2.5-related morbidity incidences, primarily from asthma cases, thereby augmenting efforts to reduce hospital admissions and alleviate negative impacts from potential delayed treatments.

Transverse uterine fundal incision for placenta praevia with accreta, involving the entire anterior uterine wall: a case series.

OBJECTIVE: To determine the feasibility and safety of transverse fundal incision with manual placental removal in women with placenta praevia and possible placenta accreta. DESIGN: Case series. SETTING: Four level-three Japanese obstetric centres. POPULATION: Thirty-four women with prior caesarean section and placenta praevia that widely covers the anterior uterine wall, in whom placenta accreta cannot be ruled out. METHODS: A transverse fundal incision was performed at the time of caesarean section and manual placental removal was attempted under direct observation. MAIN OUTCOME MEASURE: Operative fluid loss. RESULTS: The total volume of fluid lost during our operative procedure compares favourably with the volume lost during our routine transverse lower-segment caesarean sections performed in patients without placenta praevia or accreta. The average fluid loss was 1370 g. No patients required transfer to intensive care, and there were no cases of fetal anaemia. CONCLUSIONS: This procedure has the potential to reduce the heavy bleeding that arises from caesarean deliveries in women with placenta praevia and placenta accreta.

TSLC1 is a tumor-suppressor gene in human non-small-cell lung cancer.

The existence of tumor-suppressor genes was originally demonstrated by functional complementation through whole-cell and microcell fusion. Transfer of chromosome 11 into a human non-small-cell lung cancer (NSCLC) cell line, A549, suppresses tumorigenicity. Loss of heterozygosity (LOH) on the long arm of chromosome 11 has been reported in NSCLC and other cancers. Several independent studies indicate that multiple tumor-suppressor genes are found in this region, including the gene PPP2R1B at 11q23-24 (ref. 7). Linkage studies of NSCLC are precluded because no hereditary forms are known. We previously identified a region of 700 kb on 11q23.2 that completely suppresses tumorigenicity of A549 human NSCLC cells. Most of this tumor-suppressor activity localizes to a 100-kb segment by functional complementation. Here we report that this region contains a single confirmed gene, TSLC1, whose expression is reduced or absent in A549 and several other NSCLC, hepatocellular carcinoma (HCC) and pancreatic cancer (PaC) cell lines. TSLC1 expression or suppression is correlated with promoter methylation state in these cell lines. Restoration of TSLC1 expression to normal or higher levels suppresses tumor formation by A549 cells in nude mice. Only 2 inactivating mutations of TSLC1 were discovered in 161 tumors and tumor cell lines, both among the 20 primary tumors with LOH for 11q23.2. Promoter methylation was observed in 15 of the other 18 primary NSCLC, HCC and PaC tumors with LOH for 11q23.2. Thus, attenuation of TSLC1 expression occurred in 85% of primary tumors with LOH. Hypermethylation of the TSLC1 promoter would seem to represent the 'second hit' in NSCLC with LOH.

Balance of Emission and Dynamical Controls on Ozone During the Korea-United States Air Quality Campaign From Multiconstituent Satellite Data Assimilation.

Global multiconstituent concentration and emission fields obtained from the assimilation of the satellite retrievals of ozone, CO, NO2, HNO3, and SO2 from the Ozone Monitoring Instrument (OMI), Global Ozone Monitoring Experiment 2, Measurements of Pollution in the Troposphere, Microwave Limb Sounder, and Atmospheric Infrared Sounder (AIRS)/OMI are used to understand the processes controlling air pollution during the Korea-United States Air Quality (KORUS-AQ) campaign. Estimated emissions in South Korea were 0.42 Tg N for NO x and 1.1 Tg CO for CO, which were 40% and 83% higher, respectively, than the a priori bottom-up inventories, and increased mean ozone concentration by up to 7.5 ± 1.6 ppbv. The observed boundary layer ozone exceeded 90 ppbv over Seoul under stagnant phases, whereas it was approximately 60 ppbv during dynamical conditions given equivalent emissions. Chemical reanalysis showed that mean ozone concentration was persistently higher over Seoul (75.10 ± 7.6 ppbv) than the broader KORUS-AQ domain (70.5 ± 9.2 ppbv) at 700 hPa. Large bias reductions (>75%) in the free tropospheric OH show that multiple-species assimilation is critical for balanced tropospheric chemistry analysis and emissions. The assimilation performance was dependent on the particular phase. While the evaluation of data assimilation fields shows an improved agreement with aircraft measurements in ozone (to less than 5 ppbv biases), CO, NO2, SO2, PAN, and OH profiles, lower tropospheric ozone analysis error was largest at stagnant conditions, whereas the model errors were mostly removed by data assimilation under dynamic weather conditions. Assimilation of new AIRS/OMI ozone profiles allowed for additional error reductions, especially under dynamic weather conditions. Our results show the important balance of dynamics and emissions both on pollution and the chemical assimilation system performance.

