Christopher E Ormsby
Research interests
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InterestsInfectious Disease, Epidemiology of Infectious Diseases, HIV, AIDS
Publications
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1.46Impact points
Head and Neck Manifestations of the Immune Reconstitution Syndrome in HIV-Infected Patients: A Cohort Study.
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 02/2012;
Objective. To describe head and neck manifestations of immune reconstitution inflammatory syndrome (IRIS) in a cohort of HIV-infected patients receiving combined antiretroviral therapy (cART). After initiation of cART, some HIV-infected patients present a paradoxical worsening and clinical deteriora... [more] Objective. To describe head and neck manifestations of immune reconstitution inflammatory syndrome (IRIS) in a cohort of HIV-infected patients receiving combined antiretroviral therapy (cART). After initiation of cART, some HIV-infected patients present a paradoxical worsening and clinical deterioration due to pathological inflammatory reactions to infectious or noninfectious antigens, a condition known as IRIS.Study Design. Prospective study with a follow-up period of 6 to 24 months.Setting. Tertiary referral center in Mexico City.Methods. Our cohort was integrated by 165 patients who had started cART within the past 2 months prior to study entry. Patients underwent a complete ear, nose, and throat examination (ENT). Laboratory tests (hematology and blood chemistry), cultures from body fluids, and biopsies were performed.Results. Of the 165 patients studied, 21 (12.7%) presented IRIS in the head and neck region. Kaposi sarcoma was the most common presentation, observed in 7 patients. Tuberculosis-associated IRIS was observed in 6 patients with scrophulas, lymph node enlargement, or retropharyngeal abscess. Other manifestations included herpes simplex I infection and unilateral vocal fold palsy secondary to Mycobacterium avium intracelulare paratracheal abscess and scrophulas, as well as cervical lymph node histoplasmosis and facial palsy.Conclusions. To our knowledge, this is the first prospective study describing the different manifestations of IRIS in the head and neck region.
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Palatal Actinomycosis and Kaposi Sarcoma in an HIV-Infected Subject with Disseminated Mycobacterium avium-intracellulare Infection.
Case reports in medicine. 01/2012; 2012:679728.
Actinomyces and Mycobacterium avium-intracellulare are facultative intracellular organisms, members of the bacterial order actinomycetales. Although Actinomyces can behave as copathogen when anatomic barriers are compromised, its coinfection with Mycobacterium avium-intracellulare has not previously... [more] Actinomyces and Mycobacterium avium-intracellulare are facultative intracellular organisms, members of the bacterial order actinomycetales. Although Actinomyces can behave as copathogen when anatomic barriers are compromised, its coinfection with Mycobacterium avium-intracellulare has not previously been reported. We present the first reported case of palatal actinomycosis co-infection with disseminated MAC, in an HIV-infected subject with Kaposi sarcoma and diabetes. We discuss the pathogenesis of the complex condition of this subject.
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5.15Impact points
Strong human endogenous retrovirus-specific T cell responses are associated with control of HIV-1 in chronic infection.
Journal of virology. 07/2011; 85(14):6977-85.
