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Biomedical subjects

L X Zhang

Publications and source records attributed to L X Zhang.

At least 73 records · Page 4Linked to original sources

Effect of CCK-8 on audiogenic epileptic seizure in P77PMC rats.

P77PMC rat is a breed of rat with congenital audiogenic seizure(AS). AS attacks were suppressed by cholecystokinin octapeptide (CCK-8) injected intraperitoneally (i.p.) at a dose of 50 micrograms/kg, but not at 25 micrograms/kg. Radioimmunoassay study showed that the CCK-8 immunoreactivity (IR) in the cerebrocortex and hippocampus is much lower in P77PMC rats than that of Wistar rats. The results suggest that a low cerebral content of CCK-8 may account for the high susceptibility of audiogenic seizure in P77PMC rats.

Acoustic Stimulation↗

A synthetic C22 carotenoid inhibits carcinogen-induced neoplastic transformation and enhances gap junctional communication.

In 10T1/2 cells several dietary carotenoids have previously been shown to be capable of inhibiting carcinogen-induced neoplastic transformation. Two synthetic novel compounds, a C22 carotenoid, C22-polyene-tetrone-diacetal, and a C28 carotenoid, C28-polyene-tetrone, have now been tested in this system. The C22 compound was active in completely inhibiting 3-methylcholanthrene-induced transformation at 10(-5) M when added during the post-initiation phase of carcinogenesis. Gap junctional intercellular communication was strongly upregulated at this concentration. This activity has previously been shown to be highly correlated with, and has been proposed to be mechanistically linked to, inhibition of transformation by carotenoids in 10T1/2 cells. In contrast, the C28 compound, previously reported to be more active as a singlet oxygen quencher than C22, did not demonstrate activity in 10T1/2 cells in either assay system. This lack of activity was not due to chemical instability or lack of cellular uptake: the C28 compound was more stable in cell culture medium over 7 days and achieved higher cellular levels than the C22 compound (5 x 10(-11) mol/10(6) cells versus 0.5 x 10(-11) mol/10(6) cells). The activity of the C22 compound was not due to toxicity, since transformation occurred in carcinogen-treated cultures after its removal; neither was it due to antiproliferative effects on transformed cells, since the C22 compound did not prevent focus formation by transformed cells in reconstruction experiments. The demonstration that synthetic carotenoids possess biological activities comparable to the most potent naturally occurring compounds suggest that rational synthesis of compounds with improved pharmacological properties should be possible.

Acetals↗

Inhibitors of endogenous nitrogen oxide formation block the promotion of neoplastic transformation in C3H 10T1/2 fibroblasts.

The endogenous production of nitric oxide (NO) and its role in the neoplastic transformation of C3H 10T1/2 mouse fibroblasts were investigated. NO production, as indicated by NO2- in the culture medium, was increased in cells initiated with 3-methylcholanthrene or stimulated with the combination of interferon-gamma (IFN gamma, 10 ng/ml) plus bacterial lipopolysaccharide (LPS, 1 micrograms/ml). NO2- was detectable within 24-48 h of IFN gamma/LPS treatment and accumulated to micromolar concentrations within 4 days. NO production was inhibited in a dose-dependent manner by analogs of L-arginine in which the terminal guanidino nitrogen is blocked, consistent with NO production by the oxidative deamination of L-arginine by nitric oxide synthase (NOS). IFN gamma/LPS-stimulated cells expressed a 4.4 kb mRNA which hybridized to a probe for the mouse macrophage-inducible NOS. Expression of the rat cerebellar constitutive NOS was not detected in these cells. Arginine analogs added to the culture medium during the post-confluence promotional stages of the C3H 10T1/2 transformation assay blocked the formation of transformed foci in a dose-dependent manner comparable to their inhibition of NO production. These data demonstrate that C3H 10T1/2 mouse fibroblasts are a useful model for the study of the effects of endogenous NO production in carcinogenesis and suggest that NO plays a significant role in the promotional phase of neoplastic transformation of these cells.

Amino Acid Oxidoreductases↗

[Fluidity of red blood cell membrane from mouse infected with Malaria parasite].

