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Biomedical subjects

C Lu

Publications and source records attributed to C Lu.

At least 235 records · Page 13Linked to original sources
PubMed1994

Regulation of parathyroid hormone-related peptide gene expression by estrogen in GH4C1 rat pituitary cells has the pattern of a primary response gene.

The parathyroid hormone-related peptide (PTHrP) gene has been reported to be subject to a wide variety of physiological and pharmacological controls. Two distinct patterns of PTHrP mRNA response have been recognized, one characterized by a prolonged or plateau response lasting many hours to days and the second characterized by rapid induction-deinduction kinetics and lasting 1 to several hours. The kinetics of the second pattern are similar to those displayed by primary response genes like nuclear protooncogenes, cytokines, and growth factors. In GH4C1 rat pituitary cells, 17 beta-estradiol induced a rapid and transient increase in PTHrP mRNA expression, with a peak response at 1-2 h. This response appeared to be due to a rapid and transient burst in gene transcription, which by runoff analysis was maximal at 20-40 min and declined thereafter. PTHrP mRNA half-life was 30 min in these cells and was unaltered by estradiol. Cycloheximide did not block the 17 beta-estradiol-induced response but rather prolonged it, and runoff analysis revealed that this effect was due to a prolongation or persistence of PTHrP gene transcription. These findings suggest that the transient nature of the native response reflects the effects of an estrogen-inducible repressor. All of these features are characteristic of a prototypical primary response gene.

Animals↗
PubMed1994

Determination of handwash removal efficiency: incomplete removal of the pesticide chlorpyrifos from skin by standard handwash techniques.

This study was designed to develop standard procedures whereby the removal efficiency of handwash techniques can be determined. A known amount of the insecticide chlorpyrifos (Dursban), was transferred to the hands of volunteers, which were washed by a standard technique. The following experimental variables were studied: time between exposure and washing, washing solvent, and skin loading. Ethanol removed only 30% of the chlorpyrifos on skin at loadings of approximately 7 micrograms/cm2, with residence time on skin having no effect. Prewashing with ethanol increased removal efficiency. A 10% isopropanol/distilled-water wash removed 43% immediately following exposure, and 23% one hour post-exposure, with skin loadings of approximately 12 micrograms/cm2. Removal efficiency immediately following contact decreased for lower skin loading levels (21-23% for loadings of 0.1-1 micrograms/cm2). These findings indicate that substantial amounts of the insecticide were either absorbed through or adsorbed to the skin, and that pesticide residue levels recovered by standard handwashing techniques are unlikely to represent accurate estimates of dermal exposure. Approximately two-fold to five-fold underestimations of exposure can occur for pesticides with handwash procedures similar to those tested. All experimental variables studied can each alter significantly the fraction of total pesticide on skin that handwashing removes. If handwashing is to be used to estimate dermal exposure in the workplace, appropriate laboratory-based removal efficiency studies should be conducted prior to field investigations. Further efforts should be made to develop accurate and reproducible hand measurement techniques.

Adsorption↗
PubMed1994

Cytokines, growth factors and the loss of negative growth controls in the progression of human cutaneous malignant melanoma.

The development of clinically frank malignant melanomas in humans is thought to evolve over decades in a stepwise process of progression. By analogy with certain other adult cancers, eg, colorectal carcinomas, alterations in expression or function of a number of different suppressor genes might be expected to be involved in this process. This could lead to loss of expression of a number of different negative growth controls. Evidence is reviewed implicating the presence of putative suppressor genes for the melanocytic lineage located on chromosomes 9p21, 6q, and 1p. In addition, there is evidence suggesting a contribution for the p53 and NF1 tumor-suppressor genes, and the nm23 metastasis-suppressor gene, in melanoma development or progression. Additional possible suppressor genes include those encoding manganese superoxide dismutase, and possibly c-kit. An accumulation of such alterations may be responsible for the progressive loss of responsiveness to several independent growth inhibitors for melanocytes or early stage melanomas, including interleukin-6, transforming growth factor-beta, and oncostatin M. They may also be responsible for some aspects of the production of direct acting autocrine growth factors or production of angiogenesis stimulating factors, or both, by melanoma cells. The acquisition of resistance to several growth inhibitors and the multiplicity of putative suppressor gene alterations (combined with the production of multiple autocrine and paracrine growth factors) may be necessary for the evolution of nondividing single melanocytes resident in the epidermis into highly proliferative and metastatic melanomas capable of growing multicellularly in ectopic organ sites.

Chromosome Deletion↗
PubMed1994

Cutaneous neural codes for shape.

