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Biomedical subjects

J L Soto

Publications and source records attributed to J L Soto.

7 recordsLinked to original sources

A new beta 2 microglobulin mutation found in a melanoma tumor cell line.

Beta2 microglobulin mutations are an important mechanism for HLA class I total loss, (phenotype No. I) and have been described in colon carcinomas, melanomas and lymphomas. We describe a new beta2 microglobulin mutation detected in the melanoma cell line GR-34. The new mutation reported here was identified as a deletion of 4 bases (TTCT) in the highly repetitive sequence CTCTCTCTTTCT located in the leader sequence of the beta2 microglobulin gene at codon 15-16 of exon 1. The mutation produces a frameshift in the open reading frame sequence with the appearance of a stop codon at position 42. We also demonstrate that the second beta2 microglobulin gene is deleted. Comparisons with beta2 microglobulin mutations in other tumor cell lines suggest a mutation hot spot in exon 1.

Aged↗

Molecular karyotype (amplotype) of metastatic colorectal cancer by unbiased arbitrarily primed PCR DNA fingerprinting.

Genomic instability characterizes the aneuploid cancer cell. Losses of genetic material are critical in cancer by exposing recessive mutations in tumor suppressor genes. Gains of genetic material also may lead to overexpression of genes contributing to tumor progression either in the presence or absence of mutation. However, the detection of moderate gains (such as tri-tetraploidy) has been a challenge in cancer research. Unbiased DNA fingerprinting by the arbitrarily primed PCR allows the detection of moderate gains (in addition to losses) of DNA sequences of known chromosomal localization. We have generated in this manner a molecular karyotype of metastatic colon cancer. This amplotype shows that sequences from several chromosomes undergo both losses (1, 4, 9, 14, and 18) and gains (6, 7, 12, and 20) in over half of the tumors. Moreover, gains of sequences from chromosomes 8 and 13 occurred in most tumors, indicating the existence in these chromosomes of positive regulators of cell growth or survival that are under strong positive selection during tumor progression. We conclude that overrepresentation of these chromosomal regions is a critical step for metastatic colorectal cancer. Comparative amplotype analysis from primary and metastatic tumors suggest the existence in chromosome 4 of gene(s) whose loss is specifically selected in cells that reach the metastatic stage.

Alleles↗

Comparison of different electrophoretic methods for digital typing of the MS32 (D1S8) locus.

Minisatellite variant repeat mapping by polymerase chain reaction (MVR-PCR) is a new and powerful approach for individual identification from human DNA. This method has been successfully applied to the hypervariable human minisatellite MS32 (locus D1S8). In this work, we further investigate this locus using different electrophoretic techniques which include: agarose gels and nonradioactive hybridization, miniaturized polyacrylamide gels, followed by silver staining, and automatic detection of fluorescent labeled alleles. The advantages and disadvantages of each method are described. Also, MVR codes from a Galician population (NW Spain) are provided.

Chromosome Mapping↗

Regulation of the pituitary-specific transcription factor GHF-1/Pit-1 messenger ribonucleic acid levels by growth hormone-secretagogues in rat anterior pituitary cells in monolayer culture.

Pituitary-specific expression of the GH gene is dependent on a pituitary-specific transcription factor GH factor-1 (GHF-1), a homeodomain protein also known as pituitary-specific transcription factor-1 (Pit-1). The aim of this study was to investigate the regulation of GHF-1 messenger RNA (mRNA) levels in primary monolayer cultures of rat anterior pituitary cells. Specifically, in addition to direct activators of second messenger signaling systems, we studied the effects of different hormones, all of which are known to be involved in the regulation of somatotroph cell function. We found that GH-releasing hormone (GHRH) increased GHF-1 mRNA levels in a time- and dose-dependent fashion. GHF-1 mRNA levels were increased 2.5-fold (P < 0.01) after incubation for 2 h with 10(-8) M GHRH. Longer incubations (6, 12, or 24 h) with GHRH failed to show a similar stimulatory effect. A significant increase in GHF-1 mRNA concentration (1.7-fold, P < 0.01) was observed after a 2-h treatment with physiological concentrations (10(-11) M) of GHRH. The action of GHRH seems to occur at the transcriptional level without the need of protein synthesis. Thus, treatment of cells with actinomycin D (5 micrograms/ml) completely abolished GHRH-induced increase in GHF-1 mRNA levels. Cycloheximide (23 micrograms/ml) alone increased GHF-1 mRNA levels (6-fold increase after treatment for 12 h, P < 0.01), as well as potentiating GHRH-induced increase in GHF-1 mRNA concentration (9-fold increase after treatment with GHRH plus cycloheximide for 12 h, P < 0.01). The effect of GHRH on GHF-1 mRNA levels could be mimicked by direct activators of second messenger signaling systems such as forskolin (10(-5) M) or the phorbol ester tumor promoter tetradecanoyl phorbol acetate (TPA) (10(-6) M). Other peptides such as pituitary adenylate cyclase activating polypeptide-38 (10(-7) M) but not GHRP-6 (10(-10) to 10(-5) M), were also able to increase GHF-1 mRNA levels. Treatment of the cells with somatostatin (10(-6) M) for either 2 or 48 h failed to modify basal or GHRH-induced GHF-1 mRNA levels. In contrast, pretreatment of the cells with insulin-like growth factor-1 (5 nM) inhibited basal GHF-1 mRNA concentration as well as completely blunting the subsequent response to cells exposed to GHRH for 2 h. These data demonstrate that GHRH, acting at the transcriptional level and through a mechanism not dependent on protein synthesis, plays a stimulatory role on GHF-1 mRNA levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenylyl Cyclases↗

Cerebral cysticercotic arteritis: detection and follow-up by transcranial Doppler.

Intracranial arteritis is a well-known complication of cerebral cysticercosis. The aim of this study was to explore the possible role of transcranial Doppler (TCD) in the evaluation of cysticercotic arteritis in 9 patients with subarachnoid cysticercosis and stroke. Arteritis of main basal vessels was detected by TCD in 7 of 10 arterial lesions that were demonstrated by cerebral angiography. The Doppler pattern was occlusive in 2 cases and stenotic in 5. In the 3 patients with lacunar infarcts, both cerebral angiography and TCD were normal. In 6 arterial lesions followed serially with TCD a stenotic pattern resolved within 4 and 6 months in 3 cases and remained in the stenotic range at 12 months in 1 case, whereas an occlusive pattern persisted at 6 and 18 months in the other 2 cases. In conclusion, TCD may be useful to detect and follow up cerebral vasculitis due to chronic cysticercotic arachnoiditis.

Adolescent↗

[AIDS and neoplasms in Mexico].

OBJECTIVE: To describe the epidemiological profile of AIDS and malignancies in Mexico. MATERIAL AND METHODS: The study population included a group of AIDS patients seen at four National Institutes of Health and one at a general hospital in Mexico City, from 1983 to 1992. Demographic, clinical and laboratory information was obtained. RESULTS: A total of 202 patients were studied; 199 men and three women. The mean age was of 34.5 years (range 18-67 years). Kaposi's sarcoma was the most frequent malignancy, with 166 cases, followed by non-Hodgkin's lymphoma, with 33 cases. The three women had non-Hodgkin's lymphoma, one of them associated with cervical carcinoma. Rectal cancer was present in three cases. DISCUSSION: The spectrum of AIDS-associated malignancies in Mexico is similar to that described in other populations. The early diagnosis of this complication is necessary, as well as the search for therapeutic actions to prevent severe immunosuppression and the consequent appearance of malignancies.

AIDS-Related Opportunistic Infections↗