Biomedical subjects
Publications and source records attributed to J Y Lin.
Noma neonatorum is a gangrenous process that occurs in the oral, nasal or anal area and occasionally the eyelids and scrotum of the newborn. The disease is caused by Pseudomonas aeruginosa and usually affects premature ill babies during the first few weeks of life. A full-term neonate with nasal and scrotal noma is uncommon and is therefore reported.
18 trabeculectomy specimens of congenital glaucoma were examined by light and transmission electron microscopy with the finding that the primary anomalies in congenital glaucoma included the developmental defect of trabecular meshwork, excessive collagen fibrils in the trabecular matrix, shifting forward of ciliary muscle fibers, and persistent mesenchymal tissue in the chamber angle. The authors also pointed out the importance of the secondary lesions of the trabecular meshwork in the pathogenesis of congenital glaucoma.
Elevation of serum CA 125 levels is associated with malignant serous ovarian carcinomas and has been described in one patient with Meigs syndrome. We present two additional cases of Meigs syndrome with significant elevations in serum CA 125 and report the results of immunohistochemical staining for CA 125. CA 125 expression was localized to the omentum and peritoneal surfaces rather than the fibroma. We suggest that expression of CA 125 and accumulation of ascites in these two patients may have resulted from some common peritoneal process.
Though clinical results for radioimmunoconjugate therapy of most common epithelial tumors have been disappointing, dramatic responses have been observed repeatedly in the treatment of high- and low-grade malignant lymphomas. This high clinical responsiveness after radioimmunoconjugate therapy sometimes appears to be out of proportion to the calculated radiation dose absorbed by the lymphoma tissue. Here we describe some key aspects of the kinetics, dosimetry, and cellular radiobiology of murine lymphoma cells exposed to 212Bi-radiolabeled alpha-particle-emitting immunoconjugates specific for the differentiation antigen Thy 1.2. Approximately 25 cell-bound alpha-particle-emitting immunoconjugates per target cell were required to reduce clonogenic survival by 90% (the radiobiological D10). Serial kinetic analyses of the antibody and radioisotope components of the immunoconjugates revealed significant levels of dechelation and up to 7.5% cellular internalization of the isotope. Cellular radiation dosimetry performed by Monte Carlo computer simulation of alpha-particle energy deposition patterns based on the observed radiopharmacokinetics showed that the D10 resulted from approximately four alpha-particle traversals through the nucleus, corresponding to an absorbed radiation dose of approximately 0.95 Gy to the cell nucleus. Electron micrographs and DNA gel studies of murine lymphoma cells undergoing radioimmunoconjugate therapy in vivo and in vitro demonstrated bizarre blebbing patterns, condensation of chromosomal material, and internucleosomal DNA fragmentation patterns characteristic of programmed cell death (apoptosis). We conjecture that the efficacy of radioimmunoconjugates against responsive cell types may be the result of passive DNA damage by ionizing radiation and the initiation of apoptosis in response to radioimmunotherapy.
A trypsin inhibitor (ACTI) was isolated and purified from the seeds of Acacia confusa by gel filtration, and trypsin-Sepharose 4B column affinity chromatography. The molecular weight of ACTI was found to be 21,000 +/- 1,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and amino acid composition analysis. ACTI contained four half-cystine and no methionine residues, and was rich in aspartic acid, glutamic acid, glycine, leucine, and lysine residues. The native trypsin inhibitor was composed of two polypeptide chains, and it inhibited trypsin and alpha-chymotrypsin stoichiometrically at the molar ratio of 1:1 and 2:1, respectively. The amino-terminal sequence analysis of the A. confusa trypsin inhibitor A and B chains revealed a more extensive homology with Acacia elata and silk tree trypsin inhibitors, and a less extensive homology with Kunitz soybean trypsin inhibitor.
