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P Ruiz

Publications and source records attributed to P Ruiz.

At least 235 records · Page 13Linked to original sources
PubMed1992

Interleukin-7 expression during mouse thymus development.

We have monitored the expression of interleukin-7 (IL-7) in the developing embryonic mouse thymus by a combination of quantitative polymerase chain reaction (PCR) and immunofluorescence microscopy. A strong specific signal for IL-7 mRNA was detected by day 12 in the developing fetal thymus. IL-7 mRNA was found to be maximally expressed on day 15, and then decreased over the next 5 days. Immunofluorescence staining of fetal thymus sections using an anti-IL-7 antibody confirmed these PCR data. IL-7 protein expression was first detected at day 13 of development. At 14 days the intensity of the staining increased by a factor of three and stayed at this level over the next 4 days. The same anti-IL-7 antibody used for immunofluorescence, blocked the proliferation of fetal thymocytes in organotypic cultures. In addition, we detected mRNA coding for IL-2 and SCF (also known as the steel factor or KL) in embryonic thymocytes. The implications of these findings for early thymocyte growth are discussed.

Animals↗
PubMed1992

Effect of anti-CD4 antibody treatment on inflammatory arthritis in MRL-lpr/lpr mice.

MRL-lpr/lpr mice develop an inflammatory arthritis in association with other manifestations of autoimmunity. Although a variety of immune cell disturbances have been described in these mice, the relationship of these abnormalities to the pathogenesis of arthritis has not yet been determined; the role of T cells is especially unclear since synovial hypertrophy and joint erosions have been noted in some studies in the absence of a significant T cell infiltrate. Therefore, to determine if T cells are required for arthritis in MRL-lpr/lpr mice, we evaluated the effects of prolonged treatment with a monoclonal anti-CD4 antibody. Knee joints from treated mice had markedly reduced arthritis compared to saline-treated control animals as measured by the degree of synovial hypertrophy and inflammation. Nephritis in these mice was concomitantly reduced. In contrast, rheumatoid factor levels were not affected by CD4+ cell depletion, despite significant effects on anti-DNA. These results indicate that in MRL-lpr/lpr mice anti-CD4 therapy can inhibit arthritis, suggesting an important role of T cells in the pathogenesis of this lesion.

Animals↗
PubMed1992

UVB phototherapy of the pruritic papular eruption of the acquired immunodeficiency syndrome.

BACKGROUND: Pruritic papular eruption (PPE) is a chronic dermatosis frequently seen in human immunodeficiency virus (HIV)-positive patients. UVB phototherapy has been successfully used to treat a similar inflammatory condition (Ofuji disease) as well as pruritus of systemic origin. OBJECTIVE: We describe the successful treatment with UVB of seven of eight patients with PPE. METHODS: Eight HIV-positive patients with PPE were treated. The number of papules in a specified area of skin and the intensity of pruritus were monitored before, during, and after UVB phototherapy given three times a week. Biopsy specimens were taken before and after therapy and systemic immune function was evaluated. RESULTS: Both the number of papules as well as pruritus decreased after UVB treatment in all but one patient. Immunoperoxidase staining showed a relative decrease in CD4+, CD8+, and CD2+ cells in all samples studied except for the patient noted to be unresponsive to the therapy. CONCLUSION: UVB phototherapy is effective in the treatment of patients with PPE. This is associated with a significant decrease in inflammation and number of T cells from various subsets within the dermis, thereby implicating these cells in the pathogenesis of this disorder.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Thromboxane receptor blockade reduces renal injury in murine lupus nephritis.

