[Development of case report form based on clinical data interchange standards consortium on special diseases to promote the ecology construction of real-world data in China].

Real world data (RWD) refers to the data generated in routine clinical practices, daily life, and real work environment and has been widely used in clinical or public health research. Still, issues related to the quality of RWD, such as incompleteness, inconsistency, and inaccuracy, would affect the validity of real-world research. To overcome the challenges due to the lack of standardization of real world source data, case report form based on clinical data interchange standards consortium (CDISC-CRF) on certain diseases was developed to promote the ecology construction of RWD based on the data standards set by the CDISC which has been widely used. Firstly, we described how to apply data standards to make up the gap between RWD and real world evidence. Then, the process was designed to build RWD ecology based on CDISC-CRF, in which the development technology of CDISC-CRF form is mainly introduced. Finally, the application prospect and significance of building real-world data based on disease-specific CDISC-CRF are described. It is believed that the present paper can provide a new idea for promoting the ecology construction of RWD in China.

A mutation in the human apolipoprotein A-I gene. Dominant effect on the level and characteristics of plasma high density lipoproteins.

Epidemiologic and genetic data suggest an inverse relationship between plasma high density lipoprotein (HDL) cholesterol and the incidence of premature coronary artery disease. Some of the defects leading to low levels of HDL may be a consequence of mutations in the genes coding for HDL apolipoproteins A-I and A-II or for enzymes that modify these particles. A proband with plasma apoA-I and HDL cholesterol that are below 15% of normal levels and with marked bilateral arcus senilis was shown to be heterozygous for a 45-base pair deletion in exon four of the apoA-I gene. This most likely represents a de novo mutation since neither parent carries the mutant allele. The protein product of this allele is predicted to be missing 15 (Glu146-Arg160) of the 22 amino acids comprising the third amphipathic helical domain. The HDL of the proband and his family were studied. Using anti-A-I and anti-A-II immunosorbents we found three populations of HDL particles in the proband. One contained both apoA-I and A-II, Lp(A-I w A-II); one contained apoA-I but no A-II, Lp(A-I w/o A-II); and the third (an unusual one) contained apoA-II but no A-I. Only Lp(A-I w A-II) and (A-I w/o A-II) were present in the plasma of the proband's parents and brother. Analysis of the HDL particles of the proband by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed two protein bands with a molecular mass differing by 6% in the vicinity of 28 kDa whereas the HDL particles of the family members exhibited only a single apoA-I band. The largely dominant effect of this mutant allele (designated apoA-ISeattle) on HDL levels suggests that HDL particles containing any number of mutant apoA-I polypeptides are catabolized rapidly.

A splice-junction mutation responsible for familial apolipoprotein A-II deficiency.

The first case of familial apolipoprotein A-II (apo A-II) deficiency was recently reported from Hiroshima, Japan, and designated apo A-IIHiroshima. The proband had no immunologically detectable apo A-II in her plasma. DNA sequence analysis showed that the proband was homozygous for a G----A transition at position 1 of intron 3 of the apo A-II gene. A sister of the proband, who had an intermediate level of plasma apo AII, was shown to be heterozygous for this base substitution. This splice-junction alteration is most likely responsible for apo A-II deficiency, since it would be expected to completely block splicing of intron 3 from the primary transcript and therefore prevent formation of functional mRNA. This deficiency seems to have little influence either on lipid and lipoprotein profiles or on the occurrence of coronary artery disease.

Structure of the human lipoprotein lipase gene.

Human genomic clones that span the entire lipoprotein lipase (LPL) gene have been isolated and used to determine its structure. The gene is approximately 30 kilobase (kb) pairs in length in which the mRNA specifying sequence is divided into 10 exons. Exons 1-9 are of average size (105-276 bp) whereas exon 10, which specifies the entire 3' uncoding sequence, is 1948 bp in length. Exon 1 codes for the signal peptide, exon 2 includes the protein domain that was shown to bind to the lipoprotein substrate, and exons 6 and 9 code for sequences that are relatively rich in basic amino acids and therefore likely to be involved in anchoring of the enzyme to the capillary endothelium by interaction with the acidic domain of heparan sulfate. Four closely spaced mRNA 5' termini were observed, indicating multiple transcription initiation sites, one of which seems to be favored. Two potential enhancer sequence motifs in the 5' upstream region were observed. One may specify expression in response to intracellular Ca2+ mobilization, and the other may be responsible for expression in adipocytes.

Primary brainstem injury without persistent coma and decerebrate rigidity. Report of 2 cases.

Two patients with blunt head injury were examined by CT scanning. It was found that there was brainstem hemorrhage with unremarkable changes in the other parts of the brain. Physical examination showed signs of upper brainstem lesion such as discoordination, bilateral Babinski signs, and internuclear ophthalmic palsy without persistent coma and decerebrate rigidity. The diagnosis of primary brainstem injury, well healed, was established. Basing on the results of these 2 cases, we believe that primary brainstem injury does exist, but it is not necessarily associated with persistent coma and decerebrate rigidity. CT scanning for diagnosing such cases is emphasized.

[Preparation and preliminary identification of the monoclonal antibody against esophageal carcinoma].

A series of monoclonal antibody against esophageal carcinoma was prepared by ECa109 cells immunizing Balb/c mice. Hybrids secreting antibodies reacting to ECa109 were isolated and further cloned. One monoclonal antibody, 4C3, reacted only to an esophageal cancer cell line, gastric cancer and hepatocellular carcinoma cell lines. Purified 4C3 was used in ELISA test to detect tumor cells in the esophageal epithelial cells obtained by friction balloon. The result showed that the concordance rate to the result of balloon cytosmear was 62.4% (73/117). Patients, diagnosed cytologically as dyskaryosis, were often positive in ELISA test. It is proposed that 4C3 be useful in detecting pre-cancerous lesions.

The relationship between suppressor cells and malignancy.

Peripheral blood lymphocytes (PBL) from cancer patients were first tested for the proliferative response to concanavalin A (Con A). The lymphocytes which had lower response to Con A than the normal control were supposed to have relatively greater numbers of putative suppressor cells, or higher suppressive activity was anticipated in the PBL. The PBL were then treated with mitomycin C, added to normal lymphocytes in the presence of Con A, and cocultured for further investigation of the activity of the putative suppressor cells as determined by the effect of these putative cells on the responses of normal lymphocytes to Con A. In many of our studies inconsistent results showed between two types of assay systems. Not all patient's lymphocytes showing depression in response to Con A could suppress the proliferation of normal lymphocytes in response to Con A in coculture systems. However, some of the patients' lymphocytes, despite not showing a depressed response to Con A in the direct assay, were able to inhibit the response of normal lymphocytes to Con A in coculture. The contradictory data imply that it is inappropriate to conclude that suppressor cells are present at elevated levels in cancer patients by relying solely on the evidence of a depressed response to mitogens, either in a direct stimulation assay or in a coculture system. Our results possibly reflect that the development of cancer is not directly linked to the elevation of suppressor cell activity. Other more complicated mechanisms may be involved.