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Biomedical subjects

P Ruiz

Publications and source records attributed to P Ruiz.

At least 199 records · Page 11Linked to original sources
PubMed1994

Lymphoid organ production of immunomodulatory eicosanoids in mice resistant to neonatal tolerance induction.

Neonatally induced tolerance of class I and class II alloantigens is difficult to achieve in certain I-E non-expressing hosts that received semiallogeneic cells at birth from strains of mice that express I-E molecules. Although clonal deletion occurs ubiquitously after infusion of the tolerogen-bearing inoculum, the majority of these mice ultimately regain the capacity to reject donor-specific skin graft challenges in adulthood and this is associated with a reacquisition of I-E recognizing and alloreactive T cells as well as a loss of donor chimeric cells. In this study, we determined whether production levels of the eicosanoids prostaglandin E2 (PGE2) and thromboxane B2 (TxB2), both potent modifiers of lymphocyte function, were altered in lymphoid organs concomitant with a breakdown of tolerance in these mice. The levels of TxB2 and PGE2 produced by lymphoid organs were measured in the early/late post-partum periods and immediately before and after skin grafting in B10.S mice (H-2s/I-E-) that had been injected at birth with (B10.S x B10.A)F1 (H-2k/d, I-E+) lymphohematopoietic cells. Phenotypic (e.g., %V beta 11+ T cells) and functional parameters of host donor-reactive effector cell populations along with chimerism were determined simultaneously. We found that TxB2 and PGE2 production fluctuated in the early postnatal periods in naive mice and that the neonatally injected counterparts showed a significant alteration from this pattern, particularly with PGE2. As adults, injected hosts maintained an altered pattern of eicosanoid metabolism and this was accentuated after the rejection or acceptance of a donor-specific skin allograft. Specific patterns emerged after transplant challenge such that neonatally injected mice deleted of V beta 11+ T cells before grafting differed in their eicosanoid secretory profiles; moreover, injected mice that accepted (i.e., tolerant) the donor-specific allograft had a markedly different TxB2 and PGE2 profile than injected/rejecting hosts. In naive mice, the application of 2 subsequent grafts elicited a release of splenic TxB2 and PGE2 that mimicked the pattern seen in the neonatally injected hosts after 1 graft--these latter results give preliminary indication that the generation of memory T cells and the re-exposure to specific alloantigen coincides with a derangement in eicosanoid metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Simultaneous expression of CD2 on a B-cell, small lymphocytic neoplasm.

An unusual neoplasm, best classified as a B-cell chronic lymphocytic leukemia on the basis of cytofluorographic, immunohistologic, and gene rearrangement analysis also co-expressed the T-cell associated marker CD2 (sheep erythrocyte receptor), but without other cell markers restricted to T cells. This case was associated with a more aggressive course than typically seen with B-CLL or malignant lymphoma, small lymphocytic type, implying along with previous reports that CD2 expression may serve as a marker of small lymphocytic tumor cell behavior and the ultimate clinical course. Thus, surface phenotypic analysis of these particular hematopoietic neoplasms may serve not only for identification of the malignancy, but could also render prognostic information.

Antigens, CD↗
PubMed1994

Glutathione-linked detoxification pathway in normal and malignant human bladder tissue.

This study compares the levels of glutathione (GSH) and GSH-dependent detoxification enzymes, which have been implicated in anti-cancer drug resistance, in paired normal and malignant human bladder tissues, a tumor with high incidence of inherent drug resistance. Although the mean GSH transferase (GST) activity did not differ significantly in normal and neoplastic bladder tissues, this enzyme activity was relatively higher in tumor tissues of five out of ten patients as compared with corresponding normal tissues. Similarly, the mean GSH content and GSH reductase activity did not differ significantly between normal and neoplastic bladder tissues. On the other hand, the mean GSH peroxidase activity towards cumene hydroperoxide and catalase activity in bladder tumors was higher by about 1.5 and 1.4 times, respectively (P < 0.05), compared with those of normal tissues. GST isoenzymes corresponding to the three major classes (alpha, mu and pi) were expressed in every normal bladder tissue examined in the present study. Overexpression of GST pi was observed in 60% of the bladder tumors, whereas alpha and mu type GST proteins in tumor tissues were lower at frequencies of 62.5% and 37.5%, respectively, compared with the corresponding normal tissues. These results suggest that (a) elevated levels of GSH peroxidase, catalase and GST pi in human bladder tumors may contribute, at least in part, to the intrinsic drug resistance of this neoplasm and (b) anti-oxidative enzymes GSH peroxidase and/or catalase may represent markers for this neoplasia, although a large number of tissue specimens must be analyzed to validate this hypothesis.