The fluidity of membrane lipid regions of Plasmodium berghei- or Plasmodium yoelii-infected red blood cells has been determined by the fluorescence polarization technique using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a probe. The results showed that the fluidity of Plasmodium (berghei or yoelii)-infected red blood cell membranes was increased significantly as compared with that of normal controls judging from the degree of polarization and the microviscosity. Its mechanism was discussed briefly.

Animals↗

[Further report on application of DNA probe in diagnosis of vivax malaria infection].

Southern blotting with a labeled and linearized pUC 19 DNA containing a specific fragment of 0.24 kb DNA of Plasmodium vivax asexual blood stages (kindly offered by Dr. C. Kidson) was used for further identification of blood samples showing positive reaction by dot-blot hybridization. The results showed that those with positive reaction from patients with P. vivax, with P. falciparum or with fever but with negative microscopic findings were also positive by Southern blotting. It was confirmed that some of those positive with P. falciparum were likely to infect P. vivax at the same time. So did a part of those with fever but negative in the blood films (Figs. 1,2).

Animals↗

[Effect of Japanese Ganoderma Lucidum on production of interleukin-2 from murine splenocytes].

The purpose of this study was to determine the effect of Ganoderma lucidum (GL) planted in Japan on the production of Interleukin-2 (IL-2) from murine splenocytes. It was observed that hydrocortisone (HC) 0.025-1 microgram /ml could significantly antagonize the inhibitory activity of HC and CSA to increase the production of IL-2 in vitro, P < 0.01. When the splenocytes pretreated with GL alone or in combination with HC, it was shown that pretreatment alone had no significant effect on IL-2 production, but preincubating splenocytes with HC and GL resulted in a significant increase of IL-2 production when compared with that of HC group, P < 0.01. In vivo, GL 300 mg/kg could increase the production of IL-2 when oral taken GL alone or in combination of HC.

Animals↗

[Effects of microiontophoretically applied ACH and atropine on the electric activities of neurons in nucleus parafascicularis of thalamus in rats].

The effects of acetylcholine (ACh) and atropine on the electric activities of neurons of nucleus parafascicularis thalami (Pf) were observed in anesthetized rats with multimicropipette technique and iontophoresis. It was found that the spontaneous and pain-induced discharges of the Pf neurons were excited and some of non-nociceptive neurons became sensitive to nociceptive stimulation with microiontophoretically applied ACh, while microiontophoretically applied atropine could diminish the spontaneous and pain-induced discharges of the Pf neurons. The effects of ACh above could be blocked by microiontophoretically applied atropine. The results show that ACh may have excitatory effects on the electric activity of the Pf neurons by M-receptor.

Acetylcholine↗

Carotenoids up-regulate connexin43 gene expression independent of their provitamin A or antioxidant properties.

Epidemiological evidence and studies in whole animals and cell culture have indicated that carotenoids have cancer chemopreventive action. In mouse C3H10T1/2 cells, this activity is highly correlated with the ability of carotenoids to up-regulate gap junctional intercellular communication. Here, we report that in mouse cells, carotenoids increase the expression of connexin43, a gene that encodes a major gap junction protein. This effect appears unrelated to their provitamin A or antioxidant properties, since carotenoids with and without provitamin A activity increased levels of connexin43 mRNA and protein, whereas the antioxidants methyl-bixin and alpha-tocopherol were inactive. Moreover, the active carotenoid canthaxanthin did not induce the vitamin A-inducible gene retinoic acid receptor-beta. Connexin43 is the first carotenoid-inducible gene described in mammals. By indicating an additional pathway through which carotenoids function, these data provide a mechanistic basis for cancer chemoprevention by carotenoids and may lead to a re-evaluation of carotenoid physiology.

Animals↗

Tuberculosis control programme in Beijing.

