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Biomedical subjects

L Cao

Publications and source records attributed to L Cao.

232 records · Page 13Linked to original sources
PubMed1988

Hyperammonemia in anorectic tumor-bearing rats.

Plasma ammonia concentrations were significantly elevated by 150% in anorectic rats bearing methylcholanthrene sarcomas. Assessment of ammonia levels in blood draining these sarcomas indicated nearly a 20-fold increase as compared with venous blood in control rats, suggesting the tumor mass as the source of this increase in ammonia. Infusing increasing concentrations of ammonium salts produced anorexia and alterations in brain amino acids in normal rats that were similar to those observed in anorectic tumor-bearing rats. Therefore, these results suggest that ammonia released by tumor tissue may be an important factor in the etiology of cancer anorexia.

Amino Acids↗
PubMed1988

Reduction of tumor growth following treatment with a glutamine antimetabolite.

Assessment of arterial-venous differences across transplanted methylcholanthrene-induced sarcomas in rats revealed significant decreases in plasma concentrations of glutamine, serine and glucose. Treatment with the glutamine antimetabolite, acivicin, significantly reduced tumor weights by 65% at the conclusion of the experiment 34 days after tumor induction. These results suggest that glutamine is an essential metabolic substrate for tumor growth and that blockade of glutamine utilization can inhibit the growth of these transplantable sarcomas.

Amino Acids↗
PubMed1988

Reversal of neurochemical aberrations after tumor resection in rats.

Assessment of biochemical parameters in methylcholanthrene sarcoma-bearing rats 2 days after the onset of anorexia revealed several biochemical aberrations in blood and brain. Plasma levels of glucose were decreased and lactate concentrations were increased. The plasma and brain amino acid profiles were also greatly altered in these rats, characterized by increased brain concentrations of glutamine and large neutral amino acids. Analysis of regional neurotransmitter and metabolite levels by high-performance liquid chromatography suggested increases in the neuronal activity of dopamine and serotonin in each brain region examined. Surgical removal of the tumors in another group of anorectic tumor-bearing rats was followed by the return of normal feeding within 6 days. Associated with the normalization of food intake was the reversal of these biochemical aberrations in blood and brain. It is hypothesized that the utilization of glutamine and excretion of ammonia by tumor tissue is the precursor of these alterations in brain amino acids and neurotransmitters, which may be causing anorexia.

Amino Acids↗
PubMed1988

Insulin and acivicin improve host nutrition and prevent tumor growth during total parenteral nutrition.

The effect that a 14-day treatment program of total parenteral nutrition (TPN) combined with the glutamine antimetabolite, acivicin, and anabolic hormone, insulin, has on carcass weight and muscle sparing was investigated in tumor-bearing rats. Although TPN resulted in increased carcass weight gain as compared to chow-fed tumor-bearing rats, no savings in gastrocnemius muscle could be demonstrated. The combination of TPN with daily insulin treatment elicited significant increases in both carcass weight and muscle savings, with no alteration in tumor growth. Although combining acivicin with TPN halted tumor growth and increased carcass weight, the change in carcass weight was less than that observed with the insulin-TPN combination. No muscle savings were observed in the acivicin-TPN-treated rats. Yet when acivicin and insulin were combined with TPN, tumor growth was stopped, carcass weight was gained, and muscle mass was saved. Therefore, these experiments suggest that it is possible to add lean body tissue and stabilize tumor growth in rats that receive TPN through anabolic hormone treatment combined with an inhibitor of tumor metabolism.

Animals↗
PubMed1987

A method for gene disruption that allows repeated use of URA3 selection in the construction of multiply disrupted yeast strains.

In this paper, we describe a 3.8-kb molecular construct that we have used to disrupt yeast genes. The construct consists of a functional yeast URA3 gene flanked by 1.1-kb direct repeats of a bacterial sequence. It is straightforward to insert the 3.8-kb segment into a cloned target gene of interest and then introduce the resulting disruption into the yeast genome by integrative transformation. An appropriate DNA fragment containing the disruption plus flanking homology can be obtained by restriction enzyme digestion. After introducing such fragments into yeast by transformation, stable integrants can be isolated by selection for Ura+. The important feature of this construct that makes it especially useful is that recombination between the flanking direct repeats occurs at a high frequency (10(-4)) in vegetatively grown cultures. After excision, only one copy of the repeat sequence remains behind. Thus in the resulting strain, the Ura+ selection can be used again, either to disrupt a second gene in similar fashion or for another purpose.

