[Analgesic action of recombinant human interferon-alpha and its relation with opioid receptors].
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Biomedical subjects
Publications and source records attributed to Q Zhu.
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An inspection of the phi-psi angle distribution strongly suggests that protein folding is highly constrained. A number of researchers have even suggested that a relatively small set of discrete phi-psi regions might be sufficient to describe most protein conformation. The total of 541 tight turns from 101 non-identical proteins were extracted form Brookhaven DataBank. The dihedral values of tight turns were scattered into the seven regions on the Ramachandran plot. These seven regions were called A1, A2, B1, B2, B22, T1 and T2. A1 and A2 are the traditional alpha-helix regions, B1, B2 and B22 the beta-strand regions, T1 and T2 the beta-turn regions. The A2 and T2 regions were not defined as "discrete" or single points but rather as one dimensional extended states. Based on the geometry of the two central residues of the tight turns, the new classification of beta-turn was defined. This classification of the majority of beta-turns fell into only six of the possible forty nine region combinations and were identifiable with the traditional nomenclature of Venkatachalam(1), but much simpler. The function of beta-turn in the conformation of proteins was studied. The hydrophobicity for different type turns was discussed. It shows that beta-turns have very strong hydrophilic property, so they are usually situated at the folding protein surface. The features of beta-turn and its amino acid distribution in this 541 beta-turn group and different type beta-turn were given.
To obtain tolerance limit of human upper extremity with arm restraint plate on eject seat to windblast, impact was applied to the upper extremity of 13 human corpses and 7 living monkeys by a spring driven impact device. Relationship between impact load, moment of elbow joints and arm injuries with arm restraint plate were studied. Relationship between biomechanical characteristic curve of human elbow joint and clinical injuries was obtained. The results indicated that tolerance limit of human upper arm is higher than forearm. Safety limit of human anterior arm to simulated aerodynamic load is 1.26 kN.
In order to study tolerance transfer relationships between human and rhesus monkey elbow joints, torsional and bending tests were conducted on human and rhesus monkey elbow joints under the same condition, and the tolerance transfer relationships between their elbow joints were obtained by comparing and analysing their biomechanical properties. The results show that the mean load transfer ratios between human and rhesus monkey elbow joints were 3.65 and 4.28 for torsional and bending injury respectively.
Platelets are produced from megakaryocytes differentiated from megakaryoblasts, but the differentiation mechanism still remains unknown. Here, we demonstrate that a tyrosine kinase signaling regulates Wiskott-Aldrich syndrome protein (WASP), which is essential for megakaryocyte differentiation. MEG-01 megakaryoblastic cells differentiate into large multinucleated megakaryocyte-like cells characterized by microvesicle formation with a protein kinase C (PKC) activator, 12-O-tetradecanoylphorbol 13-acetate. With parallel to the differentiation, WASP begins to accumulate at microvesicles with actin filaments and associates with tyrosine-phosphorylated Shc, the phosphorylation of which is induced. Moreover, a tyrosine kinase inhibitor, herbimycin A, blocked not only phosphorylation of Shc but also microvesicle formation without affecting cell enlargement and multinucleation, whereas a PKC inhibitor, H-7, completely inhibited all these processes. Because WASP also binds to Ash/Grb2 SH3 domains and the association of Ash/Grb2 and Shc is induced by 12-O-tetradecanoylphorbol 13-acetate treatment, a signaling pathway, PKC-tyrosine kinase-Shc-Ash/Grb2-WASP, is suggested for regulating megakaryocyte differentiation. In addition, WASP antisense oligonucleotide treatment abolishes both microvesicle formation and gathering of actin filaments. These data clearly show that WASP controls the assembly of actin filaments required for microvesicle formation downstream of PKC-tyrosine kinase.
