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Biomedical subjects

C Gonzalez

Publications and source records attributed to C Gonzalez.

At least 91 records · Page 5Linked to original sources
PubMed1999

Immunologic and virologic responses to HAART in severely immunocompromised HIV-1-infected children.

OBJECTIVE: To determine the long-term immunologic and virologic effects of highly active antiretroviral therapy (HAART) in children with AIDS. DESIGN: A prospective observational study. SETTING: Two pediatric HIV clinics. PARTICIPANTS: Twenty-five protease-inhibitor naive HIV-infected children (aged 2-18 years) with advanced disease (CD4 < or =6%). INTERVENTION: HAART (one protease inhibitor and one or more nucleoside analogs). Diphtheria and tetanus immunization in six patients after 18 months of therapy. MAIN OUTCOME MEASURES: Changes in percentage of CD4 cells and plasma HIV-1 RNA levels; post-treatment assays of lymphoproliferative responses to recall antigens; CD4 cell memory phenotype. RESULTS: Median duration of follow-up was 18.8 months (range, 7.5-28 months). At baseline the CD4 cell percentage was 2% (range, 0-6%), this increased significantly to 16% (range, 3-48%) above baseline at 12 months (P = 0.002). The mean maximum CD4 cell increase was 20.7% (range 4-48%) which corresponds to 657x10(6) cells/l (range, 30-2240x10(6) cells/l) above baseline. By contrast, the median viral load was not significantly lower at 12 months than at baseline (P = 0.34), and only 25% of the patients had sustained undetectable viral load. Of the reconstituted CD4 cells 70% were naive, and none of the subjects had lymphoproliferative responses to tetanus and diphtheria although 40% did develop responses to Candida, an environmental antigen. A single immunization with diphtheria and tetanus toxoid produced lymphoproliferative responses to tetanus in three out of six patients. CONCLUSIONS: HAART was associated with sustained increases in CD4 cell counts, despite a high incidence of 'virologic failure'. CD4 counts and the proportion of naive cells were higher than have been reported in adults, which may be a reflection of greater thymic activity in children. Memory cell clones for antigens encountered in the past which are not prevalent before therapy could not be expanded without additional antigenic exposure.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Albinism and agenesis of the corpus callosum with profound developmental delay: Vici syndrome, evidence for autosomal recessive inheritance.

We report on two sibs and two other unrelated patients with agenesis of corpus callosum, oculocutaneous albinism, repeated infections, and cardiomyopathy. All manifested postnatal growth retardation, microcephaly, and profound developmental delay. Additional central nervous system anomalies present in at least one patient included hypoplasia of the cerebellar vermis, white matter neuronal heterotopia, or bilateral schizencephaly. Repeated viral, bacterial, and fungal infections were consistent with a primary immunodeficiency. However, immunological studies showed variable, nonspecific findings. Cardiomyopathy with progressive heart failure or infection led to death before age 2 years in three of the patients. This syndrome was first described by Vici et al. [1988: Am. J. Med. Genet. 29:1-8]. The four patients reported herein confirm this unique disorder. Affected sibs of both sexes born to unaffected parents provide evidence for autosomal recessive inheritance.

Adult↗
PubMed1999

Fourier-transform optical microsystems.

The design, fabrication, and initial characterization of a miniature single-pass Fourier-transform spectrometer (FTS) that has an optical bench that measures 1 cm x 5 cm x 10 cm is presented. The FTS is predicated on the classic Michelson interferometer design with a moving mirror. Precision translation of the mirror is accomplished by microfabrication of dovetailed bearing surfaces along single-crystal planes in silicon. Although it is miniaturized, the FTS maintains a relatively high spectral resolution, 0.1 cm-1, with adequate optical throughput.

Equipment Design↗
PubMed1999

Nuclease resistant hammerhead motif: from '5-ribo' to '3-ribo' model.

Previously developed '5-ribo' nuclease stabilized hammerhead motif was further refined by systematic incorporation of 1-(beta-D-xylofuranosyl) adenine (xA) and 1-(beta-D-xylofuranosyl) guanine (xG) in the place of conserved ribopurine residues of the catalytic core. Modified ribozymes substituted with xA at positions A15.1 and A6 demonstrated catalytic activity close to the parent stabilized ribozyme. Analogous guanosine substitutions at positions G5, G8, and G12 substantially lowered catalytic rates.

Adenine↗
PubMed1999

Lack of association between prior infection with Chlamydia pneumoniae and acute or chronic coronary artery disease.