To investigate the role of thromboxane A2 (TxA2) in murine lupus, we assessed the effects of the specific thromboxane receptor antagonist GR32191 on immune complex glomerulonephritis in MRL-lpr/lpr mice. Forty mg/kg/day GR32191 was given by twice daily subcutaneous injection for eight weeks beginning at 12 weeks of age. This dose completely blocked the renal vasoconstriction produced by the thromboxane agonist U46619. After eight weeks of treatment, both glomerular filtration rate (GFR) (8.9 +/- 0.6 vs. 6.8 +/- 1.1 ml/min/kg; P less than 0.05) and PAH clearance (CPAH) (37.4 +/- 2.5 vs. 29.9 +/- 3.3 ml/min/kg; P less than 0.05) were significantly higher in mice given GR32191 compared to vehicle treated animals. Administration of GR32191 also reduced proteinuria from 18.1 +/- 11.6 to 3.7 +/- 1.3 mg/24 hours (P less than 0.05). In GR32191 treated MRL-lpr/lpr mice, renal hemodynamic function and proteinuria were not significantly different from congenic MRL-+/+ controls. Thromboxane receptor blockade had striking affects on renal histomorphology reducing both hyaline thrombi in glomeruli (P = 0.022) and interstitial inflammation (P = 0.006). Glomerular crescents and severity of vasculitis also tended to be reduced in mice receiving the thromboxane receptor antagonist. The overall histopathologic score in mice given GR32191 was significantly lower than vehicle treated animals (4.7 +/- 0.5 vs. 8.4 +/- 1.5; P = 0.016). These effects of GR32191 were associated with decreased excretion of thromboxane B2 (TxB2) in urine (292 +/- 37 vs. 747 +/- 155 pg/24 hr; P less than 0.005) as well as a modest reduction in glomerular deposits of IgG (semiquantitative score 2.6 +/- 0.2 vs. 3.5 +/- 0.2; P less than 0.02). Thus, chronic thromboxane receptor blockade markedly altered the course of renal disease in MRL-lpr/lpr mice, suggesting that TxA2 is an important mediator of renal dysfunction and injury in this murine model of lupus nephritis.

Animals↗
PubMed1992

Thromboxane augmentation of alloreactive T cell function.

Thromboxane (Tx) plays a vital role in the dysfunction and ultimate rejection of MHC-disparate renal allografts. In addition to its potent vasoconstrictory properties, in vivo studies have implied that Tx is capable of promoting immune cytotoxic T cell function within transplants. In this study, we have examined the in vitro effect of Tx inhibition on alloreactive immune cells using MHC-disparate mouse strain combinations. Coculture of either Tx-synthetase or Tx-receptor inhibitors modified the response of unprimed mouse lymphoid populations in a primary MLR, implying that Tx inhibition and not endoperoxide shunting was responsible for the modulatory effects seen. For example, B10.S lymphoid cells displayed decreased proliferation to H-2 disparate B10.A cells with Tx inhibitors present during the MLR, at pharmacologically active drug concentrations. Moreover, in vitro addition of TxA2 had an augmentory effect on the response in the primary and secondary MLR. Interleukin 2 production and percentages of T cell populations in the primary MLR were not affected by the presence of these compounds, although CD4 and CD8 expression was often increased in the treated populations. Finally, alloreactive primed effector cells also displayed reduced proliferation to specific alloantigen in a secondary MLR when Tx inhibitors were also present, although responses to IL-2 by T cells were not influenced by thromboxane inhibition. These data imply that thromboxane is an important immunoregulatory mediator capable of potentiating the function of naive and primed alloreactive immune T cell populations crucial to the rejection of the transplant.

Animals↗
PubMed1992

Central nervous system expression of a monoclonal paraprotein in a chronic lymphocytic leukemia patient.

