Biomedical subjects
Publications and source records attributed to G Chen.
A standardized 10,000-volt, 2 + 0.15-A, 5-s electric burn rabbit model was established. Microscopic examination revealed that there was patchy cellular necrosis intermingled with viable cells in the muscle in the burn area. Grossly, there was a distinct interface between viable and nonviable tissues. The resulted injury correlated well with clinical features of electric burn.
After an intraperitoneal injection of cyclophosphamide in rats, there was pathologic changes in hemopoietic, immune and visceral function. Acupuncture respectively at Zusanli, Dazhui and Shenshu points could decrease the above mentioned harms in the rats, the effect of acupuncture on hemopoietic function: Dazhui more than or equal to Zusanli, Zusanli more than Shenshu; the effect of acupuncture on immune function: Zusanli more than Dazhui, Dazhui more than or equal to Shenshu; the effect of acupuncture on the function of the liver and the kidney: Shenshu more than or equal to Zusanli, Zusanli more than Dazhui. The effect of acupuncture at all three points, i.e. Zusanli. Dazhui and Shenshu was more than that at any single point due to their coordination. There was no obvious effect when acupuncture at non-acupoints on tail.
Ultrasonography (B mode) of liver and serum amino-acid levels were studied in 15 cases of schistosomiasis japonica who had been cured for more than 5-15 years. Typical B-ultrasonic images of hepatic fibrosis due to schistosomiasis were found in all patients which could be classified into three types, namely, the spotty type (I), the tortoise-shell type (II) and the net-patchy type (III) according to the patterns of echogenic bands. Moderate to marked echogenic thickening of portal vein wall, and dilation of portal and splenic veins were revealed in patients with type II and III images. Free amino acids in sera were determined by using HPLC-AAAS. The result revealed that the concentration of 8 nonessential and 3 essential amino acids (threonine, valine, tryptophan) were significantly decreased in the 15 patients. The ratio of aromatic to aliphatic amino acid was markedly elevated in 3 patients of type III. The serum amino acid imbalance was attributed to the severe hepatic damage and impaired liver function.
The content of 12 trace elements in the hair of 20 aplastic anemia patients was determined and compared with that of normal subjects as control. The results showed that patients with deficiency of yin had a significant decrease in lithium, calcium, strontium, and chromium, those with deficiency of yang had a distinct decrease in zinc magnesium barium, strontium, calcium, and lithium, and those with deficiency of both yin and yang had a general decrease in all the 12 trace elements. Changes in trace element content in hair may serve as a guide to opening up new vistas in the treatment of aplastic anemia on the basis of an overall analysis of symptoms and signs.
The population pharmacokinetics of theophylline was evaluated using 374 theophylline serum concentration measurements from 72 hospitalized patients through NONMEM analysis. An one-compartment open pharmacokinetic model with first-order absorption and first-order elimination was used. The effects of a variety of factors on Cl and Vd were investigated. Hypothesis testing to evaluated potentially significant factors produced a final regression model. There were about 1.25% per year decrease in Cl at the age of 18-77. Cl was reduced by 26.8% for patients with long history of theophylline administration and multiple dosings, and reduced by 33.9% in OLD patients. Sex, body weight, and coadministration of acetylspiramycin had no significant effects on Cl. Vd was proportional to body weight. The final regression model allowed a priori estimate of the theophylline pharmacokinetic parameters in the patients. These results may be helpful to a rational individualized theophylline dosage regimen.
The nonlinear mixed effect model (NONMEM) method for analysis of population pharmacokinetics, was applied to evaluate the relative biological availability of 2 ofloxacin (Ofl) products. The data of randomized crossover study of 2 kinds of Ofl tablets in 12 healthy volunteers were analyzed by NONMEM, as well as standard approach. The relative biological availability evaluated by NONMEM (F = 97.3 +/- 5.0%) was close to that by standard approach (F = 98.2 +/- 3.6%). NONMEM was also valid in accurately evaluating the relative biological availability using sparse clinical data (F = 91.7 +/- 8.0%) which could not be analyzed by standard approach. Thus, the usefulness and advantages of NONMEM were ascertained for the evaluation of biological availability using observational or experimental data.
