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Biomedical subjects

P Ruiz

Publications and source records attributed to P Ruiz.

At least 163 records · Page 9Linked to original sources

Issues in the psychiatric care of Hispanics.

Factors affecting the mental health care of ethnic minority groups in the United States deserve serious consideration. Hispanics, the second largest of these groups, face problems of access to care, high rates of substance abuse and HIV, and shortages of Hispanic psychiatric professionals. Recommendations for improving psychiatric care for Hispanics include changes in the areas of health insurance, research funding, affirmative action, and psychiatric training.

Cultural Characteristics↗

DNA flow cytometric measurements in breast cancer: a review of the instrumentation principles and clinical significance.

Breast cancer treatment remains a controversial and challenging issue. Treatment of this disease is often guided by the clinical stage and type of tumor present, as well as information provided by a variety of prognostic indicators which can be employed. DNA analysis by flow cytometry is a relatively new technique that is emerging as a powerful tool to predict the biologic behavior of breast tumors. A majority of studies have demonstrated that the S-phase fraction measured by DNA flow cytometric is an independent predictor of patient outcome. There is less conclusive information regarding the association of DNA ploidy with the clinical behavior of breast malignancies, although, tumor grading often closely parallels this DNA parameter. New flow cytometry methodology involves multiparameter analysis that allows a simultaneous examination of DNA ploidy and cell cycle analysis with surface or internal molecules. This newer approach permits a precise delineation of DNA characteristics in distinct cell populations within a tumor and will likely enhance the utility of this procedure in determining the biologic behavior of the breast tumor.

Biology↗

Women's advancement in medicine and academia: barriers and future perspectives.

Although women made early advancements in the field of medicine during the second half of the 19th century, they were not able to make relevant strides in both medicine and academia until the 1960s. Despite women's recent advancements, obstacles and barriers to their hope of achieving fairness and equality in their professional and academic careers still exist. These practices include professional discrimination, blatant sexism, lack of appropriate mentors, and unfair faculty promotion processes. In this article, we address the most common problems affecting women physicians' advancement in academic medicine. We also focus on the role of mentorship as a relevant and beneficial factor for progress in their medical and academic careers. Finally, we provide a perspective designed to resolve most of the barriers confronting women physicians in their quest for advancement in academic medicine.

Career Mobility↗

Early graft loss secondary to massive hemorrhagic necrosis following orthotopic liver transplantation. Evidence for cytokine-mediated univisceral Shwartzman reaction.

Massive hemorrhagic necrosis (MHN) of the liver following orthotopic liver transplantation (OLT) occurs infrequently during an otherwise uneventful recovery 1 week after OLT. It is characterized by fever and sudden deterioration of allograft function leading to failure in the absence of vascular thrombosis. The etiology is unknown, although it is usually preceded by some degree of allograft rejection. Between 6 and 8 days after OLT, four patients (out of 150) became febrile, hypotensive, and experienced a rapid rise in transaminases within 48 hr. Two patients had evidence of mild rejection; the other two had moderate to severe acute cellular rejection. All patients were ABO identical, crossmatch negative. Bolus steroids were given followed by OKT3 in the two patients with severe rejection. Although sepsis was suspected, antibiotic therapy did not ameliorate the clinical course. Each patient progressed to MHN with severe centrilobular necrosis and variable portal infiltrate. High levels of interferon-gamma and tumor necrosis factor-alpha occurred prior to the rise in transaminases in each MHN patient (155 +/- 39 pg/ml and 414 +/- 201 pg/ml, respectively) compared with levels in OLT patients with severe rejection (14 +/- 4 pg/ml and 26 +/- 5 pg/ml, respectively, P < 0.05). These data support the concept of a cytokine-mediated inflammatory response leading to a univisceral Shwartzman reaction in the transplanted liver. Early recognition of this syndrome and retransplantation are critical for survival.

Adult↗

Destructive allograft fungal arteritis following simultaneous pancreas-kidney transplantation.

