Mechanism of action of camptothecin.
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Biomedical subjects
Publications and source records attributed to C T Lin.
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A system for the design and analysis of seat support and buttock tissue interfaces has been developed. It has the ability to control the seating surface shape while measuring the pressure applied to the buttocks by the surface. Pressures are measured over an 11 x 12 rectangular array of support elements using silicon pressure sensors mounted in a swiveling head atop each support element. Control of surface shape is mediated by selective linear translation of the support elements along their respective vertical axes. Closed-loop control of the system allows for the dynamic formulation of a support surface on the basis of programmable criteria. The system is intended to function as a research tool to facilitate the study of the relationships between support surface shape and interface pressure, and support surface shape and soft tissue distortion. The purpose of this paper is to present the system instrumentation and the rationale behind its design and development. The paper also presents the results of several tests to evaluate the accuracy and performance of the system. This evaluation included a pilot study on 10 able-bodied subjects. The results of these system evaluations indicate that the system is capable of making repeatable and precise measurements of pressure and surface element position and can formulate support surface shapes that satisfy specified optimization criteria.
Here were report the first canine infectious cyclic thrombocytopenia (CICT) found in Taiwan. Platelet-specific inclusions were detected in the blood smear of a military working dog. To identify the etiologic agent, the patient's blood was transmitted to three six-month-old German Shepherd dogs. The Ehrlichia platys-like inclusions were observed six to eight days after inoculation. Indirect fluorescent antibody test showed that the serum from the patient reacted specifically with the microorganisms within the platelets. Typical hematologic manifestations of E. platys infection, cyclic parasitemia and concomitant thrombocytopenia, were observed in these dogs. The prevalence of CICT in north Taiwan was also studied, and the incidence was 8.9% (4 out of 45) in civilian dogs and 97.1% (34 out of 35) in dogs from a heavily tick infested kennel.
The lateral mobility of membrane proteins can reflect the extent of various protein-protein interactions. Using the fluorescence recovery after photobleaching technique, we have studied the lateral mobility of human Fc gamma RIIa and some Fc gamma RIIa mutants expressed in either P388D1 cells, a mouse macrophage-like cell line, or in Chinese hamster ovary (CHO) cells [1]. After treatment with phorbol myristate acetate (PMA), only the Fc gamma RIIa molecules capable of mediating rapid endocytosis of immune complexes exhibited a reduced lateral diffusion coefficient with respect to untreated controls. Wild type Fc gamma RIIa expressed in CHO cells, and nonfunctional Fc gamma RIIa mutants expressed in P388D1 cells did not show any differences upon PMA treatment. This finding suggests that protein kinase C activation evokes additional protein-protein interactions with the cytoplasmic domain of functional Fc gamma RIIa, which reduced receptor lateral mobility. The identity of these putative interacting proteins and the nature of the interactions remain to be elucidated.
p53 is the most frequently mutated gene in human cancer. Naturally occurring mutations of p53 are mainly located within a region containing residues 100-300 and are predominantly of missense type, resulting in loss of the protein's DNA binding activity. Here we show that this type of mutation also represses the p53 N-terminal activation domain. The repression activity is localized in the central region of mutant p53 containing residues 101-318. Interestingly, the central region of a temperature-sensitive mutant p53N247I possesses a movable and regulable inactivation function. It represses other activities present on the same polypeptide chain without strict regard to the configuration of that polypeptide only at the nonpermissive temperature (37 degrees C) and not at the permissive temperature (30 degrees C). Furthermore, this mutant p53 region exhibits no other activity, and its function is independent of endogenous p53 status.