Eight percent of the human genome is composed of human endogenous retroviruses (HERVs), which are thought to be inactive remnants of ancient infections. Previously, we showed that individuals with early HIV-1 infection have stronger anti-HERV T cell responses than uninfected controls. In this study,... [more] Eight percent of the human genome is composed of human endogenous retroviruses (HERVs), which are thought to be inactive remnants of ancient infections. Previously, we showed that individuals with early HIV-1 infection have stronger anti-HERV T cell responses than uninfected controls. In this study, we investigated whether these responses persist in chronic HIV-1 infection and whether they have a role in the control of HIV-1. Peripheral blood mononuclear cells (PBMCs) from 88 subjects diagnosed with HIV-1 infection for at least 1 year (median duration of diagnosis, 13 years) were tested for responses against HERV peptides in gamma interferon (IFN-γ) enzyme immunospot (ELISPOT) assays. Individuals who control HIV-1 viremia without highly active antiretroviral therapy (HAART) had stronger and broader HERV-specific T cell responses than HAART-suppressed patients, virologic noncontrollers, immunologic progressors, and uninfected controls (P < 0.05 for each pairwise comparison). In addition, the magnitude of the anti-HERV T cell response was inversely correlated with HIV-1 viral load (r(2) = 0.197, P = 0.0002) and associated with higher CD4(+) T cell counts (r(2) = 0.072, P = 0.027) in untreated patients. Flow cytometric analyses of an HLA-B51-restricted CD8(+) HERV response in one HIV-1-infected individual revealed a less activated and more differentiated phenotype than that stimulated by a homologous HIV-1 peptide. HLA-B51 tetramer dual staining within this individual confirmed two different T cell populations corresponding to these HERV and HIV-1 epitopes, ruling out cross-reactivity. These findings suggest a possible role for anti-HERV immunity in the control of chronic HIV-1 infection and provide support for a larger effort to design an HIV-1 vaccine that targets conserved antigens such as HERV.
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4.91Impact points
Severe 2009 pandemic influenza A (H1N1) infection and increased mortality in patients with late and advanced HIV disease.
AIDS (London, England). 02/2011; 25(4):435-9.
To describe the clinical course of infection by 2009 (H1N1) influenza virus in different stages of HIV disease. Prospective, observational study. During the pandemic period, HIV-infected patients presenting respiratory symptoms at a third level referral hospital in Mexico City were tested for 2009 i... [more] To describe the clinical course of infection by 2009 (H1N1) influenza virus in different stages of HIV disease. Prospective, observational study. During the pandemic period, HIV-infected patients presenting respiratory symptoms at a third level referral hospital in Mexico City were tested for 2009 influenza A (H1N1) viral RNA. Clinical files were prospectively analyzed. Infection by H1N1 was confirmed in 30 (23.8%) of the total 126 HIV-infected patients studied. In the group of patients with 2009 H1N1 virus infection, 16 (53.3%) were hospitalized, 12 (40%) had active opportunistic infections and six (20%) died. In the group of 96 patients not infected with 2009 H1N1 virus, 54 (56.25%) were hospitalized with opportunistic infections and 12 (12.5%) died. For all hospitalized patients, being on HAART and having undetectable HIV viral loads at hospitalization was associated with higher survival (P = 0.019). Patients with 2009 H1N1 virus infection had a higher mortality rate, even after adjusting for HAART (P = 0.043). Coinfection by HIV and H1N1 2009 virus was more severe in patients with opportunistic infections, as shown by longer hospital stays (P = 0.0013), higher rates of hospitalization (P < 0.0001), use of mechanical ventilation (P = 0.0086) and death (P = 0.026). Delayed administration of oseltamivir in hospitalized patients was significantly associated with mortality (P = 0.0022). Our data suggest that infection by 2009 H1N1 is more severe in HIV-infected patients with late and advanced HIV disease than in well controlled patients under HAART.
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9.32Impact points
A 2-year-old girl positive for 2009 AH1N1 pandemic influenza.
Annals of neurology. 01/2011; 69(1):217; author reply 217-8.
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4.41Impact points
National prevalence and trends of HIV transmitted drug resistance in Mexico.
PloS one. 01/2011; 6(11):e27812.