Fungal arteritis of the Y graft used to revascularize the whole pancreas graft developed in 2 recipients of simultaneous pancreas-kidney transplant that were performed within 36 hr of each other. The vascular infection became manifest 6-7 days following transplantation. In both patients, the vasculitis culminated in an arterial rupture that required immediate operative intervention. This compromise of the Y grafts contributed to loss of both pancreatic grafts and necessitated vascular reconstruction to reperfuse the lower extremity. To date, both patients continue to experience normal kidney transplant function.

Adult↗

Neonatal transplantation tolerance is associated with a systemic reduction in memory cells, altered chimeric cell phenotype, and modified eicosanoid and cytokine production.

Certain B10 background mice are resistant to tolerance induction following a neonatal inoculation of semiallogeneic class I/II MHC-disparate cells despite early thymic clonal deletion of alloreactive cells. The emergence of memory T cells and persistence of particular chimeric cells in the thymus has an association with this resistance. In these studies, we utilized a hemisplenectomy technique to examine systemic cell populations of adult Bl0.S (H2s, H2E-) mice that received (Bl0.S x B10.A)F1 cells at birth and before and following application (and rejection or acceptance) of Bl0.A (H2k/d, H2E+) skin grafts. Prior to skin graft challenge, tolerant mice had reduced splenic levels of memory (CD45hi, PgP-1hi, Mel-14neg) T cells as compared with the rejecting recipients and following B10.A graft challenge, the nontolerant mice showed a further increase in these cells. Elevated pretransplant levels of donor H2Kk+ cells coexpressing B220, CD11b, or CD3 were seen in the tolerant mice. Following skin grafting, splenic chimerism was reduced with differing chimeric cell phenotypes between the tolerant and nontolerant mice. In vitro production of PGE2 in a MLC was delayed in the tolerant mice with minimal production of IL-2 and IL-4. Nontolerant mice made high levels of TxB2 and heightened, early production of IL-2 and IL-4 during the MLC. Thus, tolerance induction is associated with increased numbers of particular chimeric cells, fewer peripheral lymphoid immunocompetant memory T cells, impaired eicosanoid secretion, and reduced alloreactivity and alloantigen-driven IL-2/IL-4 production. It appears that alloreactive cells necessary to break tolerance are generated when fewer class II+ (e.g., B220+, CD11b+) chimeric cells are present and that there is a coexistence of effector and regulatory T cell subpopulations in the nontolerant mice. By comparison, tolerance acquisition does not appear associated with the presence or generation of a predominant subtype of T cell but rather is likely more dependent upon clonal deletion processes.

Animals↗

Cytofluorographic evidence that thymocyte dipeptidyl peptidase IV (CD26) activity is altered with stage of ontogeny and apoptotic status.

CD26 is a multifunctional molecule implied to have a variety of roles in the immune response including its activity as a membrane exopeptidase (Dipeptidyl peptidase IV) which cleaves several protein molecules. In order to further define the expression and functional activity of CD26 in the developing thymus, we utilized a nondisruptive, cytofluorogenic assay which allowed simultaneous measurement of DPP IV activity with a fluorochrome-conjugated peptide substrate and surface staining of the T lymphocyte lineage antigens CD4 and CD8. Neonatal and adult murine thymi were examined using the three-color assay and significant differences in DPP IV activity were found among the thymocyte subsets defined by their CD4/CD8 phenotype. Single-positive cells bore higher activity than CD4-/CD8- cells and neonates had higher activity than adults. Thymocytes with characteristics consistent with apoptotic cells expressed higher DPP IV activity. Thus, DPP IV appears to be upregulated both as thymocytes mature and among thymocytes which are undergoing programmed cell death. These results suggest that CD26 is ontogenically controlled during T cell maturation and may play a role in thymic deletion of emerging clones.

Amino Acid Sequence↗

Modulation of renal disease in autoimmune NZB/NZW mice by immunization with bacterial DNA.

