Biomedical subjects

P Ruiz

Publications and source records attributed to P Ruiz.

At least 181 records · Page 10Linked to original sources

PubMed1995

Peripheral gamma delta T-cell populations in HIV-infected individuals with mycobacterial infection.

Previous studies have suggested that gamma delta T cells can be increased in HIV-1-seropositive individuals, although characterization of gamma delta T cell subtypes and correlation with clinical status of these patients have not been performed. We investigated groups of HIV-seropositive persons to determine the prevalence of elevated levels of gamma delta T cells and whether any gamma delta T cell subtypes were preferentially expressed. Since a large proportion of human gamma delta T cells appear to be reactive to proteins encoded by mycobacteria, we also examined our patients for the incidence of mycobacterial infection. Our results show that a significant number of HIV-positive patients have an elevated number of gamma delta T cells in their peripheral blood as compared to normal controls. HIV-seropositive patients with clinical or laboratory evidence of mycobacterial infection had statistically significant increases in the percentage and total numbers of gamma delta T cells over the HIV-positive persons without mycobacterial infection. An examination of the subtypes of gamma delta T cells revealed that certain subtypes such as V gamma 9+ and V delta 2+ T cells were preferentially elevated in the mycobacteria-positive patients. These results suggest that an increased number of gamma delta T cells in HIV-positive patients is most often seen in the setting of an opportunistic mycobacterial infection and that specific gamma delta T cell subtypes are stimulated under these conditions. The role of these increased number of gamma delta T cells in HIV-associated disease is unclear but is likely a component of the response and degree of host resistance to this organism.

AIDS-Related Opportunistic Infections↗

PubMed1995

De novo membranoproliferative glomerulonephritis in hepatitis C virus-infected renal allograft recipients.

Hepatitis C virus (HCV) is the leading cause of non-A, non-B hepatitis among renal allograft recipients. We sought to identify and describe a proteinuric renal disease occurring in our HCV-infected renal transplant patients. Patients with proteinuria exceeding 1 g/day were identified from a cohort of 98 HCV-infected kidney recipients. Qualitative and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and restriction fragment-length polymorphism of the amplified RT-PCR product was performed to detect circulating HCV RNA, viral titer, and strain type, respectively. An immune complex nephritis (ICN) of the membranoproliferative pattern (MPGN) was found on five of eight biopsies. Two patients infected with the Hutch strain-type developed nephrotic-range proteinuria within three months posttransplant while the remaining three MPGN patients had been transplanted greater than 5 years prior to the onset of proteinuria. Testing for rheumatoid factors, cryoglobulins, hypocomplementemia, and circulating immune complexes failed to show a consistent pattern. Sucrose density gradient (SDG) equilibrium centrifugation was used to determine the buoyant-density of HCV virions from control (HCV-infected nonproteinuric recipients; n = 5) and nephrotic patients (n = 5). Whereas HCV virions from the control patients had a low buoyant density on sucrose gradients, a substantial percentage of the circulating HCV RNA from the MPGN patients was present in the high-density fractions in association with IgM and IgG. Treatment of the pooled high-density layers with NP40 followed by recentrifugation resulted in a shift of the HCV RNA to the medium-density layers. In conclusion, MPGN developed in five HCV-infected kidney recipients despite pharmacologic immunosuppression. Both the physicochemical properties of the HCV virions on SDG and their association with IgG and IgM in the high-density layers provide indirect evidence for the presence of circulating complexes of anti-HCV antibody and HCV antigen(s).

Adult↗

PubMed1995

Acute graft loss secondary to necrotizing vasculitis. Evidence for cytokine-mediated Shwartzman reaction in clinical kidney transplantation.