Since 1978 a new tuberculosis control programme based on modern concepts has been started in Beijing. The main goals of the programme were: (1) To prioritize the control of sources of infection; (2) to instigate fully supervised treatment (FST) for new smear-positive patients; (3) to extend services to the rural areas. A four-level network of tuberculosis control services has been organized both in urban and rural areas. Tuberculosis control has been integrated into rural primary health care. Coverage of FST among new smear-positive cases increased to 93% in 1990. A standard regimen, 1HS/11H2S2 has been used for initial treatment. A reserve regimen of RFP and EMB was added to those who failed to convert in 6 months. Since 1988 a 6-month intermittent short-course regimen has been introduced as standard regimen. Case-finding has been intensified since 1980 through symptomatics. Control of chronic excreters was achieved through FST of new smear-positive cases and fully supervised retreatment of old chronic cases. The new tuberculosis control programme has proved highly successful in controlling sources of infection. The prevalence of smear-positive pulmonary tuberculosis in Beijing during the national surveys in 1979, 1984-1985 and 1990 was 127, 56 and 16 per 100,000 respectively. The average annual reduction rate was 17%. This successful experiment has been recognized as a model for the whole country.

Antitubercular Agents↗

Inhibition of cellular transformation by triphenylmethane: a novel chemopreventive agent.

Triphenylmethane (TPM) was found to inhibit 3-methyl-cholanthrene-induced neoplastic transformation of 10T1/2 cells in a dose-dependent manner (ED50 = 2.8 microM). This activity was independent of any effect on intercellular communication and did not appear to be directly related to the general antioxidant properties of TPM as measured by cellular thiobarbituric acid-reactive substances. Triphenylmethanol (TPMOL) and diphenylmethane also inhibited transformation (ED50 = 6.9 and 90 microM respectively). TPM had no effect on the proliferation of exponentially growing cells. At higher concentrations TPM and its analogues enhanced plating efficiency of cells indicating no significant toxicity for these compounds at levels up to 50 microM. The inhibitory effects of TPM on transformation were reversible when TPM was removed from the medium. While TPM had no effect on the growth of fully transformed cell lines, it was able to inhibit the growth of 1/3 neoplastic foci in the presence (but not absence) of 10T1/2 cells. TPM was found to stimulate protein kinase C (PKC) activity for both crude C3H10T1/2 cytosolic PKC and purified PKC obtained from rat brain. The ability of TPM to stimulate PKC activity appeared to be dependent on [CaCl2] and the order of reagent addition in the assay. Tamoxifen, a structurally related compound to TPM, was also found to enhance PKC activity over the same concentration range but was less potent than TPM. The biological effects of TPM and related compounds indicate that they function in a manner distinct from other highly unsaturated transformation inhibitors such as carotenoids and retinoids. The inability of triphenylene to inhibit transformation suggests that a reactive methyl carbon may be essential for activity.

Animals↗

Suppression of audiogenic epileptic seizures by intracerebral injection of a CCK gene vector.

P77PMC rat is a breed of rat with congenital audiogenic seizure (AS). AS attacks could be suppressed by cholecystokinin octapeptide (CCK-8) injected intracerebroventricularly (i.c.v.). In the present study we made i.c.v. injection of plasmid pSV2-beta Gal or pSV2-CCK encapsulated with lipofectin. Expression of pSV2-beta Gal in brain occurred from d 1 to d 14, with maximal expression at d 3 and d 4. After i.c.v. injection of pSV2-CCK plasmid, the AS of the P77PMC rats was markedly reduced, which was most obvious at d 3 and d 4. The time course of the AS repression was almost identical with that of pSV2-beta Gal expression. The results suggest that the repression of the AS in P77PMC rats is accounted for by the expression of foreign CCK gene in brain tissue.

Acoustic Stimulation↗

Carotenoids enhance gap junctional communication and inhibit lipid peroxidation in C3H/10T1/2 cells: relationship to their cancer chemopreventive action.

