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Biomedical subjects

Q Cai

Publications and source records attributed to Q Cai.

At least 91 records · Page 5Linked to original sources
PubMed1995

Effects of caloric restriction on age-related oxidative modifications of macromolecules and lymphocyte proliferation in rats.

Decreased immune function associated with aging has been demonstrated in both humans and animals. We hypothesize that reactive oxygen species (ROS)-mediated damage to biological macromolecules may contribute to compromised immune response during aging. In this study, we compared the levels of lipid peroxidation and oxidatively modified proteins in plasma and splenocytes, and the mitogen-induced T lymphocyte proliferation in ad lib-fed (AL) and caloric restricted (CR) Fischer 344 x BNF1 male rats at the ages of 5, 18, and 31 months. The results show that AL rats exhibit an age-related decrease in proliferative response of splenic lymphocytes to phytohemagglutinin (PHA) and concanavalin A (Con A). This functional decline in T-lymphocytes during aging is inversely correlated to the levels of both lipid peroxidation and protein carbonyl in the plasma and splenic lymphocytes. Caloric restriction, however, can partially reverse the age-dependent decrease in T lymphocyte proliferation and significantly reduce lipid peroxidation and protein carbonyl contents in plasma and splenocytes. The above observations support the hypothesis that the age-associated declines in immune function are related to the oxidative modification of biological macromolecules, which in turn may lead to enzyme inactivation, membrane disruption, and cell senescence. One of the mechanisms by which caloric restriction reverses declined immune function in aged rats is hypothesized to be through reduction in ROS production and thereby protection of cellular macromolecules against oxidative damage.

Aging↗
PubMed1995

Antioxidative properties of histidine and its effect on myocardial injury during ischemia/reperfusion in isolated rat heart.

We wished to determine whether histidine scavenges hydroxyl radical, H2O2, and superoxide anion in vitro and to investigate the protective effect of histidine on isolated perfused rat hearts after global ischemia (40 min) and reperfusion (30 min) (I/R). Left ventricular (LV) function was recorded and coronary effluent was collected for measurement of lactate dehydrogenase (LDH) before ischemia and at 5, 10, 15, and 30 min of reperfusion. At the end of the experiment, a portion of the LV wall was fixed with 2% glutaraldehyde for morphological analysis; the remaining heart was immediately frozen in liquid nitrogen for determination of adenine nucleotides. Histidine effectively quenched hydroxyl radicals and H2O2, but not superoxide anions, in in vitro and in vivo conditions. Hearts treated with histidine exhibited significantly greater functional recovery during reperfusion as compared with nontreated hearts (p < 0.05). Cell morphology was well preserved, and enzyme release was significantly attenuated by histidine treatment (p < 0.05). Histidine raised the ATP level to 73% and the creatine phosphate level to 68% of normal control during reperfusion. Total adenine nucleotide pool and energy charge rate in histidine-treated hearts significantly increased as compared with those in nontreated hearts (p < 0.05), but no effect on ATP and creatine phosphate was noted during ischemia, Histidine prevents postischemic reperfusion injury in isolated heart by inhibiting reactive O2 species and preserving high-energy phosphates (HEP).

Adenosine Triphosphate↗
PubMed1995

Antioxidant and antipromotional effects of the soybean isoflavone genistein.

Antioxidant and antipromotional effects of the soybean isoflavone genistein have been studied in HL-60 cells and the mouse skin tumorigenesis model. Effects of structure-related flavone/isoflavones on hydrogen peroxide (H2O2) production by 12-O-tetradecanoylphorbol-13-acetate (TPA)-activated HL-60 cells and superoxide anion (O2-) generation by xanthine/xanthine oxidase were compared. Of tested isoflavones, genistein is the most potent inhibitor among TPA-induced H2O2 formation by (dimethyl sulfoxide) DMSO-differentiated HL-60 cells, daidzein is second, and apigenin and biochanin A show little effect. In contrast, genistein, apigenin, and prunectin are equally potent in inhibiting O2- generation by xanthine/xanthine oxidase, with daidzein showing a moderate inhibitory effect and biochanin A exhibiting no effect. These results suggest that the antioxidant properties of isoflavones are structurally related and the hydroxy group at Position 4' is crucial in both systems. Dietary administration of 250 ppm genistein for 30 days significantly enhances the activities of antioxidant enzymes in the skin and small intestine of mice. Further studies show that genistein significantly inhibits TPA-induced proto-oncogene expression (c-fos) in mouse skin in a dose-dependent manner. In a two-stage skin carcinogenesis study, low levels of genistein (1 and 5 mumol) significantly prolong tumor latency and decrease tumor multiplicity by approximately 50%. We conclude that genistein's antioxidant properties and antiproliferative effects may be responsible for its anticarcinogenic effect. Its high content in soybeans and relatively high bioavailability favor genistein as a promising candidate for the prevention of human cancers.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

Genetically marking human cells--results of the first clinical gene transfer studies.