An unusual complication of chronic lymphocytic leukemia (CLL) is reported. The patient, a 79-year-old man, had a long standing history of CLL, that had been complicated by the development of a Guillain-Barré-like syndrome and a peripheral biclonal gammopathy. The biclonal immunoglobulins identified in the serum were IgM lambda and IgG lambda. The patient's condition progressed and he eventually developed ophthalmologic complications. Cerebrospinal fluid (CSF) obtained during evaluation of his visual dysfunction contained numerous small, mature lymphocytes consistent with the presence of CLL cells in the central nervous system (CNS); immunoperoxidase staining of these cells revealed a monoclonal population. Protein electrophoretic evaluation of the patient's CSF showed a single monoclonal band and immunofixation electrophoresis of the CSF revealed that the immunoglobulin present was IgG lambda. No evidence for the monoclonal IgM paraprotein identified in serum could be appreciated in the CSF by immunofixation. Taken together, these findings strongly implied that there was CNS involvement by the leukemia and this process caused the patient's neurologic symptoms. Furthermore, this study demonstrates that chronic lymphocytic leukemia should also be considered as one of the hematopoietic malignancies associated with monoclonal gammopathies involving the CNS.

Aged↗
PubMed1992

Characterization of Fc gamma receptors on a human erythroleukemia cell line (HEL).

It has been established that human platelets express a single class of Fc gamma receptors that has been designated Fc gamma RII. However, the function of this receptor on these cells and its regulation are less certain. Studies to further investigate Fc gamma RII on platelets are limited by the inability to culture platelets in vitro. Therefore, identification of a human cell line that expresses Fc gamma RII as its only Fc gamma receptor as well as other platelet characteristics would be of potential importance. To this end, we examined Fc gamma receptor expression by the human erythroleukemia (HEL) cell line, which expresses platelet/megakaryocyte surface proteins. Flow cytometry studies on HEL cells with anti-Fc gamma receptor monoclonal antibodies revealed that, similar to platelets and megakaryocytes, Fc gamma RII is the only Fc gamma receptor expressed on the cell surface. Furthermore, Northern blot analysis revealed that Fc gamma RII is the only Fc gamma receptor mRNA present. Stimulation with dimethylsulfoxide (DMSO) or 12-O-tetradecanoylphorbol-13-acetate (TPA) did not alter Fc gamma RII protein or mRNA expression. Ligand binding studies with [125I]IgG trimer indicated that HEL cells express 92,240 +/- 5030 binding sites per cell, with a kd of 1.94 +/- 0.31 x 10(-8) M. Similar to human platelets, HEL cells preferentially bound oligomeric IgG, and this binding was ionic strength dependent. These observations are similar to those previously observed with Fc gamma RII on human platelets and suggest that the HEL cell Fc gamma receptor is similar, if not identical to the platelet Fc gamma RII receptor. HEL cells may serve as a model for the study of platelet/megakaryocyte Fc gamma RII.

Humans↗
PubMed1991

Immunohistochemical localization, purification, and characterization of human urinary bladder glutathione S-transferases.

This study describes immunohistochemical localization, purification and characterization of glutathione S-transferase (GST) of human urinary bladder. Even though all the three major classes of isoenzymes (alpha, mu, and pi) were expressed in human bladder, more than 90% of total GST activity was accounted for by a pi class anionic form. Human bladder alpha, mu, and pi class GSTs were immunologically related to respective isoenzymes of other human tissues. GST pi was present in all 13 samples analyzed, whereas GST alpha and mu were detected in nine and eleven samples, respectively. GST alpha of human bladder appeared to be unique, because unlike this class of GSTs of other human tissues, bladder enzyme had lower affinity for GSH linked to epoxy-activated Sepharose 6B affinity resin. Immunohistochemical staining indicated localization of GST alpha in epithelial surface cells, underlying submucosa and smooth muscle, whereas mu and pi class isoenzymes were predominantly distributed in epithelial surface cells. These results suggest that human bladder GSTs may play an important role in providing protection against xenobiotics because epithelium is considered a target for several carcinogens and all the three classes of isoenzymes are expressed in these cells.

Adult↗
PubMed1991

Neuroleptic malignant syndrome: a complication of neuroleptics and cocaine abuse.

