HNPCC associated with germline mutation in the TGF-beta type II receptor gene.
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Adaptor Proteins, Signal Transducing↗
Biomedical subjects
S L Lu
Publications and source records attributed to S L Lu.
The development of nao li shen and its clinical application.
The traditional Chinese medicine Nao Li Shen (containing ginseng, gastrodia tuber, chuanxiong rhizome and red sage root) is used in craniocerebral injury, cervical spondylosis and cerebrovascular diseases. The preparation, as an orally administered liquid, was tested in Mongolian gerbils and shown to increase tolerance to ischaemia and anoxia. Clinical use of the preparation resulted in improvement in 96% of 202 patients, as judged by right cerebral blood flow, TCD and CT examination. We conclude that Nao Li Shen has a positive curative effect upon craniocerebral injury and sequelae of cerebrovascular diseases.
Adult↗
Genomic structure of the transforming growth factor beta type II receptor gene and its mutations in hereditary nonpolyposis colorectal cancers.
To characterize the tumorigenetic role of the transforming growth factor beta type II receptor (RII) gene, we defined its genomic structure, which consists of seven exons. The sequences of exon-intron junctions were determined to facilitate mutation analysis of each exon. Twenty-five carcinomas and five adenomas from hereditary nonpolyposis colorectal cancer patients were analyzed for mutations in the entire coding region. Four missense mutations (two in adenomas and two in carcinomas) were found in the 10 cases carrying the polyadenine deletions in one allele. These results indicate that RII shares the two-hit inactivation mechanism with tumor suppressor genes and that mutations of it may occur in the early stage of tumorigenesis.
Adult↗
Loss or somatic mutations of hMSH2 occur in hereditary nonpolyposis colorectal cancers with hMSH2 germline mutations.
Hereditary nonpolyposis colorectal cancer (HNPCC) is a major cancer susceptibility syndrome known to be caused by the inheritance of mutations in DNA mismatch repair genes, such as hMSH2, hMLH1, hPMS1 and hPMS2. To investigate the role of genetic alterations of hMSH2 in HNPCC tumorigenesis, we analyzed 36 Japanese HNPCC kindreds as to hMSH2 germline mutations. Moreover, we also examined somatic mutations of hMSH2 or loss of heterozygosity at or near the hMSH2 locus in the tumors from the hMSH2-related kindreds. Germline mutations were detected in five HNPCC kindreds (5/36, 14%). Among them, three were nonsense mutations, one was a frameshift mutation and the other was a mutation in an intron where the mutation affected splicing. Loss of heterozygosity in four and somatic mutations in one were detected among the eight tumors with hMSH2 germline mutations. All these alterations were only detected in genomic instability(+) tumors, i.e., not in genomic instability(-) ones, indicating that mutations of hMSH2 were responsible for at least some of the tumors with genomic instability. These data establish a basis for the presymptomatic diagnosis of HNPCC patients, and constitute further evidence that both DNA mismatch repair genes and tumor suppressor genes may share the same requirement, i.e., two hits are necessary to inactivate the gene function.
Alleles↗
Mutations of the transforming growth factor-beta type II receptor gene and genomic instability in hereditary nonpolyposis colorectal cancer.
To determine the relation between the mutation of the TGF-beta type II receptor gene and genomic instability in the tumorigenesis of hereditary nonpolyposis colorectal cancer (HNPCC), we screened genomic DNA of 38 tumors from 25 HNPCC patients, 15 colorectal cancers from familial adenomatous polyposis patients, and 8 sporadic endometrial cancers, in two areas containing a (A)10 repeat or a (GT)3 repeat of the gene. Seventeen of the 24 (71%) genomic instability-positive HNPCC tumors carried one or two A deletions in the (A)10 repeat, while none of the 14 genomic instability-negative tumors did. These deletions inactivate the receptor through a frameshift mutation and the resultant protein truncation. No mutation was detected in the (GT)3 repeat sequence, but we found a missense mutation of codon 537 in the same area in one tumor. One A deletion was also detected in a genomic instability-positive sporadic endometrial cancer, but none in familial adenomatous polyposis tumors. No mutations were detected in the corresponding normal cells of these cases, indicating a somatic mutation. These data suggest that the TGF-beta type II receptor gene is a major target of genomic instability in HNPCC tumorigenesis.