In the pursuit of peripheral neural representations of shape for the sense of touch, a series of two- and three-dimensional objects were stroked across the fingerpad of the anesthetized monkey and responses evoked in cutaneous mechanoreceptive primary afferent nerve fibers recorded. Responses of slowly adapting fibers (SAs) and rapidly adapting fibers (RAs) were recorded to the stroking of a cylinder, a sphere, several ellipsoids, and a pattern of alternating convex and concave cylindrical bars. The compressional force was maintained constant during a stroke, and the stroke velocities as well as orientations of the objects and stroke trajectories were varied between separate sets of trials. The major geometrical properties of the shapes were well represented in the spatiotemporal responses of the afferent fiber populations, particularly those of the SAs. Intensive parameters of shapes, such as the magnitude of change in skin curvature produced as a result of contact with the object surface, were encoded in the discharge rates of SAs and RAs, but this neural code was also influenced by changes in stroke velocity. Spatial parameters of shapes such as the extent of contact and the changes in contour that characterize a shape as belonging to a particular category (such as a sphere as opposed to a cylinder) are encoded in the spatially distributed discharge rates of the SA population. This spatial response profile provides a neural code that is probably invariant with moderate changes in the way the object comes in contact with the skin, such as the contact force or the orientation of the object.

Animals↗
PubMed1994

Developmental changes in modulation of calcium currents of rabbit ventricular cells by phosphodiesterase inhibitors.

BACKGROUND: We have previously shown major differences in beta-adrenergic and muscarinic modulation of L-type calcium currents (ICa) in newborn and adult rabbit heart. However, little is known about developmental changes in modulation of ICa by phosphodiesterases (PDEs), which also regulate intracellular cAMP concentration by its hydrolysis. METHODS AND RESULTS: Enzymatically isolated adult and newborn (1- to 3-day-old) rabbit ventricular myocytes were used to study the effects of PDE inhibitors on ICa measured by the whole-cell patch-clamp method. 3-Isobutyl-1-methyl-xanthine (IBMX), a nonselective PDE inhibitor, increased ICa in a dose-dependent manner for both groups. The maximal effect of IBMX, expressed as percentage increase in ICa over control levels, was greater for newborn myocytes than for adult myocytes, but the effects of IBMX applied alone were observed only at concentrations > 10 mumol/L. The concomitant use of 0.1 mumol/L isoproterenol produced a significant potentiation of the IBMX effect on ICa, with a significant additive effect of IBMX in newborn myocytes even at 0.05 mumol/L IBMX. The concomitant use of a subthreshold concentration of IBMX (0.1 mumol/L) did not potentiate the dose dependence of adult ICa on isoproterenol but did markedly potentiate the dose dependence of newborn ICa on isoproterenol. The Emax and EC50 of isoproterenol in the presence of 0.1 mumol/L IBMX on newborn ICa were 235% and 8 nmol/L, respectively, whereas the Emax and EC50 of isoproterenol in the absence of IBMX on newborn ICa were 111% and 81 nmol/L, respectively. The addition of 50 mumol/L IBMX to 10 mumol/L isoproterenol markedly increased the newborn ICa density up to a level equivalent to that reached with 200 mumol/L cAMP in the pipette (14.9 +/- 1.2 versus 13.4 +/- 0.7 pA/pF). Our data suggest that the inhibition constant (Ki) of IBMX for inhibiting PDEs that participate in the regulation of ICa is much lower in newborn than in adult myocytes. Milrinone 1 mumol/L, a selective PDE III inhibitor, increased the 0.1 mumol/L isoproterenol-stimulated ICa of adult myocytes but had no significant additive effect for the 0.1 mumol/L isoproterenol-stimulated ICa of newborn myocytes. Rolipram 1 mumol/L, a selective PDE IV inhibitor, increased the 0.1 mumol/L isoproterenol-stimulated ICa for newborn myocytes but had no significant additive effect for the 0.1 mumol/L isoproterenol-stimulated ICa for adult myocytes. CONCLUSIONS: These results suggest that the most important PDE isozyme for regulation of ICa of rabbit myocytes changes from PDE IV to PDE III during the postnatal period.

1-Methyl-3-isobutylxanthine↗
PubMed1994

[Effects of delayed fluid resuscitation on dynamic properties of erythrocyte membrane protein after burn shock].

