Structural aspects of conformational changes in ligand binding by antibody fragments.
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Animals↗
Biomedical subjects
L Shan
Publications and source records attributed to L Shan.
[Using ELISA to evaluate the serologic and epidemiologic effect following rabies vaccination].
After vaccinating the people bitten by animals against rabies, we have examined their serum antibodies by using ELISA. One year later, we sent a mail to everyone of them inquiring if he had contracted rabies. The response rate was 85%. The case fatality rate of the positive antibody group was 0.24% (1/415). The case fatality rate of the negative antibody group was 3.16 (3/95). It showed that there was significant difference in the case fatality rate of rabies between the two groups, (P = 0.022). The dead person of the positive antibody group was bitten on his cheek by a rabid dog. He had not cleaned his wound. He had received 6 injections of rabies vaccines. His incubation period was 28 days. The P/N of serum antibody on the 28th day was 3.27.
Adult↗
[Effect of phorbol ester on tissue-type plasminogen activator (t-PA) secretion in endometrial carcinoma cell line in vitro].
A plasminogen activator (PA) system is involved in ovulation, implantation, tumor invasion and metastasis. In order to clarify the regulation of this PA system in endometrial cells, we examined which agent affecting cellular function altered tissue-type plasminogen activator (t-PA) secretion by endometrial carcinoma cell line (KLE cells) in vitro. Triiodothyronine, retinoic acid, insulin, 8-bromo-cAMP, PDGF, IGF-I, basic FGF or TNF-alpha did not alter t-PA secretion while the activator of protein kinase C, phorbol myristate acetate (PMA) stimulated t-PA secretion in a dose-dependent fashion (10(-10)-10(-8) M). The time required to give a statistically significant increase in t-PA over control was 3 hours, and the maximal increase was seen after 24 hours of exposure. Another active phorbol ester, PDD also stimulated t-PA secretion while inactive forms of phorbol ester, 4 alpha-PDD and phorbol did not alter it. Cholera toxin or 8-bromo-cAMP did not affect t-PA secretion, but enhanced PMA-stimulated t-PA secretion. Cycloheximide and actinomycin D completely abolished PMA-stimulated t-PA secretion. These results suggest that (1) t-PA secretion in the endometrial carcinoma cell is modulated by a protein kinase C system, (2) This effect is through new RNA production and protein synthesis. (3) There is a complicated relationship between protein the kinase C and protein kinase A system as to the regulation of t-PA secretion. This would be a suitable model to clarify the PA system in endometrial cells.
8-Bromo Cyclic Adenosine Monophosphate↗
Three-dimensional structure of an Fv from a human IgM immunoglobulin.
An IgM(kappa) immunoglobulin from a patient (Pot) with Waldenstrom's macroglobulinemia was hydrolyzed with pepsin to release a fragment consisting of the 'variable' (V) domains of the light and heavy chains plus eight residue 'tails' from the 'constant' (C) domains. The crystal structure of this fragment was determined at 2.3 A resolution by molecular replacement and crystallographic refinement methods. When examined separately, the light chain component closely resembles another human kappa chain (Rei) in both the beta-pleated sheet regions and the 'hypervariable' loops. The conserved pleated sheets in the heavy chain are similar to those in the human Kol IgG1 protein, but the third hypervariable loop in particular is different from that in any immunoglobulin structure described to date. As in the Kol protein, this loop blocks the access to any internal active site along the light-heavy chain interface. Unlike the Kol protein, however, the loop does not protrude beyond the boundaries of a conventional antigen combining site. Instead, it forms a very compact structure, which fills almost all residual space between the domains. This is an example of one dominant complementarity-determining region (CDR) essentially negating the diversity possible with five other CDRs in the two chains. Ordered water molecules are associated with light chain constituents along the interface, but not with CDR3 of the heavy chain. In screening exercises the Pot IgM failed to bind a wide variety of peptides. Together, the results suggest that ligand binding can only occur on external surfaces of the protein. These surfaces carry a limited number of side chains usually assigned to CDRs in more typical antibodies.
Amino Acid Sequence↗
[Adenosquamous carcinoma arising in benign cystic teratoma of ovary].
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Adenocarcinoma↗
[The Nd: YAG laser in the treatment of colonic polyps].
The result of Nd: YAG laser therapy in 31 patients with pathologically verified rectosigmoid polyps was presented. Except one case with large adenomatous polyp recurring two months after the primary treatment, all other patients were cured clinically on their first therapy. There were no severe complications, and the longest follow-up period was 14 months. The authors came to the conclusion that compared with other modalities, Nd: YAG laser therapy is safe, effective, and low recurrence rate.
Colonic Polyps↗
Comparison of the three-dimensional structures of a humanized and a chimeric Fab of an anti-gamma-interferon antibody.