Adult↗
PubMed1994

The role of nitric oxide in the pathogenesis of spontaneous murine autoimmune disease: increased nitric oxide production and nitric oxide synthase expression in MRL-lpr/lpr mice, and reduction of spontaneous glomerulonephritis and arthritis by orally administered NG-monomethyl-L-arginine.

MRL-lpr/lpr mice spontaneously develop various manifestations of autoimmunity including an inflammatory arthropathy and immune complex glomerulonephritis. This study examines the role of nitric oxide, a molecule with proinflammatory actions, in the pathogenesis of MRL-lpr/lpr autoimmune disease. MRL-lpr/lpr mice excreted more urinary nitrite/nitrate (an in vivo marker of nitric oxide production) than did mice of normal strains and MRL-(+/+) and B6-lpr/lpr congenic strains. In addition, MRL-lpr/lpr peritoneal macrophages had an enhanced capacity to produce nitric oxide in vitro as well as increased nitric oxide synthase activity, and certain tissues from MRL-lpr/lpr mice had increased expression of inducible nitric oxide synthase (NOS) mRNA and increased amounts of material immunoreactive for inducible NOS. Oral administration of NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor, prevented the development of glomerulonephritis and reduced the intensity of inflammatory arthritis in MRL-lpr/lpr mice. By using interspecific backcross mice, the gene for inducible NOS (Nosi) was mapped to mouse chromosome 11. This chromosomal localization was different from those loci that we have previously demonstrated to be linked to enhanced susceptibility to renal disease in an MRL-lpr/lpr cross. However, the chromosomal location of the NOS gene was consistent with an insulin-dependent diabetes locus identified in an analysis of nonobese diabetic (NOD) mice. These results suggest that elevated nitric oxide production could be important in the pathogenesis of autoimmunity, and that treatments to block the production of nitric oxide or block its effects might be valuable therapeutically.

Administration, Oral↗
PubMed1994

Antineoplastic and antiviral activities of podophyllotoxin related lignans.

28 cyclolignans, most of them derived from podophyllotoxin, have been evaluated for their antineoplastic and antiviral activities. They were subjected to screening against P-388 murine leukemia, A-549 human lung carcinoma, and HT-29 colon carcinoma, while antiviral assays were performed on herpes simplex virus type I infecting fibroblasts of monkey kidney (HSV/CV-1) and on vesicular stomatitis virus infecting fibroblasts of hamster kidney (VSV/BHK). A number of substances were active in both groups of assays at concentrations below 1 microM; deoxypodophyllotoxin (1) being the most potent compound in all cases.

Animals↗
PubMed1994

Human T lymphocyte subpopulation and NK cell alterations in persons exposed to cocaine.

Immunophenotypic changes in peripheral blood mononuclear cells were analyzed by flow cytometry in several patient groups positive for cocaine in their urine. Single- and dual-color immunofluorescence staining was performed to examine total numbers of NK, T, and B cells, as well as the coexpression of surface molecules on T cells associated with memory function, helper/inducer capacity, and activation status. In addition, levels of several serum proteins (including immunoglobulins) and other demographic variables were evaluated. Our results show that cocaine-intoxicated patients display reductions in the total percentage of CD4+ T cells and increases in the number of NK cells. Dramatic shifts within certain T cell subpopulations were also observed. In particular, there appeared to be a preferential stimulation of "activated" T cells as indicated by increased levels of class II+ CD4 and CD8 T cells and IL2r+ CD4 T cells. "Memory" CD8+ T cell subpopulations (i.e., CD45RO+) were reduced in the cocaine-positive patients, whereas CD45R+/CD8+ T cells were accordingly increased in the same individuals. In some cases, direct correlation could be established between certain T cell percentages and cocaine levels. None of the serum protein levels measured appeared to be influenced by cocaine. These findings demonstrate that cocaine utilization is associated with variations in levels of certain T cell subpopulations and other immune cells. This may represent a disruption of particular immunologic cell networks which could ultimately influence host resistance to infection and malignancy.

Acute-Phase Proteins↗
PubMed1994

Alpha 6 integrin distribution in human embryonic and adult tissues.

Alpha 6 integrin is an adhesion molecule that connects cells with extracellular matrix molecules of the laminin family. The laminin interaction seems to be essential for cell differentiation during embryogenesis and for the subsequent maintenance of tissue integrity in the adult. Alpha 6 integrin can also interact with laminin-independent cellular ligands and in this way plays a role in homing of leucocytes. Furthermore, in cancer biology alpha 6 integrin has an important role in metastasis and as a possible new prognostic factor; exact knowledge of alpha 6 integrin distribution in normal human tissues is therefore a crucial element. By immuno-histochemical methods we have screened alpha 6 integrin expression of representative human tissues from the adult and the embryonic organism. All tested epithelia were alpha 6 integrin positive, except for the endocrine cells of the pancreas and the adrenal glands. Heterogeneous staining was found on non-epithelial tissues. Strong staining was evident in peripheral nerves (Schwann cells), germ and Sertoli cells, endothelia, and smooth muscle cells of the myometrium. Weak staining was found in nerve cells of the stratum granulosum, the microglia, Kupffer's cells and stromal cells of the ovary. All fibroblasts, striated muscle cells and astrocytes were negative. The tissue distribution of alpha 6 integrin and the semi-quantitative estimation of their expression level should provide a better understanding of alpha 6 integrin function under normal and pathological conditions, in particular in tumour progression.