Both intracellular (lysate thiol, lysate glutathione and lysate superoxide dismutase) and extracellular (plasma thiol, plasma glutathione and membrane thiol) antioxidant buffering levels were measured in red blood cells from patients with pregnancy-induced hypertension (PIH). We found the following. (1) The levels of plasma thiol and plasma glutathione in PIH women with proteinuria were markedly lower than that in the normal pregnancy. (2) The concentrations of lysate glutathione and superoxide dismutase in PIH women with proteinuria were significantly decreased compared with that in the normal pregnancy. (3) With the exception of plasma and lysate glutathione, all the tested antioxidant markers were not significantly different between PIH women without proteinuria and normal pregnancy. (4) There was no statistical correlation between antioxidant buffering level and BP in patients with PIH. We concluded that both extracellular and intracellular antioxidant buffering levels were decreased in patients with PIH, especially in those with proteinuria. The reduction of the antioxidant buffering level could account for several important pathophysiological features of PIH, such as the elevation of intracellular calcium, decreased red blood cell deformability and endothelial damage.
Nonischemic arterial high flow priapism caused by traumatic laceration of a branch of the penile cavernous artery is rare. We report a case of laceration of the left and right branches of the intracavernous artery, which was confirmed by selective internal pudendal arteriography. Bilateral cavernous artery embolization was performed using gelatin sponge and detumescence occurred immediately. Normal potency was evident 4 months later. Our case demonstrates that selective cavernous arterial embolization is a safe and effective therapy for arterial priapism and that erectile function can return to normal.
Patients with Alzheimer's disease (AD) have been reported to have abnormalities in peripheral cells similar to some of those found in the brain, including decreased levels of protein kinase C (PKC) in fibroblasts. Since increasing evidence suggests that lithium affects PKC function, we investigated the effects of 3 weeks of lithium administration on the immunolabeling of 4 PKC isozymes (alpha, beta, epsilon, and zeta) in particulate and soluble fractions from platelets of 7 patients with probable AD and 6 age-matched controls. AD patients had significantly less particulate or membrane-associated PKC zeta than normals during the placebo phase (P < 0.003). After 3 weeks of lithium treatment, AD patients had significantly less membrane-associated PKC alpha (P < 0.002), epsilon (P < 0.003), and zeta (P < 0.001) than normals. This is the first report of a difference in PKC in blood cells between AD and control subjects. These findings appear to indicate that some PKC isozymes may be differentially regulated in AD versus elderly controls, at least as evidenced in this peripheral cellular system.
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In families that included two or more siblings with schizophrenia or schizo-affective disorder male-male pairs were found to share alleles at the androgen receptor (AR) gene (in Xq11.2-q12) above chance expectation (p < 0.003); female-female and mixed sex pairs showed no such tendency. The findings are compatible with X-Y linkage or with an X-linked contribution to liability in males.
The relationship between X chromosome-linked adrenoleukodystrophy and the red/green color pigment gene cluster on Xq28 was investigated in a large kindred. The DNA in a hemizygous male showed altered restriction fragment sizes compatible with at least a deletion extending from the 5' end of the color pigment genes. Segregation analysis using a DNA probe within the color pigment gene cluster showed significant linkage with adrenoleukodystrophy (logarithm of odds score of 3.19 at theta = 0.0). These data demonstrate linkage, rather than association, between a unique molecular rearrangement in the color pigment gene cluster and adrenoleukodystrophy. The DNA changes in this region are thus likely to be helpful for determining the location and identity of the responsible gene.
The effect of thaliblastine (TBL, NSC-68075), a plant alkaloid, in over-coming multidrug resistance was investigated in doxorubicin (ADR)-resistant murine leukemic P388/R-84 cells. In the soft agar clonogenic assay, a nontoxic concentration of TBL (2 microM) reduced the 50% inhibitory dose of ADR (1-h exposure) from 10.8 to 1.4 microM with a dose modification factor of 7.7. Continuous treatment of P388/R-84 cells with ADR and TBL for 24 h further lowered the 50% inhibitory dose from 3.5 to 0.07 microM, the resistance level being decreased from 233-fold in the absence of TBL to 4.7-fold in the presence of TBL as compared to the parental P388 cells. Although ADR or TBL individually had no detectable effects on cell cycle traverse, the combination of the two drugs caused a significant G2 block. Flow cytometric analysis showed that TBL enhanced ADR retention in P388/R-84 cells in a dose- and time-dependent manner. TBL partially blocked the photolabeling of P-glycoprotein with [3H]azidopine, and this blocking effect was further enhanced in combination with ADR. Our results indicate that TBL can reverse multidrug resistance by direct interaction with P-glycoprotein, thereby increasing cellular ADR retention.
