[Problems in interventional therapy of coronary heart disease].
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Biomedical subjects
Publications and source records attributed to G Zhu.
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Activated epidermal growth factor receptor (EGFR) undergoes autophosphorylation on several cytoplasmic tyrosine residues, which may then associate with the src homology-2 (SH2) domains of effector proteins such as phospholipase C gamma-1 (PLC gamma-1). Specific phosphotyrosine (pTyr)-modified EGFR fragment peptides can inhibit this intermolecular binding between activated EGFR and a tandem amino- and carboxy-terminal (N/C) SH2 protein construct derived from PLC gamma-1. In this study, we further explored the molecular recognition of phosphorylated EGFR988-998 (Asp-Ala-Asp-Glu-pTyr-Leu-Ile-Pro-Gln-Gln-Gly, I) by PLC gamma-1 N/C SH2 in terms of singular Ala substitutions for amino acid residues N- and C-terminal to the pTyr (P site) of phosphopeptide I. Comparison of the extent to which these phosphopeptides inhibited binding of PLC gamma-1 N/C SH2 to activated EGFR showed the critical importance of amino acid side chains at positions P+2 (Ile994), P+3 (Pro995), and P+4 (Gln996). Relative to phosphopeptide I, multiple Ala substitution throughout the N-terminal sequence, N-terminal sequence, N-terminal truncation, or dephosphorylation of pTyr each resulted in significantly decreased binding to PLC gamma-1 N/C SH2. These structure-activity results were analyzed by molecular modeling studies of the predicted binding of phosphopeptide I to each the N- and C-terminal SH2 domains of PLC gamma-1.(ABSTRACT TRUNCATED AT 250 WORDS)
The NMRPipe system is a UNIX software environment of processing, graphics, and analysis tools designed to meet current routine and research-oriented multidimensional processing requirements, and to anticipate and accommodate future demands and developments. The system is based on UNIX pipes, which allow programs running simultaneously to exchange streams of data under user control. In an NMRPipe processing scheme, a stream of spectral data flows through a pipeline of processing programs, each of which performs one component of the overall scheme, such as Fourier transformation or linear prediction. Complete multidimensional processing schemes are constructed as simple UNIX shell scripts. The processing modules themselves maintain and exploit accurate records of data sizes, detection modes, and calibration information in all dimensions, so that schemes can be constructed without the need to explicitly define or anticipate data sizes or storage details of real and imaginary channels during processing. The asynchronous pipeline scheme provides other substantial advantages, including high flexibility, favorable processing speeds, choice of both all-in-memory and disk-bound processing, easy adaptation to different data formats, simpler software development and maintenance, and the ability to distribute processing tasks on multi-CPU computers and computer networks.
Chlamydomonas reinhardtii mutant 31-4E lacks ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco; EC 4.1.1.39) holoenzyme due to a mutation in the chloroplast rbcL gene. This mutation causes a glycine54-to-aspartate substitution within the N-terminal domain of the Rubisco large subunit. In the present study, photosynthesis-competent revertants were selected to determine whether other amino acid substitutions might complement the primary defect. Revertants were found to arise from only true reversion or either of two forms of pseudoreversion affecting residue 54. One pseudorevertant has a glycine54-to-alanine substitution that decreases the accumulation of holoenzyme, but the purified Rubisco has near-normal kinetic properties. The other pseudorevertant has a glycine54-to-valine substitution that causes an even greater decrease in holoenzyme accumulation. Rubisco purified from this strain was found to have an 83% decrease in the Vmax of carboxylation and an 18% decrease in the CO2/O2 specificity factor. These results indicate that small increases in the size of amino acid side chains can influence Rubisco assembly or stability. Even though such changes occur far from the active site, they also play a significant role in determining Rubisco catalytic efficiency.
OBJECTIVE: To explore mitochondrial dysfunction in Parkinson's disease (PD) using 31P magnetic resonance spectroscopy of resting muscle. DESIGN: Case-control study (28 PD patients and 28 normal controls) determining resting forearm inorganic phosphate/phosphocreatine (Pi/PCr) ratio. RESULTS: Significant difference (p = 0.004, one-tailed test) in Pi/PCr ratio between PD patients (0.122) and controls (0.104). No correlation of Pi/PCr ratio with duration, severity, or speed of onset of disease. Positive correlation of Pi/PCr ratio with age in control group; reversed in PD group. CONCLUSIONS: Suggests small generalized mitochondrial defect in PD. The possibility that earlier onset of disease is associated with more severe mitochondrial dysfunction needs further study.