One hundred and sixty psychiatric patients on Neuroleptics, with and without a history of substance abuse were daily monitored in order to establish the incidence of neuroleptic malignant syndrome in these two groups. Four (5.1%) of the cocaine abusers and none of the non-cocaine abusers developed neuroleptic malignant syndrome when treated with neuroleptics. Thus we argue that psychiatric patients with a history of cocaine abuse may be more at risk of developing neuroleptic malignant syndrome when treated with neuroleptics, possibly associated with the blockade of dopamine (D2-receptors) by neuroleptics and the activation of dopamine/5-HT receptors by cocaine-induced dopamine.

Antipsychotic Agents↗
PubMed1991

Physiologic role for enhanced renal thromboxane production in murine lupus nephritis.

To investigate the physiologic significance of enhanced renal thromboxane production in murine lupus nephritis, we measured renal hemodynamics and eicosanoid production in MRL-lpr/lpr mice from 8 to 20 weeks of age. Over this age range, MRL-lpr/lpr mice develop an autoimmune disease with nephritis similar to human systemic lupus erythematosus (SLE). In these studies, glomerular filtration rate (GFR) and PAH clearance (CPAH) decreased progressively with age in MRL-lpr/lpr mice, but not in controls. This impairment of renal hemodynamics was associated with increased renal thromboxane production, as well as increased excretion of both thromboxane B2 (TxB2) and 2,3-dinor TxB2 in urine. There was an inverse correlation between renal thromboxane production in MRL-lpr/lpr mice and both GFR and CPAH. Furthermore, there were positive correlations between thromboxane production by the kidney and both the severity of renal histopathology and serum anti-DNA antibody levels measured in individual animals. Enhanced urinary excretion of TxB2 and the development of renal dysfunction also coincided temporally with the appearance of increased levels of interleukin 1 beta (IL-1 beta) mRNA in renal cortex. Acute administration of the specific thromboxane receptor antagonist GR32191 to MRL-lpr/lpr mice restored GFR to normal in early stages of the autoimmune disease. However, in animals with more advanced nephritis, the effect of acute thromboxane receptor blockade on renal hemodynamics was less marked. We conclude that thromboxane A2 is an important mediator of reversible renal hemodynamic impairment in murine lupus, especially in the early phase of disease.

Age Factors↗
PubMed1991

Genetic control of inflammatory arthritis and glomerulonephritis in congenic lpr mice and their F1 hybrids.

MRL-lpr/lpr mice spontaneously develop a complex immunological disease characterized by glomerulonephritis, inflammatory erosive arthritis and the production of rheumatoid factors (RF) and anti-DNA antibodies. We have previously reported that, of congenic lpr strains, only MRL-lpr/lpr mice develop synovial pathology suggesting that both the lpr gene and another gene(s) in the MRL background are necessary for the development of arthritis. To define further the genetics of arthritis and its relationship to glomerulonephritis and autoantibody production, we studied disease expression in MRL-lpr/lpr and C57BL/6-lpr/lpr mice and their offspring (BM-lpr/lpr and MB-lpr/lpr). At 6 months of age these mice were killed and bled, and their kidneys and knee joints were removed for pathological studies. Fourteen of 28 MB-lpr/lpr mice displayed synovial hypertrophy, while eight of 28 had significant synovial inflammation. BM-lpr/lpr mice showed similar changes: nine of 22 and eight of 22 exhibited synovial hypertrophy and inflammation respectively. Joints from MRL-lpr/lpr mice revealed 13 of 17 with synovial hypertrophy and 12 of 17 with inflammation, while none of 14 B6-lpr/lpr mice had synovial changes. Renal pathology was minimal in the F1 mice with only mild hypercellularity in seven of 21 MB-lpr/lpr and five of 22 BM-lpr/lpr mice. All MRL-lpr/lpr mice, in contrast, had marked glomerular changes with 12 of 17 exhibiting glomerular crescents. Only one F1 mouse had both arthritis and renal abnormalities. IgM RF levels were elevated in all four experimental groups, but did not correlate with the presence or severity of arthritis. IgG RF levels were elevated in the MB-lpr/lpr and MRL-lpr/lpr mice, but did not correlate with the degree of arthritis. These results indicate that renal disease and arthritis develop independently in lpr mice, possibly on a genetic basis, and that the presence and titer of autoantibodies do not correlate with tissue injury.