Transmitted drug resistance (TDR) remains an important concern for the management of HIV infection, especially in countries that have recently scaled-up antiretroviral treatment (ART) access. We designed a study to assess HIV diversity and transmitted drug resistance (TDR) prevalence and trends in M... [more] Transmitted drug resistance (TDR) remains an important concern for the management of HIV infection, especially in countries that have recently scaled-up antiretroviral treatment (ART) access. We designed a study to assess HIV diversity and transmitted drug resistance (TDR) prevalence and trends in Mexico. 1655 ART-naïve patients from 12 Mexican states were enrolled from 2005 to 2010. TDR was assessed from plasma HIV pol sequences using Stanford scores and the WHO TDR surveillance mutation list. TDR prevalence fluctuations over back-projected dates of infection were tested. HIV subtype B was highly prevalent in Mexico (99.9%). TDR prevalence (Stanford score>15) in the country for the study period was 7.4% (95% CI, 6.2∶8.8) and 6.8% (95% CI, 5.7∶8.2) based on the WHO TDR surveillance mutation list. NRTI TDR was the highest (4.2%), followed by NNRTI (2.5%) and PI (1.7%) TDR. Increasing trends for NNRTI (p = 0.0456) and PI (p = 0.0061) major TDR mutations were observed at the national level. Clustering of viruses containing minor TDR mutations was observed with some apparent transmission pairs and geographical effects. TDR prevalence in Mexico remains at the intermediate level and is slightly lower than that observed in industrialized countries. Whether regional variations in TDR trends are associated with differences in antiretroviral drug usage/ART efficacy or with local features of viral evolution remains to be further addressed.
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4.21Impact points
Dissociation of CD154 and cytokine expression patterns in CD38+ CD4+ memory T cells in chronic HIV-1 infection.
Journal of acquired immune deficiency syndromes (1999). 10/2010; 55(4):439-45.
Expression of the activation antigen CD38 on T cells is a strong predictor of the risk of HIV disease progression, but it is not known whether CD38 is a marker or mediator of dysfunction. We examined the relationship between CD38 expression and responses to T-cell receptor stimulation in central mem... [more] Expression of the activation antigen CD38 on T cells is a strong predictor of the risk of HIV disease progression, but it is not known whether CD38 is a marker or mediator of dysfunction. We examined the relationship between CD38 expression and responses to T-cell receptor stimulation in central memory and effector memory CD4 T cells in HIV-infected persons and in healthy controls. Basal CD38 expression was preserved by blocking golgi transport with brefeldin A. Intracellular expression of interleukin 2, interferon γ, and CD154 was measured after stimulating peripheral blood mononuclear cells with the superantigen staphylococcal enterotoxin B with or without anti-CD28 costimulation. Interferon-γ responses were comparable or increased in stimulated CD38 memory cells, and the interleukin 2 responses of costimulated CD38 central memory cells were decreased in HIV infection. In CD38 cells and especially in CD38 cells of HIV-infected persons, stimulated memory cells more often failed to express CD154 (CD40 ligand) when induced to express cytokine. A dissociated cytokine and CD154 expression by memory CD4 T cells may impair interactions between T cells and antigen-presenting cells, contribute to impaired immunity and help explain the relationship between CD38 expression and disease progression in chronic HIV infection.
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1.05Impact points
Risk factors for immune reconstitution inflammatory syndrome under combination antiretroviral therapy can be aetiology-specific.
International journal of STD & AIDS. 08/2010; 21(8):573-9.
In order to discriminate general from aetiology-specific risk factors for immune reconstitution inflammatory syndrome (IRIS), we followed up, during six months, 99 patients with advanced HIV infection commencing antiretroviral therapy (ART) without active opportunistic infections or evident inflamma... [more] In order to discriminate general from aetiology-specific risk factors for immune reconstitution inflammatory syndrome (IRIS), we followed up, during six months, 99 patients with advanced HIV infection commencing antiretroviral therapy (ART) without active opportunistic infections or evident inflammation. IRIS predictors were determined by univariate analysis using clinical data from 76 ART-responding patients either completing follow-up or developing IRIS, and by multivariate analysis of inflammation, disease progression and nutrition status variables. We identified 23 primary IRIS events (30.3%). Univariate predictors for all IRIS events were higher platelet counts and lower CD4/CD8 ratio, whereas subclinical inflammation was the multivariate predictor. Platelets, alkaline phosphatase levels and %CD8 T-cells in univariate analysis also predicted mycobacteria-associated IRIS independently, remaining elevated during follow-up. Herpesvirus IRIS was predicted by platelets and inflammation. Indicators of advanced HIV disease and subclinical inflammation jointly predict IRIS, and some are specific of the underlying microbial aetiology, possibly explaining previous reports.