Detection of aberrations of the p53 alleles and the gene transcript in human tumor cell lines by single-strand conformation polymorphism analysis.

Aberrations of the p53 gene and its transcript in ten human tumor-derived cell lines were investigated by single-strand conformation polymorphism analysis of polymerase chain reaction products. This method can detect loss of one of the two alleles and a point mutation in the remaining allele simultaneously. Aberrations were newly found in four tumor cell lines. Three cell lines had lost one of the alleles and had a point mutation in the other. These point mutations, resulting in amino acid substitutions, were in the region of the p53 gene, which is highly conserved in different species. All the mutated genes were expressed and produced mRNAs with point mutations. One cell line did not contain any detectable transcript of the p53 gene, although no structural aberration of the gene was detected in the regions analyzed. Most of the cell lines found to carry aberrations of the p53 gene in this work have previously been reported to have mutations in oncogenes or in a tumor suppressor gene other than the p53 gene. These results provide additional examples of multiple genetic changes in the genesis of human tumors.

Aberrations of the tumor suppressor p53 and retinoblastoma genes in human hepatocellular carcinomas.

Aberrations of the p53 gene in 43 primary hepatocellular carcinomas (HCCs) were examined by single-strand conformation polymorphism analysis of polymerase chain reaction products. Of these hepatocellular carcinomas, 22 were advanced HCCs, and 21 were early HCCs. Structural abnormalities of the p53 gene were observed in eight of the 22 advanced HCCs, but in none of the early HCCs. Of the eight tumors with an abnormal p53 gene, seven had lost one of the two p53 alleles and, in the seven tumors with identifiable mutations, point mutations were found in four tumors and deletions of several nucleotides were observed in two tumors. The remaining one retained both alleles and carried two point mutations. In addition to the aberrations of the p53 gene, loss of the retinoblastoma gene or loss of heterozygosity at chromosome 13q was observed in six of seven informative cases of eight tumors carrying a mutated p53 gene. These results suggest the involvement of at least two tumor suppressor genes in a late stage of hepatocarcinogenesis.

Amplification of protooncogenes in surgical specimens of human lung carcinomas.

The possible existence of amplification or rearrangement of protooncogenes was examined in more than 100 surgical specimens of human lung carcinoma. Protooncogenes were amplified in 28% of the carcinomas. About 90% of the amplified genes were of the myc, ras, or erbB family. Of the myc family genes, myc was amplified in 14 of 137 tumors and L-myc in four of 108 tumors, but N-myc was not amplified. A high frequency of amplification of myc was observed in squamous cell carcinomas (seven of 37) and of L-myc in small cell carcinomas (two of six). Of the ras family genes, K-ras-2 was amplified in six of the 137 tumors and N-ras in two of the 137 tumors, but no amplification of H-ras-1 was detected. Seven of the eight cases of amplified ras genes were in advanced pathological stages. Of the erbB family genes, erbB-1 (epidermal growth factor receptor) was amplified in 10 of 114 tumors and erbB-2 (HER-2/neu) in one of 51 tumors. Amplifications of the myc, ras, and erbB family genes might be one of the crucial DNA abnormalities involved in the development of human lung carcinomas.

Joining of the c-myc gene and a line 1 family member on chromosome 8 in a human primary giant cell carcinoma of the lung.

A rearranged c-myc gene found in a human primary giant cell carcinoma of the lung was analyzed. The rearrangement was found in the region about 6 kilobase pairs upstream of the c-myc gene. The breakpoint was joined to a sequence carrying a Line 1 (L1) family member located on chromosome 8. This in vivo rearrangement of the c-myc gene specific to tumor cells may represent one mechanism of activation of a protooncogene during tumorigenesis or tumor progression in human cancer.

