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Biomedical subjects

J Leon

Publications and source records attributed to J Leon.

At least 37 records · Page 2Linked to original sources
PubMed1995

Lack of correlation between c-myc expression and programmed or experimentally-induced cell death during chick limb development.

The protooncogene c-myc positively regulates cell death in most in vitro cell model systems under conditions of restricted proliferation, and it has been proposed that cell death is a physiological function of c-myc. To investigate possible changes in c-myc expression concomitant with programmed cell death, we have analyzed c-myc mRNA expression during chick limb development. Expression of c-myc was high in the premuscular masses at earlier stages and in the chondrogenic condensations at later stages of limb development, as demonstrated by in situ mRNA hybridization in sections and whole-mount. However, we did not detect c-myc expression in specific limb areas where massive apoptosis was occurring. Furthermore, when the apical ridge was removed from stage 20 wing buds, there was no increase in the expression of c-myc in the subridge mesoderm, despite the extensive cell death induced by this surgical manipulation. Therefore, our results show no correlation between elevated c-myc expression and either programmed or experimentally-induced apoptosis in the developing limb. These results argue against a role of c-myc in cell death occurring in vivo.

Animals↗
PubMed1994

Apolipoprotein E expression in the cerebellum of normal and hypercholesterolemic rabbits.

We have studied the expression of apolipoprotein E (ApoE) mRNA in the cerebella of control and experimental rabbits fed with a cholesterol-rich diet for 8 weeks. Cholesterol-treated rabbits show a dramatic increase in serum cholesterol levels; however, no significant variations in the expression level of cerebellar ApoE mRNA were found in comparison to control rabbits. In addition, no differences were observed between control and hypercholesterolemic rabbits in the in situ hybridization pattern of ApoE mRNA on cerebellar cortex sections. ApoE mRNA was localized in astroglial processes associated with Purkinje cell bodies and dendrites, granule cell clusters, blood vessels and nerve fibers of the white matter. No expression of ApoE mRNA was observed in Purkinje and granule cell neurons. Polarized light examination of cryostat cerebellar sections revealed the absence of cholesterol-rich microglia/macrophage cells induced by the hypercholesterolemia. In this way, neither reactive microglial cells nor perivascular phagocytes were found by ultrastructural analysis in hypercholesterolemic conditions. The pattern of glial fibrillary acidic protein of the astroglial cells of the cerebellar cortex as well as their nuclear size were unchanged following cholesterol treatment, indicating the absence of astroglial activation induced by hypercholesterolemia. Our results suggest that cerebellar ApoE does not contribute to the general cholesterol homeostasis outside of the brain and supports the view that this cerebellar ApoE is involved in paracrine and autocrine functions particularly related with synapse turnover and membrane remodelling of astroglial cells.

Animals↗
PubMed1992

Placebo-controlled efficacy study of hepatitis A vaccine in Valdivia, Chile.

A placebo-controlled, double-blind study on the efficacy of a hepatitis A vaccine (SmithKline Beecham Biologicals) was started in a region of Chile in September 1990, using hepatitis B vaccine as control. A total of 260 healthy children, 6-15 years of age, negative for antibody to hepatitis A virus (anti-HAV), antibody to HAV immunoglobulin M (IgM), hepatitis B surface antigen, and antibody to hepatitis B surface and core antigens by ELISA tests within 7 days before vaccination, were randomly assigned to two study groups: 128 children received the vaccine with a yellow label (group 1), and 132 children the vaccine with an orange label (group 2) at months 0, 1 and 6. Blood for serology and transaminase determination was drawn at months 1, 2, 6, 7 and 12. Both vaccines were tolerated equally well and no serious side effects were seen. In group 1 (presumed hepatitis A vaccine group), anti-HAV was detected (20% inhibition was used as the cut-off level) in 122 of 128 children (95.5%) tested at month 1, in 126 of 127 (99.2%) at month 2, in 126 of 127 (99.2%) at month 6 and in 126 of 126 (100%) at month 7. One anti-HAV seroconversion seen at month 1 was associated with presence of anti-HAV IgM and therefore probably represents HAV infection. Geometric mean anti-HAV concentration of the other children was 128, 342, 214 and 2301 mIU/ml at months 1, 2, 6 and 7, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

ras activation in human tumors and in animal model systems.