Escherichia coli↗
PubMed1987

Acivicin reduces tumor growth during total parenteral nutrition (TPN).

Glutamine appears to be an important substrate for tumor growth. Since tumor growth rate may be stimulated by total parenteral nutrition (TPN), we investigated the effect of the glutamine antimetabolite, acivicin, on methylcholanthrene sarcoma growth in rats maintained on TPN or on rat chow. Acivicin treatment significantly reduced tumor growth by 67% in rats receiving TPN and by 71% in rats maintained on chow. Carcass weights were significantly increased by TPN in both acivicin-treated and saline solution-treated tumor-bearing rats. Tumor-carcass ratios were significantly decreased in both groups of acivicin-treated tumor-bearing rats. Acivicin treatment or a similar approach may therefore be useful for stabilizing tumor growth in patients receiving TPN.

Animals↗
PubMed1983

Zinc-induced seizures: a new experimental model of epilepsy.

Seizures produced by intracerebral injection of zinc sulfate in rabbits are a new chronic model of experimental epilepsy. The main features of this model are: the animals are easily controlled, the electrocorticogram is conveniently recorded, the endpoints are definite, and the rate of seizure is higher than with other methods. The commonly used antiepileptic drugs, such as phenobarbital (30 mg/kg), diphenylhydantoin (30 mg/kg), nitrazepam (3 mg/kg), and sodium valproate (300 mg/kg), have therapeutic effects in treating this experimental epilepsy, when they are given intravenously. But they can not protect the rabbits from death, except phenobarbital.

Animals↗
PubMedDate not supplied

Binding of human leukocytes to fibronectin is augmented by an anti-CD44 mAb (TL-1) and blocked by another anti-CD44 mAb (Hermes-3) but not by anti-VLA-4/VLA-5 mAbs.

Fibronectin (FN) forms meshworks in extracellular spaces, and it plays an important role in cellular trafficking. Lymphoid cells are activated by binding to FN of the VLA-4 and VLA-5 receptors. CD44 also acts as a receptor of FN, but the mechanism and physiologic regulation of their binding are poorly understood. We have developed an anti-CD44 monoclonal antibody (mAb) (TL-1) in which lymphoid cells are activated and form homotypic cell aggregation. In this study, we found that the adhesion of CEM, HSB2, and LAD lymphoid cells to FN was augmented by TL-1 treatment and was apparently blocked by another anti-CD44 mAb (Hermes-3), but TL-1 Fab' fragments treatment did not induce FN-binding. A similar phenomenon is reported in the binding of the CD44 molecule to HA. This augmentation was not inhibited by the CS1 and RGD peptides of FN or by anti-VLA-4 and -VLA-5 mAbs; it was energy-dependent and associated with cytoplasmic actin filaments. Tl-1 treatment did not alter the cell surface expression of CD44 molecules. These findings above suggested that activated and/or altered cell surface distribution of CD44 molecules via a conformational change augmented the avidity of its binding to FN, which may be similar to lymphocyte-hyaluronate and lymphocyte-endothelial cell binding. As the Hermes-3 binding site is also involved in the interaction between lymphocytes and endothelial cells, activation of lymphocytes via CD44 molecules may facilitate the binding of lymphocytes to endothelial cells, extravasation, and migration to inflammatory sites rich in FN.

Adjuvants, Immunologic↗
PubMedDate not supplied

Localization of heme oxygenase-2 and modulation of cGMP levels by carbon monoxide and/or nitric oxide in the retina.

