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Biomedical subjects

J Pena

Publications and source records attributed to J Pena.

At least 37 records · Page 2Linked to original sources

Effect of oral glucose ingestion on hepatic non-esterified fatty acids and ketone body metabolism in normal dogs.

The time course of changes in hepatic lipid metabolism (non-esterified fatty acids (NEFA), ketone body) after ingestion of glucose was assessed in normal dogs. Glucose ingestion suppressed significantly (p less than 0.01) the amount of NEFA reaching the liver (12.4 +/- 1.0 to a nadir of 2.9 +/- 0.6 mumol/kg/min at 80 min) and increased significantly (p less than 0.05) net hepatic balance (-1.8 +/- 0.6 to 0.5 +/- 0.4 mumol/kg/min at 120 min). After glucose ingestion, the amount of total ketone body presented to the liver decreased significantly (p less than 0.05) to a nadir of 1.1 +/- 0.4 mumol/kg/min at 60 min and gradually increased after 120 min. These changes reflect the increased insulin secretion induced by glucose ingestion. The hyperinsulinemia would inhibit peripheral lipolysis and stimulate esterification of fatty acids. It would reduce ketone body concentration both by a direct effect on hepatic production as well as the consequence of diminished NEFA levels. In summary, the present study clearly demonstrated the time course changes in NEFA and ketone body level after oral glucose ingestion.

Animals↗

Isolation of a novel tumor protein that induces resistance to natural killer cell lysis.

The human metastatic tumor cell line CAP-2, produces a soluble factor that induces resistance to NK lysis of K-562 susceptible leukemia cell line, and does not inhibit the cytotoxic capacity of effector cells. The use of sequential HPLC, hydrophobic interaction chromatography, and reverse phase chromatography, coupled with cytotoxic assays, resulted in the isolation and separation to homogeneity of a novel protein responsible for this biologic activity. Size estimation studies based on TSK HPLC columns showed that this protein has a mass of 8 to 12 kDa. The amino acid composition analysis of the CAP-2 protein calculated from HPLC chromatograms shows that this protein contains around 108 amino acids. Subsequent gas phase sequence analysis, however, was hampered because the N terminus of this protein was blocked and therefore unsuitable for sequencing by Edman degradation. The functional studies showed that the NK lysis-resistance activity of the CAP-2 protein is mediated by interaction with and nonspecific binding to NK target cells. The lymphokine-activated killer and macrophage-mediated cytotoxicity and mitogen-induced proliferation is not affected. Unexpectedly, the CAP-2 protein appears to be mitogenic to its own cell line. Thus, the induction of NK lysis-resistance and the mitogenic activity showed by CAP-2 protein could contribute to the tumor growth and metastatic establishment.

Amino Acids↗

Fasting and postabsorptive hepatic glucose and insulin metabolism in hyperthyroidism.

The effect of thyroid hormone excess on hepatic glucose balances and fractional hepatic extraction of insulin and glucagon was examined in six conscious dogs with catheters in the portal vein, hepatic vein, and femoral artery and Doppler flow probes on the portal vein and hepatic artery. An oral glucose tolerance test was performed before and after the animals were made hyperthyroid by intramuscular thyroxine administration (100 micrograms.kg-1.day-1) for 10 days. In the basal state and after oral glucose, insulin and glucagon levels in the three vessels and the basal fractional hepatic extraction of insulin and glucagon were not significantly modified by thyroid hormone. These results suggest that in short-term thyrotoxicosis insulin secretion is not impaired, and the rise in fasting plasma glucose and increased hepatic glucose production could reflect hepatic insulin resistance, increased availability of precursors for gluconeogenesis, or increased glycogenolysis. Hyperthyroidism significantly increased basal flows in the portal vein (14.7 +/- 0.6 vs. 12.9 +/- 0.5 ml.kg-1.min-1), the hepatic artery (4.8 +/- 0.3 vs. 3.9 +/- 0.2 ml.kg-1.min-1) and vein (19.6 +/- 0.7 vs. 16.9 +/- 0.4 ml.kg-1.min-1), the fasting plasma glucose concentration (104 +/- 3 vs. 92 +/- 2 mg/dl), and basal hepatic glucose output (2.1 +/- 0.2 vs. 1.5 +/- 0.2 mg.kg-1.min-1). It did not alter the nonhepatic splanchnic uptake of glucose, the percent of orally administered glucose that appeared in the portal vein (47 +/- 2 vs. 45 +/- 11%), the percent of hepatic uptake of glucose (59 +/- 11 vs. 74 +/- 22%), or the shape of the glucose tolerance test.

Animals↗

Differential expression of HLA-DR and HLA-DQ antigens on normal cells of the myelomonocytic lineage.