We have previously demonstrated that diverse carotenoids inhibit chemically induced neoplastic transformation in 10T1/2 cells. To address their mechanism of action, the effects of six diverse carotenoids, with or without provitamin A activity, on gap junctional communication and lipid peroxidation have been investigated. beta-Carotene, canthaxanthin, lutein, lycopene and alpha-carotene increased gap junctional intercellular communication in a dose-dependent manner in the above order of potency, whereas m-bixin was inactive at concentrations up to 10(-5) M. alpha-Tocopherol, a potent chain-breaking antioxidant, caused a marginal enhancement of junctional communication. The enhancement of junctional communication by diverse carotenoids showed a strong statistical correlation with their previously determined ability to inhibit methylcholanthrene-induced neoplastic transformation (r = -0.75). All carotenoids tested inhibited lipid peroxidation, but with differing potencies. alpha-Tocopherol was the most active inhibitor followed by m-bixin. The capacity of carotenoids or alpha-tocopherol to inhibit lipid peroxidation was neither consistent with their ability to inhibit neoplastic transformation (r = 0.30) nor to increase junctional communication (r = 0.12). Since junctional communication appears to play an important role in cell growth control and carcinogenesis, we propose that in this system carotenoid-enhanced intercellular communication provides a mechanistic basis for the cancer chemopreventive action of carotenoids. These data also imply that carotenoids function in a manner analogous to retinoids in the 10T1/2 assay system. Interestingly this activity appears independent of their provitamin A status.

Animals↗

[Inhibitory effect of tripterine on activities of IL-1, IL-2 and release of PGE2].

Tripterine is one of the components isolated from Tripterygium wilfordii Hook. Previous studies demonstrated that tripterine inhibited not only humoral and cellular immune responses but also some inflammatory responses. The present investigation attempted to observe effect of the drug on productions of IL-1 from macrophages, IL-2 from splenocytes and PGE2 from synovial cells. The results showed that tripterine (0.1-1.0 microgram/ml) significantly inhibited IL-1 activity of murine peritoneal macrophages induced by LPS. Because both intracellular and extracellular IL-1 activities were decreased, so tripterine might be able to reduce the production and release of IL-1. Besides, inhibition of IL-1 production was observed when macrophages were pretreated with the drug for 8 h and 16 h. A good relationship was found between the effect and concentration of tripterine which inhibited IL-2 production from ConA-activated murine splenocytes. Kinetic study indicated that IL-2 production was decreased when splenocytes were pretreated with the drug for 3 h, 6 h and 12 h. Synovial cells obtained from rabbit knee joint were cultured successfully. A23187 was found to augment PGE2 synthesis modestly. Tripterine significantly reduced PGE2 release from synovial cells in a concentration dependent manner.

Animals↗

[Studies on RESA in Plasmodium falciparum culture medium].

P. falciparum grown in the complete RPMI 1640 medium (containing about 10% normal rabbit serum) for 24 h was collected at about 5% parasitemia. The medium was centrifuged at 500g for 20 min and the supernatant was then centrifuged once more at 40,000g for 30 min. Ten serum samples from falciparum malaria patients with anti-RESA antibodies collected from Yunnan Province were mixed with different dilutions of the culture supernatant, incubated at 37 degrees C for 2h and then at 4 degrees C overnight, and used for conducting RESA-IFA test. The titers of RESA-IFA test of all samples were reduced as compared with controls. When heated supernatant was used in the test, the inhibitory activity remained unchanged. The results indicate that RESA in the supernatants was soluble and heat-stable. To establish the origin of the reacting antigens in the inhibition experiments, the soluble fraction of sonicated merozoite-enriched collection and sonicates of ghost made from normal O phenotype erythrocytes were used in the inhibition RESA-IFA test with sera containing anti-RESA antibodies. The results showed that merozoite-enriched preparations were fully inhibitory at the concentration of 3.1 micrograms/ml, while no inhibition was observed at 0.2 micrograms/ml. In contrast, similar extracts made from normal erythrocyte ghosts were not inhibitory until concentrations about 30 times higher than that of merozoite antigen.

Adolescent↗

[Immunosuppressive and antiinflammatory activities of tripterine].

Tripterine is one of the active components isolated from Tripterygium wilfordii Hook.f. In this study tripterine was shown to inhibit the antibody response of mouse splenocytes to SRBC both in vitro and in vivo either by primary or secondary stimulation. Tripterine was also found to significantly inhibit cotton pellet induced granuloma growth in rats and depress the delayed hypersensitive reaction of mouse skin to dinitrochlorobenzene (DNCB). Besides, it also increased the sleeping time of mouse induced by pentobarbital sodium. From the results stated above, it appears that tripterine might be useful in the treatment of inflammatory diseases or autoimmune diseases.

Animals↗