The rapid development of both knowledge and techniques in molecular biology have made it possible to engineer genetic constructs and transfer them into cells of individuals with various diseases. Such gene therapies may alleviate or perhaps even cure diseases for which no adequate treatment now exists. One potential application is to treat genetic disease by inserting a normal gene into cells in individuals with a "malfunctioning" gene. The added genetic information could allow these cells to function properly and might reduce or eliminate the sequelae of the disease. Such genetic manipulation could also be used to combat other diseases using the same general technique. For example in cancer patients, various cytokine genes inserted into tumor cells may serve as components of a tumor vaccine because such cytokine-secreting tumor cells can induce a significant T-cell response in experimental animal models when compared with non-gene-modified tumors, ultimately leading to a systemic immune response. In addition to treating patients, transferred genes also can serve as markers to obtain important information about the fate of otherwise indistinguishable cells. For example, we used a genetic marker to label tumor-infiltrating lymphocytes (TILs) to monitor their in vivo survival and ability to "home" to tumor sites. Gene markers also were transferred into autologous bone marrow cells to study the mechanism of tumor relapse. This review will focus primarily on studies using gene markers to track TILs after transfer. We will focus on the following issues: (a) that TILs are potent antitumor cells, mediating partial and complete responses in patients with melanoma; (b) the importance of the initial gene marked TIL study; (c) safety considerations in the use of gene marking/gene therapy; (d) results of gene-marked TIL studies; and (e) other gene-marked cells.

Animals↗
PubMed1995

Inhibitors of renal epithelial phosphate transport in tumor-induced osteomalacia and uremia.

Tumors such as sclerosing hemangiomas are sometimes associated with hypophosphatemia and osteomalacia, both of which disappear on removal of the tumor. We identified a heat labile, 8,000-25,000 dalton, inhibitor of renal epithelial phosphate transport in supernatants of cultured sclerosing hemangioma cells obtained from a patient with oncogenic osteomalacia and hypophosphatemia. The inhibitor does not alter glucose or alanine transport in renal epithelial cells, and has a mechanism of cellular action distinct from that of parathyroid hormone (PTH) in that it inhibits phosphate transport in renal epithelia without increasing concentrations of cyclic 3',5' adenosine monophosphate (cAMP); it's activity is not blocked by a PTH receptor antagonist. Sclerosing hemangioma cells also produce a material that cross-reacts with antisera directed against PTH and tumor tissue sections immunostain with PTH antibodies. We have characterized a cDNA that encodes the PTH immunoreactive material. In its longest open reading frame the cDNA encodes a protein of 381 amino acids that does not resemble PTH in its primary structure. Opossum kidney cells transfected with the cDNA do not produce a product that inhibits phosphate transport. Dialysates from patients with end-stage renal disease also contain a substance(s) that inhibits phosphate and glucose transport in opossum kidney cells. The inhibitor(s) of phosphate uptake in dialysates is a heat labile, approximately 30,000 dalton substance that inhibits phosphate transport by a cAMP-independent mechanism. Determination of the structures and physiology of these phosphate transport inhibitors is likely to yield insights into the control of phosphate homeostasis.

Amino Acid Sequence↗
PubMed1995

Pharmacokinetics of ceftizoxime in renal failure patients without dialysis.

AIM: To investigate the pharmacokinetics of ceftizoxime (Cef) in renal failure patients without any dialysis and supply the basis for a suitable clinical regimen. METHODS: Cef in plasma and urine was assayed by HPLC. RESULTS: After injecting Cef 16.7 mg kg-1, Cef concentration in blood was described as a 2-compartment open model. The main pharmacokinetic parameters were Vd 0.55 +/- 0.17 L kg-1; AUC 879 +/- 460 mg L-1 h; Cl 27 +/- 11 mL kg-1 h-1. T1/2 beta was 15 +/- 4 h. CONCLUSION: T1/2 beta in renal failure patients was about 10 times longer than that in normal volunteers. The clinical regimen should be adjusted in renal failure patients with infection, either prolonging the interval between Cef administration, or decreasing Cef dosage.