PURPOSE: To test the antiviral effect of ganciclovir released from biodegradable polymer microspheres in rabbit eyes inoculated with human cytomegalovirus (HCMV). METHODS: Human cytomegalovirus (5 x 10(3) plaque forming unit in 0.1 ml Hank's balanced salt solution) was inoculated 4 days after gas compression vitrectomy. Injected after 2 days was 10 mg of 300- to 500-micron ganciclovir-loaded microspheres (89.77 micrograms ganciclovir/mg) suspended in 0.1 ml of 2% hydroxypropylmethylcellulose. Blank microspheres were injected as control specimens. Vitritis, retinitis, and optic neuritis were graded from 0(+)-4+ for 14 days to separate the early HCMV-induced disease events from later nonspecific host inflammatory responses. Ganciclovir-loaded microspheres also were injected and observed for biodegradation and tissue reaction for 8 weeks. RESULTS: In eyes injected with ganciclovir-loaded microspheres, vitritis decreased from days 3 to 14, and retinitis and optic neuritis decreased from days 3 to 9. In eyes injected with blank microspheres, vitritis increased from days 3 to 7, retinitis increased from days 3 to 9, and optic neuritis increased from days 3 to 14. Immunofluorescence of HCMV antigens in retinal tissues was shown only in eyes injected with blank microspheres. Histopathologic analysis showed minimal focal disruption of the retinal architecture in eyes injected with ganciclovir-loaded microspheres. Disorganization of the normal retinal architecture was observed in eyes injected with blank microspheres. No adverse tissue reaction was observed clinically and histopathologically in eyes injected with ganciclovir-loaded microspheres after 8 weeks. CONCLUSIONS: Ten milligrams of 300 to 500 microns ganciclovir-loaded poly(D,L-lactide-co-glycolide) microspheres control the progression of fundus disease in HCMV-inoculated rabbit eyes.
HeLa cells were transfected with full-length multidrug resistance protein (MRP) cDNA and with MRP cDNAs that had been mutated at certain nucleotide binding domains. Stable transfectants were isolated and those producing equivalent amounts of P190 were tested in cytotoxicity assays using a variety of chemotherapeutic agents. The results demonstrate that deletions in the C-motif of NBD1 or the A-motif of NBD2 have a pronounced effect in reducing resistance levels to adriamycin, vincristine, or etoposide (VP-16). Single-site mutations of lysine in these same motifs reduce IC50 values but less than that observed with the deletion mutants. Additional studies have demonstrated an increase in drug accumulation and reduction in drug efflux in NBD deletion and single-site mutants. The results of this study therefore identify two lysines of the NBD A- and C-motifs that are critical for MRP-mediated multidrug resistance. The results also provide definitive evidence that resistance occurring as a result of MRP overexpression is related to enhanced levels of an ATP-dependent efflux pump.
Chronic alcohol administration to male animals is associated with testicular atrophy and gonadal failure. The Sertoli cell seems to be the first testicular cell injured as a result of alcohol exposure. To investigate the adverse effects of ethanol on testicular and particularly Sertoli cell function, the consequences of in vivo and in vitro ethanol exposure on rat Sertoli cell mRNA and protein levels of transferrin and ornithine decarboxylase were investigated. In vivo, ethanol exposure enhanced the levels of both hepatic and testicular (Sertoli cell) transferrin protein and mRNA. Ethanol exposure also enhanced testicular, but not hepatic, levels of ornithine decarboxylase protein and mRNA. These in vivo findings were confirmed when isolated Sertoli cells were studied in vitro. Specifically, ethanol exposure increased Sertoli cell transferrin protein and mRNA levels. Ethanol exposure increased Sertoli cell ornithine decarboxylase mRNA and protein when cultured in serum-free media, but not when cultured in the presence of serum. These studies demonstrate that ethanol exposure of rat Sertoli cells is associated with alterations in the levels of mRNA and protein that are known to be important in the process of spermatogenesis. These findings add to the body of evidence that suggests that, within the testes, the Sertoli cell may be an important target for ethanol-induced gonadal injury.