BACKGROUND: Higher than normal serologic titers and the detection of bacteria within atheroma have suggested an association between Chlamydia pneumoniae (C. pneumoniae) infection and coronary heart disease (CHD), but the relationship has not been well established. HYPOTHESIS: The study was designed to establish a lack of relationship between chronic C. pneumoniae infection and CHD. METHODS: Chlamydia-specific IgG-antibody was assayed using an indirect immunofluorescence test in the serum of 159 patients with severe arterial disease and 203 patients with a heart valve prostheses and no demonstrable CHD. Fatal and nonfatal vascular events and systemic thromboembolism were recorded over a 2-year period. RESULTS: In the arterial group 107 patients (67.3%) and in the valvular group 120/203 (59.1%) were positive for C. pneumoniae antibody. The number of patients with fatal or nonfatal vascular events (double end point) in the arterial and valvular groups was 23 and 2, respectively (p < .0001). Triple end points (fatal plus nonfatal vascular events plus thromboembolism) were also more frequent in the arterial group (p < 0.002). The prevalence of chlamydia antibody positivity was the same in the arterial and valvular groups, and the occurrence of clinical events was also the same for chlamydia-positive (227 patients) as for chlamydia-negative (135 patients). After adjustment for confounding variables, only arterial disease was a predictive factor for double (OR 17.0; 95% CI 3.94-73.3) or triple (OR 3.12; 95% CI 1.56-6.25) end points. CONCLUSION: We find C. pneumoniae chronic infection not to be an independent risk factor for acute or chronic arterial disease.

Acute Disease↗
PubMed1999

Increased adherence of fluconazole-resistant isolates of Candida species to explanted esophageal mucosa.

The adherence of fluconazole-resistant and fluconazole-susceptible isolates of Candida albicans to explanted rabbit esophageal mucosa was examined in vivo. Among six Candida albicans isolates collected from HIV-infected patients, three fluconazole-resistant (MIC > 64 microg/ml) isolates attached more avidly than three fluconazole-susceptible strains (MIC < or = 0.5 microg/ml) to esophageal mucosa (P < or = 0.05). When three strains each of six different Candida spp. were compared, the more inherently fluconazole-resistant isolates adhered more avidly in the following order: Candida glabrata>Candida krusei>Candida albicans fluconazole-sensitive>Candida tropicalis>Candida parapsilosis. Nonetheless, fluconazole-resistant Candida albicans demonstrated the greatest degree of adherence in comparison to all fluconazole-susceptible Candida albicans (P<0.001) and to all Candida spp. tested (P<0.001). Thus, the refractoriness of esophageal candidiasis in patients infected with fluconazole-resistant isolates may be related to both in vitro drug resistance and increased mucosal adherence.

Animals↗
PubMed1999

Adenosine inhibits L-type Ca2+ current and catecholamine release in the rabbit carotid body chemoreceptor cells.

In an in vitro preparation of the intact carotid body (CB) of the rabbit, adenosine (100 microM) inhibited hypoxia-induced catecholamine release by 25%. The specific A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 1 microM) prevented the inhibition and increased the response to hypoxia further. In isolated chemoreceptor cells from the same species, adenosine inhibited voltage-dependent Ca2+ currents by 29% at 1 microM (concentration producing half-maximal inhibition, IC50 = 50 nM). This inhibition was mimicked by R(-)N6-(2-phenylisopropyl)-adenosine and 2-chloroadenosine (1 microM), two purinergic agonists poorly active at the intracellular ('P') site, and persisted in the presence of dipyridamole (a blocker of adenosine uptake; 1 microM) and was fully inhibited by 8-phenyltheophylline (10 microM). The A1 antagonists DPCPX (10 microM) and 8-cyclopentyl-1,3-dimethylxantine (0.1 microM) inhibited the effect of adenosine by 93% (IC50 = 0.14 microM) and 59%, respectively. The inhibition of the Ca2+ current (I(Ca)) was reduced by nisoldipine (an L-type Ca2+ channel antagonist) by nearly 50%, and was unaltered by omega-conotoxin GVIA, a blocker of N-type Ca2+ channels. Adenosine did not affect the voltage-dependent Na+ current (I(Na)) or K+ current (I(K)). We conclude that adenosine A1 receptors are located in chemoreceptor cells and mediate the inhibition of L-type Ca2+ channels and thereby the release of catecholamines produced by hypoxia. The data also indicate that endogenous adenosine acts as a physiological negative modulator of the chemoreceptor cell function. The previously reported excitatory action of adenosine on the activity of the sensory nerve of the CB is discussed in terms of a balance between the inhibition mediated by A1 receptors and the excitation mediated by A2 receptors.