Ceftizoxime↗
PubMed1994

Modulation of the excitability of avian peripheral nerves by vitamin D: relation to calbindin-D28k, calcium status and lipid composition.

Calbindin-D28k (CaBP), previously localized in some of the cell bodies of ganglia of the avian intestinal (Remark's) nerve, was shown to be vitamin D-dependent. In the present studies, the effect of vitamin D3 on electrophysiological properties of this nerve was examined in vitro. Electrical stimulation of the nerve yielded a compound action potential with two primary components, Peaks I and II. Peak II, suppressed by hexamethonium bromide or Ca(2+)-free buffer, is synaptically mediated. The transit time between the two peaks was unaffected by vitamin D3. The apparent conduction velocity, defined as [(activation time + transit time)/nerve length], was increased by vitamin D-deficiency and decreased by vitamin D3 repletion, the latter decrease due entirely to an increase in activation time. Activation time after vitamin D-repletion was correlated with an increase in CaBP and plasma Ca2+ levels. However, normalization of plasma Ca2+ by supplementation of vitamin D-deficient diets with excess calcium (2.5 and 4.0%) also resulted in an increase in activation time, without affecting neuronal CaBP levels. Vitamin D3 also decreased the conduction velocity and increased CaBP of the vagus nerve and, by lipid analysis, was shown to increase and decrease its phosphatidylcholine and phosphatidylethanolamine content, respectively, and to decrease its phospholipid/cholesterol ratio. Modulation of peripheral nerve activity by vitamin D3 is related to calcium status and perhaps to changes in lipid composition. The functional role of CaBP in the behaviour of this complex nerve remains unknown.

Animals↗
PubMed1994

Construction and characterization of retroviral vectors expressing biologically active human interleukin-12.

Interleukin-12 (IL-12) is a heterodimeric cytokine originally defined by its ability to induce the maturation of cytolytic lymphocytes and by its capacity to effectively synergize with IL-2 in the induction of cytolytic activity. Recent studies in mice have demonstrated the ability of IL-12 to cause tumor regression and stimulate long-term antitumor immunity in treated animals. To examine the antitumor effect of direct gene transfer of IL-12 into tumors, we have developed retroviral vectors that coordinately express both subunits of IL-12. An MFG-based retroviral vector was used to generate a recombinant retrovirus in which a long terminal repeat (LTR)-driven polycistronic transcript encodes both subunits of human IL-12: hp35 and hp40 cDNAs are linked and coexpressed using the internal ribosome entry site (IRES) from the encephalomyocarditis virus (DFG-hIL-12). In addition, two IRES sequences were used to express both subunits of IL-12 and a neomycin resistance (neoR) selectable marker gene from the same polycistronic message (TFG-hIL-12). The amphotropic DFG-hIL-12 and TFG-hIL-12 viruses were used to infect both human and murine cell lines as well as primary tumor cultures. The production of human IL-12 by the nonselected, infected cells was measured in both a PHA blast proliferation bioassay and an ELISA and ranged from 15 to 40 ng/10(6) cells per 24 hr. Following G418 selection of TFG-hIL-12-infected cells, the level of expression of IL-12 was significantly higher (up to 120 ng/10(6) cells per 24 hr). The IL-12 protein secreted by the infected cells exhibited all of the biologic activities of recombinant hIL-12: proliferation of activated natural killer (NK) and T cells, stimulation of interferon-gamma (IFN-gamma) induction by NK and T cells, and enhancement of lymphokine-activated killer (LAK) activity. These retroviral vectors expressing human IL-12 should be useful in evaluating the biological properties of IL-12 as well as for use in clinical trials for gene therapy of patients with cancer.

Animals↗
PubMed1993

Vitamin D and adaptation to dietary calcium and phosphate deficiencies increase intestinal plasma membrane calcium pump gene expression.

The effect of vitamin D and other variables on the synthesis of the chicken intestinal plasma membrane calcium pump (PMCA) mRNA was assessed. The DNA probe for Northern analysis was obtained by reverse transcription and PCR with intestinal poly(A)+ RNA, using two 20-mer oligonucleotide primers homologous to the 3' coding region of the human teratoma PMCA. An EcoRI restriction fragment of the PCR product was cloned into the pBluescript II KS(-) phagemid vector, and the chimeric plasmid was used to transform Escherichia coli. The amino acid sequence deduced from the nucleotide DNA sequence of the PCR product and the cloned DNA were 96% homologous with the teratoma sequence. Northern blots of intestinal poly(A)+ RNA with 32P-labeled DNA showed the presence of three major species of chicken PMCA mRNAs at about 6.6, 5.4, and 4.5 kb. Northern analysis with the chicken PMCA DNA indicated that repletion of vitamin D-deficient chickens with vitamin D increased PMCA mRNAs in the duodenum, jejunum, ileum, and colon. After injection of 1,25-dihydroxyvitamin D3 intravenously into vitamin D-deficient chickens, duodenal PMCA mRNA tended to increase by 2 hr, reached a maximum at about 16 hr, and returned to baseline levels at 48 hr. Adaptation of chickens to either a calcium- or phosphorus-deficient diet resulted in a 2- to 3-fold increase in duodenal PMCA mRNA. These results indicate that vitamin D and specific variables that affect calcium absorption through the vitamin D-endocrine system increase intestinal PMCA gene expression.