Animals↗
PubMed1991

Enhanced renal leukotriene production in murine lupus: role of lipoxygenase metabolites.

To investigate the potential role of leukotrienes in murine lupus, we measured renal hemodynamics and renal leukotriene production in MRL-lpr/lpr mice at 12 and 20 weeks of age. Over this age range, these animals develop overt manifestations of autoimmune disease with nephritis similar to human SLE. In the current study, we demonstrated that glomerular filtration rate (GFR) and PAH clearance (CPAH) deteriorated with age in MRL-lpr/lpr mice, but not in MRL(-)+/+ controls. Impaired renal hemodynamic function in MRL-lpr/lpr mice was associated with enhanced ionophore-stimulated production of both leukotriene B4 (LTB4) and leukotriene C4 (LTC4) by preparations of renal cortex. There was a significant inverse correlation between GFR and in vitro production of both LTC4 and LTB4 in kidneys from MRL-lpr/lpr mice, but not in control animals. In addition, in vitro LTC4 production was correlated with the severity of renal histomorphologic abnormalities. Administration of the specific peptidoleukotriene receptor antagonist SKF104353 to 20 week old MRL-lpr/lpr mice significantly improved both GFR and CPAH, whereas this agent had no effect of renal hemodynamics in MRL(-)+/+ controls. These results suggest that renal production of LTC4 and LTB4 is increased in MRL-lpr/lpr mice with nephritis, and that enhanced production of peptidoleukotrienes causes reversible renal dysfunction. Increased leukotriene production within the kidney may therefore be important in the pathogenesis of lupus nephritis.

Animals↗
PubMed1991

EA-1, a novel adhesion molecule involved in the homing of progenitor T lymphocytes to the thymus.

The mouse progenitor T lymphocyte (pro-T) cell line FTF1 binds in vitro to thymus blood vessels, the thymic capsule, and liver from newborn mice. A mAb, EA-1, raised against an embryonic mouse endothelial cell line, blocked adhesion. The antibody also interfered with pro-T cell adhesion to a thymus-derived mouse endothelial cell line; it had no effect on the adhesion of mature T lymphocytes and myeloid cells. The antigen recognized by EA-1 is located on the vascular endothelium of various mouse tissues and absent on pro-T cells. EA-1 antibody precipitates molecules with apparent molecular weights of 110,000, 140,000, 160,000, and 200,000. Immunoclearing and binding-inhibition studies with antibodies against known adhesion molecules suggest that the EA-1 antigen is a novel adhesion molecule involved in colonization of the embryonic thymus by T cell progenitors.

Animals↗
PubMed1991

In vivo glucocorticoid modulation of guinea pig splenic macrophage Fc gamma receptors.