The dynamic properties of membrane protein are closely correlated to the membrane functions in erythrocytes. The anion transport function of band 3 protein, the constituents and the translational diffusion of membrane protein was detected in 25% TBSA burn rats. The changes in membrane protein SH were investigated by using the spin label of 3-maleimide-proxyl. The results showed that, in delayed fluid resuscitation group after burn shock, membrane crosslinking protein appeared in erythrocytes, the function of band 3 protein was damaged, the recovery time after fluorescence photobleaching of membrane protein was obviously prolonged, and the ratio of peak heights of strong to weak immobilization was increased, especially in the six-hour delayed resuscitation group, suggesting that the ischemia-reperfusion injury was more serious during the early shock stage. The authors believe that the results may represent the mechanism of damage biological membrane after burns. The alterations of membrane properties caused by free radicals play an important role in erythrocyte injury.

Animals↗
PubMed1994

[Clinical significance of intraoperative frozen biopsy of cervical lymph node for laryngeal cancer].

The results of intraoperative and postoperative pathologic examination in 102 cases of laryngeal cancer were reported. The overall consistent rate of intraoperative and postoperative biopsy was 114/116(98%). The consistent rate of positive result was 40/40(100%), while the consistent rate of negative result was 74/76(97%). The pathological and clinical results showed that the intraoperative frozen biopsy could confirm the metastasis of cervical lymph node. When frozen biopsy was positive, the neck dissection should be performed. When frozen biopsy was negative, the neck dissection should not be performed in most cases, or the functional neck dissection may be performed in some cases.

Adult↗
PubMed1994

Studies on the induction of cross-resistance by low dose radiation or by low concentrations of chemicals.

The cross-resistance induced by low-level radiation and low concentration of chemical mutagens was studied using human lymphocytes in vitro and mouse bone marrow cells and germ cells in vivo. The chemical mutagens used in these experiments included the MMC, H2O2 and CP. The results reported here, in addition to those that have appeared in the literature, show the following features documented for the first time: (1) MMC as an adaptive treatment could also induce the adaptive response to radiation-induced cytogenetic damage; (2) resistance against MMC-induced damage could be induced by low dose radiation in vivo; (3) it is in mouse germ cells that low dose radiation or chemical mutagens could induce the cross-adaptation; (4) the cells pretreated by low dose X-rays could show the high resistance to H2O2-induced cytogenetic damage; (5) CP as D1 treatment could not induce the adaptive response to radiation and low dose radiation also could not induce the adaptive response to CP.

Adaptation, Physiological↗
PubMed1994

[Reoperation for advanced recurrent laryngeal cancer after surgery].

Thirty-four cases of advanced recurrent laryngeal cancers after operation were treated surgically with satisfactory results. Postoperative 1-, 3- and 5-year survival rates were 63%, 40% and 40% respectively. The surgical procedures and experiences were described. We believe that surgical extirpation should be considered the best method in the management of advanced recurrent laryngeal cancer in spite of operative difficulties and dangers.

Adult↗
PubMed1994

Variant sublines of early-stage human melanomas selected for tumorigenicity in nude mice express a multicytokine-resistant phenotype.

Surgical removal of early-stage radial growth phase or vertical growth phase primary cutaneous human melanomas usually results in cure of the disease. Hence there are few examples of genetically-related paired human melanoma cell lines for study in which one member of the pair is from a curable early-stage lesion and the partner is a more aggressive malignant variant. A rapid method of obtaining such variants is described. It consists of injecting cells from established early-stage radial growth phase or vertical growth phase melanoma cell lines--which are normally non- or poorly tumorigenic in nude mice--into such hosts, where the cell inoculum is co-mixed with Matrigel, a reconstituted basement membrane extract. This resulted in the rapid formation of progressively growing solid tumors from which permanent cell lines were established. Subsequently, the sublines were found to be frankly tumorigenic upon retransplantation into new nude mouse hosts in the absence of Matrigel co-injection. This process was repeated a second time, resulting in the isolation of secondary sublines, manifesting a stepwise increase in tumorigenic properties. The tumorigenic variant sublines were examined for their relative sensitivity to a panel of different cytokines that are normally growth inhibitory for melanoma cells from early-stage primary lesions. All the sublines were found to express an increased resistance to the cytokines transforming growth factor-beta, interleukin-6, interleukin-1 and tumor necrosis factor-alpha, and did so in a stable manner. Thus the results support the hypothesis that a progressive multicytokine resistance accompanies the progression of human melanoma. The availability of such related sublines should provide a valuable resource to help study the changes associated with, and perhaps causative of, disease progression in human malignant melanomas.

Animals↗
PubMed1993

Increased resistance to oncostatin M-induced growth inhibition of human melanoma cell lines derived from advanced-stage lesions.