Aberrations of the p53 tumor suppressor gene in human non-small cell carcinomas of the lung.

Aberrations of the p53 gene in 115 surgical specimens of non-small cell carcinomas of the lung were examined by single-strand conformation polymorphism analysis of polymerase chain reaction products. Structural abnormalities of the p53 gene were observed in 60 tumors (52%), i.e., 8 of 14 large cell carcinomas, 24 of 58 adenocarcinomas, 25 of 37 squamous cell carcinomas, and 3 of 6 adenosquamous carcinomas. Direct sequencing of abnormal DNA fragments revealed 45 single-base substitutions, 9 deletions or insertion of a short nucleotide sequence, and 3 two-base substitutions in 57 tumors. In the other 3 tumors, loss of one of the p53 alleles was observed, with no mutation in the other allele. Allelic loss of the p53 gene was observed in 14 of 43 informative cases (33%), and in 11 of the 14 cases the remaining allele was mutated. The aberrations of the p53 gene were not limited to a particular histological type or clinical stage. Their high frequency suggests that they were involved in the genesis of non-small cell carcinomas of the lung. The mutation frequency (46%) of the p53 gene in tumors carrying mutated ras genes was essentially the same as the overall frequency in lung cancers, suggesting that accumulation of mutations in these two genes in a tumor is a random phenomenon.

Association of CYP1A1 germ line polymorphisms with mutations of the p53 gene in lung cancer.

We reported an association of smoking-induced lung cancer susceptibility with the human cytochrome P450 1A1 (CYP1A1) polymorphisms in our previous studies. To investigate a relationship between genetically determined individual predispositions and mutations of target genes in the early stage of lung carcinogenesis, we examined p53 mutations in relation to germ line polymorphisms of the CYP1A1 and GSTM1 genes, using surgical specimens of 148 non-small cell lung cancer patients who were smokers. The frequency of p53 mutations among heavy smokers was higher than in patients who had never smoked [P < 0.01; odds ratio (OR), 3.74; 95% confidence interval (CI), 1.46-9.56]. By single-strand conformational polymorphism, aberrant migration bands of p53 gene fragments were detected in 56 cases (38%). Smokers with susceptible rare homozygous alleles of either the MspI or Ile-Val polymorphism of the CYP1A1 gene have a 4.5-fold (P < 0.005; OR, 4.48; 95% CI, 1.64-12.26) or 5.5-fold (P < 0.01; OR, 5.52; 95% CI, 1.55-19.64) higher risk of having a mutation of the p53 gene than those with nonsusceptible predominant homozygous alleles of the gene. Non-small cell lung cancer patients with a susceptible CYP1A1 genotype were at remarkably high risk of having a mutation of the p53 gene when the genotype was combined with a deficient genotype, GSTM1(-). However, there was no difference between the types of p53 mutation and genotypes of the drug-metabolizing enzymes. These results showed that CYP1A1 germ line polymorphisms, which were associated with the genetic predisposition for lung cancer, were related to cigarette smoking-associated p53 mutations.

myc family gene abnormality in lung cancers and its relation to xenotransplantability.

In order to study the relationship between tumor transplantability to the nude mouse and abnormality of the myc family genes (c-myc, N-myc, L-myc) in human primary lung cancers, 32 various lung cancers were analyzed for abnormality of the myc family genes by Southern blot hybridization, and were transplanted s.c. into nude mice. Southern blot analysis showed that four non-small cell carcinomas and three small cell carcinomas had amplified c-myc and L-myc genes, respectively. Allelic deletion of the L-myc gene was observed in seven cancers, of which two also had an additional band of the c-myc gene or amplification of the L-myc gene. No abnormality of the N-myc gene was observed in this series. Of 13 cancers with abnormality of the myc family genes, 11, including all tumors with myc gene amplification, were transplantable to nude mice. Of 19 tumors without any abnormalities of the myc family genes, however, only five were transplantable to nude mice (P less than 0.005). These results indicate that abnormality of the myc family genes, especially gene amplification, might promote tumorigenic ability in xenotransplantation of lung cancers and this phenomenon might be closely related to the function of the myc gene.

Loss of the same alleles of HRAS1 and D11S151 in two independent pancreatic cancers from a patient with multiple endocrine neoplasia type 1.