We have previously shown that HLA-class II antigens have a differential expression on acute myeloblastic leukaemia (AML) blasts. These cells express HLA-DR molecules but the HLA-DQ antigens are undetectable. In this paper we study the expression of HLA-DR and HLA-DQ antigens, using monoclonal antibodies (MoAbs), on normal cells of the myelomonocytic lineage: the common myelomonocytic progenitor (CFU-GM) and the monocytes, by techniques of inhibition of CFU-GM growth and double immunofluoroscence, respectively. The results show that HLA-DR and HLA-DQ antigens are differentially expressed on normal myelomonocytic cells. While HLA-DR molecules are expressed on CFU-GM and on the majority of peripheral blood monocytes, HLA-DQ antigens are not expressed on CFU-GM and only present on a subpopulation of monocytes. This data further confirms that HLA-DR and HLA-DQ molecules are coded by different genes with independent regulation of the gene expression not only on myeloid leukaemias but also on normal cells of the myelomonocytic lineage.

Adult↗

Effect of phorbol ester TPA on macrophage metabolic activity.

Metabolically active macrophages are known to play a role in tumor immune surveillance, not only as effector cells but also as collaborators in T cell mediated immune response. The present work reports that non-toxic concentrations of the tumor promoter TPA, stimulate the adherence of murine peritoneal macrophages after short time incubation, while TPA pretreatment for periods longer than 4 hrs suppresses phagocytosis, RNA and protein synthesis by these cells. Although inhibition of macrophage metabolic activity could play an additional role in tumor promotion, the enhancing and depressing effects of TPA on the immune system must be weighed before it can be assumed that TPA acts in vivo primarily to depress the immune system.

Animals↗

An immunological study of nine proteins in CSF and serum of a group of epileptic patients.

The concentrations of nine proteins, alpha-1-acid glycoprotein, antitrypsin, prealbumin, transferrin, albumin, IgG, ceruloplasmin, IgA and alpha-2-macroglobulin, have been determined in the serum and CSF of two groups of patients, one control and one experimental, by an immunological method. The experimental group were patients suffering from grand mal epilepsy. The control group showed no detectable neurological disorder. In the group of grand mal epileptics, only prealbumin showed a significant elevation in CSF when compared with the control group. In contrast, the rest of the proteins are decreased with respect to the controls except for alpha 1-acid glycoprotein and transferrin. The results from this study also suggest that something more than an ultrafiltration process dependent upon molecular weight, is important in determining the concentration of some serum proteins in the CSF.

Adult↗

Study of three hypervariable DNA loci (D1S7; D7S22 and D12S11) in three European populations.

To investigate the population genetic characteristics and genetic affinity, DNA profiles of three highly polymorphic VNTR (variable number of tandem repeats) loci (D1S7; D7S22 and D12S11) were studied in 405 individuals from three major European populations (English, Spanish and Basques). Like other studies on VNTRs, a large significant heterozygote deficiency was observed in all three populations. This decrease was ascribed to the limitation, coalescence and non-detectibility of alleles associated with the RFLP (restriction fragment length polymorphism) technique, through which the VNTR loci are genotyped. When the non-detectable alleles were taken into consideration, analyses of fragment sizes at these loci within each sample, as well as their fixed binned analyses, reveal that the assumptions of independence of allelelic occurrences within and between loci are valid for this European data. By comparing genetic variation at three VNTR loci with 17 blood groups, proteins and HLA loci in three well defined European populations, it is shown that the pattern of differentiation at these sets of loci are in general parallel especially for the hypervariable loci HLA and VNTR. Fixed-bin allele frequencies, therefore, are the best descriptions of such a database both for population genetic and forensic calculation studies. The Basques, with regard to VNTR loci, do not show any reduced genetic variability compared to other two European populations (English and Spanish).

Chromosome Mapping↗

Anthropology of the apoplipoprotein E (apo E) gene: low frequency of apo E4 allele in Basques and in tribal (Baiga) populations of India.

The distribution of apolipoprotein E (apo E) polymorphism was examined in 11 population groups not previously studied for this system. There is a marked difference in phenotype and gene frequency between the populations of England and Spain. The south European populations of Basques and Spanish non-Basques showed greater similarity to the populations of South Asia. The study clearly indicates that the distribution of apo E alleles does match with regions showing a high mortality rate of coronary heart disease. The data presented also indicate that authochthon groups such as Basques in Europe and tribals in India may throw better light on the role of apolipoproteins in the regulation of lipid levels in disease.

Alleles↗

MHC class I expression on human tumour cells and their susceptibility to NK lysis.

Although natural killer (NK) activity is not restricted by the major histocompatibility complex (MHC), it has been suggested that the level of expression of MHC antigens by target cells may influence their lysis by NK cells. We have studied the NK susceptibility of 20 cell lines obtained from primitive and metastatic human tumours and the K562 cell line treated with gamma-interferon, phorbol ester TPA and tumour factor NK-RIF. When the levels of MHC class I antigen expression on the human tumour cell lines and their NK susceptibility were compared, no relationship between these two parameters was observed. Furthermore the treatment of K562 with either gamma-interferon, TPA or NK-RIF decreased its NK susceptibility independently of MHC class I expression. These results indicate that the MHC class I antigen is not the only factor directly involved in NK susceptibility and suggest that other membrane structures modulated by gamma-interferon, TPA or NK-RIF may also influence NK susceptibility.

Cytotoxicity, Immunologic↗