Preautoimmune New Zealand Black/White (NZB/NZW) mice immunized with Escherichia coli (EC) double standard (ds) DNA produce antibodies that bind mammalian dsDNA and display specificities similar to spontaneous lupus anti-DNA. Since calf thymus (CT) dsDNA fails to induce these antibodies, these results suggest a special potency of foreign DNA in inducing serological manifestations of lupus in a susceptible host. To assess the effects of DNA immunization on clinical manifestations in NZB/NZW mice, we measured renal disease and survival of mice immunized with either (a) EC dsDNA as complexes with methylated bovine serum albumin (mBSA) in adjuvant; (b) CT dsDNA with mBSA in adjuvant; (c)mBSA alone in adjuvant; or (d) unimmunized. After immunization with EC dsDNA, NZB/NZW mice developed significant levels of anti-dsDNA antibodies. Nevertheless, these mice had less proteinuria, nitrate/nitrite excretion, and glomerular pathology than mice immunized with either mBSA alone, CT dsDNA/mBSA complexes, or unimmunized mice. Survival of the EC dsDNA immunized mice was significantly increased compared with the other mice. Furthermore, immunization of mice after the onset of anti-DNA production and proteinuria stabilized nephritis and prolonged survival. The improvement in renal disease occurred despite the expression of autoantibodies that bound mammalian dsDNA as well as glomerular antigens. These results suggest that bacterial DNA has immunological properties that attenuate murine lupus despite the induction of pathogenic antibodies.

Animals↗

The cellular basis of metastasis.

The molecular basis of tumorigenesis and metastasis has been under intense analysis over the last few years. Tumor progression is a multistep process involving the interplay of several molecules. Initiated by spontaneous mutations, cellular alterations occur, which may result in a metastatic phenotype. The transition from a nonmalignant to a malignant cell is governed by mechanisms similar to those implicated in normal cellular differentiation and development. Epithelial cells might lose their polarity and adhesive contacts to become invasive carcinoma cells. Such a complex transformation has been summarized in the term epithelial-mesenchymal transition (EMT). In the analysis of tumor progression it is of particular interest that metastasis-specific gene products are involved in embryonic development and, furthermore, play a role in blood cell migration, tissue remodeling, and wound healing during adulthood. Herein we present a synopsis of the newest developments in molecular biology with respect to tumorigenesis and metastasis in the light of specific molecules involved in EMT.

Animals↗

Longitudinal induced IL-2 mRNA monitoring in renal transplant patients immunosuppressed with cyclosporine and in unmodified canine renal transplant rejection.

Immune monitoring of transplant patients to define optimal immunosuppression continues to be important, as rejection occurs despite adjustment of dosaging of CsA or even FK506 to achieve "therapeutic-range" blood levels. Because CsA is known to inhibit upregulation of IL-2 mRNA transcription, we prospectively sequentially measured (induced) IL-2 mRNA in PHA-stimulated PBMC cultures from transplant recipients of kidneys from living-related donors (n = 15) using a quantitative PCR assay, with a potential 24-hour turnaround time, to define immunologic events in real time. Reproducible individual patient sensitivity or refractoriness to CsA was determined pretransplant, by adding a range of CsA concentrations to the PBMC cultures and constructing induced IL-2 mRNA regression inhibition curves. However, this was not predictive of rejection episodes, but did correlate well with individual differences in IL-2 mRNA levels posttransplant, despite similar maintenance trough blood concentrations of CsA between patients. In this prospective study, seven patients experienced rejection episodes despite therapeutic CsA trough levels. Three of these, plus one not receiving CsA therapy, who happened to be prospectively tested at the time that rejection was clinically diagnosed, had a decrease in induced IL-2 mRNA before treatment was instituted. As a correlation to this observation in patients, induced IL-2 mRNA levels in unmodified rejection were sequentially measured in PBMC cultures in autologous vs allogeneic canine renal transplants and IL-2, IL-10, TNF-alpha, and IFN-gamma mRNA were also measured in kidney biopsies. Sequential PHA lymphoproliferation assays of [3H] thymidine incorporation on patient and dog PBMC cultures were also performed. Similar to the observations in patients, unmodified rejection in the canine renal allograft model also was accompanied by a decline of PHA-induced IL-2 mRNA in PBMCs as the serum creatinine concentrations became elevated. In the dog kidney biopsies at later phases of rejection, IL-10 mRNA levels were also significantly elevated (p = 0.032).

Animals↗

Routine use of the piggyback technique in pediatric orthotopic liver transplantation.