Adult↗
PubMed1994

Fish oil feeding modulates leukotriene production in murine lupus nephritis.

Diets enriched with fish oil (FO) ameliorate kidney disease in the MRL-lpr/lpr murine model of lupus nephritis. Although the mechanisms of this effect are not known, FO is rich in the polyunsaturated fatty acid eicosapentaenoic acid (EPA) which may have profound effects on eicosanoid metabolism. In MRL-lpr/lpr mice, FO feeding reduces renal production of cyclooxygenase metabolites. However, EPA may also affect the metabolism of arachidonate by the 5-lipoxygenase (5-LO) pathway and enhanced production of 5-LO metabolites has been implicated in the pathogenesis of kidney disease in MRL-lpr/lpr mice. We therefore investigated the effects of FO feeding on production of 5-LO metabolites in 20 week old MRL-lpr/lpr mice. After 8 weeks of dietary supplementation with FO, both renal hemodynamic function and glomerular histology were improved compared to safflower oil (SO) controls. Amelioration of kidney disease was associated with alterations in the pattern of leukotriene production by macrophages and kidneys from FO fed mice. There was a significant decrease in the production of leukotriene B4 (LTB4) and tetraene peptidoleukotrienes by peritoneal macrophages isolated from mice given FO compared to control animals. Similarly, dietary supplementation with FO decreased renal production of LTB4. Reduced production of tetraene leukotrienes was accompanied by a modest increase in the production of pentaene leukotrienes by macrophages from FO fed mice. We speculate that this modulation of leukotriene production by FO feeding may have beneficial effects on renal disease in autoimmune nephritis.

Administration, Oral↗
PubMed1994

Family planning needs of male chronic mental patients in the general hospital psychiatry clinic.

We investigated the parenting history, contraceptive behavior, and contraceptive needs of 35 male chronic mental patients seen at an urban outpatient psychiatric clinic. Most patients had fathered children, but 60% of the children less than 16 years of age were not being reared by their biological father. Forty-one percent of the patients who had sexual intercourse during the preceding year and had not wanted children reported that they or their sexual partner had not used contraception at the time of last intercourse. Patients were reportedly at significant risk of fathering unwanted children and sexually transmitted diseases. Strategies for preventing unwanted pregnancies within this population are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Differential patterns of T cell clonal deletion in neonatal H-2 tolerance and I-E/Mls induced self-tolerance.

The pattern of clonal deletion of putative I-E-reactive (V beta 11) and Mls-reactive (V beta 3) T cells was evaluated and compared by cytofluorographic and immunohistochemical methods in a model of neonatal H-2 tolerance and in I-E- or Mls-bearing strains of mice which normally delete these cell populations (self-tolerance). The ontogeny of deletion of V beta 11+ cells was studied by evaluating thymic changes from birth until maturity in B10.S (H-2s/I-E-), B10.A (H-2k/d/I-E+) and B10.S mice intravenously infused at birth with (B10.SxB10.A)F1 lymphohaematopoietic cells. The reduction in V beta 11+ cells was most prevalent in the medullary region of the naive B10.A and neonatally injected B10.S animals and was corroborated by flow cytometry which demonstrated a marked reduction in single CD4 and CD8 positive B beta 11 T cells when compared to naive B10.S mice. However, immunohistochemistry illustrated that 'deletion' was never complete since V beta 11+ cells remained in the thymic cortex and splenic lymphoid follicles. By comparison, DBA/2 mice (Mlsc+ and previously documented to have decreased levels of V beta 3+ cells) showed a different pattern of deletion of V beta 3+ T cells than what was found for T cells bearing V beta 11 in animals deleting this population. DBA/2 thymi contained fewer thymic V beta 3- cells and there was more complete elimination of these cells, particularly in the periphery, by flow cytometry and immunohistology. The mice which do not delete V beta 3 cells (Mlsc-) showed that the majority of V beta 3- cells were located in the medulla with a few cells distributed in the cortical region. This pattern was notably different than the distribution of V beta 11 cells in thymi. Despite their location by histology, the majority of remaining V beta 3+ cells were dual CD4/CD8 positive (CD4+CD8+) by flow cytometric analysis. Our data illustrate that V beta 11 and V beta 3 T cells appear to be eliminated (i.e. 'deleted') at similar stages of maturation (single positive) during self-tolerance as well as in a neonatal H-2 tolerance model. However, the degree of elimination and the location of the cells remaining in these mice is dramatically different, depending on which T cell population is being evaluated and which deleting ligand is presented intrathymically. Thus, the accepted tenet of dual CD4+CD8+ cells localizing to the thymic cortex appears to have exceptions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Borderline tuberculoid Hansen's disease in AIDS.