The objective of this work is to compare the three-dimensional structures of "humanized" and mouse-human chimeric forms of a murine monoclonal antibody elicited against human gamma-interferon. It is also to provide structural explanations for the small differences in the affinities and biological interactions of the two molecules for this antigen. Antigen-binding fragments (Fabs) were produced by papain hydrolysis of the antibodies and crystallized with polyethylene glycol (PEG) 8,000 by nearly identical microseeding procedures. Their structures were solved by X-ray analyses at 2.9 A resolution, using molecular replacement methods and crystallographic refinement. Comparison of these structures revealed marked similarities in the light (L) chains and near identities of the constant (C) domains of the heavy (H) chains. However, the variable (V) domains of the heavy chains exhibited substantial differences in the conformations of all three complementarity-determining regions (CDRs), and in their first framework segments (FR1). In FR1 of the humanized VH, the substitution of serine for proline in position 7 allowed the N-terminal segment (designated strand 4-1) to be closely juxtaposed to an adjacent strand (4-2) and form hydrogen bonds typical of an antiparallel beta-pleated sheet. The tightening of the humanized structure was relayed in such a way as to decrease the space available for the last portion of HFR1 and the first part of HCDR1. This compression led to the formation of an alpha-helix involving residues 25-32. With fewer steric constraints, the corresponding segment in the chimeric Fab lengthened by at least 1 A to a random coil which terminated in a single turn of 310 helix. In the humanized Fab, HCDR1, which is sandwiched between HCDR2 and HCDR3, significantly influenced the structures of both regions. HCDR2 was forced into a bent and twisted orientation different from that in the chimeric Fab, both at the crown of the loop (around proline H52a) and at its base. As in HCDR1, the last few residues of HCDR2 in the humanized Fab were compressed into a space-saving alpha-helix, contrasting with a more extended 310 helix in the chimeric form. HCDR3 in the humanized Fab was also adjusted in shape and topography. The observed similarities in the functional binding activities of the two molecules can be rationalized by limited induced fit adjustments in their structures on antigen binding. While not perfect replicas, the two structures are testimonials to the progress in making high affinity monoclonal antibodies safe for human use.
Amino Acid Sequence↗
Cytologic grading of invasive breast carcinoma. Correlation with clinicopathologic variables and predictive value of nodal metastasis.
OBJECTIVE: To estimate cytologic grade and correlate it with the other known prognostic factors, such as tumor differentiation, growth fraction, estrogen receptor status and nodal status. STUDY DESIGN: Fine needle aspirates from 104 invasive ductal carcinomas were stained by the Papanicolaou method and examined for necrosis, cellular size, nuclear/cytoplasmic ratio, nuclear pleomorphism, nucleoli, chromatin granularity and density of chromatin. We established a semiquantitative scoring system based on the above features and correlated cytologic findings with clinicopathologic variables. RESULTS: Histologic grade correlated positively with cytologic grade and negatively with estrogen receptor positivity. Moreover, high cytologic grade was associated with nodal metastasis and proliferative index labeling by MIB-1. CONCLUSION: This study showed that our grading system for breast cancer on fine needle aspiration cytology is feasible on a routine diagnostic basis. Cytologic grading can provide more information than usual on tumor biologic behavior.
Antigens, Nuclear↗
Thymidine phosphorylase expression in invasive carcinoma: correlations with clinicopathologic variables and in vitro chemosensitivity to 5-fluorouracil.
BACKGROUND: Thymidine phosphorylase (TP) is critical for angiogenic activity, but little information is available on the relationship between TP expression and other Clinicopathologic variables. Furthermore, the relationship between TP and chemosensitivity is still debated. MATERIALS AND METHODS: The expression of TP was examined in 116 primary breast carcinomas and in vitro chemosensitivity was assessed in 67 of them by histoculture drug response assay (HDRA) using 5-fluorouracil (5-FU). RESULTS: Tumor cell TP expression was significantly inversely correlated with histological grade and positively correlated with Bcl-2 expression, but no association with other tumor variables was found. Unexpectedly, TP immunoreactivity was not related to 5-FU chemosensitivity. CONCLUSION: The present results suggest that TP is important for remodeling the existing vasculature early in tumor development and intraductal extension, expressions of TP and Bcl-2 are tightly linked and TP status can not generally predict chemotherapeutic sensitivity for 5-FU as a single molecular marker.
Antimetabolites, Antineoplastic↗
Novel polymorphisms in prostate specific antigen gene and its association with prostate cancer.
Prostate-specific antigen (PSA) is now used widely for the diagnosis and monitoring of patients with prostate cancer. The PSA gene is a target of the androgen receptor (AR) which interacts with androgen response elements (AREs) in the PSA gene promoter. Recently, we identified two novel polymorphisms in the PSA promoter ARE2 region in breast cancer. We hypothesized that some genetic variations might also exist in the AREs of prostate cancer, and that feature might correlate with cancer development and/or progression. To test this hypothesis, three AREs of the PSA gene promoter were characterized for 47 prostate cancer cases and 105 controls from the Japanese population. We demonstrated the presence of two polymorphisms at positions -252 (G or A) and -205 (A or AA), which were the same as those we have found in breast cancer. Interestingly, the -252 A was linked with the presence of -205 AA, and the -252 G was always linked with the presence of -205 A. Therefore, only A-AA and G-A (-252--205) alleles were present in the Japanese population. The proportion of patients who were either heterozygotes or homozygotes for the A-AA allele was not significantly different from that observed among 105 individuals without cancer (p = 0.726). However, comparing with G-A allele homozygotes, prostate cancer patients carrying at least 1 A-AA alleles tended to exhibit high serum PSA levels (p = 0.0002), poor differentiation (p = 0.0149) and advanced clinical stage (p = 0.0077). These results suggest that the novel polymorphisms identified in the PSA gene promoter may affect transcriptional activity of the PSA gene, and an excess of PSA production may enhance rapid progression of prostate cancer.
Aged↗
Phenomenological theory on refrigeration effect of practical type-I superconductor.
In accordance with the phenomenological theory of thermodynamics, we discussed the Magnetocaloric effect of type-I superconductors, which are exposed to a varying magnetic field. It is concluded theoretically that the refrigeration effect is closely associated with demagnetization effect for practical specimens, which is different from the situation for ideal superconductor sample having no demagnetization effect. From the thermodynamic formulation of superconductivity, we deduced the integrating function of the thermal effect. By numerical calculation, we found a quantitative relation between the refrigeration effect and the demagnetizing factor which is determined by the shape of the sample.
Electric Conductivity↗