Amino Acid Sequence↗
PubMed1993

The hypoxic moderation of systemic hypertension in spontaneously hypertensive rats.

The mechanism of hypoxic moderation of systemic systolic blood pressure was investigated in spontaneously hypertensive rats (SHR). Male SHR rats were divided into hypoxic (H, 5000 m for 15 d) and normoxic (N) groups. The systemic blood pressure of SHR-H (24.9 +/- 1.2 kPa) was found to be 3 kPa lower than that in SHR-N (27.0 +/- 1.3 kPa) (P < 0.05). This protective effect may have been related to the adaptive changes in vascular reactivity which manifested as an increase in the relaxation response of the aorta to ACh (P < 0.01) and a drop in its contraction in response to 5-HT (P < 0.05) following hypoxic exposure. The hypoxic moderating effect against the development of systemic hypertension may have also been related to the increased plasma levels of ANP observed.

Altitude↗
PubMed1993

[Electrophoretic analysis of isoenzyme and protein patterns of Romanomermis yunanensis and R. culicivorax (Nematoda:Mermithidae)].

Isoenzyme electrophoretic patterns of lactate dehydrogenase (LDH), malate dehydrogenase (MDH), esterase (EST) and peroxidase (PO) of post-parasitic juveniles and adults of Romanomermis yunanensis and R. culicivorax were analysed by disc electrophoresis, respectively. The protein patterns of the two species of Romanomermis were compared by vertical slab SDS polyacrylamide gel electrophoresis. The results showed marked differences in isoenzyme patterns (number of bands and/or Rf) of LDH and MDH between the two species of Romanomermis, but the similar positions of isoenzyme bands denoted a certain genetic relationship between them. No band was found in the isoenzyme patterns of PO and EST. Distinct differences in protein pattern were observed between the two species of Romanomermis, but some common bands in pattern reflected the phylogenetic relationships of these species. The differences of isoenzyme and protein patterns observed in this study have provided the reason for identifying and differentiating the two species of Romanomermis at the molecular level.

Animals↗
PubMed1992

Use of T-cell growth factors (interleukins 2, 4, 7, 10, and 12) in the evaluation of T-cell reactivity to melanoma.

Melanoma represents the single best example of a human tumor that has been shown to elicit specific T-cell reactivity. The responsiveness of some patients with metastatic melanoma to treatment with the prototypic T-cell growth factor (TCGF), interleukin-2 (IL-2), indicates that T cells play a role in antitumor immunity. Interleukin-4 (IL-4), another TCGF that has been administered clinically to humans, was not associated with tumor response in our trials conducted at the Surgery Branch of the National Cancer Institute. Combination trials of IL-2 with IL-4 have shown no increase in responsiveness of melanoma or other tumors when compared to IL-2 alone. However, enhanced expansion of tumor-infiltrating lymphocytes (TILs) in vitro has been observed with combinations of low-dose IL-2 and IL-4. We have begun a study evaluating the trafficking of such expanded lymphocytes following their adoptive transfer in association with systemic administration of IL-2 and IL-4. We have established several TIL cultures from fresh tumor samples, maintained them in long-term culture, and marked them with the neomycin phosphotransferase gene using the LNL6 retroviral vector. Such TILs appear to demonstrate no notable alterations in phenotype or cytolytic activity when compared to their nontransduced counterparts. In addition to IL-2 and IL-4, there are a variety of other novel TCGFs that are now available for evaluation in preclinical and clinical trials. IL-7 induces proliferation and lymphokine-activated killer (LAK) cell activity from human peripheral blood mononuclear cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗
PubMed1992

The relationship between the changes in plasma atrial natriuretic peptide and renin angiotensin contents and hemodynamics in pulmonary hypertensive rats.