The DNAs from two independent pancreatic cancers (tumors 1 and 2) in a patient with multiple endocrine neoplasia type 1 were analyzed. No amplification or gross rearrangement of 19 protooncogenes was observed. However, Southern blot analysis using polymorphic DNA probes revealed loss of heterozygosity at loci on chromosome 11p in both tumors. In tumor 1, an extensive region including the HRAS1, PTH, CALCA, and D11S151 loci was deleted, while in tumor 2 loss of heterozygosity was limited at the HRAS1 and D11S151 loci. Because loss of heterozygosity at other chromosomal loci in the two tumors was quite rare, loss of genes on 11p might be nonrandom. It is noteworthy that the same allele at the HRAS1 locus and also the same allele at the D11S151 locus were lost in the two independent tumors. These results suggest that loss of genes at the HRAS1 and/or D11S151 loci plays an important role unmasking the remaining sequences probably having a recessive mutation.

Loss of heterozygosity at 11p15 in malignant glioma.

Deletions of loci on chromosome 11p have been found frequently in several malignant tumors including gliomas, suggesting the presence of tumor suppressor genes. We analyzed 38 gliomas [26 malignant gliomas (grades III and IV) and 12 less malignant gliomas (grade I and II)] for loss of heterozygosity using microsatellite sequences on 11p as polymorphic markers. Loss of heterozygosity was found in 8 of 26 malignant gliomas (31%) but not in the less malignant gliomas. In the region with loss of heterozygosity, loci on 11p15.5-pter were commonly deleted. Our results suggest that a putative tumor suppressor gene involved in malignant progression of gliomas is located in an approximately 21-cM region on 11p15.5-pter.

Deletions of chromosome 13q, mutations in Retinoblastoma 1, and retinoblastoma protein state in human hepatocellular carcinoma.

Twenty-one tumors from 18 patients (two independent tumors were obtained from each of three patients) with hepatocellular carcinomas were examined for loss of heterozygosity (LOH) at loci on chromosome 13q, using 15 polymorphic nucleotide sequences of microsatellites as genetic markers. The results revealed LOH in a common region between the centromeric D13S127 locus (13q12.2-q14.1) and the telomeric D13S137 (13q14.3) locus, including the RB1 locus, in nine of 21 tumors. Immunohistochemical staining of paraffin-embedded tumor sections indicated loss of retinoblastoma (RB) protein expression in all tumors showing LOH except one. Absence of RB protein expression was also observed in three of 12 tumors without LOH. Single-strand conformation polymorphism analysis of polymerase chain reaction products using primers flanking all 27 exons of the RB1 gene, as well as nucleotide sequencing, revealed tumor-specific small deletions of the RB1 coding region in the remaining RB1 allele of two tumors having LOH at the RB1 locus with concomitant loss of RB protein expression. Our results indicate that the loss of a region of chromosome 13q including the RB1 locus significantly (P < 0.006) correlates with loss of RB protein in hepatocellular carcinomas. However, tumor-specific mutations of the RB1 gene were detected in only two of 13 tumors with LOH and/or lack of RB protein expression, indicating that analysis of the RB1 status at the protein level in these tumors may be more sensitive than the actual mutational analysis.

p53 gene mutations in gastric cancer metastases and in gastric cancer cell lines derived from metastases.

Structural alterations of the p53 gene were investigated in tissue specimens of gastric and cervical cancers and in cell lines of gastric, esophageal, and cervical cancers, by polymerase chain reaction-single-strand conformation polymorphism analysis. Two of the four gastric cancer metastases and four of the eight cell lines originally established from gastric cancer metastases were found to have p53 gene alterations in the exon 5 to 11 region; point mutations and amino acid replacements were detected in a liver and an ovary metastasis at exon 7, in the TMK1 and MKN1 cell lines at exon 5, and in the OKAJIMA cell line at exon 10. The normal allele was not found in these cell lines. In the KATO-III cell line, gross deletion and rearrangement of the p53 gene were noted. However, no p53 mutations were identified in 19 primary lesions of gastric cancer, suggesting that the p53 gene abnormality preferentially occurs in the advanced stages of gastric cancer. In contrast to the gastric cancer, none of the 13 esophageal cancer cell lines, including two cell lines established from metastases, and none of the four cervical cancer cell lines showed any aberration in exons 5 to 11 of the p53 gene. During the course of the study, a novel polymorphism in intron 7 of the p53 gene was found, which can be recognized by restriction enzyme digestions of the polymerase chain reaction product.