Human melanomas can become progressively resistant to the growth-inhibitory effects of a broad family of structurally diverse cytokines which includes interleukin 6 (IL-6). Uncovering this multicytokine resistance was made possible by the availability of cell lines established from early-stage radial growth phase or vertical growth phase primary melanomas as well as more advanced primary lesions and distant metastases. Because Oncostatin M (OSM) is also a member of the IL-6 family we evaluated the effects of this cytokine on the growth of human melanoma cell lines obtained from different stages of disease progression. The results showed that three different cell lines derived from early-stage melanomas were strongly growth inhibited by OSM, as they are by IL-6. Three cell lines, established from advanced-stage melanomas, were growth inhibited by OSM, but much higher concentrations (in the range of 10-fold) were required to obtain 50% growth inhibition; these cell lines were not inhibited by IL-6. Three other cell lines that were IL-6 resistant (two of which were advanced stage) were also found to be OSM resistant. Only one advanced-stage IL-6-resistant cell line was found to be highly sensitive to OSM-mediated growth inhibition. In addition, we found that variants isolated from early-stage WM35 melanoma cells that possess a much more aggressive tumorigenic phenotype in nude mice were significantly more resistant to both OSM- and IL-6-mediated growth inhibition. The results demonstrate that OSM can function as a growth inhibitor of human melanoma cells but that its ability to do so is progressively diminished or lost with disease progression. This finding is consistent with the concept of acquired "multicytokine resistance" during melanoma progression.

Cell Division↗
PubMed1993

Interleukin-6 undergoes transition from paracrine growth inhibitor to autocrine stimulator during human melanoma progression.

The ability to penetrate the dermal basement membrane and subsequently proliferate in the underlying mesenchyme is one of the key steps in malignant progression of human melanomas. We previously undertook studies aimed at assessing how normal dermal fibroblasts (one of the main cellular components of mesenchyme) may affect the growth of human melanoma cells and facilitate the overgrowth of malignant subpopulations (Cornil, I., D. Theodorescu, S. Man, M. Herlyn, J. Jambrosic, and R. S. Kerbel. 1991. Proc. Natl. Acad. Sci. USA. 88:6028-6032). We found that melanoma cell lines from early-stage (metastatically incompetent) lesions were growth inhibited whereas those from advanced-stage (metastatically competent) lesions were stimulated under the same conditions by co-culture with fibroblasts; conditioned medium from such cells gave the same result. Subsequent studies using biochemical purification and neutralizing antibodies revealed the inhibitory activity to be identical to interleukin-6 (IL-6). We now report that addition of purified recombinant human IL-6 resulted in a growth inhibition in vitro by G1/G0 arrest of early, but not advanced stage melanoma cells. Despite this alteration in response there was no significant difference in melanoma cell lines of varying malignancy in respect to their expression of genes encoding the IL-6 receptor, or gp130, the IL-6 signal transducer. Scatchard analysis also revealed similar [125I]IL-6 binding activities in both IL-6 sensitive and resistant groups. However, studies of IL-6 production indicated that five out eight IL-6 melanoma cell lines known to be resistant to exogenous IL-6-mediated growth inhibition constitutively expressed mRNA for IL-6; they also secreted bioactive IL-6 into culture medium. To assess the possible role of this endogenous IL-6 in melanoma cell growth, antisense oligonucleotides to the IL-6 gene were added to cultures of melanoma cells. This resulted in a significant growth inhibition only in cell lines that produced endogenous IL-6. In contrast, neutralizing antibodies to IL-6 were ineffective in causing such growth inhibition. This indicates that endogenous IL-6 may behave as a growth stimulator by an intracellular ("private") autocrine mechanism. Thus, a single cytokine, IL-6, can switch from behaving as a paracrine growth inhibitor to an autocrine growth stimulator within the same cell lineage during malignant tumor progression. Such a switch may contribute to the growth advantage of metastatically competent melanoma cells at the primary or distant organ sites and thereby facilitate progression of disease.

Base Sequence↗
PubMed1993

[Experimental research of acupuncture manipulation of reinforcing and reducing by lifting and thrusting needle on the animal].

The experiment were performed on model rabbits injected with large dosage of Dexamethasone (DXM) for 5 days. Reinforcing manipulation (RIM), reducing manipulation (RDM), and electric stimulation (ES) were respectively used to puncture Zusanli (ST 36) points for 5 days to observe the change on temperature, body weight, corticosterone assay, testosterone assay, and the amplitude of the plethysmogram. The result showed that there was a similar syndrome of the kidney deficiency after injecting DXM. The body weight was increased in the DXM control group, decreased in the RDM group and had no significant influence in the other groups. The body weights between the reinforcing manipulation and the reducing manipulation groups had obvious difference. But the other indices of observation had no significant influence among the different groups. So there wasn't significant difference on most of observed signs among the RIM group, the RDM group and ES group. The study of acupuncture manipulation will have yet to be further done.

Acupuncture Therapy↗