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[Differing response to GnRH antagonists in cycles of ovarian hyperstimulation plus intrauterine insemination].
Ginecología y obstetricia de México. 01/2010; 78(1):15-28.
To compare two flexible protocols of GnRHant in OH plus IUI vs a control group without GnRHant. Randomized controlled trial 90 infertile patients were analyzed in 116 cycles of IUI. Cycles were randomized in 3 groups; group 1: started GnRHant when the leading follicle reached 14mm, group 2: when it ... [more] To compare two flexible protocols of GnRHant in OH plus IUI vs a control group without GnRHant. Randomized controlled trial 90 infertile patients were analyzed in 116 cycles of IUI. Cycles were randomized in 3 groups; group 1: started GnRHant when the leading follicle reached 14mm, group 2: when it reached 16mm and group 3: without GnRHant hormonal determinations were done during OH. Main outcomes were: premature LH raise incidence, premature luteinization (PL) and pregnancy rate per cycle. Premature LH rise incidence was 2.6% (3 cycles) and PL 6% (7 cycles). Group 1 didn't present cycles with LH rise or PL, groups 2 and 3 presented LH rise in 3.1% and 1.8% and PL in 12.5% and 5.4% respectively. Pregnancy rate with GnRHant was 16.4% (95% IC 8.1-28.1) vs. 7.2% (95% le 2.0-17.5%) without GnRHant (group 3) (p = 0.16): groups 1 and 2 represented a pregnancy rate of 20.6% (95% IC 7.9-39.7) and 12.5% (95% IC 3.5-28.9%) respectively (p = 0.49). Mature follicles number reached meaning difference between all groups (p = 0.04) specially between groups 1 and 2 (p = 0.02). A trend to elevate pregnancy rates was observed with GnRHant specially with when it was started when leading follicle reached 14 mm (p > 0.05). Starting GnRHant with 16 mm was not totally usefully to prevent PL.
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29.75Impact points
Influenza: making privileged data public.
Science (New York, N.Y.). 09/2009; 325(5944):1072; author reply 1072-3.
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47.05Impact points
Pneumonia and Respiratory Failure from Swine-Origin Influenza A (H1N1) in Mexico.
The New England journal of medicine. 07/2009;
BACKGROUND: In late March 2009, an outbreak of a respiratory illness later proved to be caused by novel swine-origin influenza A (H1N1) virus (S-OIV) was identified in Mexico. We describe the clinical and epidemiologic characteristics of persons hospitalized for pneumonia at the national tertiary ho... [more] BACKGROUND: In late March 2009, an outbreak of a respiratory illness later proved to be caused by novel swine-origin influenza A (H1N1) virus (S-OIV) was identified in Mexico. We describe the clinical and epidemiologic characteristics of persons hospitalized for pneumonia at the national tertiary hospital for respiratory illnesses in Mexico City who had laboratory-confirmed S-OIV infection, also known as swine flu. METHODS: We used retrospective medical chart reviews to collect data on the hospitalized patients. S-OIV infection was confirmed in specimens with the use of a real-time reverse-transcriptase-polymerase-chain-reaction assay. RESULTS: From March 24 through April 24, 2009, a total of 18 cases of pneumonia and confirmed S-OIV infection were identified among 98 patients hospitalized for acute respiratory illness at the National Institute of Respiratory Diseases in Mexico City. More than half of the 18 case patients were between 13 and 47 years of age, and only 8 had preexisting medical conditions. For 16 of the 18 patients, this was the first hospitalization for their illness; the other 2 patients were referred from other hospitals. All patients had fever, cough, dyspnea or respiratory distress, increased serum lactate dehydrogenase levels, and bilateral patchy pneumonia. Other common findings were an increased creatine kinase level (in 62% of patients) and lymphopenia (in 61%). Twelve patients required mechanical ventilation, and seven died. Within 7 days after contact with the initial case patients, a mild or moderate influenza-like illness developed in 22 health care workers; they were treated with oseltamivir, and none were hospitalized. CONCLUSIONS: S-OIV infection can cause severe illness, the acute respiratory distress syndrome, and death in previously healthy persons who are young to middle-aged. None of the secondary infections among health care workers were severe. Copyright 2009 Massachusetts Medical Society.