A small number of kidney transplant recipients abruptly lose function secondary to acute renal artery or vein thrombosis or more rarely a form of necrotizing vasculitis. We report a group of four kidney transplant recipients who lost renal function and share the following features: (1) diabetes (type I, insulin-dependent diabetes mellitus, type II or steroid-induced); (2) abrupt change/loss of renal function; (3) a concomitant clinical event (fever, viral symptoms, menometrorrhagia, viremia, bacteremia); (4) severe necrotizing vasculitis with hemorrhagic necrosis on histopathology; (5) patent renal artery and vein at time of transplant nephrectomy (i.e., no vascular thrombosis); and (6) high levels of peripheral serum gamma-IFN 1-5 days before transplant nephrectomy (467 +/- 175 pg/ml) compared with that of patients experiencing severe rejection (8.4 +/- 3.7 pg/ml) (P < 0.002). These data support the concept of a cytokine (IFN-gamma)-mediated accelerated inflammatory response resulting in graft loss from necrotizing vasculitis--the clinical equivalent of an organ-specific Shwartzman reaction.

Adult↗

PubMed1995

High expression level of alpha 6 integrin in human breast carcinoma is correlated with reduced survival.

We recently reported that alpha 6 integrin mediates experimental metastasis in mice by functioning in the adhesion of tumor cells to the vascular endothelium. In the current study, we investigated the expression of human alpha 6 integrin in invasive breast carcinomas of 119 women. In 50% of the tumors alpha 6 integrin was expressed in the majority of the cells, and this expression was correlated with reduced survival time. By contrast, the 24% of patients with breast tumors devoid of alpha 6 integrin expression all survived. The tumors were also evaluated for clinical risk factors including histological grading and steroid receptor level. The combination of these factors with alpha 6 integrin expression was superior in predicting overall survival than considering the other factors alone. The correlation with decreased survival time was consistent, regardless of whether the tumors expressed the alpha 6 integrin A or B forms, which differ in their cytoplasmic domain. On the basis of this pilot study we consider alpha 6 integrin expression to be a novel prognostic marker for human breast cancer.

Animals↗

PubMed1995

The muscle-specific phosphoglycerate mutase gene is specifically expressed in testis during spermatogenesis.

Spermatogenesis is a dramatic differentiation process which involves very selective but poorly characterized gene-expression patterns. To gain insight into this process, we have investigated the expression during spermatogenesis of the genes that encode phosphoglycerate mutase, an essential glycolytic enzyme for the spermatozoa energy supply. By using cDNA and genomic probes we demonstrate the presence in testis of a mRNA corresponding to the muscle-specific phosphoglycerate mutase which shows a longer poly(A) tail. This muscle-specific gene is submitted to developmental regulation during testis maturation and begins to be expressed at postnatal day 22, when germ cells start to enter into meiosis. Northern blot and in situ hybridization experiments show that in contrast to what happens during skeletal-muscle differentiation, PGAM-M gene expression during spermatogenesis is not coupled to constitutive phosphoglycerate mutase (PGAM-B) gene repression. Thus, the muscle-specific PGAM-M gene constitutes a meiotic gene and therefore represents a very interesting model to study differential tissue-specific gene expression.

Animals↗

PubMed1995

Characterization of donor chimerism, alloreactive host T cells and memory cell development in thymi from mice resistant to neonatal transplantation tolerance.

Certain B10 background mouse strains are resistant to tolerance induction after neonatal inoculation of class I/II MHC-disparate F1 hybrid cells. Despite initial thymic deletion of alloreactive cells, the majority (95%) of these mice reacquire the capacity to reject donor allografts. These current studies examined thymi of adult B10.S (H-2S/H-2E-) mice that neonatally received (B10.S x B10.A)F1 cells, before and after rejection or acceptance of B10.A (H-2k/d/H-2E+) skin grafts. Alloreactive thymic V beta 11+ and V beta 5+ T cells were often reduced in the injected recipients preceding allograft challenge. In some mice a single B10.A skin graft generated an increase in these T cell populations concurrent with allograft rejection. Injected mice that accepted B10.A skin grafts (i.e., tolerant) or that rejected two sequential B10.A grafts often had a reduction of these T cells. Thymic memory cells (CD44high+) were present before transplant in injected mice and reduced in the tolerant mice. Donor chimeric cells were identified in the majority of injected mice before transplant and diminished after B10.A graft application. A greater proportion of chimeric cells coexpressed CD11b or B220 in the tolerant mice. Thus, neonatally injected B10.S mice resistant to tolerance induction reacquire immunocompetent thymic T cells bearing characteristics of memory T cells that could mediate graft rejection. Finally, the initial presentation of chimeric cells (e.g., macrophages) that may efficiently present class I Ags through H-2E likely increases the possibility of adult tolerance.

