Biomedical subjects
Publications and source records attributed to F Gonzalez.
This report describes the histopathological and ultrasound biomicroscopy findings of a 35-year-old woman with keratoconus who developed an irreversible mydriasis after keratoplasty.
OBJECTIVE: To determine if long-term therapy with aspirin or basic amino acids for subjects with NIDDM reduces the severity of clinical complications and/or reduces tissue levels of markers of glycooxidative damage. RESEARCH DESIGN AND METHODS: Subjects with NIDDM were administered either aspirin (100 mg/day) or a combination of basic amino acids consisting of L-arginine (2 g/day) plus L-lysine (0.5 g/day) for 1 year. The study was double-blind and placebo-controlled. The presence and severity of retinopathy, nephropathy, and neuropathy were assessed in all subjects at 4-month intervals, as were serum blood glucose, glycohemoglobin levels, and presence of albuminuria. Collagen cross-linking and collagen glycation were measured in skin collagen obtained by biopsy at the beginning and the end of the study. Skin biopsies were also obtained from age-matched control subjects. RESULTS: Skin samples obtained from NIDDM subjects at the beginning of the study had significantly increased levels of glucitolyllysine, pentosidine, and hydroxypyridinium, as compared with age-matched control subjects. Pentosidine levels were significantly correlated with severity of retinopathy and neuropathy, but not nephropathy. Subjects receiving aspirin, but not amino acids or placebo, had significantly decreased levels of skin pentosidine after 1 year of therapy. CONCLUSIONS: It is concluded that 1) low-dose aspirin may reduce glycooxidative damage in people with NIDDM, and 2) treatment may need to continue for more than 1 year before clinical status improves.
The identity and abundance of self-peptide/MHC class I complexes that serve as ligands for alloreactive T cells remain largely unknown. Using the Kb-restricted, alloreactive T cells as a probe, the Ag precursor gene, adenosine phosphoribosyl transferase (APRT), was isolated by expression cloning. Its naturally processed product was identified as the SLVELTSL (SEL8) octapeptide. The SEL8 peptide shared five residues with the previously identified SVVEFSSL (JAL8) peptide that stimulated the same T cell, but lacked the critical phenylalanine/tyrosine residue at the primary p5 anchor position. Despite the absence of this key conserved anchor residue, SEL8 was bound tightly by Kb MHC and yet was expressed at less than 10 copies/cell. Mutations in the donor APRT gene in the APC caused a concomitant loss in the ability of APCs to stimulate T cells. The results confirm that the display of peptide/MHC complexes in cells exceeds the predictions based upon consensus motifs, and that CD8+ alloreactive and conventional Ag-specific T cells are indistinguishable in their ability to recognize unique and rare peptide/MHC class I complexes.
STUDY OBJECTIVE: To measure the incidence of nausea and vomiting in outpatients in relation to selection of, or withholding of, intraoperative opioid. DESIGN: Prospective, randomized, double-blind control trial. SETTING: University general hospital. PATIENTS: 200 unpremedicated ASA status 1 and 11 patients, 8 to 80 years old, undergoing general anesthesia for ambulatory surgery. INTERVENTION: Patients were randomized to four groups, three of which received equipotent doses of different opioids intravenously (i.v.) during induction of anesthesia. Group 1 received nalbuphine 0.25 mg/kg, Group 2, alfentanil 20 ug/kg; Group 3, fentanyl 2 ug/kg; and Group 4, normal saline. MEASUREMENTS AND MAIN RESULTS: We evaluated (1) incidence and severity of nausea and vomiting in the postanesthesia care unit (PACU) and over the next 24 hours; (2) time to PACU discharge; (3) need for antiemetic therapy; and (4) need for analgesic rescue in the PACU. The incidences of nausea and vomiting were similar in all groups, as were time to discharge, antiemetic, and nonsteroidal antiinflammatory drug requirements. The highest incidences of nausea and vomiting occurred at 6 hours in all groups (23% and 9.5%, respectively). Group 1 required lower rescue doses of morphine in the PACU but this result may have been an artifact due to employing the mixed agonist-antagonist opioid, nalbuphine, in this group. CONCLUSIONS: Opioid administration at the doses employed during induction of anesthesia does not promote postoperative nausea or vomiting, nor increase length of stay in the PACU.