Heme oxygenase-2 (HO-2) synthesizes carbon monoxide (CO), a modulator of soluble guanylate cyclase (sGC). To examine this signal transduction pathway in the retina, we immunocytochemically localized HO-2, and investigated the effects of CO on cGMP levels. In turtle, HO-2-like immunoreactivity (-LI) was in all photoreceptors, some amacrine cells, and in numerous bipolar and ganglion cells. HO-2-LI colocalized with sGC activity in many cells. In rat, HO-LI was found only in the inner retina, in ganglion and amacrine cells. In turtle, stimulation with CO alone primarily increased cGMP-LI in bipolar cells in the visual streak. Stimulation with a combination of CO and nitric oxide (NO) dramatically increased cGMP-LI throughout the retina, in comparison to the smaller increases seen with NO or CO alone. These data suggest that CO is an endogenous modulator of the sGC/cGMP signaling pathway in many retinal neurons, and can dramatically amplify NO-stimulated increases in cGMP.

Animals↗
PubMedDate not supplied

Gamma-atrial natriuretic peptide 1-25 is found in bipolar cells in turtle and rat retinas.

Immunocytochemistry was used to reveal a population of bipolar cells that contain gamma-atrial natriuretic peptide 1-25 (gamma-ANP) in turtle retina. This same antibody was also used in rat retina as a comparative control. The retinas were examined by both conventional light microscopy and confocal microscopy with double-labeling to determine whether protein kinase C-alpha-like immunoreactivity (PKC-alpha-LI) was colocalized with the gamma-ANP-LI. Some thick sections of turtle retina immunostained with only the gamma-ANP antibody were also examined by electron microscopy. In rat, a subpopulation of bipolar cells with axons terminating close to the ganglion cell layer was labeled. Double-labeling experiments indicated that the gamma-ANP-LI and PKC-alpha-LI were colocalized in rat retina, and thus all the bipolar cells with gamma-ANP-LI were rod bipolar cells. In turtle, the gamma-ANP antibody labeled certain bipolar cells that were characterized by bistratified axon terminals arborizing on the borders of strata S2/3 and S3/4 in the inner plexiform layer (IPL). Double labeling with PKC-alpha antibody indicated that bipolar cells with gamma-ANP-LI were not the same bipolar cell types with PKC-alpha-LI. Thus, gamma-ANP-LI appears to be a new marker for a distinct type of bipolar cell in turtle retina. At the ultrastructural level, the gamma-ANP-LI was visible throughout the cytoplasm of the bipolar cells from dendrites to axon terminals. In the outer plexiform layer (OPL), labeled dendrites contacted photoreceptor pedicles almost exclusively at narrow-cleft basal junctions, but infrequently formed the central element at a photoreceptor ribbon synapse. In the IPL, axon terminals with gamma-ANP-LI made ribbon synapses onto a combination of amacrine and ganglion cells. Since narrow-cleft basal junctions and photoreceptor ribbon-related junctions are known to be associated with ON-center bipolar cells in turtle, and since the axon terminals of bipolars with gamma-ANP-LI stratify primarily in the ON-strata of the IPL, we suggest that these cells are likely to be ON-center cells. It is possible that the gamma-ANP may be involved in regulating the activity of Na+/K+ ATPase or in the modulation of cGMP levels.

Animals↗
PubMedDate not supplied

In vitro effects of epristeride on sperm in rats, dogs and man.

The study was conducted to evaluate in vitro effects of epristeride on sperm in rats, beagle dogs and man. Semen samples were divided into 4 groups and treated with vehicle and epristeride. Motility and motile rate of sperm were videotaped and analyzed with CASA system after 1 h and 2 h incubation periods. Percentage of motile sperm (MOT) of rat sperm decreased after the treatment with epristeride (final concentrations were 0.6, 6 and 60 micromol/L) for 1 h, and MOT of rat sperm treated with middle dose and high dose levels of epristeride also decreased after 2 h, while MOT of dog sperm that treated with three dose levels of epristeride decreased after 2 h. Amplitude of lateral head displacement (ALH) and MOT of human sperm decreased after 2 h with 4.8 micromol/L epristeride treatment. Curvilinear velocity (VCL) and straight-line velocity (VSL) of rat sperm and human sperm changed after 2 h, but there were no significant differences. Therefore, epristeride had a toxic effect on sperm, and the effect varied in different species.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMedDate not supplied

Tumor cell membrane cathepsin B.

