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Biomedical subjects

M Serrano

Publications and source records attributed to M Serrano.

At least 145 records · Page 8Linked to original sources
PubMed1989

Signals at the bacteriophage phi 29 DNA replication origins required for protein p6 binding and activity.

Protein p6 of Bacillus subtilis phage phi 29 binds specifically to the ends of the viral DNA that contain the replication origins, giving rise to a nucleoprotein structure. DNA regions recognized by protein p6 have been mapped by deletion analysis and DNase I footprinting. Main protein p6-recognition signals have been located between nucleotides 62 and 125 at the right phi 29 DNA end and between nucleotides 46 and 68 at the left end. In addition, recognition signals are also present at other sites within 200-300 bp at each phi 29 DNA end. Protein p6 does not seem to recognize a specific sequence in the DNA, but rather a structural feature, which could be bendability. The formation of the protein p6-DNA nucleoprotein complex is likely to be the structural basis for the protein p6 activity in the initiation of replication.

Bacteriophages↗
PubMed1989

Suppressor T-cell activity in chronic hepatitis B-virus infection: relationship with the presence of HBV-DNA in serum.

Suppressor T-cell activity and allogeneic T-cell response to concanavalin A (ConA) were investigated in 46 patients chronically infected with hepatitis B virus (HBV). Thirty-eight patients had chronic active hepatitis, seven of whom were superinfected with Delta virus, and eight were healthy chronic HBV carriers. T-cell suppressor activity was in the normal range in healthy carriers and in patients negative for serum HBV-DNA, independent of the e antigen status. In contrast, the group of patients positive for HBV-DNA exhibited a significant reduction in suppressor activity. Longitudinal studies in patients who cleared serum HBV-DNA demonstrated that suppressor T-cell activity became normal thereafter. These results suggest a relationship between suppressor T-cell function and the stage of viral replication in individuals with chronic HBV infection.

Adult↗
PubMed1989

Somatostatin analogues inhibit growth of pancreatic cancer by stimulating tyrosine phosphatase.

Several analogues of somatostatin were examined in the Mia PaCa-2 human pancreatic cancer cell line for their ability to promote tyrosine phosphatase activity affecting the receptors for the epidermal growth factor. The inhibition of growth of the Mia PaCa-2 cells in culture was also evaluated to determine the mechanism of action of somatostatin analogues and their relative effectiveness in inhibiting cancer growth. Of the analogues tested D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) caused the greatest stimulation of tyrosine phosphatase activity. Analogue D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) had less effect but was more potent than somatostatin-14. Analogue D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr(ol) (SMS 201-995) produced no significant dephosphorylation. The analogues displayed the same order of activity in assays on growth inhibition of Mia PaCa-2 cells in cultures. Analogue (SMS-201-995) caused virtually no tyrosine phosphatase stimulation or growth inhibition in this cancer cell line, although it possesses a much higher antisecretory activity than somatostatin-14 in normal tissues. These observations indicate that somatostatin and some of its analogues can act as growth inhibitors in cancer cells through the activation of tyrosine phosphatase. These data reinforce the view that somatostatin analogue RC-160 and related compounds could be used for treatment of pancreatic cancer.

Antineoplastic Agents↗
PubMed1989

A pilot study of thymus extract in chronic non-A, non-B hepatitis.

In previous studies it has been suggested that activation of cellular immunity may have a role in controlling the activity of chronic non-A, non-B liver disease. We conducted a pilot study of therapy with a bovine thymus extract for 6 weeks in 15 consecutive patients with chronic non-A, non-B hepatitis, most of them sporadic cases. Treatment induced immunomodulation, and in five patients a significant but transient diminution in aminotransferase levels was observed associated with increments in several parameters of cellular immunity. This suggests that a longer administration of this or other related compounds, or treatment with a more potent immunomodulating agent, might be effective in these patients.

Animals↗
PubMed1989

Opioid peptides modulate the organization of vimentin filaments, phagocytic activity, and expression of surface molecules in monocytes.

It is theorized that intermediate filaments are important in the modulation of membrane activity and cell motility; however, their functions are unknown. The assembly and organization of these filaments are under hormonal regulation. We investigated in human monocytes the in vitro effects of Met-enkephalin, Leu-enkephalin, and beta-endorphin on the expression of immunoreactive cytoskeletal vimentin filaments. We simultaneously examined their effect on the phagocytosis of Candida albicans and on the membrane display of surface molecules. The three opioid peptides markedly reduced the expression of vimentin filaments, the phagocytic activity, and the display of HLA-DR molecules at concentrations of 10(-6), 10(-8), and 10(-10) M. On the other hand, the intravenous administration of fentanyl, a synthetic opiate agonist, to patients undergoing surgery induced similar changes in monocytes. In other experiments, 10(-8) M beta-endorphin also decreased the expression of CR3 but did not influence the display of CD13, a surface protein of unknown function. Expression of vimentin filaments correlated directly with the display of HLA-DR antigens and CR3 and with the phagocytic activity. The results of this paper indicate that opiates and opioids, neuropeptides known to be released during stress, can directly depress several monocyte functions. Furthermore, from these data it may be speculated that intermediate filaments may regulate the membrane expression of some surface molecules and the phagocytic process.

Antigens, Surface↗
PubMed1989

Naloxone-reversible monocyte dysfunction in patients with chronic fatigue syndrome.