Animals↗

PubMed1995

CD44 isoforms during differentiation and development.

During mouse early development cell adhesion molecules are indispensable for the embryo organisation. A family of molecules probably involved in development is the transmembrane glycoprotein CD44 family, which exists in multiple isoforms. These are generated by alternative splicing of the pre-mRNA, resulting in the enlargement of the extracellular part of the molecule. The standard form of CD44 is widely expressed in adult tissues and in embryos from day 9.5 post coitum onwards, while the numerous variant isoforms exhibit highly specialised patterns of expression that are already in the egg cylinder at day 6.5 of development. In lymphohemopoiesis, specific variant isoforms also emerge at decisive differentiation stages. Although specific ligands for the variant region still await isolation, the highly organised expression of CD44 variant isoforms suggests they have a pivotal role in cellular interactions during early development, pattern formation and hemopoiesis.

Alternative Splicing↗

PubMed1995

Alpha 6 integrins participate in pro-T cell homing to the thymus.

During embryogenesis, colonization of the thymic rudiment by hemopoietic progenitor cells depends on the adhesion of these cells to the jugular endothelium. Previously, we showed that progenitor T cells (pro-T cells) interact with alpha 6 integrins present on vascular endothelium. Here, we demonstrate that anti-alpha 6 integrin antibodies reduced the number of thymocytes up to 80% in a congenic mouse model for thymus colonization by pro-T cells. In organotypic thymus cultures, the anti-alpha 6 integrin antibodies did not influence T cell development and proliferation. From this, we conclude that alpha 6 integrin participates in thymus homing. During mouse thymus ontogeny, alpha 6 integrin mRNA and protein expression was found as early as day 10 of development; at day 11, perithymic endothelial cells were alpha 6 integrin positive. Two alpha 6 integrin mRNA exist which are produced by alternative exon usage. The longer form, alpha 6 integrin, predominates during early embryonic stages, while the shorter alpha 6A form was present later during development. Although alpha 6 integrins can be displayed by immature thymocytes, strongest expression was found on intra- and perithymic vascular endothelium. These data suggest that alpha 6 integrins are involved in the homing of pro-T cells to the developing thymus by mediating adhesion of pro-T cells to the vascular endothelium.

Animals↗

PubMed1995

The effects of short-term treatment with the prostaglandin E1 (PGE1) analog misoprostol on inflammatory mediator production in murine lupus nephritis.

MRL-lpr/lpr mice spontaneously develop an autoimmune disease with nephritis similar to human systemic lupus erythematosus. In these animals, treatment with E-series prostaglandins ameliorates renal disease and prolongs survival, perhaps by modulating production of cytokines or eicosanoids. To further define the mechanisms of action of E-series prostaglandins in established murine lupus nephritis, we administered the prostaglandin E1 (PGE1) analog misoprostol to 20-week-old MRL-lpr/lpr mice by twice-daily subcutaneous injection. After 2 days of treatment, misoprostol reduced renal cortical interleukin-1 beta (IL-1 beta) mRNA levels compared to vehicle-treated controls (0.19 +/- 0.06 (misoprostol) vs 0.50 +/- 0.04 (vehicle) densitometry units; P < 0.005). A similar reduction in cortical IL-1 beta mRNA levels was found in left kidneys harvested from MRL-lpr/lpr mice following 2 days of treatment with misoprostol compared to right kidneys harvested from the same animal prior to the first dose of PGE1 analog (0.12 +/- .05 (left) vs 0.39 +/- 0.18 (right) densitometry units; P < 0.05). This reduction in cortical IL-1 beta mRNA levels was not associated with alterations in renal production of thromboxane B2, PGE2, or leukotriene B4 or with significant changes in the severity of renal inflammatory cell infiltrates. Time-course studies indicated that IL-1 beta mRNA levels were decreased within 24 hr of initiating misoprostol therapy. This reduction in IL-1 beta mRNA levels was transient because levels were not reduced after 1 week of treatment with the PGE1 analog.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

The influence of variable-region somatic mutations on the specificity and pathogenicity of murine monoclonal anti-DNA antibodies.