Adenosine↗
PubMed1999

Expanding contraceptive choice: findings from Brazil.

This article presents findings from a participatory action research project in a municipality in southern Brazil that models a new and holistic approach to broadening women's contraceptive choices. The project encourages a collaborative process between researchers, community members, and public health managers to diagnose service-delivery problems, to design and implement interventions, and to evaluate their effectiveness. Findings from the baseline evaluation revealed major constraints in availability of and access to family planning and reproductive health services for women, as well as severe deficiencies in quality of care. Interventions designed to address these weaknesses, bound by the limited resources of the public sector, focused on training, restructuring of providers' roles and service-delivery patterns, the management process, the creation of a referral center, and the introduction of injectables, vasectomy services, and a program for adolescents. Evaluation results show the project's considerable impact in broadening reproductive options, although not all issues, especially those related to sustainability, have been resolved.

Adolescent↗
PubMed1999

Effects of the hematoregulatory peptide SK&F 107647 alone and in combination with amphotericin B against disseminated candidiasis in persistently neutropenic rabbits.

The effects of the hematoregulatory peptide SK&F 107647 were examined in a persistently and profoundly neutropenic rabbit model of disseminated candidiasis in order to determine its potential to enhance resistance against infection and its role as an adjunct to conventional antifungal chemotherapy. In healthy animals, SK&F 107647 elicited a time-dependent increase in CD11b-positive monocytes and neutrophils. When administered to neutropenic rabbits infected with Candida albicans, no significant differences in the number of CFU per gram in any of the tissues tested compared with the number in untreated control rabbits were detected. However, when SK&F 107647 was administered in combination with low doses of amphotericin B, there was a significant reduction in organism burden in the lungs, liver, spleen, and kidneys compared with the burdens in the organs of untreated control animals and in the lungs and kidneys compared with the burdens in the lungs and kidneys of animals treated with amphotericin B alone. These data suggest a potential role for this peptide as adjunctive therapy in combination with conventional antifungal agents in the treatment of disseminated candidiasis in the setting of profound and persistent neutropenia.

Adjuvants, Immunologic↗
PubMed1999

NADPH oxidase inhibition does not interfere with low PO2 transduction in rat and rabbit CB chemoreceptor cells.

The aim of the present work was to elucidate the role of NADPH oxidase in hypoxia sensing and transduction in the carotid body (CB) chemoreceptor cells. We have studied the effects of several inhibitors of NADPH oxidase on the normoxic and hypoxia-induced release of [3H]catecholamines (CA) in an in vitro preparation of intact CB of the rat and rabbit whose CA deposits have been labeled by prior incubation with the natural precursor [3H]tyrosine. It was found that diphenyleneiodonium (DPI; 0.2-25 microM), an inhibitor of NADPH oxidase, caused a dose-dependent release of [3H]CA from normoxic CB chemoreceptor cells. Contrary to hypoxia, DPI-evoked release was only partially Ca2+ dependent. Concentrations of DPI reported to produce full inhibition of NADPH oxidase in the rat CB did not prevent the hypoxic release response in the rat and rabbit CB chemoreceptor cells, as stimulation with hypoxia in the presence of DPI elicited a response equaling the sum of that produced by DPI and hypoxia applied separately. Neopterin (3-300 microM) and phenylarsine oxide (0.5-2 microM), other inhibitors of NADPH oxidase, did not promote release of [3H]CA in normoxic conditions or affect the response elicited by hypoxia. On the basis of effects of neopterin and phenylarsine oxide, it is concluded that NADPH oxidase does not appear to play a role in oxygen sensing or transduction in the rat and rabbit CB chemoreceptor cells in vitro and, in the context of the present study, that DPI effects are not related to NADPH oxidase inhibition.

Animals↗
PubMed1999

Effects of ticlopidine or ticlopidine plus aspirin on platelet aggregation and ATP release in normal volunteers: why aspirin improves ticlopidine antiplatelet activity.