The theoretical advantages of the piggyback technique over conventional orthotopic liver transplantation are as follows. (1) Continuous venous decompression during the anhepatic phase is provided without venovenous bypass. (2) Warm ischemia time can be shortened because there is no need for the infrahepatic vena cava anastomosis. The following report is a review of the authors' experience with this method in children during the past year at their institution. Analyses of intraoperative hemodynamics and blood loss, postoperative renal function, patient and graft survival, and length of hospital stay have shown excellent results. There were no intraoperative deaths, and causes of death and graft loss were not related to the technique. The authors conclude that children who undergo liver transplantation can be very satisfactorily managed with the piggyback operation, and this technique may be more advantageous than the conventional method.

Adolescent↗

Targeted mutation of plakoglobin in mice reveals essential functions of desmosomes in the embryonic heart.

Plakoglobin (gamma-catenin), a member of the armadillo family of proteins, is a constituent of the cytoplasmic plaque of desmosomes as well as of other adhering cell junctions, and is involved in anchorage of cytoskeletal filaments to specific cadherins. We have generated a null mutation of the plakoglobin gene in mice. Homozygous -/- mutant animals die between days 12-16 of embryogenesis due to defects in heart function. Often, heart ventricles burst and blood floods the pericard. This tissue instability correlates with the absence of desmosomes in heart, but not in epithelia organs. Instead, extended adherens junctions are formed in the heart, which contain desmosomal proteins, i.e., desmoplakin. Thus, plakoglobin is an essential component of myocardiac desmosomes and seems to play a crucial role in the sorting out of desmosomal and adherens junction components, and consequently in the architecture of intercalated discs and the stabilization of heart tissue.

Animals↗

How well does the psychiatry residency in-training examination predict performance on the American Board of Psychiatry and Neurology. Part I. Examination?

OBJECTIVE: Scores on the American College of Psychiatrists' Psychiatry Residency In-Training Examination (PRITE) were correlated with scores on the American Board of Psychiatry and Neurology (ABPN) Part I examination in psychiatry. METHOD: Pearson correlations between 1992 PRITE scores and 1994 ABPN Part I psychiatry scores were calculated. Analyses were based on 701 examinees. RESULTS: There was a moderate correlation between scores on the PRITE and ABPN Part I examination in psychiatry and a low correlation of neurology scores. CONCLUSIONS: These correlations were observed even though the two examinations differ in their purposes, content outlines, development, and administration.

Educational Measurement↗

Impairment of the liver insulin receptor autoactivation cascade at full-term pregnancy in the rat.

Partially purified liver insulin receptors from full-term pregnant rats show decreased autophosphorylation rates if compared with receptors from virgins. We studied the molecular mechanism of this phenomenon, looking at possible structural and functional changes of several domains. The ATP-binding domain seems to be unaltered in receptors from pregnant rats since Km for ATP was similar to that observed in virgins. In contrast, the Vmax. is decreased some 45%, suggesting changes in the kinase domain. Truncation of a fragment of 10 kDa from the C-terminal tail does not normalize the kinase activity in receptors from pregnant rats, suggesting that this domain is not involved in the inhibitory regulation. Treatment with alkaline phosphatase increases the [32P]Pi incorporation into receptors from pregnant rats; however, the autophosphorylation remains lower than that observed in virgin rats. Tryptic phosphopeptide maps of phosphorylated receptors show that the same phosphopeptides are present in receptors from virgin and pregnant rats. However, the progression through the autoactivation cascade in the kinase domain is impaired in receptors from pregnant rats. Differences in the cleavage by trypsin at the two alternative sites in the kinase domain were observed, indicating possible structural changes in receptors from pregnant rats that could be related to the impairment of the autoactivation cascade. Integrity of the alpha- and beta-subunits, as well as differential expression of the two receptor isotypes, were shown to be unaltered. We conclude that (1) the decreased autophosphorylation rate of the liver insulin receptor from pregnant rats is associated with the impairment of its autoactivation cascade, probably as a consequence of the basal Ser/Thr phosphorylation; and (2) the inhibition of the autoactivation cascade does not account for the overall inhibition of autophosphorylation observed in receptors from pregnant rats.

Adenosine Triphosphate↗