Antibodies to DNA (anti-DNA) occur prominently in systemic lupus erythematosus and provoke inflammatory damage in the kidneys. To determine the factors that confer pathogenicity on antibodies of this specificity, we investigated the in vitro and in vivo glomerular binding by members of four clonally related sets of monoclonal anti-DNA antibodies from lupus mice. Somatic mutations within the clonal sets enhanced binding to double-stranded DNA (dsDNA). Binding to permeabilized glomeruli in vitro was observed among affinity-purified preparations of these antibodies independent of specificity for dsDNA. In normal mice injected with hybridoma cell lines, nephritis as assessed by histology and immunofluorescence did not correlate with antibody affinity for DNA. By multivariate analysis, in vitro glomerular binding was the most predictive parameter of histologic outcome. These findings indicate that somatic mutations occurring during maturation of the autoimmune response do not necessarily enhance pathogenicity.

Amino Acid Sequence↗

PubMed1995

Assessing, diagnosing and treating culturally diverse individuals: a Hispanic perspective.

Psychiatry has always been influenced by culture. The cultural identity of both providers and consumers, their cultural perceptions of mental illness and its treatment, their psychosocial and socioeconomic environment, all could have a major impact on the psychiatric diagnosis made, on the treatment chosen, and on the ultimate outcome of a therapeutic intervention. Within this context, I will, in this article, examine the most important cultural connotations in today's mental health system. I will define the Hispanic-American population of this country since this ethnic group is the one that I will use as a model. I will also depict the most prominent mental health traits of this population. Additionally, I will review the cultural barriers that impede the access and retention of Hispanic-American patients into the mental health system. Finally, I will advance areas for future research in the field of cultural psychiatry. Hopefully, this article will stimulate investigators to conduct further research in the field of cultural psychiatry and to help improve the mental health care system of culturally diverse individuals residing in this country.

Cultural Diversity↗

PubMed1995

Immunopathological characteristics of in situ T-cell subpopulations in human immunodeficiency virus-associated nephropathy.

Human immunodeficiency virus-associated nephropathy (HI-VAN) is a common form of nephropathy present in HIV-infected individuals that clinically presents with proteinuria that is frequently in the nephrotic range, less often with hematuria, and with a course that may evolve to irreversible azotemia ultimately resulting in renal failure. Pediatric and adult HIV-positive patients both experience HIVAN morphologically after displaying focal segmental glomerulosclerosis, diffuse mesangial hyperplasia, microcystic tubular dilatation, interstitial inflammation, edema, and fibrosis. There is minimal information regarding the interstitial inflammatory cell infiltrate, despite the possibility that these cells may play an important role in the etiology of HIVAN. This study was designed to characterize and compare several morphological and immunopathological features of clearly established HIVAN, particularly the hematopoietic cell markers present on the interstitial inflammatory cells and the state of T-lymphocyte activation (ie, class II expression). Quantitative grading of HIVAN kidneys showed that CD4-positive and CD8-positive T cells comprised the major cell populations in the interstitium, often with CD4-positive T cells exceeding or being equivalent in number to CD8-positive T cells. B cells and macrophages were negligible components of the infiltrate. Human leukocyte antigen-DR class II molecules were found to be increased on the interstitial T cells as well as on all glomerular cells and endothelial cells. There was no significant relationship established between the immunophenotype of the interstitial inflammatory cells and other morphological, ultrastructural, immunofluorescent, or clinical features. These data imply that the inflammatory infiltrate in HIVAN is largely composed of activated T cells. At this point the role of these interstitial T cells in HIVAN is undetermined, although it can be speculated that they may be participating as antiviral or autoreactive immune effector cells imparting renal injury in this entity.

AIDS-Associated Nephropathy↗

PubMed1995

Role of platelet activating factor in kidney transplant rejection in the rat.