Simian virus 40 (SV40) T antigen binds to the tumor suppressor p53 protein, and this association may contribute to oncogenic transformation by the virus. We investigated the importance of this binding on transformation by examining three replication-competent mutants of SV40 (402DE, 402DN, and 402DH). These mutants express T antigens defective in binding to human and monkey p53s but retain some binding with mouse p53. All showed significant reduction in their ability to induce transformed cell foci of two normal human cell lines as well as a slight reduction with mouse embryo cells. Other comparable mutants which express T antigens retaining the ability to complex with p53 were able to induce foci at wild-type levels in both human and mouse cells. Further studies were performed with five T-antigen-positive clones isolated from the few human cell foci that appeared after transfection with 402 mutant DNAs. All five clones reached senescence at about the same point as did the parental untransformed cells. However, six other human cell clones obtained after transfection with DNA from nondefective mutants or wild-type virus were still growing well at more than 10 passages beyond their expected life span. These results suggest that the ability of T antigen to form stable complexes with p53 is necessary for SV40 to extend the life span and partially transform human cells in culture.
We generated a number of simian virus 40 (SV40) mutants with single amino acid substitutions in T antigen between residues 388 and 411. All but one mutant (398LV) replicated like wild-type SV40 and gave rise to normal-size plaques. Three different mutations at residue 402 (Asp to Glu, Asn, or His) totally prevented the formation of stable complexes with the cellular protein p53 in monkey cells but had no effect on virus replication. Only one other mutation in this region, involving residue 401 (Met to Thr), slightly inhibited the formation of T-monkey p53 complexes. The three mutant T antigens with substitutions at residue 402 also formed no stable complexes with human p53 but generated low levels of complexes with mouse p53. These results indicate that residue 402 is critical for binding to monkey and human p53 proteins and is important for binding to mouse p53. We suggest that it is one of several points of contact. In cells infected with any one of the three residue 402 mutant viruses. T antigen and p53 became increasingly phosphorylated, as they were in cells infected with wild-type virus. Our data therefore show that stable T-p53 complexes are not required for replication of SV40 in culture or for enhanced phosphorylation of either protein.
In patients with endometrial carcinoma, preoperative identification of poor prognostic factors is helpful in planning therapy. Extended surgical staging, including pelvic and periaortic node dissection, is indicated in patients with deep myometrial invasion or high-grade tumor, or when other risk factors for extrauterine spread are present. In this study, cervical cytology was reviewed in 86 patients with endometrial carcinoma, all of whom underwent surgical staging, to correlate the cytologic results with surgical and pathologic findings. Cervical cytology was normal in 20 patients (23%), whereas suspicious or malignant endometrial cells were present in 23 and 43 cases (27 and 50%), respectively. Suspicious or malignant cervical cytology was associated with deeper myometrial invasion (P = .011), higher postoperative tumor grade (P = .006), positive peritoneal washings (P = .012), and more advanced stage by International Federation of Gynecology and Obstetrics criteria (P = .024). When compared with patients with normal cervical cytology, those who had malignant endometrial cells had over twice the risk of deep myometrial invasion (67 versus 30%), twice the risk of grade 2 or 3 tumor (60 versus 30%), and three times the risk of positive peritoneal washings (33 versus 10%). Seventy-four percent of patients with malignant cervical cytology were stage IC or more. In contrast, 70% of patients with normal cervical cytology were stage IA or IB. Patients with endometrial carcinoma who have malignant endometrial cells detected by cervical cytology are at increased risk of having a deeply invasive, high-grade, advanced-stage tumor, and therefore are more likely to require extended surgical staging.
We investigated whether the p53 protein of SV40-transformed mouse cells reacted with the conformation-dependent monoclonal antibody pAb246. This antibody can usually distinguish between a p53 with anti-proliferative activity like the wild-type protein (pAb246+) and a mutated form of p53 with oncogenic activity (pAb246-). Of the 13 cell lines that were screened, 12 contained the pAb246+ form of p53 and one had the pAb246- form. We showed that SV40 did not induce an activating mutation in the p53 of this latter cell line, because the cells from which it was derived were also pAb246-. Cascade immunoprecipitation experiments demonstrated that in three SV40-transformed cell lines that were examined, all of the p53 was of the pAb246+ form making it unlikely that small amounts of pAb246- p53 were responsible for the transformation properties of these cells. We therefore concluded that SV40-mediated transformation of murine cells is not dependent on the activation of their p53 to an oncogenic form, and that, in all probability, transformation is allowed to occur in part because the anti-proliferative activity of p53 is blocked by SV40 T antigen.