Aspirin and ticlopidine are used to prevent arterial thrombosis. In some clinical settings ticlopidine is administered with aspirin for improving antithrombotic effect. We administered aspirin (100 mg/day), ticlopidine (500 mg/day), or ticlopidine and aspirin for 7 days to healthy volunteers. Platelet aggregation and ATP release induced by sodium arachidonate, ADP, or a combination of both were measured. Sodium arachidonate (0.25 mmol/L), which produces no platelet aggregation, combined with adenosine diphosphate (1 mumol/L), which produced a reversible platelet aggregation of 20% after ticlopidine, resulted in a synergistic platelet aggregation response in normal (74.6 +/- 9.2%) and in ticlopidine platelet-rich plasma (59.1% +/- 14.9%, p < 0.0001). Synergism after sodium arachidonate (0.75 mmol/L) plus adenosine diphosphate (4 mumol/L) fell from 75.8% +/- 11.0% and 59.1% +/- 15.6% after ticlopidine or aspirin, respectively, to 14.8% +/- 18.0% (p < 0.0001) after ticlopidine plus aspirin. Aspirin and ticlopidine alone did not inhibit adenosine triphosphate release as thoroughly as did aspirin plus ticlopidine. Aspirin or ticlopidine does not adequately prevent platelet activity as ticlopidine plus aspirin do. Addition of aspirin to treatment with ticlopidine improves their antiplatelet activity and better results could be obtained in arterial thrombotic prevention strategies.

Adenosine Triphosphate↗
PubMed1999

CD4 TCRBV CDR3 analysis in prevalent SLE cases from two ethnic groups.

We examined CD4+ T cell TCRBV-CDR3 transcripts from 19 lupus patients and 16 controls to test the hypothesis that CD4+ TCRBV-CDR3 expression in SLE differs from normals. Within the disease group we also performed exploratory analyses to determine the association between risk of oligoclonality and HLA-DRB specificities and the duration of the CDR3 patterns. Oligoclonal patterns consistent with CDR3 restriction were three times more likely in SLE than in controls (OR = 3.7). TCRBV1, BV4, BV5.1, BV7, BV9, BV18 and BV22 gene segment CDR3 patterns of oligoclonality were seen exclusively among lupus patients. HLA-DRB3 increased the risk of oligoclonal expression in SLE. In four patients studied over time, the pattern of TCRBV-CDR3 expression was stable in a second sample obtained 6-14 months later. The increased frequency of CD4+ T cell TCRBV-CDR3 oligoclonal expression in SLE when compared to controls and the persistence of these patterns are consistent with an expanded pool of autoreactive CD4 T cells in SLE which recognize peptides derived from autoantigens. The association of HLA-DRB3 genes with increased risk of CDR3 oligoclonality among the SLE subjects is compatible with the hypothesis that molecules encoded by HLA-DRB3 may facilitate autoantigen recognition by CD4 T cells.

Adult↗
PubMed1999

Cytological characterisation of the mutant phenotypes produced during early embryogenesis by null and loss-of-function alleles of the gammaTub37C gene in Drosophila.

We have studied the mutant phenotypes brought about during early embryogenesis by mutation in the gammaTub37C gene, one of the two isoforms of gamma-tubulin that have been identified in Drosophila. We have focused our attention on fs(2)TW1(1) and fs(2)TW1(RU34), a null and a hypomorph allele of this gene, whose sequences we report in this work. We have found that the abnormal meiotic figures observed in mutant stage 14 oocytes are not observed in laid oocytes or fertilised embryos, suggesting that these abnormal meiotic figures are not terminally arrested. We have also concluded that both null and hypomorph alleles lead to a total arrest of nuclear proliferation during early embryogenesis. This is in contrast to their effect on female meiosis-I where hypomorph alleles display a much weaker phenotype. Finally, we have observed that null and hypomorph alleles lead to some distinct phenotypes. Unfertilised laid oocytes and fertilised embryos deficient for gammaTub37C do not contain polar bodies and have a few bipolar microtubule arrays. In contrast, oocytes and embryos from weaker alleles do not have these microtubule arrays, but do contain polar bodies, or polar-body-like structures. These results indicate that gammaTub37C is essential for nuclear proliferation in the early Drosophila embryo.

Alleles↗
PubMed1998

Simultaneous vs sequential initiation of therapy with indinavir, zidovudine, and lamivudine for HIV-1 infection: 100-week follow-up.