Base Sequence↗
[Effect of arginine supplementation on T-lymphocyte function in burn patients].
It is well accepted that nutritional support improves the immunologic functions in burn patients. Arginine has been demonstrated to have tissue--specific properties which influence certain components of the immune system. A series of experiments were carried out in this study, in order to evaluate the immune effect of arginine on T lymphocyte functions in burn patients. Two groups of burn patients with comparable clinical protocol receiving same nutritional administration except the amount of arginine in the nutrients were studied. In one group, 2% of energy supplied by arginine was added in their nutrients, while, the control group received 2% of energy from amino acid compounds instead. The T lymphocyte immune parameters were determined on days 3, 7, 14, 21 and 28 postburn. The data showed that the 2% of total energy supplied by arginine was found to significantly enhance the T lymphocyte response to PHA, CD4 phenotype expression, CD4/CD8 ratio, IL-2 production and IL-2 receptor expression, as compared with the control group. It suggests arginine should become one of the most important nutrients supplied to burn patients.
Adolescent↗
[The depressive disorder in burn patients].
The CES-D, HAMD and ABSH scales were used to assess the incidence of depressive disorder in 30 burn patients during hospitalization and in 26 patients after they re-entered the society. The results indicated that the occurrence of depressive symptoms (70%) and depression (40%) in hospitalized burn patients increased significantly as compared to the control group and a group of surgical patients. Furthermore, 30 burn patients were divided into three groups according to the extent and the site of their burns, and it was found that the incidence of depressive symptoms and the degree of depressive reaction both in group I (TBSA = 55.44 +/- 22.09%) and group III (TBSA = 6.03 +/- 6.03%, with electrical injury, facial burn, hot roller injury) were significantly higher than those in group II (TBSA = 5.49 +/- 4.19%), but there was no statistical difference between group I and group III. The incidence of depressive symptoms assessed by the CES-D scale in burn patients after they re-entered the society increased obviously as compared with normal control (46.15% vs. 10%). Furthermore, there was a negative correlation between CES-D scores andse. ABSH scorThe CES-D score was also found to be negatively correlated to the scores in four aspects (physical, mental, social and general) in ABSH scale. We conclude that burn injuries can complicate the depressive disorder. Cosmetic deformity and loss of function may be the main causes of the increase in the incidence of depressive disorder during hospitalization, while the occurrence of depressive disorder when they re-entered the society may be related to physical disabilities, mental status and social adaptability.
Adult↗
[Changes in plasma immunologic reactive beta-endorphin and their effect on lymphocyte response to phytohemagglutinin after thermal injury].
The study of immunosuppression after thermal injury has aroused great interest. The present study is an investigation of changes of plasma ir-beta EP in patients and their effect on lymphocyte responses to PHA following thermal injury, in order to establish a relationship between the immune and neuroendocrine system. Plasma ir-beta EP in eighteen burn patients was determined using the radioimmunoassay. At the same time, autoplasma and the autoplasma treated with anti-beta EP serum had been both tested for their effect on lymphocyte responses to PHA. The levels of plasma ir-beta EP were found to be elevated significantly in every phases during the first three days postburn (P < 0.0005-P < 0.001), and then declined to the normal level on the fourth or fifth day postburn. The lymphocytes cultured with autoplasma showed their inhibited responses to PHA during the first three days postburn and returned to normal on the fourth or fifth day postburn, while the autoplasma treated with anti-beta EP serum had an effect to improve the lymphocyte responses to PHA. The findings suggest that burn stress is a strong stimulation which may elevate plasma ir-beta EP and which in turn decrease the lymphocyte response to PHA. We assume that increased plasma ir-beta EP may be one of the main causes of immunosuppression after thermal injury.
Adolescent↗
Clinical application of a patient-controlled apparatus for ventricular administration of morphine in intractable pain: report of 28 cases.
The authors developed a patient-controlled apparatus (L-224) for ventricular administration of pain-relieving medication and utilized it in the treatment of 28 patients with intractable pain. The initial dose of morphine hydrochloride was 1 mg, which afforded pain relief for an average of 170 hours. At an average dose of 1.8 mg, the average time of pain relief obtained was 137 hours. Therefore, they conclude that L-224 is a satisfactory apparatus for the ventricular administration of pain medication; it is patient controlled, safe, and reliable in clinical application.