OBJECTIVE: The infection of Hepatitis B virus (HBV) in the uterus may occur in neonates born to HBV carrier mothers. The rates of intrauterine transmission in these neonates were 10%-16%, Recent studies on the methods of combined passive and active immunizations indicate an efficacy approaching 70%-90%, but intrauterine infection of HBV is the major cause of failure of vaccination to combat hepatitis B in neonates born to HBV carrier mothers. We studied the interruptive effect of HBV specific immunoglobulin (HBIG) before delivery in the prevention of intrauterine transmission of HBV. METHODS: Of 3632 pregnant women, two hundred and four were HBV carriers; they were randomly divided into an HBIG group and a control group. Each subject in the HBIG group received 200 IU of HBIG intramuscularly at 3, 2 and 1 month before delivery. The subjects in the control group did not receive any specific treatment. Blood tests were conducted for all the subjects and their neonates after birth. Blood specimens were tested for HBsAg and HBeAg by enzyme immunoassay (Abbott Kits). RESULTS: The results showed that the rates of intrauterine transmission in the two groups were 5.7% and 14.7% respectively (X2 = 4.58 P < 0.05). No significant differences were observed for the positive rates of HBsAg and HBeAg between the two groups after delivery, but titer of HBsAg was reduced significantly in the HBIG group (t = 4.82, P < 0.01). CONCLUSIONS: Our study suggests that HBV infection in the uterus may be interrupted using multiple HBIG intramuscularly before delivery without any side effects.
OBJECTIVE: To investigate clinical reasonable dose of methyl carboprost suppository (15-methyl-PGF2 alpha) for induction of labor. METHOD: A total of 150 gravidas with singleton pregnancy and cephalic presentation, accepted for induction of labor, were randomly allocated into 3 groups: group 1, 15-methyl-PGF2 alpha 0.100 mg (n = 50); group 2, 0.125 mg (n = 50); and group 3, 0.200 mg (n = 50). RESULTS: The success rates of induction were 90.0%, 94.0% and 100.0% for group 1, 2 and 3, respectively. As cervical Bishop score < or = 5, the cases needed oxytocin intravenous infusion during the active phase were 48.5%, 40.7% and 5.0%, respectively; cervical Bishop score > or = 6, the cases were 11.8%, 13.0% and 0.0%, respectively. There were 3 cases of precipitate delivery in group 2 and 3. No uterine hyperstimulation occurred in group 1 and 2, while 3 cases of uterine hyperstimulation in group 3. CONCLUSION: (1) A single maximum dose of 15 methyl-PGF2 alpha for term labor induction should be < 0.200 mg. (2) The different dose was chosen according to cervical Bishop score, i.e. 0.200 mg or 0.125 mg for Bishop score < or = 5, and 0.100 mg for Bishop score > or = 6.
HPV structural antigens and HPV 6, 11, 16, 18 DNA sequences were detected with immunohistochemical staining and DNA dot blot hybridization in papillomas and squamous cell carcinomas of the throat and larynx. The positive rates of HPV antigens and HPV DNA sequences in 11 cases of papillomas were 45.5%, respectively, while the positive rates of HPV in 22 cases of squamous cell carcinomas were 22.7% and 27.3% respectively. The positive rates of HPV were in accord with those by histologic study in papilloma. The results indicate that the papillomas and squamous cell carcinomas of the throat and larynx may be related with HPV infection.