Platelet activating factor (PAF) is a potent lipid mediator with a broad range of biologic activities. Experimental evidence suggests that PAF plays a role in the pathogenesis of a variety of inflammatory processes including allograft rejection. In this study, we evaluated the effects of the PAF antagonist BN52021 on the course of renal allograft rejection in a rat model. Kidneys from ACI (RT1a) rats were transplanted into fully allogeneic PVG (RT1c) rat recipients. Animals received 60 mg/kg/day of the PAF antagonist or vehicle beginning immediately prior to the transplantation procedure. In rats treated with the PAF antagonist, allograft GFR and plasma flow were maintained at levels that were significantly greater than controls. Despite the improvement in renal allograft function, BN52021 had no effect on allograft histomorphology and both groups manifested intense inflammatory cell infiltration consistent with acute cellular rejection. PAF antagonism reduced urinary excretion of thromboxane metabolites and decreased thromboxane production by homogenates prepared from kidney allografts. The PAF antagonist had no effect on urinary excretion of peptidoleukotriene metabolites or on the production of LTB4 by allografts. These data support a role for PAF in the pathophysiology of acute renal allograft rejection, and they suggest that the hemodynamic effects of PAF during rejection may be mediated through stimulation of thromboxane A2. In view of the beneficial effects of PAF blockade in rejection as well as recent reports describing efficacy in models of cyclosporine nephrotoxicity, PAF antagonists may have clinical applications in human renal allograft recipients.

Animals↗

PubMed1995

In vitro activity of roxithromycin against the Mycobacterium tuberculosis complex.

Roxithromycin has recently been shown to possess significant in vitro activity against a variety of atypical mycobacteria such as the M. avium complex, M. scrofulaceum, M. szulgai, M. malmoense, M. xenopi, M. marinum, and M. kansasii and rare pathogens like M. chelonei and M. fortuitum. In the present investigation, screening of its in vitro activity was further extended by testing it against 34 strains belonging to the M. tuberculosis complex (including M. tuberculosis, M. africanum, M. bovis, and M. bovis BCG). The MICs were determined by the radiometric BACTEC 460-TB methodology at pHs of both 6.8 and 7.4, as well as with 7H10 agar medium by the 1% proportion method. With the exception of M. bovis BCG (MIC ranges, 0.5 to 4 micrograms/ml at pH 6.8 and 0.25 to 2 micrograms/ml at pH 7.4), MICs for all of the isolates were significantly greater (MIC ranges, 32 to > 64 micrograms/ml at pH 6.8 and 16 to > 32 micrograms/ml at pH 7.4) than those reported previously for atypical mycobacteria. Roxithromycin MICs of 64 or > 64 micrograms/ml for all of the M. tuberculosis isolates screened were found by the 7H10 agar medium method. Roxithromycin, however, showed a pH-dependent bactericidal effect against M. tuberculosis because the drug was relatively more active when it was used at pH 7.4 than when it was used at pH 6.8. We conclude that roxithromycin per se is not a drug of choice for the treatment of M. tuberculosis infection or disease; however, considering its pharmacokinetics, eventual anti-tubercle bacillus activity in an in vivo system cannot yet be excluded. We suggest that the use of roxithromycin in chemoprophylactic regimens for the prevention of opportunistic infections (including M. avium complex infections) in patients with AIDS should be carefully monitored, and patients should be enrolled in such a regimen only after it has been excluded that the patient das an underlying infection of disease caused by M. tuberculosis.

Hydrogen-Ion Concentration↗

PubMed1995

Effect of EXP 3174 on blood pressure of normoreninemic renal hypertensive rats.