Environmental agents such as radiation and chemicals are known to cause genetic damage. Alterations in a limited set of cellular genes called proto-oncogenes lead to unregulated proliferation and differentiation. We have studied the role of the ras gene family in carcinogenesis using two different animal models. In one case, thymic lymphomas were induced in mice by either gamma or neutron radiation, and in the other, keratoacanthomas were induced in rabbit skin with dimethylbezanthracene. Human keratoacanthomas similar to the ones induced in rabbits were also analyzed. We found that different types of radiation such as gamma rays and neutrons, induced different point mutations in ras genes. A novel K-ras mutation in codon 146 has been found in thymic lymphomas induced by neutrons. Keratoacanthomas induced in rabbit skin by dimethylbenzanthracene show a high frequency of H-ras-activated genes carrying a mutation in codon 61. The same is observed in human keratoacanthomas, although mutations are in both the 12th and the 61st codons of the H-ras gene. H-ras activation is less frequent in human squamous cell carcinomas than in keratoacanthomas, suggesting that ras genes could play a role in vivo in differentiation as well as in proliferation.

3T3 Cells↗
PubMed1991

Oncogene involvement in tumor regression: H-ras activation in the rabbit keratoacanthoma model.

Activated H-ras genes are present in a number of skin tumors induced in animals by carcinogen treatment. The involvement of the ras oncogenes in tumorigenesis was investigated in keratoacanthomas, benign and self-regressing tumors, as well as malignant squamous cell carcinomas. Both tumors were induced in rabbit ears by repeated applications of 7,12 dimethylbenz(a)anthracene (DMBA). The rabbit H-ras gene was cloned and sequenced. PCR analysis revealed that approximately 82% of the keratoacanthoma DNAs contained an A:T to T:A transversion in codon 61. The relative levels of H-ras transcript were increased in keratoacanthomas compared to normal skin and the activated allele was expressed in tumors, even during the regressing phase. Although a G:C to A:T mutation in codon 12 of the H-ras and an activated N-ras gene were found in two squamous cell carcinomas, the frequency of H-ras activation in codon 61 was much lower (40%) in the malignant tumours induced by the same carcinogen treatment. Therefore, DMBA induced at least two types of genetic lesions in this system: H-ras activation, present in most regressing keratoacanthomas, and activation of other unidentified oncogenes which may result in the development of malignant tumors. Our observations indicate that expression of an activated H-ras gene, in this system, is neither sufficient to induce a malignant phenotype nor even capable of maintaining the growth of a benign tumor and suggest that it could be involved in tumor regression.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Oncogene activation in human benign tumors of the skin (keratoacanthomas): is HRAS involved in differentiation as well as proliferation?

In vitro DNA amplification followed by oligonucleotide mismatch hybridization was used to study the frequency of HRAS mutations in the benign self-regressing skin tumors keratoacanthomas and in squamous cell carcinomas. We used freshly obtained keratoacanthomas as well as Formalin-fixed paraffin-embedded tissues from both types of tumors. DNA from 50 samples of each tumor type was analyzed for activating mutations involving codons 12 and 61. A relatively high percentage (30%) of HRAS mutations was found in the keratoacanthomas compared with 13% in the squamous cell carcinomas. The most frequent mutation identified is the A-T-to-T.A transversion in the second position of codon 61. The present findings demonstrate the involvement of the HRAS oncogene in human benign tumors. Moreover, they indicate that an activated HRAS oncogene is not sufficient to maintain a neoplastic phenotype and argue against a role of HRAS in the progression of skin tumorigenesis.

Animals↗
PubMed1989

Hemodialysis-related induction of beta-2-microglobulin and interleukin-1 synthesis and release by mononuclear phagocytes.