PURPOSE: To report choroidal vascular abnormality in unilateral Purtscher's retinopathy. METHODS: Fluorescein angiography and indocyanine green angiography with a scanning laser ophthalmoscope were used to examine a 19-year-old man four days, three months, and five months after sustaining an injury in a car accident. RESULTS: Indocyanine green angiography showed an area of choroidal hypofluorescence that continued to be present up to five months after the accident. CONCLUSIONS: Choroidal vasculature may be affected in Purtscher's retinopathy. Disorder in the choroidal microcirculation could be an additional cause of the resulting poor vision observed in some patients with Purtscher's retinopathy.
Explore the source record for details and available documents.
The differences between the two monocular receptive fields of cortical cells were measured and compared to their disparity tuning in the awake behaving monkey. Several receptive field properties (direction selectivity, orientation preference, eye preference and response modulation) were determined for each eye using sweeping bright bars. The disparity sensitivity of these cells was also assessed by plotting their response profile, determined for each cell under strictly binocular cyclopean stimulation (dynamic random dot stereograms, RDS). We have found that large differences between the two monocular receptive fields were infrequent and, apparently, not related with the disparity sensitivity profile. We conclude that the monocular asymmetries tested in this study and the sensitivity to positional binocular disparities present in RDS, might be linked to different mechanisms involved in depth perception in the visual system.
OBJECTIVE: To examine the hypothesis that, in polycystic ovary syndrome (PCOS), ovarian steroids induce adrenal enzyme dysfunction or adrenal androgen hyperresponsiveness to ACTH. DESIGN: Prospective controlled clinical study. SETTING: Reproductive endocrinology unit of an academic medical center. PATIENTS: Twelve women with PCOS who had adrenal androgen excess were compared with five weight-matched ovulatory women. In half of the women with PCOS, prestudy screening was suggestive of mild 3 beta-hydroxysteroid dehydrogenase (HSD) deficiency. INTERVENTIONS: Basal and adrenal dynamic blood sampling before and after GnRH agonist (GnRH-a) administration for 6 months. MAIN OUTCOME MEASURES: Basal E2 and androgen levels as well as dexamethasone-suppressed, ACTH-stimulated 17 alpha-hydroxyprogesterone, 17 alpha-hydroxypregnenolone, and androgen levels before and after ovarian suppression. RESULTS: Although none of the subjects with PCOS proved to have mild 3 beta-HSD deficiency, the majority of them (58%) met the criteria for 17,20 lyase hyperactivity before and after GnRH-a therapy. As a group, the remaining subjects with PCOS exhibited an elevated DHEAS response to ACTH before GnRH-a treatment, which may have normalized after GnRH-a treatment. CONCLUSION: Adrenal androgen excess in PCOS may be heterogeneous in etiology, whereas 17,20 lyase hyperactivity appears to be an intrinsic adrenal disorder, adrenal androgen hyperresponsiveness to ACTH may be ovarian induced. Reliance on historical controls may lead to overdiagnosis of mild 3 beta-HSD deficiency.
The study purpose was to identify risks, benefits and costs associated with an expanded donor protocol. The protocol design evaluated organs rescued using expanded donor criteria and weighed all costs associated with doing so. Costs were measured against conditions experienced with expanded and traditional criteria and recipient outcome. Traditional donors were between 5 and 55, with negative serologies, and no history of hypertension or diabetes. "Expanded donors" were between 55 and 75 or less than 5, with a history of hypertension, diabetes and/or sero-positive for Hepatitis C. During this study 73 donors met criteria from which 200 organs were transplanted. Defined costs and outcomes for recipients were tracked. Using expanded criteria: costs averaged 20% more per organ; OPO personnel spent an average of 6 hours more time on-site; an additional 12-14 hours in placement activity; and average organs per donor decreased. Heart patient and graft survival rates for traditional and expanded donor organs were comparable. Kidney patients transplanted from this pool experienced a decrease in patient (P = .14) and a significant decrease in graft (P = .02) survival rates. Patient (P = .05) and graft (P = .01) survival rates were significantly lower in liver patients transplanted with expanded donor organs. Two hundred transplants occurred using expanded donor criteria. Costs for the OPO increased appreciably. Heart and kidney utilization from these donors seems justified. It is thought that liver recipients' results were due to utilizing them in sicker patients. Recovery of organs from donors using expanded criteria appears to be a reasonable way of increasing organ supply.