This study examined the effect on mean blood pressure of a new orally active nonpeptide angiotensin II (Ang II) receptor antagonist, EXP 3174, in doses that completely block exogenous Ang II action. Anesthetized and conscious two-kidney, two clip chronic renovascular hypertensive rats and sham-operated animals were used. In anesthetized hypertensive rats, intracerebroventricular administration of the inhibitor had no effect on blood pressure, whereas blood pressure was normalized by intravenous injection of the antagonist (163 +/- 12 to 110 +/- 9 mm Hg, P < .05). In sham anesthetized rats, intravenous injection of EXP 3174 also lowered blood pressure (112 +/- 6 to 96 +/- 6mm Hg, P < .05). In conscious rats, intravenous EXP 3174 induced a fall in pressure that was larger in hypertensive (156 +/- 9 to 132 +/- 5 mm Hg, P < .05) than in sham (104 +/- 3 to 94 +/- 4 mm Hg, P < .05) rats. Plasma renin activity was very high in anesthetized animals (hypertensive versus sham, 87.8 +/- 8.3 versus 95.7 +/- 10.2 ng Ang I/mL per hour); differences were not significant either between anesthetized hypertensive and sham or in conscious animals (hypertensive versus sham, 9.42 +/- 1.58 versus 6.74 +/- 2.32 ng Ang I/mL per hour). Angiotensinogen concentration was higher in cerebrospinal fluid in anesthetized hypertensive rats (36.4 +/- 3.0 versus 26.0 +/- 2.4 ng Ang I/mL, P < .05) and in the artery wall of hypertensive conscious rats (103.1 +/- 10.3 versus 75.2 +/- 7.8 ng Ang I/g, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen↗

PubMed1995

Effects of methylphenidate in HIV-related depression: a comparative trial with desipramine.

This report is a randomized, double-blind, comparative trial of desipramine with the psychomotor stimulant methylphenidate. Twenty HIV antibody-positive patients with depressive symptoms were randomly assigned to either drug. After individual dose titration, the mean daily dose of desipramine was 150 mg. and methylphenidate 30 mg. daily. The differences in responses between desipramine and methylphenidate were not statistically significant on various measures of depression. The antidepressant effect of methylphenidate did not occur any faster than that of desipramine. Both significantly reduced depressive and anxious symptomatology over the blinded portion of the treatments. Thus, methylphenidate relieves depressive symptomatology with efficacy similar to that of desipramine, offering an alternative to patients who are unable to tolerate standard tricyclic antidepressant therapy. The dopaminergic effects of methylphenidate are likely to mediate its antidepressant effects.

Adult↗

PubMed1995

The economics of pain. Mental health care costs among minorities.

In this article, we have underlined the importance of providing high-quality health and mental health services to the ethnic minority populations of the United States. We also have highlighted the complexities associated with the provision of these services, with special attention to the factors affecting health insurance coverage and the patients' socioeconomic conditions. Finally, we have advanced some potential solutions to the current health care crisis, particularly as they relate to minorities. In reviewing these solutions, we have focused primarily on the role of the service providers, third-party payors, poverty, and cultural and language barriers.

Culture↗

PubMed1994

Impaired function of macrophage Fc gamma receptors and bacterial infection in alcoholic cirrhosis.

BACKGROUND: Bacterial infection is a frequent and often fatal complication in patients with cirrhosis. Macrophages play an important part in the host defense against infection because their Fc gamma receptors recognize antibody-coated bacteria. METHODS: We prospectively studied macrophage Fc gamma-receptor function in vivo and in vitro in 49 patients with alcoholic cirrhosis, 10 alcoholics without cirrhosis, and 20 normal volunteers. RESULTS: The clearance of IgG-sensitized autologous red cells was decreased in 37 of the 49 patients with cirrhosis but in none of the subjects without cirrhosis. In the 49 patients clearance was inhibited by a mean (+/- SE) of 47 +/- 3 percent at 1 hour and 53 +/- 3 percent at 1 1/2 hours, as compared with the clearance in the normal controls (P < 0.001). The impairment of macrophage Fc gamma-receptor-dependent clearance correlated with the degree of liver insufficiency but not with age, sex, nutritional status, HLA haplotype, or the presence of circulating immune complexes. The clearance of unsensitized and heat-altered autologous erythrocytes was normal. In vitro recognition of IgG-sensitized red cells by monocytes from the patients was not significantly decreased. During a two-year follow-up period, 11 patients had severe bacterial infections, and in 4 they were fatal. The mean clearance of IgG-sensitized red cells in these 11 patients (half-time, 126.2 +/- 22 hours) was significantly impaired, as compared with that in the 38 patients without severe infection (half-time, 32.2 +/- 18 hours, P < 0.001). CONCLUSIONS: The function of macrophage Fc gamma receptors is impaired in patients with alcoholic cirrhosis, and this impairment probably contributes to the high incidence of bacterial infections among such patients.

Antigen-Antibody Complex↗