We have investigated beta 2-microglobulin (beta 2M) synthesis and release by blood leukocytes and isolated mononuclear phagocytes. Recent interest in beta 2M has developed since the discovery that this protein forms amyloid fibrils in patients undergoing long-term, chronic hemodialysis and that these patients have greatly elevated levels of monomeric beta 2M in their circulation. Since hemodialysis-related factors that increase beta 2M production are unknown, we evaluated beta 2M production by freshly prepared leukocytes and monocyte-derived macrophages under a variety of conditions. We utilized a novel enzyme-linked immunoabsorbant assay to quantitate beta 2M concentrations, and monitored interleukin-1 and beta 2M synthesis by immunoprecipitation. Incubation of leukocytes with Cuprophan or Hemophan does not increase beta 2M release. Adherence of macrophages onto polystyrene or Cuprophan membranes induces neither interleukin-1 nor beta 2M synthesis or release. In contrast, interaction of macrophages with lipopolysaccharide, gamma-interferon, tumor necrosis factor, or interleukin-1 induces synthesis and release of beta 2 M, indicating that beta 2 M synthesis is increased during macrophage activation. Exposing leukocytes or macrophages to changes in osmotic or oncotic pressure induces a rapid release of beta 2M and interleukin-1 into the cellular medium. These results suggest that during hemodialysis, beta 2M production is more likely to result from endotoxin contamination, or osmotic and oncotic changes, rather than direct interaction of mononuclear phagocytes with Cuprophan membranes.

Cells, Cultured↗
PubMed1989

Evaluation of normal triiodothyronine and tetraiodothyronine concentrations in llamas (Lama glama).

Basal serum triiodothyronine (T3) and tetraiodothyronine (T4) concentrations have not been established for the llama (Lama glama). In addition, changes in T3 and T4 concentrations in response to thyroid-stimulating hormone (TSH) administration have not been determined, making clinical evaluation of problems referable to thyroid dysfunction difficult. In study 1, basal T3 and T4 concentrations were determined in serum samples collected from 132 clinically healthy llamas. The llamas were allotted to 3 groups: mature intact or neutered males (group I, n = 25), nonpregnant sexually mature females (group II, n = 21), and pregnant females (group III, n = 86). A mean concentration and a 95% confidence interval were computed for each group. An analysis of variance (ANOVA) indicated that a single confidence interval range (0.45 to 4.18, mean = 1.37 ng T3/ml) adequately defined the normal T3 concentrations for all groups. An ANOVA indicated that the T4 concentrations for the female populations (groups II and III) could be combined with a normal confidence interval range of 39 to 204 ng/ml (mean = 88 ng/ml), whereas a separate range (70 to 220 ng/ml, mean = 124 ng/ml) was determined for the male population. An ANOVA indicated that a single confidence interval range (0.0066 to 0.0321, mean = 0.0146) adequately defined the normal T3/T4 ratio for all groups. In study 2, T3 and T4 concentrations were evaluated in 10 healthy llamas immediately preceding and at 2, 4, 6, 8, and 24 hours after the IV administration of 3 IU of TSH/44 kg of body weight. The T3 and T4 concentrations were significantly higher by 2 hours after TSH administration in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

H-ras activation in benign and self-regressing skin tumors (keratoacanthomas) in both humans and an animal model system.

The involvement of the ras oncogenes in tumorigenesis was investigated in keratoacanthomas, which are benign and self-regressing skin tumors, both in humans and in a corresponding animal model system. Keratoacanthomas were induced on rabbit ears by repeated applications of 7,12-dimethylbenz(a)anthracene. About 60% of the tumor DNAs produced transformed foci after transfection into NIH 3T3 cells, and in all of them the transforming gene was identified as H-ras by Southern and Northern (RNA) hybridization. Immunoprecipitation experiments suggested that the transforming rabbit H-ras protein carried a mutation in codon 61. In addition, an activated H-ras gene was detected in a human keratoacanthoma by using a nude mouse tumorigenesis assay after transfection of tumor DNA into NIH 3T3 cells. This is the first report of ras activation in a benign human tumor. The transforming human H-ras gene showed a point mutation in codon 61 that would result in leucine instead of the glutamine present in the normal gene product. The finding of ras activation in tumors that are not only benign but also self-regressing indicates that activated ras genes are not sufficient to maintain a neoplastic phenotype, although they likely play a role in early stages of tumorigenesis.

9,10-Dimethyl-1,2-benzanthracene↗