Although glucocorticoids are widely used in the treatment of immunohematologic disease, their relative efficacy is uncertain. We used an animal model, which has helped to elucidate the role of splenic macrophage Fc gamma receptors in the clearance of IgG-coated cells, to investigate whether each Fc gamma receptor is modulated by glucocorticoids to the same extent and to examine the relative potency of three commonly used glucocorticoids. Cortisol, prednisone, and dexamethasone all impaired the clearance of IgG-coated erythrocytes. However, dexamethasone was more effective than either prednisone or cortisol (P less than 0.001). Furthermore, splenic macrophages isolated from glucocorticoid-treated animals expressed impaired Fc gamma receptor function. This effect was greater in macrophages isolated from dexamethasone-treated animals, as compared to either cortisol- or prednisone-treated animals (P less than 0.001). To assess the effect of glucocorticoids on the two types of guinea pig splenic macrophage Fc gamma receptors, Fc gamma R1,2 and Fc gamma R2, specific immunoglobulin isotypes were used to measure macrophage binding of IgG-sensitized erythrocytes. Cortisol and prednisone primarily affected Fc gamma R2, whereas dexamethasone inhibited the function of both guinea pig Fc gamma receptors. Furthermore, dexamethasone was more effective (P less than 0.01) than either prednisone or cortisol in inhibiting the ability of both receptors to bind IgG-sensitized cells. Fluorescence-activated cell sorter analysis and fluorescence microscopy with monoclonal antibodies specific for each of these two receptors demonstrated that essentially all splenic macrophages expressed both receptors, and that these glucocorticoids decreased the level of each Fc gamma receptor protein expressed, rather than altering receptor mobility and clustering in the macrophage membrane. The effect on both Fc gamma receptors was greatest with dexamethasone and least with cortisol. These studies demonstrate the significant role of guinea pig splenic macrophage Fc gamma R2 in immune clearance and in the binding of IgG-coated cells. They demonstrate a differential effect of glucocorticoid hormones on Fc gamma receptor function and on surface receptor protein. Furthermore, they suggest that dexamethasone may be a more effective glucocorticoid than either prednisone or cortisol in inhibiting the clearance of IgG-coated cells by its effect on splenic macrophage Fc gamma receptors.

Animals↗
PubMed1991

Pertussis immunization patterns in special care nursery graduates.

Controversy exists regarding immunization with pertussis vaccine of high-risk special care nursery graduates. Our study compared the immunization status of 38 high-risk, 30 low-risk, and 57 normal infants utilizing an immunization response form. Comparison of the three infant groups revealed that complete or incomplete immunization varies, depending on group status. Of 38 infants at high risk for developmental delay, 22 (57.9%) were not immunized against pertussis by age one. Physicians cited concerns related to previous neurologic injury and increased liability for vaccine-related injury as major reasons for deferring vaccination. Recommendations for improving current guidelines and practice are outlined.

Brain Damage, Chronic↗
PubMed1990

Impaired function of macrophage Fc gamma receptors in end-stage renal disease.

Infection is a frequent complication in patients undergoing hemodialysis for end-stage renal disease and is the primary cause of mortality among such patients. Macrophages are important in host defense against infection largely because their Fc gamma receptors recognize antibody-coated bacteria. We therefore studied macrophage Fc gamma-receptor function in vivo and in vitro in 56 patients with end-stage renal disease who were on hemodialysis and in 20 healthy volunteers. The clearance of IgG-coated (sensitized) autologous red cells was decreased in 53 patients. The inhibition of clearance in the 56 patients was 52 +/- 3 percent at 1 hour, 41 +/- 5 percent at 1 1/2 hours, and 29 +/- 5 percent at 2 hours (P less than 0.001). The clearance of unsensitized erythrocytes and heat-altered autologous erythrocytes was normal. The impairment of clearance was not correlated with age, sex, nutritional status, HLA haplotype, or the presence of circulating immune complexes. The recognition of these IgG-sensitized red cells in vitro by Fc gamma RI (an Fc gamma-receptor protein that binds monomeric IgG) on blood monocytes from the patients was also significantly decreased (P less than 0.001) but was partially improved by hemodialysis. Nine patients had severe infections during a two-year follow-up period. The clearance of IgG-coated cells in these patients (half-time, 12.9 +/- 1.7 hours) was significantly impaired, as compared with that in the 47 patients without severe infections (half-time, 4.4 +/- 1.8 hours; P less than 0.001). We conclude that macrophage Fc gamma-receptor function is impaired in patients with end-stage renal disease who are undergoing hemodialysis, and that this impairment probably contributes to the observed immunodepression and high prevalence of infection among such patients.

Adult↗