This study is based on questionnaire data gathered from 33 students in the first class of the first BSN programme in the People's Republic of China. They were asked to describe the characteristics of a good nurse and characteristics of a bad nurse. These students had just completed their pre-nursing courses and were entering the nursing part of their education. They identified personal qualities, behaviour and knowledge areas as the overall categories for these characteristics.
A highly specific monoclonal antibody (anti-AFP) against alpha-fetoprotein (AFP) was linked to N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) to form conjugates which were purified with a protein A-sepharose CL-4B affinity column. The conjugate, PDP-Anti-AFP was then covalently coupled to the toxic abrin-A chain to synthesize immunotoxins. The immunotoxin, anti-AFP-abrin-A conjugate, which was also purified with a protein A-sepharose CL-4B affinity column, had a molecular weight of 180,000 and had 80% antigen-binding activity that of anti-AFP activity and 92% toxicity of abrin-A chain. The immunotoxin showed selective cytotoxicities toward the AFP secreting human hepatoma cell lines, such HepG2 and Hep3B, but not toward AFP non-secreting human hepatoma cell line, PLC/PRF/5.
The effect of folate deficiency on homocysteine metabolism was examined in rats given a folate-deficient diet. Total homocysteine was determined in serum stored at -22 degrees C for 3 wk. All animals in the control group had more than 20 ng.ml-1 of serum folate and more than 1000 pg.ml-1 of serum cyanocobalamin throughout the experimental period. In contrast, serum folate in animals given the folate-deficient diet decreased to less than 3 ng.ml-1 after 4 wk and to less than 2 ng.ml-1 (a subnormal level) after 10 wk of the experiment while serum cyanocobalamin remained at more than 1000 pg.ml-1 throughout the experiment. In the control group, mean serum total homocysteine +/- SD was 4.04 +/- 1.07 nmol.ml-1 during the 20 wk of experiment. At the 10th wk before serum folate reached subnormal levels, the animals given the folate-deficient diet had a mean serum total homocysteine of 7.67 +/- 1.53 nmol.ml-1, demonstrating a significant increase (P less than 0.001). No further significant increase of mean serum total homocysteine concentrations was observed after serum folate became subnormal. This study demonstrated for the first time that a selective deficiency of folic acid caused a 2-4 fold increase in serum total homocysteine when serum folate was at low normal and at subnormal levels in rats.
The purpose of this study was to elucidate the influence of thyroxine on the serum thyroxine-binding globulin (TBG) levels. Serum TBG levels were determined in 100 normal people, 100 cases of simple goiter, 50 cases of nodular goiter, 50 cases of Graves' disease and 70 cases of autoimmune thyroiditis (35 cases in the euthyroid state, and 35 cases in the hypothyroid state). The serum TBG levels were 14.3 +/- 0.3 micrograms/ml (mean +/- SE) in the normal control, 14.1 +/- 0.4 micrograms/ml in simple goiters, 14.9 +/- 0.5 micrograms/ml in nodular goiters, 13.0 +/- 0.5 micrograms/ml in Graves' disease, 15.0 +/- 0.6 micrograms/ml in euthyroid autoimmune thyroiditis and 17.4 +/- 0.8 micrograms/ml in hypothyroid autoimmune thyroiditis. The serum TBG levels were significantly decreased in Graves' disease (p less than 0.05) and significantly increased in hypothyroid autoimmune thyroiditis (p less than or equal to 0.01) as compared with the control. Serum TBG levels were determined after treatment by antithyroid drugs in 25 cases of Graves' disease, by thyroxine replacement therapy in 15 cases of hypothyroid autoimmune thyroiditis and by thyroxine suppression therapy in 25 cases of nodular goiter. Serum TBG levels increased significantly after treatment with antithyroid drugs (p less than 0.005) in Graves' disease. Serum TBG levels decreased significantly both after treatment with thyroxine (p less than 0.01) in hypothyroid autoimmune thyroiditis and after treatment with thyroxine (p less than 0.005) in nodular goiter. This evidence supports the conclusion that T4 may decrease serum concentrations of TBG.