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Our results suggest that the growth of tumors was significantly suppressed when the high-dose rIL-2 (2 x 10(4)U/day) was injected i.p. in mice bearing subcutaneously (s. c.) transplanted tumors. The inhibition effect on the growth of mouse hepatoma HAC was more potent than that on S180 group. It was found that rIL-2 increased significantly the survival of BALB/C mice bearing HAC tumor (P < 0.001). We have also shown that the adoptive transfer of unfractionated LAK cells plus rIL-2 was more effective than rIL-2 alone. The results also indicated that adherent LAK cells (A-LAK) in combination with rIL-2 had higher antitumor effects as compared to standard LAK cells plus rIL-2.
Thirty postmenopausal women, including 26 with history of hysterectomy and bilateral salpingooophorectomy due to uterine myoma and 4 with natural menopause without any diseases were randomly allocated into two groups. Fifteen subjects received medroxyprogesterone acetate (MPA) 10 mg twice daily for three months, the other 15 received both MPA 10 mg twice daily and cyclopentylethinyl estriol (CEE3) 5 mg once a month for three months. Fasting urinary calcium/creatinine (Ca/Cr) and hydroxyproline/creatinine (OHpr/Cr) ratio, serum calcitonon (CT) and alkaline phosphatase (AKP) concentrations were measured before and after treatment in all subjects. The results showed that in both groups, the fasting urinary Ca/Cr and OHpr/Cr ratio reduced significantly, while serum CT and AKP increased significantly after treatment. The changes of these parameters were not significantly different between these two groups. These data indicated that progestin alone appeared effective in preventing postmenopausal osteoporosis.
Mice of Kunming strain were infected with Schistosoma japonicum cercariae previously incubated with various concentrations of acridine mutagen ICR-170 for different time durations. At 6 weeks after infection, the mice were autopsied. The results showed that 24 out of 28(85.7%) adult female worms had deformed or lacked ovaries and vitelline glands when the cercariae were treated with the agent at a concentration of 10 micrograms/ml and incubated at 30.5 degrees C for 30min. No apparent changes were observed in the male worms inhabiting the mesenteric and portal veins with the females worms in their gynecophoral canals. The mutagenized female schistosomes obtained from the present experiment might be served as another form of attenuated worms for the induction of protective immunity.
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The effects of T II (extracted from Tripterygium wilfordii) and substance P (SP) on imunoregulation were investigated. It has been shown that Tripterygium wilfordii is an immunosuppresive. In order to assess the immunosuppression elicited by T II was mediated by SP in spinal dorsal horn, Wistar rats were injected intrathecally with capsaicin (CAP) to deplete SP in spinal dorsal horn prior to T II given orally. The level of interleukin 2 (IL-2) produced by splenic lymphocytes of rats and the contents of SP in some brain areas and spinal cord in mice were assayed after T II treatment. Our findings were as follows: 1. The level of IL-2 was decreased significantly after T II treatment only. However the level of IL-2 was increased markedly after CAP was given intrathecally. Moreover, CAP administration also enhanced the level of IL-2 even in immunosuppression group induced by T II treatment. 2. SP contents in spinal cord, hypothalamus and brain stem of mice were increased dramatically during immunosuppression produced by T II. The results suggested that SP in spinal dorsal horn was involved in regulation of cellular immunity, the suppressive effect of T II on cellular immunity might be mediated by SP in spinal dorsal horn.
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Photoaffinity labeling and site-directed mutagenesis have been used to identify amino acid residues of the phospholipase C gamma 1 (PLC gamma 1) N-terminal SH2 domain involved in recognition of the activated epidermal growth factor receptor (EGFR). The photoactive amino acid p-benzoylphenylalanine (Bpa) was incorporated into phosphotyrosine-containing peptides derived from EGFR autophosphorylation sites Tyr992 and Tyr1068. Irradiation of these labels in the presence of SH2 domains showed cross-linking which was time-dependent and specific; labeling was inhibited with non-Bpa-containing peptides from EGFR in molar excess. The phosphotyrosine residue on the peptides was important for SH2 recognition, as dephosphorylated peptides did not cross-link. Radiolabeled peptides were used to identify sites of cross-linking to the N-terminal SH2 of PLC gamma 1. Bpa peptide-SH2 complexes were digested with trypsin, and radioactive fragments were purified by HPLC and analyzed by Edman sequencing. These experiments showed Arg562 and an additional site in the alpha A-beta B region of the SH2 domain, most likely Glu587, to be labeled by the Tyr992-derived peptide. Similar analysis of the reaction with the Tyr1068-derived photoaffinity label identified Leu653 as the cross-linked site. Mutation of the neighboring residues of Glu587 decreased photo-cross-linking, emphasizing the importance of this region of the molecule for recognition. These results are consistent with evidence from the v-Src crystal structure and implicate the loop spanning residues Gln640-Ser654 of PLC gamma 1 in specific recognition of phosphopeptides.
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