Differing roles for [Ca2+]i transients in Fc gamma R-mediated phagocytosis have been suggested based on the observations that antibody-opsonized erythrocyte phagocytosis by human neutrophils shows a [Ca2+]i dependence, while that by murine macrophages appears [Ca2+]i-independent. To explore whether this difference might reflect different receptor isoforms or different cell types, we studied the [Ca2+]i dependence of receptor-initiated phagocytosis by human Fc gamma RIIa and a panel of Fc gamma RIIa cytoplasmic domain mutants expressed in murine P388D1 cells and by human Fc gamma R endogenously expressed on human neutrophils and monocytes. Wild-type and point mutants of huFc gamma RIIa stably transfected into murine P388D1 cells have different capacities to initiate a [Ca2+]i transient, which are closely correlated with quantitative phagocytosis (r = 0.94, p < 0.0001). Phagocytosis both by huFc gamma RIIa in P388D1 cells and by huFc gamma RIIa endogenously expressed on neutrophils and blood monocytes shows [Ca2+]i dependence. Phagocytosis of antibody-opsonized erythrocytes by neutrophils demonstrated greater susceptibility to [Ca2+]i quenching compared with Fc gamma RIIa-specific internalization with E-IV.3, suggesting that the phagocytosis activating property of Fc gamma RIIIb in neutrophils also engages a [Ca2+]i-dependent element. In contrast, phagocytosis by human Fc gamma RIa, endogenously expressed on blood monocytes, is [Ca2+]i-independent. Despite the importance of a consensus tyrosine activation motif for both receptors, Fc gamma RIa and Fc gamma RIIa engage at least some distinct signaling elements to initiate phagocytosis. The recognition that both of the phagocytic receptors on murine macrophages and human Fc gamma RIa associate with the Fc epsilon RI gamma-chain, which contains a tyrosine activation motif distinct from that in the Fc gamma RIIa cytoplasmic domain, suggests that [Ca2+]i-independent phagocytosis is a property associated with the utilization of gamma-chains by Fc gamma R.
Although the statistical method of partial least squares (PLS) is widely used for the analysis of the relationship between molecular properties and biological potency, it is recognized that PLS detects only linear relationships. We tested two types of properties: simulated univariate data and electrostatic molecular field as a function of Hammett sigma constants. In both cases we compared relationships in which the function is linear, asymptotic, or rises to an optimum and then falls. We found that PLS analysis of the matrix of the distances between every pair of compounds detects all three types of relationships with the same quality of cross-validation. The successful application of the method requires that the distance matrices be constructed such that each contains only information about one property (for example, the electrostatic field around the functional group of interest). Carbo and Hodgkin similarities perform less well than distances.
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The coding region of copper/zinc-superoxide dismutase (Cu/Zn-SOD) cDNA from sweet potato, Ipomoea batatas (L.) Lam. cv. Tainong 57, was introduced into an expression vector, pET-20b(+). The Cu/Zn-SOD purified by His-tagged technique showed two active forms (dimer and monomer). The amount of proteins of dimer and monomer appeared to be equal, but the activity of dimeric form was seven times higher than that of monomeric form. The enzyme was dissociated into monomer by imidazole buffer above 1.0 M, acidic pH (below 3.0), or SDS (above 1%). The enzyme is quite stable. The enzyme activity is not affected at 85 degrees C for 20 min, in alkali pH 11.2, or in 0.1 M EDTA and also quite resistant to proteolytic attack. Dimer is more stable than monomer. The thermal inactivation rate constant kd calculated for the monomer at 85 degrees C was 0.029 min-1 and the half-life for inactivation was about 28 min. In contrast, there is no significant change of dimer activity after 40 min at 85 degrees C. The enzyme dimer and monomer retained 83% and 58% of original activity, respectively, after 3 h incubation with trypsin at 37 degrees C, while those retained 100% and 31% of original activity with chymotrypsin under the same condition. These results suggest subunit interaction might change the enzyme conformation and greatly improve the catalytic activity and stability of the enzyme. It is also possible that the intersubunit contacts stabilize a particular optimal conformation of the protein or the dimeric structure enhances catalytic activity by increasing the electrostatic steering of substrate into the active site.