The lysosomal cysteine peptidase cathepsin B was found to be associated with plasma membrane/endosomal fractions of murine B16 amelanotic melanoma cells. Confocal microscopy with three dimensional image analysis indicated that cathepsin B was associated with the external basal cell surface, which would be consistent with its proposed role in degradation of extracellular matrix proteins. We purified and partially characterized cathepsin B from homogenates of murine liver and B16 amelanotic melanoma cells and from lysosomal and membrane/endosomal fractions of the B16 tumor cells. By SDS-PAGE under reducing conditions, the purified cathepsin B from the tumor homogenates was resolved as a single protein band of Mr 31000, corresponding to the single chain form of cathepsin B. In contrast, cathepsin B from liver homogenates was resolved as two bands of Mr 31000 and 24000, corresponding to the single chain and the heavy chain of the double chain form, respectively. The tumor cathepsin B consisted of four isozymes with pIs of 5.64, 5.33, 5.2 and 5.1, whereas the liver cathepsin B consisted of five isozymes with pIs of 5.64, 5.5, 5.45, 5.35 and 5.3. The additional acidic isoforms of cathepsin B in the B16 tumor probably reflect altered glycosylation in tumors. The commonality of isoforms in the B16 plasma membrane/endosomal and lysosomal fractions suggests that retrograde trafficking of cathepsin B from the lysosome to the endosome and its exocytotic release result in the association of cathepsin B with the tumor cell membrane.

Animals↗
PubMedDate not supplied

Subcellular localization of neuronal nitric oxide synthase in turtle retina: electron immunocytochemistry.

Recent studies imaging nitric oxide (NO) production in the retina have indicated a much wider distribution of NO production than would be suggested by previous light-microscopic localizations of neuronal nitric oxide synthase (nNOS). To help resolve this discrepancy, the present study analyzed the ultrastructural localization of nNOS-like immunoreactivity (-LI) in all layers of the retina. In the ellipsoids of rod photoreceptors and the accessory elements of double cones, nNOS-LI was associated with some atypical mitochondria. In the outer plexiform layer, nNOS-LI was in some postsynaptic horizontal and bipolar cell processes at photoreceptor ribbon synapses. In some amacrine and ganglion cell somata, nNOS-LI was diffusely localized in the cytoplasm and associated with the endoplasmic reticulum. In the inner plexiform layer, nNOS-LI diffusely filled some amacrine cell processes, while in other amacrine cells nNOS-LI was selectively localized at the presynaptic specializations of conventional synapses. Neuronal NOS-LI was also found at membrane specializations in bipolar cell terminals that were distinct from their normal ribbon synapses. Finally, some nNOS-LI was found in mitochondria in Muller cells. The diverse subcellular localizations of nNOS-LI indicates that NO may play distinct functional roles in many retinal cells, which correlates well with the widespread NO production found in previous NO imaging studies.

Amacrine Cells↗
PubMedDate not supplied

Paracrine stimulation of keratinocytes in vitro and continuous delivery of epidermal growth factor to wounds in vivo by genetically modified fibroblasts transfected with a novel chimeric construct.

BACKGROUND: Growth factors play an important role in tissue repair. While the effectiveness of growth factor therapy in animal wound healing models and limited human clinical trials has been demonstrated, the ideal method for their administration to the wound remains unclear. Experimental data suggest that the continuous presence in the early stages of wound repair is beneficial. MATERIALS AND METHODS: We have constructed a novel chimeric expression plasmid in which the biologically active portion of the human epidermal growth factor (EGF) gene is fused in-frame to the human granulocyte colony-stimulating factor signal sequence. RESULTS: Clonally selected human fibroblasts transfected with this construct secrete biologically active EGF. After the transplantation of irradiated gene-transfected fibroblasts suspended in fibrin glue to murine full-thickness wounds, EGF can be demonstrated for at least seven days in the wounds, slowly decreasing from initially 470 pg/ml to 140 pg/ml on day 7. No EGF was found in the wound at day 14. CONCLUSIONS: A single application of irradiated EGF genetransfected fibroblasts to wounds can thus continuously deliver the transgene in vivo and could be used to administer drugs to the wound bed during the crucial first seven days of wound-healing.

Amino Acid Sequence↗