A two-phase liquid-culture system was used to substantially amplify and differentiate erythroblasts, starting with mononuclear cells from the blood of normal adults, newborn infants, and patients with sickle cell anemia. After the first 7 days (phase 1), in medium plus fetal bovine serum (FBS) alone, or in combination with stem cell factor (SCF) or conditioned medium (CM), the cell number was unchanged, and the cells all looked like lymphocytes. These cells were then diluted into medium with erythropoietin (Ep) alone, with Ep and either SCF or CM, or in methylcellulose with the same factors (phase 2). After 14 days in liquid phase 2 with SCF and Ep, the cell numbers increased an average of 30-fold in the sickle, 24-fold in the newborn, and 4-fold in the normal adult cultures; almost all the cells were erythroblasts and erythrocytes. SCF in phase 1 increased the number of late progenitors (CFU-E) assayed in methylcellulose, with the largest number in sickle, followed by newborn cultures and then adult cultures. We conclude that erythroid progenitor cells survive for at least 7 days without Ep (but with FBS). Progenitor cells are amplified, particularly with SCF. Later in culture, SCF with Ep increases the final number of differentiated erythroid cells. Both the early and the late effects of SCF are most effective in sickle, followed by newborn cultures and then adult cultures.
Using electronic states and phonon states from the first-principles calculations and including both conventional electron-phonon charge coupling and Jahn-Teller coupling, we predict Tc and other superconducting properties. The only adjustable parameter in the theory is the screening length, Rsc. Using Rsc = 0.8-1.0 A, we find excellent agreement with experiment for Tc (16-18 K), pressure dependence of Tc (Delta Tc = -6 to -10 K for 1 GPa), and 12 C to 13 C isotope shift (alphaC = 0.2); experimental values: 19 K, -7 K, and 0.3, respectively.
Adult diarrheal rotavirus (ADRV) is a currently noncultivatable group B human rotavirus responsible for epidemic outbreaks of gastroenteritis in China. Gene segment 5 of ADRV encodes the major inner capsid protein, VP6. ADRV gene 5 was inserted into a recombinant baculovirus by homologous recombination between baculovirus shuttle plasmid pACYM1-AD5 and AcNPV genomic DNA. Baculovirus recombinants were selected visually and plaque purified and VP6 expression was detected by Coomassie staining of PAGE-separated proteins. The baculovirus-expressed gene 5 polypeptide is 44 kDa, the same as for the major inner capsid protein present on EDTA-treated ADRV virions and in vitro-expressed VP6 protein. The expressed protein is oligomeric and in the absence of reducing agents multimerizes to apparent trimer, hexamer, and greater molecular mass as assayed by SDS-PAGE. The VP6 protein is immunoprecipitable by hyperimmune serum to ADRV, human ADRV convalescent serum, by a group B-specific monoclonal antibody and by porcine group B rotavirus infection serum. The baculovirus-expressed protein is immunogenic and antibodies to the expressed protein recognize ADRV virions. The ADRV VP6 protein should be useful for developing diagnostic assays for serum antibodies to group B rotavirus as well as for generating hyperimmune serum and monoclonal antibodies for detecting viral antigen from ADRV and other group B rotaviruses.
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At a concentration of 2.5 mM, nicotinamide (NA), an inhibitor of poly(ADP-ribose) polymerase (PARP), significantly potentiated the cytotoxicity of cisplatin (DDP) in a DDP-resistant rat ovarian tumor cell line (O-342/DDP) in vitro, whereas the same treatment had no substantial effect on DDP's cytotoxic activity against the DDP-sensitive parental line (O-342). Furthermore, in a nude mouse model where the O-342/DDP tumor grew intraperitoneally, whereas DDP given alone at 1 mg/kg x 3 exhibited no antitumor activity as compared with control values due to the resistance, NA given at a nontoxic dose (5 mmol/kg x3) significantly increased the mean survival time (MST) of the tumor-bearing NMRI nude mice from 20.7 days in the DDP-treated group to 29.0 days in the combination group. Mechanism studies showed that endogenous PARP activity (incorporation of tritiated nicotinamide adenine dinucleotide, [3H]-NAD) was 2.6 times higher in O-342/DDP than in O-342 cells and that the presence of 2.5 mM NA during the incubation with the isotope resulted in 73.3% inhibition of the enzyme activity in O-342/DDP cells but in only about 30% inhibition in the sensitive line. However, treatment with NA during and after DDP exposure failed to produce any significant effect on the formation of DNA single-strand breaks (SSB) but decreased the induction of DNA interstrand cross-links (ISCL) by DDP in the sensitive and resistant cell lines. These results suggest that NA might have some clinical potential in reversing DDP resistance, and further studies are therefore warranted to confirm the resistance-reversing effect of NA in other DDP-resistant cell lines.