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This paper addresses the structure and an associated on-line learning algorithm of a feedforward multilayer connectionist network for realizing the basic elements and functions of a traditional fuzzy logic controller. The proposed Fuzzy Adaptive Learning Control Network (FALCON) can be contrasted with the traditional fuzzy logic control systems in their network structure and learning ability. An on-line structure/parameter learning algorithm, called FALCON-ART, is proposed for constructing the FALCON dynamically. The FALCON-ART can partition the input/output space in a flexible way based on the distribution of the training data. Hence it can avoid the problem of combinatorial growing of partitioned grids in some complex systems. It combines the backpropagation learning scheme for parameter learning and the fuzzy ART algorithm for structure learning. More notably, the FALCON-ART can on-line partition the input/output spaces, tune membership functions, and find proper fuzzy logic rules dynamically without any a priori knowledge or even any initial information on these. The proposed learning scheme has been successfully used to control two unstable nonlinear systems. They are the seesaw system and the inverted wedge system.
A cushion device and B+M mode ultrasonography technique were used in 30 healthy volunteers to study tongue movement during swallowing. M-mode images show an amplitude-time diagram, in which the entire tongue movement during swallowing can be easily scrutinized. The different tongue movements during swallowing result in several turning points on the graph of the M-mode sonogram, which divide the oral swallowing phase into five subphases (I, IIa, IIb, IIIa, IIIb). Based on this new classification of swallowing, the tongue movements of the participants were interpreted and classified.
Tyrosine phosphorylation plays a critical role in Fc gamma RIIA signaling. In a mouse macrophage cell line transfected with human Fc gamma RIIA, cross-linking Fc gamma RIIA led to the transient generation of inositol 1, 4, 5-trisphosphate (IP3), [Ca2+]i flux, and rapid tyrosine phosphorylation of cellular substrates, including Shc, PLC-gamma 1, and a tyrosine kinase p72syk. In addition, tyrosine phosphorylated Fc gamma RIIA was co-precipitated with activated PLC-gamma 1. In contrast, no tyrosine phosphorylation of Shc or PLC-gamma 1 was detected in cells transfected with mutant receptors that failed to trigger [Ca2+]i flux. PMA inhibits both tyrosine phosphorylation of Shc and IP3 production leading to [Ca2+]i flux. However, PMA does not affect tyrosine phosphorylation of PLC-gamma 1 and p72syk. These results suggest that tyrosine phosphorylation of Shc and PLC-gamma 1 is important for the initiation of [Ca2+]i flux, and that activation of protein kinase C may modulate the activity of PLC-gamma 1 through serine/threonine phosphorylation.
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Receptors for the Fc domain of IgG (Fc gamma Rs) on leukocytes mediate a pleiotropic response following cross-linking by immune complexes. Signaling events following cross-linking of B and T cell antigen receptors, Fc epsilon RI, and Fc gamma Rs share common elements. In each, signaling is initiated by receptor cross-linking by antigen or immune complexes and results in the activation of src family kinases and ZAP-70-related tyrosine kinases, which associate with members of the receptor complex. Subsequent events include phosphorylation on tyrosine of multiple cellular substrates including phospholipase C gamma 1 and PI3-kinase. The [Ca2+]i flux is an event secondary to phospholipase C gamma 1 activation. Protein tyrosine kinase inhibitors block both early events such as [Ca2+]i flux and the later effects of cytokine release and cellular proliferation.
Flame atomic absorption spectrophotometric methods were developed for, arsenic, selenium, copper, zinc and iron in hair samples. Data from blackfoot disease patients at five clinical stages were compared with those from healthy controls. The copper and zinc concentrations showed only slight differences in all clinical stages, which indicated the less relation to blackfoot disease. The decrease of selenium and iron in all stages was attributed to the antagonistic effect of arsenic; arsenic increased in the first and second stages, but decreased in the later stages. The decrease of selenium and iron during the progression of the disease is thought to be due to persistence of the antagonistic effect of arsenic in the initial stages, so that very low concentrations of selenium are found in the advanced stages, despite the later decrease of arsenic. There was also a progressive decrease of iron with advance of the disease, and the later stages also showed a decrease in haemoglobin. It was shown that arsenic is a major cause of blackfoot disease, and that it antagonises selenium and iron, which decreased in the advanced clinical stages of the disease.