Adult↗
Immunocytochemical and electron microscopic study of hepatitis B virus antigen and complete particle production in hepatitis B virus DNA transfected HepG2 cells.
The relationship between the presence of hepatitis B virus antigens, their localization and hepatitis B virus replication was studied in different clones of cultured HepG2 hepatoblastoma cells transfected with cloned hepatitis B virus DNA. Intracellular hepatitis B virus antigens were detected by immunofluorescence. The production of these antigens was evaluated in the culture media by enzyme-linked immunoassay. Hepatitis B virus DNA was detected using dot-blot hybridization. Three types of HBcAg staining were observed in transfected HepG2 cells: (a) cells with nuclear HBcAg, (b) cells with cytoplasmic HBcAg and (c) cells with both nuclear and cytoplasmic HBcAg. Cell types b and c also expressed hepatitis B virus DNA in their culture media. Our results suggest that cytoplasmic HBcAg may be more involved than nuclear HBcAg in hepatitis B virus replication. The site of hepatitis B virus formation in hepatocytes was studied by electron microscopic examination of a specific hepatitis B virus producer clone, thereby allowing detection of intracellular Dane particles more easily than liver biopsy samples from infected patients. Dane particles and HBsAg filaments were found in large, dilated structures probably related to the endoplasmic reticulum. Budding of core particles into cisternae of endoplasmic reticulum-related structures appears to be a possible mechanism for hepatitis B virus formation; our results suggest that the exocytosis of cisternae to extracellular spaces may be a mechanism for release of hepatitis B virus particles.
Blotting, Southern↗
Retinal adaptation effects on the patterned VEP and ERG.
The patterned visually evoked potential (pVEP) and patterned electroretinogram (pERG) after light and dark adaptation were investigated in 10 visually normal human observers. The influence of retinal preadaptation on the pVEP appeared to be dependent on the stimulus field size. With a 6 degree field size retinal adaptation effects were not apparent, but with a 12 degree field size the amplitudes of the dark-adapted steady-state pVEP (ssVEP) and transient pVEP (tVEP) were significantly larger than the light-adapted amplitudes. Similarly pERG's elicited by a 12 degree field size produced larger amplitude dark-adapted results. The implications of these findings are discussed. Monitoring the temporal changes in the pVEP subsequent to different retinal preadaptation levels proved to be inconclusive for the conditions studied.
Adaptation, Ocular↗
Selection of a Brucella vaccine strain of low residual virulence by chemical mutagenesis.
Following incubation of the oral vaccine Brucella suis strain 2 with diethyl sulphate (DES), a mutant designated strain S105 was selected by screening surviving bacteria for reduced virulence for mice. Strain 105 also showed low residual virulence for guinea-pigs and, unlike the parent strain, did not initiate abortion in pregnant sheep and goats after parenteral administration. Nevertheless, it was as effective as the parent strain in stimulating protective immunity to Brucella melitensis when given as an oral vaccine to sheep under both experimental and field conditions.
Animals↗
Computerizing the medical staff office.
To assist its medical staff in making appointments and reappointments to the medical staff, delineating clinical privileges, and maintaining quality assurance information, as well as to streamline clerical duties in the medical staff office, El Camino Hospital (a 460-bed acute care facility in Mountain View, California) developed a comprehensive, computerized medical staff quality assurance database (MESQUAD). This article describes MESQUAD as a program developed by one hospital to meet its unique needs.
California↗
A study of delayed hypersensitivity and desensitization in guinea pigs after Brucella infection.
We made use of the guinea pig model to demonstrate delayed hypersensitive manifestations in the knee as well as the liver rather than the skin. Experiments revealed that several factors took part in this immune response, i.e. nature of sensitizing agents, route and dosage of allergen procured and functional involvement of local tissue or organ. For instance, the knee swelling was triggered by intraarticular introduction of allergen while the distended liver gave rise to a pathogenic fatal outcome after large dose intravenously. Animal models were also established to abolish partially all these forms of immune reactions in a duration of limited time as a result of desensitization by brucellysin. These immune manifestations and their possible correlation to the pathogenesis of brucellosis were discussed.
Allergens↗
Insulin secretion and metabolic changes in maturity onset diabetes mellitus and glucose intolerance.
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Adult↗