We studied monocyte function in 35 consecutive patients with chronic fatigue syndrome (CFS) and 25 healthy controls. Eighty-five per cent of the patients showed monocyte dysfunction characterized by marked reduction in the number of monocytes displaying immunoreactive cytoskeletal vimentin filaments, a low phagocytosis index, and a reduced expression of HLA-DR antigens. These values increased dramatically after incubation of the patients' monocytes with the opioid antagonist naloxone. Other immunological abnormalities also noted in the patients were low lymphocyte blastogenesis and diminished numbers of monocytes displaying receptors for Fc of IgG (FcR) and C3b (CR1). These findings suggest that an increased opioid activity acting through a classical receptor mechanism is active on monocytes from a high proportion of patients with CFS and that this represents a novel example of immunomodulation by opioid peptides in human disease. We suggest that endogenous opioids are involved in the pathogenesis of the chronic fatigue syndrome.

Adult↗
PubMed1988

Protein-primed replication of bacteriophage phi 29 DNA.

The replication of phi 29 DNA-protein p3 represents a simple model system to study the protein-priming mechanism of initiation of replication. The phi 29 DNA polymerase involved both in the initiation and elongation steps of phi 29 DNA-protein p3 replication, is a very processive enzyme and it is able to produce strand-displacement in the absence of other proteins. To correlate functional and structural domains in the phi 29 DNA polymerase point mutants in the most carboxyl region of amino-acid homology with other DNA polymerases have been constructed. Most of the mutations had a decreased initiation and elongation activity, but normal 3'----5' exonuclease activity, suggesting that this region contributes to the active domain for initiation and elongation. Point and deletion mutants in the terminal protein have allowed the mapping of one DNA-binding region and two DNA-polymerase-binding regions. The viral protein p6, which stimulates the initiation of replication, binds to a set of specific signals present at both phi 29 DNA ends. A good correlation of binding and stimulation of replication has been obtained by using fragments containing phi 29 DNA-terminal sequences and deletion mutants of protein p6. The viral protein p5 has been shown to bind to single-stranded DNA, to protect the latter against nuclease digetion, and to stimulate phi 29 DNA-protein p3 replication in vitro.

Bacteriophages↗
PubMed1988

Interaction of the bacteriophage phi 29 protein p6 with double-stranded DNA.

The Bacillus subtilis bacteriophage phi 29 protein p6 binds to double-stranded DNA, but not to single-stranded DNA, as determined by a gel retardation assay. The nature of the interaction was further studied by DNase I "footprinting" experiments. Protein p6 binds to fragments containing the right or left terminal sequences of phi 29 DNA, producing a characteristic pattern of hypersensitive bands spaced about 24 nucleotides apart along most of the fragment, flanking protected regions. Binding of protein p6 to an internal phi 29 DNA fragment was also observed, but the footprint pattern was more salt sensitive than that obtained with the terminal phi 29 DNA fragments. By electron microscopy, protein p6 was shown to cover the DNA, totally or partially, from one end. In addition, binding of protein p6 to relaxed circular DNA induced positive supercoiling, indicating that a topological change in the DNA occurred.

Bacillus subtilis↗
PubMed1987

Interleukins in chronic active hepatitis B. Relationship with viral markers.

Interleukin-2, a product of helper T cells, is essentially involved in the regulation of cell-mediated immunity. Two monocyte-derived factors, interleukin-1 and prostaglandin E2, influence interleukin-2 synthesis with opposite actions. To analyse immunoregulatory function in HBsAg-positive chronic active hepatitis, T cell subsets in peripheral blood and the levels of interleukin-2, interleukin-1 and prostaglandin E2 in supernatants from lectin- or lipopolysaccharide-activated peripheral mononuclear cell cultures were determined in 16 healthy controls and 33 patients with chronic active hepatitis B. Interleukin-2 activity was comparable to the controls in patients without delta infection who had seroconverted to anti-HBe (group 1), but it was significantly reduced in both HBeAg-positive subjects (group 2) (P less than 0.05 vs. controls and group 1) and those cases with positive delta markers (group 3) (P less than 0.01 and less than 0.05 vs. controls and group 1, respectively). In group 3, interleukin-2 was similarly diminished in both anti-HTLV-III-positive and -negative cases as well as in HBeAg- and anti-HBe-positive subjects. Notwithstanding the changes in interleukin-2 activity, no significant differences in the number of T4 cells, or in the levels of either interleukin-1 or prostaglandin E2, were found among the various groups of subjects studied. However, in those groups with reduced interleukin-2 activity an increased number of T8 cells was observed. It is suggested that the low levels of interleukin-2 found in the replicative phase of chronic active hepatitis B and in delta superinfection reflect a disturbed immunoregulation that may contribute to persistent viral replication in these two conditions.

Adult↗
PubMed1987

[Kinetin and the germinating capacity of Lupinus multilupa seeds].

The effect of kinetin (10(-6) M and 10(-4) M) on the germinating capacity and incorporation of 8-C14 adenine into DNA, RNA and RNA Poly A+ of embryos and cotyledons from Lupinus multilupa L. seeds have been studied. Kinetin enhanced the germinative capacity of the seeds and the incorporation of 8-C14 adenine into DNA, RNA and Poly A+ of embryos and cotyledons. However, there seems to be no close relationship between the DNA and RNA biosynthesis of embryos and cotyledons and the ability of the seeds to germinate and their embryos to continue growing.

DNA↗