Mutations in an Alu repeated sequence associated with the DXS43 locus in human small cell lung cancers.

Point mutations in an Alu repeated sequence associated with the DXS43 locus were identified in two out of 10 human small cell lung cancers. Since these aberrations were identified in DNA from both metastatic lesions and primary lesions from the same patient, they would appear to have occurred at a relatively early stage. Although this sequence is not apparently associated with known genes, these tumor-specific mutations occurred at an early stage may play an important role in tumorigenesis.

Homozygous deletion of the MTS1/p16 and MTS2/p15 genes and amplification of the CDK4 gene in glioma.

Loci on chromosome 9p are frequently deleted in several malignant tumors, suggesting the presence of putative tumor suppressor genes. The MTS1/p16 and MTS2/p15 genes on 9p are considered to be candidates. Binding of p15 and p16 cell cycle-regulatory proteins to the cyclin dependent protein kinase CDK4 inhibits CDK4/cyclin D dependent phosphorylation of retinoblastoma protein. We analysed the DNAs from 37 gliomas of several grades of malignancy for allelic loss of chromosome 9p and aberrations of the MTS1/p16 and MTS2/p15 genes. We detected losses of one allele and homozygous deletions at loci, including those of the MTS1/p16 and MTS2/p15 genes, in 10 and 3 tumors, respectively. However, we did not detect any tumor-specific mutation in the two genes. The CDK4 gene was amplified in two malignant gliomas without homozygous deletion of the MTS1/p16 and MTS2/p15 genes and one malignant glioma with an allelic loss of the genes. These data suggest that aberrations of the genes coding for components of the cell cycle-regulatory system occurred in at least 15 of 37 gliomas.

Detection of ras gene mutations in human lung cancers by single-strand conformation polymorphism analysis of polymerase chain reaction products.

A simple, sensitive method of DNA analysis of nucleotide substitutions, namely, single-strand conformation polymorphism analysis of polymerase chain reaction products (PCR-SSCP analysis), was used for detection of mutated ras genes in surgical specimens of human lung cancer. Of a total of 129 tumors analysed, 22 contained a mutated ras gene. Of the 66 adenocarcinomas analysed, 14 contained an activated c-Ki-ras2 gene (the mutations in codon 12 in 6, in codon 13 in 4, in codon 18 in one, and in codon 61 in 3), one contained a c-Ha-ras1 gene with a mutation in codon 61 and 3 contained N-ras genes with mutations (in codon 12 in one and in codon 61 in 2). Mutated rats genes were also found in 2 of 36 squamous cell carcinomas (c-Ha-ras1 genes with mutations in codon 61) and 2 of 14 large cell carcinomas (c-Ki-ras2 genes with mutations in codon 12). No mutation of the ras gene was detected in 8 small cell carcinomas and 5 adenosquamous cell carcinomas. These results indicate that activation of the ras gene was not frequent (17%) in human lung cancers, that among these lung cancers mutation of the ras gene was most frequent in adenocarcinomas (27%) and 73% of the point mutations were in the c-Ki-ras2 gene in codon 12, 13, 18 or 61.

A new RFLP in intron 1 of the human c-Ha-ras1 gene and its close relationship with the variable tandem repeats in the region 3' to the gene.

Based on restriction fragment length polymorphism (RFLP) analysis of BamHI or MspI fragments, the human c-Ha-ras1 alleles could be divided into two major groups, one having about 80 copies of a 28 base pair (bp) sequence in the variable tandem repeat (VTR) region 1.4-kilobase pairs (kb) downstream from the end of the coding exon and the other having 40 copies of the sequence. We found a second RFLP in intron 1 of the c-Ha-ras1 gene at a position about 80 bp upstream from the 5'-end of exon 1. The size of the PstI fragments carrying this region is either 371 or 359 bp depending on the numbers of a hexanucleotide sequence, GGGCCT. In larger fragments, the unit sequence was repeated four times, while in smaller fragments it was repeated twice. Unexpectedly, we found that the alleles with 80 copies of the 28 bp sequence in the VTR region all carried two repeats of GGGCCT in intron 1, while alleles with 40 copies all had four repeats of the GGGCCT sequence.