CONTEXT: Combination antiretroviral therapy can markedly suppress human immunodeficiency virus (HIV) replication but the duration of HIV suppression varies among patients. OBJECTIVE: To compare the antiretroviral effect of a 3-drug regimen started simultaneously or sequentially in patients with HIV infection. DESIGN: A multicenter, randomized, double-blind study, modified after at least 24 weeks of blinded therapy to provide open-label 3-drug therapy with follow-up through 100 weeks. SETTING: Four clinical research units PATIENTS: Ninety-seven patients with HIV infection who had taken zidovudine for at least 6 months with serum HIV RNA level of at least 20000 copies/mL and CD4 cell count of 0.05 to 0.40 x 10(9)/L. INTERVENTIONS: Patients were initially randomized to receive 1 of 3 antiretroviral regimens: indinavir, 800 mg every 8 hours; zidovudine, 200 mg every 8 hours and lamivudine, 150 mg every 12 hours; or all 3 drugs. After at least 24 weeks of blinded therapy, all patients received open-label 3-drug therapy. MAIN OUTCOME MEASURES: Antiretroviral activity was assessed by changes in HIV RNA level and CD4 cell count from baseline. Data through 100 weeks were summarized. RESULTS: Simultaneous initiation of indinavir, zidovudine, and lamivudine suppressed HIV RNA in 78% (25/32) of contributing patients to less than 500 copies/mL and increased CD4 cell count to a median of 0.209 x 10(9)/L above baseline at 100 weeks. When these 3 drugs were initiated sequentially, only 30% to 45% of contributing patients (10 of 33 in the zidovudine-lamivudine group and 13 of 29 in the indinavir group, respectively) had a sustained reduction in HIV RNA to less than 500 copies/mL, and median CD4 cell count increased to 0.101 to 0.163 x 10(9)/L above baseline at 100 weeks. CONCLUSIONS: A 3-drug combination of indinavir, zidovudine, and lamivudine started simultaneously has durable antiretroviral activity for at least 2 years. Sequential initiation of the same 3 drugs is much less effective.

Anti-HIV Agents↗
PubMed1998

Interactions between mgr, asp, and polo: asp function modulated by polo and needed to maintain the poles of monopolar and bipolar spindles.

We describe genetic interactions between mutations in mgr, asp, and polo, genes required for the correct behaviour of the spindle poles in Drosophila. The phenotype of a polo1 mgr double mutant is more similar to mgr than polo1, but the frequency of circular monopolar figures (CMFs) seen with either mutant alone is additive, suggesting that the two gene products are required for independent functions in the formation of bipolar spindles. The aspE3 mgr double mutant arrests much earlier in development than either mutant alone, indicative of a strong block to cell proliferation. We discuss whether the lack of microtubular structures in these cells reflects an extended mitotic arrest, or if it is a more direct consequence of the double mutant combination. A polo1 aspE3 double mutant shows a dramatic synergistic increase in mitotic frequency. The loss of CMFs normally associated with the polo1phenotype suggests that the Asp microtubule-associated protein is required to maintain the structure of spindle poles. We speculate that Asp protein might be a substrate for the serine-threonine protein kinase encoded by polo.

Animals↗
PubMed1998

Unilateral peripapillary myelinated retinal nerve fibers associated with strabismus, amblyopia, and myopia.

PURPOSE: To describe the association of unilateral peripapillary myelinated retinal nerve fibers with myopia, strabismus, and amblyopia and to propose a possible pathologic mechanism. METHODS: Four patients who have the findings associated with unilateral peripapillary myelinated nerve fibers are described and reviewed. RESULT: All patients had poor visual outcomes despite treatment with full cycloplegic refraction and appropriate patching. CONCLUSIONS: Although the origin of this association is unknown, we believe that peripapillary myelinated nerve fibers in a unilateral myopic eye may be secondary to an imbalance between the process of myelination and the formation of the lamina cribrosa. Good results have been reported with amblyopic therapy; however, it is our experience that these patients are somewhat refractory to amblyopia therapy.

Amblyopia↗
PubMed1998

Indiana Youth Access Project: a model for responding to the HIV risk behaviors of gay, lesbian, and bisexual youth in the heartland.

The Indiana Youth Access Project (IYAP) is supported by the Special Projects of National Significance Program, Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) Bureau, Health Resources and Services Administration. The IYAP is a model HIV care program being developed at the Indiana Youth Group, Inc. (IYG) in conjunction with the Indiana State Department of Health and Indiana University. Previous studies indicate that gay, lesbian, and bisexual youth are at increased risk of acquiring HIV because of the stigmatization and social marginalization they experience as a result of their sexual identities. During the course of the first 3 years of the demonstration, the program has served 418 young people, including nine who are HIV infected. The IYAP targets the special needs of this special population by confronting institutional barriers which limit these young people's access to HIV care services, assisting them in building stronger peer support networks, and providing them with professional case management and related services. The model builds upon the successful peer-support program established at IYG by incorporating a unique set of health, mental health, and social case-management services provided by trained professionals. In addition, the program incorporates an extensive peer-counselor training and outreach program which targets street youth and other at-risk young people. The program has provided education and training workshops on the special needs of gay, lesbian, and bisexual youth to thousands of health care, education, and social service professionals both in central Indiana and around the nation.

Acquired Immunodeficiency Syndrome↗