We performed an immunohistochemical analysis of a skin lesion from a patient with AIDS who had borderline tuberculoid Hansen's disease. We also evaluated other laboratory features and performed peripheral blood flow cytometric analysis. The in situ immunologic response to Mycobacterium leprae was minimally affected by concomitant infection and immunosuppression by HIV. The skin demonstrated the typical characteristics of borderline tuberculoid lesions. These results indicate that although a patient with HIV infection may have laboratory evidence typical of the immunosuppression seen in AIDS, the immunologic response to M. leprae is essentially unchanged.

AIDS-Related Opportunistic Infections↗
PubMed1994

Duplicate prealbumin bands in urine. Association with hepatorenal failure.

By electrophoresis, prealbumin is seen as a discrete band anodic to the albumin fraction. Cases of duplicate bands in the prealbumin region have been described previously in serum, cerebrospinal fluid, and urine, and have had an association with varied clinical entities. The authors describe a novel association of severe hepatic and renal failure with the presence of prominent duplicate prealbumin bands in urine.

Acute Kidney Injury↗
PubMed1994

Human immunodeficiency virus and the substance abuser: public policy considerations.

Until recently, the abuse of intravenous drugs was perceived as a problem of the United States, and the acquired immunodeficiency syndrome (AIDS) epidemic was seen mainly as a sexually transmitted disease that tended to affect homosexuals from industrialized nations. However, these perceptions are no longer valid. At present, the abuse of intravenous drugs constitutes the second most common cause of AIDS in the United States and in Europe. This trend has led to a review of the current strategies in the fight against infection with the human immunodeficiency virus (HIV). We analyzed the current epidemiologic trends regarding infection with HIV; we examined the behavioral manifestations of intravenous drug users, particularly from a sexual point of view; and finally, we reviewed the most relevant governmental public policy positions related to drug abuse, specially that focusing on "damage control."

Acquired Immunodeficiency Syndrome↗
PubMed1993

Neovascularization and the appearance of morphological characteristics of the blood-brain barrier in the embryonic mouse central nervous system.

Vascularization and expression of blood-brain barrier (bbb)-associated morphological characteristics during the embryonic development of the mouse central nervous system (CNS) was studied by ultrastructural analysis. At embryonic day 9 (E9) capillaries were only found in the perineural mesenchymal tissue. These capillaries showed fenestrations, and pericyte like cells (PC) were found joined to the vessel walls. Around E10 endothelial cells (EC) together with PC started invading the intraneural section. At this stage, the immigrating endothelial cells lost their fenestrations and exhibited numerous, partly extended junctional complexes, which appeared 'tight' in some places. A first intraneural anastomotic plexus was observed at E10, as evidenced by the presence of blood cells in all capillary lumens. While the number of junctional complexes remained constant in intraneural capillaries, the frequency of pinocytotic vesicles decreased significantly from E10 to E17. These findings indicate that from the first day of intraneural vascularization onwards, the morphological properties of the bbb are present in the early embryonic mouse cerebral cortex.

Animals↗
PubMed1993

Induction of immune-mediated glomerulonephritis in normal mice immunized with bacterial DNA.

Normal mice immunized with bacterial DNA produce high titers of anti-DNA antibodies and represent a new model for autoantibody production in systemic lupus erythematosus. To determine whether DNA immunization can also provoke clinical manifestations of lupus, the occurrence of nephritis in immunized mice was assessed and correlated with levels of anti-DNA as well as antibodies to glomerular antigens. BALB/c mice immunized with Escherichia coli single-stranded DNA in complexes with methylated bovine serum albumin in adjuvant showed increased proteinuria compared to control mice immunized with mBSA alone. Furthermore, DNA immunized mice had significantly greater glomerular proliferative changes and immunoglobulin deposition than control mice. In an in vitro assay, sera from DNA immunized mice exhibited greater binding to glomerular antigens than sera from control mice. Compared to sera, renal eluates from DNA-immunized mice were enriched for anti-DNA and glomerular binding activity. These data indicate that immunization of normal mice with E. coli DNA induces an immune-mediated proliferative glomerulonephritis that is likely secondary to the renal deposition of anti-DNA antibodies.

Animals↗