In a study on metabolism of aluminium in rats, two doses of aluminium, 100 mg/kg and 40 mg/kg, were administered through gastric tube in SD rats to observe its storage, distribution in various tissues and 48-hour excretion in urine and feces. Results showed that storage and distribution of aluminium in various tissues were different in two doses during different time periods. Apparent absorption rates of aluminum were 19.07-19.45 and 3.50-7.72 percent and apparent retention rates were 16.89-20.67 and 3.76-13.48 percent 24 and 48 hours after its intake, respectively, in high dose group, and those in low dose group were 29.40-36.58 and 3.76-13.48 percent and 29.27-36.43 and 3.69-13.35 percent, respectively. In high dose group, contents of aluminium in liver 0.5 hours, in kidney one hour, in brain 48 hours after intake were higher than those in other time periods. The highest content of aluminum was in the liver, and the next in the brain and kidney, in low aluminium group, and that in brain of the rats 24 and 48 hours after intake in the high dose group were significantly higher than those in the low dose group (P < 0.01). It suggests that different doses of aluminium had certain affinity to the brain of rats. Cumulative excretion of aluminium in urine and feces accounted for 1.08-1.22 and 0.11-0.31, and 97.01-99.13 and 86.55-96.07 percent of the total intake, respectively, in the high and low dose groups.
Nerve injury following operation is one of the main causes of the iatrogenic peripheral nerve injury. In order to learn lessons from these cases, one hundred and seven cases of peripheral nerve injury complicated with the orthopedic operations were analyzed. Forty-four cases were cutting injury during operation, made up 41% of all cases and 27 cases were stretch and compression injury, made up 25%. The involved nerves included 41 radial nerves and 24 common peroneal nerves, composing 60.7% of all nerve injury. The operations responsible were mainly the bone and joint operations, which made up 81%. The cause, prophylaxis, diagnosis and treatment were discussed. The rich appropriate knowledge of anatomy and responsibility of the surgeon were emphasized in order to prevent the occurrence of complication. Once the injury was suspected, diagnosis should be made promptly and effective treatment should be performed in time.
The transcription activator protein-1 (AP-1) complex is a heterodimer consisting of Fos and Jun family members. We found that extracellular ATP stimulated AP-1 DNA binding activity in cerebral cortical astrocyte cultures. This activity was maximal at 1 h and persisted for at least 3 h post-treatment. Shift-Western blotting indicated the presence of c-Fos in the AP-1 complexes. Stimulation of AP-1 binding by ATP was due to activation of P2 rather than P1 purinoceptors. The protein kinase C (PKC) inhibitor Ro 31-8220 markedly reduced P2 purinoceptor-mediated AP-1 induction. The induction of AP-1 complexes by ATP may contribute to changes in gene expression which underlie the trophic effects of extracellular ATP on astrocytes.
In the thymus, maturing lymphocytes receive activation signals mediated by the T-cell antigen receptor (TCR) that either promote clonal survival (positive selection) or induce apoptosis (negative selection). This balance between life and death is mirrored by the sensitivity of cortical thymocytes to apoptotic death induced by antibodies against the CD3 component of the TCR signal-transduction complex, bacterial superantigens that bind to the TCR beta-chain, and corticosteroids. In contrast, mature peripheral T cells are positively activated by anti-CD3 antibody or superantigens and are resistant to steroid-induced death. Here we show that in splenic germinal centres, T cells regain thymocyte-like sensitivity to TCR- and steroid-induced apoptosis and undergo antigen-driven positive and negative selection. T-cell responses elsewhere in the spleen are unaccompanied by programmed cell death. Our observations define a new differentiation pathway for peripheral T cells and suggest that germinal centres induce a lymphocyte phenotype necessary for the maintenance of self-tolerance.