Processing of intracellular proteins yields 8-11 residue peptides that are displayed on the APC surface as peptide/MHC class I complexes. The remarkably precise excision of antigenic peptides from their precursor polypeptides raises the question of whether specific flanking residues influence presentation efficiency. Here we addressed this question by analyzing the generation of OVA/Kb or influenza nucleoprotein/Db complexes in APC expressing precursors with varying N- or C-terminal flanking residues. We find that T cell responses were not significantly affected by varying the N-terminal flanking residue in the precursors. In contrast, presentation of peptide/MHC complexes was inhibited with the addition of a single C-terminal flanking residue. The most dramatic inhibition was observed with isoleucine, leucine, cysteine, and proline as the C-terminal flanking residues. These residue-specific variations in presentation activity could not be accounted for by differences in the stimulatory activity of corresponding synthetic peptides but were proportional to the relative amounts of naturally processed peptides recovered in the cell extracts. These findings suggest differences in the susceptibility of N- vs C-terminal flanking residues to proteolytic cleavage during Ag processing. The strong influence of specific C-terminal flanking residue(s) could be an important factor affecting the choice of peptides presented to T cells on the APC surface.
A V79 Chinese hamster cell line was constructed for stable expression of human cytochrome P450 2E1 (CYP2E1) by integration of a SV40 Early promoter recombinant CYP2E1 cDNA into the chromosomal DNA. The cDNA encoded CYP2E1 was effectively expressed and enzymatically active, as shown by hydroxylation of chlorzoxazone and of p-nitrophenol, at rates of about 70 pmol x mg-1 total protein x min-1. CYP2E1 content and activity was increased upon cultivation in the presence of ethanol indicating a substrate mediated stabilization effect. A similar stabilizing effect was also observed for inhibitors of CYP2E1, e.g. imidazole, 4-methylpyrazole, and isoniazid. The feasibility of the newly established cell line V79MZh2E1 for toxicological studies was shown by CYP2E1-mediated activation of N-nitrosodimethylamine and p-nitrophenol and a dose-dependent cytotoxic and mutagenic effect.
Self or foreign cellular proteins provide peptides for presentation by major histocompatibility complex (MHC) class I molecules on the surface of antigen presenting cells (APC). Surprisingly, several studies have shown that T-cells can recognize APC transfected with antigen genes that were not present in the appropriate translational context. To understand the basis of this phenomenon, APC were transfected with DNA constructs encoding the OVA257-264 (SL8) peptide, but with varying translation initiation codons. We report that, in addition to ATG, 6 other codons (ATT, ACG, CTG, GCG, TGG, GAT) also allowed presentation to SL8-Kb-specific T-cells. Significantly, this set includes 3 of 4 known non-ATG translation initiation codons strongly suggesting that cryptic translation accounts for this phenomenon. Although expression of the SL8-Kb complex was readily detected by T-cell activation, the amount of processed peptides was below detection limit (< 30 copies/cell) in cell extracts. Thus, the fortuitous presence of these cryptic translation initiation sites in transcribed genes can explain how peptide MHC complexes were obtained in sufficient amounts for T-cell activation. The translation initiation codons identified here could also be useful for identifying potential open reading frames that possess biological and/or immunological activities.