Pulmonary artery pressure (PAP) increased significantly in rats after hypobaric hypoxic exposure for 15 days (CH15) (P less than 0.001) and was maintained at the same level after prolonged hypoxic exposure for 40 days (CH40). There were no significant changes in carotid systolic and diastolic blood pressure in CH15 and CH40 rats. The contractility of the right and left ventricles of CH15 and CH40 rats showed no difference as compared with the control group. Plasma atrial natriuretic peptide (ANP) content in CH40 rats was obviously increased (P less than 0.001), while angiotensin II (AII) dropped markedly (P less than 0.05). Plasma renin activity was increased in both hypoxic groups (P less than 0.05 respectively). These results indicate that during chronic hypoxia, plasma ANP and the renin-angiotensin system (RAS) play an important role in the modulation of pulmonary as well as systemic hemodynamics. They may work cooperatively to limit the development of pulmonary hypertension and to maintain systemic blood pressure within the normal range.

Angiotensin II↗
PubMed1991

Hormonal effects on the sulfhydryl groups associated with intestinal brush border membrane proteins.

Previous studies demonstrated that the administration of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) to cholecalciferol-deficient chicks rapidly increases the reactivity and amount of the sulfhydryl (HS-) groups in intestinal brush border membranes (BBM). In the present study, the tissue and hormonal specificity of this effect was investigated. The HS- groups of intestinal and renal BBM were enhanced by vitamin D-3 and/or 1,25(OH)2D3, but no change was noted in isolated intestinal mitochondria and purified intestinal basolateral membranes, cardiac sarcolemma and erythrocyte membranes. Other steroid hormones including estradiol, testosterone, aldosterone, cortisol, dexamethasone and progesterone, yielded a response similar to 1,25(OH)2D3 on BBM HS- groups. Triiodothyronine and retinoic acid also resulted in an increase in intestinal BBM HS- groups. In a kinetic approach, using a specific sulfhydryl fluorescent probe (N-7-dimethylamino-4-coumarin-3-yl-maleimide, DACM), the reactivity of the BBM HS- groups was increased by estrogen and testosterone, as was previously shown for 1,25(OH)2D3. Intestinal BBM proteins, labeled with DACM, were separated by gel electrophoresis. Fluorescence scans of the gel showed two heavily labeled bands, one of 110 kDa, putatively brush border myosin I, and one of 43 kDa, putatively actin. Labeling of the 110 kDa protein was increased by 1,25(OH)2D3 and estradiol. Further studies are required to elucidate the physiological meaning of these hormone-mediated increases in reactivity and amount of the BBM sulfhydryl groups, as well as the nature of the intermediate biochemical reactions involved in this response.

Animals↗
PubMed1991

[Protective effect of sheng mai injection on myocardial injury induced by adriamycin in cultured myocardial cells].

The effect of sheng mai injection (SMI) on adriamycin-induced cardiotoxicity in cultured myocardial cells was examined. Adriamycin treatment (1 mg/L) for 4 h of culture age, increased remarkably the leakage of lactate dehydrogenase (LDH) from the myocardial cells, and induced the damage of ultrastructure. SMI (30 mg/L, 100 mg/L, 300 mg/L) had no effects on these changes induced by adriamycin. The results showed that SMI had no direct protective effect on adriamycin cardiotoxicity in cultured myocardial cells. It's protective effect on adriamycin cardiotoxicity seems to be in whole body level, the mechanism of which was relating to the metabolism of the drug in organism, and is worthy of further research.

Animals↗
PubMed1990

Antibody-dependent cellular cytotoxicity mediated by CD16+ lymphocytes from HIV-seropositive homosexual men.

We investigated the ability of peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-seropositive asymptomatic and mildly symptomatic homosexual men with known time of seroconversion to mediate antibody-dependent cellular cytotoxicity (ADCC) specific for HIV. PBMC from HIV-seronegative and -sero-positive subjects lysed T (CEM) cells persistently infected with HIV to a significantly greater degree than uninfected CEM cells in the presence of HIV antibody-positive serum in a 4-hr 51Cr release assay. The response was mediated by CD16+ cells. ADCC responses were lower in PBMC of 13 men tested 9 to 25 months (average, 16.1 months) after seroconversion to HIV as compared with seronegative subjects, and were further decreased in 11 men tested 26 to 38 months (average, 31.6 months) after seroconversion. Decreases in numbers of circulating CD16+ cells appeared to contribute to depression in ADCC activity. The suppressive effect of HIV infection on ADCC effector cell activity may be important in the immunopathogenesis of acquired immune deficiency syndrome.

Antibodies↗