Calreticulin was identified by immunochemical and sequence analyses to be the higher molecular mass (60 kDa) component of the polypeptide doublet previously observed in a rat liver Golgi endomannosidase preparation obtained by chromatography on a Glc alpha 1 --> 3Man-containing matrix. The affinity for this saccharide ligand, which paralleled that of endomannosidase and was also observed with purified rat liver calreticulin, suggested that this chaperone has lectin-like binding properties. Studies carried out with immobilized calreticulin and a series of radiolabeled oligosaccharides derived from N-linked carbohydrate units revealed that interactions with this protein were limited to monoglucosylated polymannose components. Although optimal binding occurred with Glc1Man9GlcNAc, substantial interaction with calreticulin was retained after sequential trimming of the polymannose portion down to the Glc1Man5GlcNAc stage. The alpha 1 --> 6-mannose branch point of the oligosaccharide core, however, appeared to be essential for recognition as Glc1Man4GlcNAc did not interact with the calreticulin. The carbohydrate-peptide linkage region had no discernible influence on binding as monoglucosylated oligosaccharides in N-glycosidic linkage interacted with the chaperone to the same extent as in their unconjugated state. The immobilized calreticulin proved to be a highly effective tool for sorting out monoglucosylated polymannose oligosaccharides or glycopeptides from complex mixtures of processing intermediates. The copurification of calreticulin and endomannosidase from a Golgi fraction in comparable amounts and the strikingly similar saccharide specificities of the chaperone and the processing enzyme have suggested a tentative model for the dissociation through glucose removal of calreticulin-glycoprotein complexes in a post-endoplasmic reticulum locale; in this scheme, deglucosylation would be brought about by the action of endomannosidase rather than glucosidase II.
This study investigated the effect of intermittent perfusion (IP) pressures on functional preservation of the cold-stored isolated rat heart. The heart was flushed with cardioplegic solution #11 with ethylene diamine-tetraacetic acid and 2, 3-butanedione monoxime (CP-11EB), and stored at 0 degree C for 24 hr. During storage, the heart was intermittently perfused for 3 min at 10 and 17 hr of storage with 25 degrees C oxygenated CP-11EB. The IP pressures studied were: 20, 30, 40, 50, 60, 70, 80, and 100 mm Hg. Poststorage recovery of function was assessed with 30 min of working reperfusion. Control function of the unstored heart was: aortic flow (AF), 51.3 +/- 2.2 ml/min; coronary flow (CF), 25.8 +/- 1.2 ml/min; cardiac output (CO), 77.7 +/- 2.3 ml/min; work, 92.0 +/- 4.9 g-m/min; and coronary vascular resistance (CVR), 2.64 +/- .21 mm Hg-min/ml. Functional return in the 30,40,50,60,70, and 80 mm Hg groups was similar. Recovery in a representative group (60 mm Hg) was: AF, 52 +/- 3%; CF, 41 +/- 2%; CO, 48 +/- 3%; work, 42 +/- 3%; and CVR, 225 +/- 10% of the control. The total IP volume in this group was 71.0 +/- 1.7 ml; total lactate dehydrogenase (LDH) release during IP was 8.62 +/- .37 units/g dry; and end-storage tissue lactate was 52.6 +/- 6.4 mumole/g dry. As IP pressure decreased to 20 mm Hg, cardiac functional recovery declined significantly to AF, 35 +/- 6%; CF, 33 +/- 2%; CO, 34 +/- 5%; and work, 27 = 4% of control (P < .05 vs. 60 mm Hg group). The total IP volume decreased to 10.1 +/- .9 ml, tissue lactate content rose to 87.1 +/- 10.9 (P < .05 vs. 60 mm Hg group), but LDH release fell to 5.59 +/- .46 (P < .05 vs. 60 and 100 mm Hg groups). When IP pressure increased to 100 mm Hg, cardiac function was depressed with AF recovered to 25 +/- 3%; CF, 30 +/- 3%; CO, 26 +/- 3%; work, 21 +/- 3%; and CVR, 294 +/- 26% of control (P < .05 vs. 60 mm Hg group). IP volume increased to 100.7 +/- 2.4 ml; total LDH release increased to 19.1 +/- 1.2 (P < .05 vs. 60 mm Hg group), although tissue lactate (58.9 +/- 3.9) was not different from the 60 mm Hg group. End-storage tissue wet/dry weight ratio and myocardial adenosine triphosphate content were not different among the 20, 60, and 100 mm Hg groups. In conclusion, IP has a broad pressure optimum ranging from 30 to 80 mm Hg for 24-hr hypothermic preservation of the rat cardiac explant.