Abrin B chain and trypsin inhibitor isolated from Acacia confusa (ACTI) were covalently linked to form a chimeric protein (ANB-ACTI) with N-succinimidyl-3-(-2-pyridyldithio)propionate. The chimeric protein had 31% of trypsin inhibitory activity of ACTI and 7% of hemagglutinating activity of abrin B chain, but no inhibition on protein biosynthesis. ANB-ACTI had strong inhibitory effects on the growth of sarcoma 180 cells and Hela cell culture while the mixture of an equivalent amount of free abrin B chain and ACTI did not. The results suggests that abrin B chain of chimeric protein may act as a vector to carry ACTI into the tumor cells. ACTI into the tumor cells. ACTI in the chimeric protein potentiates its antitumor activity as well as its resistance to tryptic digestion.
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A plasmid DNA library was constructed from restriction endonuclease digested genomic deoxyribonucleic acid (DNA) of a virulent strain of Mycobacterium tuberculosis isolated from sputum of a patient. The sensitivity and specificity of two of the cloned DNA fragments in detecting M. tuberculosis and its related DNA sequences were analysed by DNA-to-DNA hybridization. The level of detection was determined to be 50 picograms of M. tuberculosis DNA, which is approximately equivalent to 10,000 mycobacterial genomes. These two M. tuberculosis DNA probes did not cross-hybridize to DNA of non-mycobacterial origin, nor with DNA from 9 out of 11 other mycobacterial species. Mycobacterial DNA sequences could be detected in 134 of 441, or 30.4%, of various types of uncultured clinical specimens from 365 patients by the DNA probes, whereas traditional culture method showed only a 19.0% positivity rate for the same specimens (p less than 0.001). The overall sensitivity and specificity of the DNA probes in detecting M. tuberculosis are 90.5% and 83.8% respectively. The DNA hybridization test may become a useful tool for the early and rapid determination of mycobacterial infection in uncultured clinical specimens.
The antimutagenic activities of extracts of 36 commonly used anticancer crude drugs from Chinese herbs were studied by using the Salmonella/microsomal system in the presence of picrolonic acid or benzo[a]pyrene to test whether they contain direct or indirect antimutagens. Each crude drug was extracted with boiling water for 2 h, the method which is commonly used by Chinese people to prepare the drug for oral intake. The extracts of Pteris multifida P. showed the highest antimutagenic activity against picrolonic acid-induced mutation. The extracts of 6 other different kinds of Chinese herbs were shown to have a moderate antimutagenic activity against picrolonic acid-induced mutation, and they are: Actinidia chinensis P., Artemisia lavendulaefolia DC. and Crotalaria sessiflora L., Prunella vulgaris L., Paris polyphylla S. and Ampelopsis brevipedunculata T. The extracts of Smilax china L., Prunella vulgaris L. and Actinidia chinensis P. were demonstrated to inhibit the mutagenicity of benzo[a]pyrene completely. The 12 other kinds of extracts of Chinese herbs which had a moderate antimutagenic activity against benzo[a]pyrene were: Pteris polyphylla S., Ampelopsis brevipedunculata T., Duchesnea indica F., Gossypium herbaceum L., Lithospermum erythrorrhizon SZ., Artemisia lavendulaefolia DC., Selaginella doederleinii H., Dianthus superbus L., Centipeda minima ABA., Curcuma zedoaria R., Marsdenia tenacissima WA. and Kalopanax septemlobus K. Among them, there were 5 kinds of crude drugs, Actinidia chinensis P., Artemisia lavendulaefolia DC., Prunella vulgaris L., Paris polyphylla S. and Ampelopsis brevipedunculata T., containing antimutagenic factors against both picrolonic acid- and benzo[a]pyrene-induced mutation.
We have constructed a recombinant plasmid pCPS12 containing the hepatitis B viral surface antigen (HBsAg) gene linked to the mouse metallothionein promoter on a BPV-pML2 vector. Two stable clones S12-8 and S12-2, obtained by transfection of the mouse C127 cells with pCPS12 propagated in dam+ dcm+ and dam- dcm- Escherichia coli respectively, exhibited different types of response to 5-azacytidine (5-aza-CR) and cadmium (Cd) induction. In S12-8, the productivity of HBsAg was enhanced by 5-aza-CR or 5-aza-CR plus Cd, but not by Cd alone. In S12-2, the expression of HBsAg was not affected by 5-aza-CR but was induced by Cd in the presence or absence of 5-aza-CR. This suggests that methylation may be important in controlling the HBsAg expression and the inducibility of Cd in the transfectants.