OBJECTIVE: To reevaluate the clinical significance of elevations of adrenal androgens in polycystic ovary syndrome (PCOS). METHODS: Thirty women with PCOS and ten ovulatory controls were evaluated. Serum dehydroepiandrosterone (DHEA) sulfate and 11 beta-hydroxyandrostenedione were measured before and after 3 and 6 months of GnRH agonist (GnRH-A) therapy. All controls and 15 women with PCOS received intravenous ACTH before and after GnRH-A therapy. RESULTS: Twenty-one (70%) of the women with PCOS had elevations of DHEA sulfate, and 16 (53%) had elevations in 11 beta-hydroxyandrostenedione. Only two women with PCOS had normal values of both adrenal androgens. After GnRH-A therapy, only 11 subjects (37%) had elevated values of DHEA sulfate. Four of 16 women had reductions in 11 beta-hydroxyandrostenedione. Only those with elevated baseline DHEA sulfate levels had reductions after GnRH-A therapy. The reduction of DHEA sulfate with GnRH-A correlated with the reduction in androstenedione. Of the subjects who had reductions in DHEA sulfate with GnRH-A therapy, there was a blunted response of DHEA to ACTH after treatment. CONCLUSION: Our findings suggest that the ovary may influence the prevalence and magnitude of adrenal androgen excess in PCOS.
An increased incidence of premature atherosclerotic arterial occlusive disease was recently reported in young adults. This condition is characterized by early occurrence of severe symptoms, lower incidence of typical cardiovascular risk factors for atherosclerosis, different natural course of arterial disease vis-a-vis older population, and poor outcome of a standard treatment. This report describes a young man with aggressive arterial occlusive disease in the lower extremities and symptom-free occlusions of coronary and renal arteries in association with high levels of lipoprotein(a). Microscopic early atherosclerotic changes were noted in the occluded arteries of the amputated leg. Premature atherosclerotic arterial occlusive disease in young adults has different clinical and pathological patterns, necessitating a different approach for evaluation and treatment.
Explore the source record for details and available documents.
In the present study we have examined the potential contribution of IL-2/IL-2R interactions in CD3-mediated responses by T lymphocytes from patients with systemic lupus erythematosus (SLE). T-cells from SLE patients showed normal IL-2 production when activated with OKT3 MAb and submitogenic concentrations of PMA, in cultures in which uptake of endogenous IL-2 was prevented by pretreatment with anti-Tac MAb. In contrast, PHA-induced IL-2 production was lower in patients under the same conditions. Under these stimulatory conditions the proportions of T-cells expressing IL-2R CD25 molecules was comparable in patients and controls. There was earlier and higher binding of exogenously added IL-2 in T lymphocytes from patients activated via the CD3 pathway. Furthermore, these cells responded to IL-2 with stronger proliferative responses than cells from control subjects. These findings may partly explain the increased proliferative responses of SLE T-cells when stimulated via the CD3 pathway.
BACKGROUND: It has been reported that scleral buckling reduces the blood flow velocity in retinal vessels. Blood flow changes may also appear in other ocular and extraocular vessels. This study describes the blood flow velocity changes in the ophthalmic artery (OA) after performing this procedure. METHODS: The study was carried out in 12 patients (12 eyes) with rhegmatogenous retinal detachment. Color Doppler imaging was used to measure the peak and average blood flow velocity in the OA. Measurements were taken 1 day before and 2 days after scleral buckling surgery was performed. Intraocular pressure (IOP) was measured prior to each ultrasound study. RESULTS: We found that statistically significant reductions in the peak flow velocity (33%) and average flow velocity (31%) occur in the OA after scleral buckling. All patients showed an increase in IOP after surgery. CONCLUSION: Buckling surgery reduces the blood flow velocity in the OA. Since the OA is the origin of the arterial branches that supply blood to the eye, our results suggest that scleral buckling may decrease not only retinal but also choroidal blood perfusion. Some extraocular structures might also be affected.
A new system capable of generating static and dynamic random-element stereograms is designed and implemented. The stereogram is composed of a rectangle that can be varied in size, element density, orientation, and horizontal and vertical disparities, and can be swept at several velocities. The system is based on an inexpensive personal computer (Amiga 500), designed to work as a slave system under the control of a host computer (e.g. any personal computer). A colour monitor or two black and white monitors are suitable display devices to view the stereograms. This system is used to perform psycophysical experiments in humans and neurophysiological experiments in behaving monkeys, with the purpose of studying depth perception and binocular vision.