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Endoscopic assessment of adenoid size is an indicator of tissue virologic response to highly active antiretroviral therapy.
Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale. 05/2009; 38(2):255-60.
OBJECTIVE: To compare human immunodeficiency virus viral load (HIVVL) in plasma versus the adenoid HIVVL during highly active antiretroviral therapy (HAART). DESIGN: Adenoid biopsies were taken basally and after 3 and 6 months of treatment. Also, the adenoid diameter by simple endoscopy was measured... [more] OBJECTIVE: To compare human immunodeficiency virus viral load (HIVVL) in plasma versus the adenoid HIVVL during highly active antiretroviral therapy (HAART). DESIGN: Adenoid biopsies were taken basally and after 3 and 6 months of treatment. Also, the adenoid diameter by simple endoscopy was measured, and its correlation with adenoid HIVVL was calculated. SETTING AND PATIENTS: A public tertiary care human immunodeficiency virus (HIV) hospital research centre. Twenty-seven antiretroviral-naive HIV-infected patients, with a mean age of 34.7 years, were included in the study. MAIN OUTCOME MEASURE: Correlation between adenoid diameter and plasma and tissue HIVVL. RESULTS: At 3 months, although plasma HIVVL reduced by almost 5 log to a level below 1 log, adenoid HIVVL only decreased 2.36 log, remaining well over 4 log. At 6 months, plasma HIVVL further decreased to 0.205 log, but adenoid HIVVL remained at 2.424 log. Adenoid diameter also decreased over time, with means at 8.52, 5.61, and 4 mm, respectively. It significantly correlated with plasma and adenoid viral load, but the correlation was higher with the biopsies. CONCLUSION: HIVVL in adenoid tissue is more resilient to HAART than plasma VL and may need more than 6 months to reach asymptomatic levels. Nevertheless, simple endoscopic measurement of the adenoid diameter is a good indicator of viral load decrease in this tissue.
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1.05Impact points
Identification of oral candidosis, hairy leukoplakia and recurrent oral ulcers as distinct cases of immune reconstitution inflammatory syndrome.
International journal of STD & AIDS. 05/2009; 20(4):259-61.
Oral lesions such as candidosis, hairy leukoplakia (HL) and oral ulcers are strikingly absent in the numerous reports of immune reconstitution inflammatory syndrome (IRIS). To document oral manifestations attributable to immune reconstitution, we conducted a longitudinal follow-up of a cohort of HIV... [more] Oral lesions such as candidosis, hairy leukoplakia (HL) and oral ulcers are strikingly absent in the numerous reports of immune reconstitution inflammatory syndrome (IRIS). To document oral manifestations attributable to immune reconstitution, we conducted a longitudinal follow-up of a cohort of HIV+ individuals starting highly active antiretroviral therapy (HAART) and completing oral pathology follow-up up to 12 weeks after treatment initiation. HIV-infected patients had oral examinations, CD4+ T-cell count and viral load determinations performed at baseline, and at weeks 4, 8 and 12 after HAART initiation. Among individuals with satisfactory viral response and recovery of >/=50 CD4+ T-cell/microL, eight patients complied with strict IRIS criteria: two developed clinical signs of oral candidosis (OC), two oral ulcers, three HL and one Kaposi's sarcoma. CD4+ T-cell counts at symptom onset suggested no remaining immune suppression. Our findings show that cases of OC, HL and recurrent ulcers can be instances of IRIS.
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2.88Impact points
Later onset of herpes zoster-associated immune reconstitution inflammatory syndrome.
HIV medicine. 04/2009;
Objectives The aim of the study was to determine whether immune reconstitution inflammatory syndrome (IRIS) associated with herpes zoster occurs on a different time frame from other instances of IRIS. Methods Statistical analysis of onset times of herpes zoster-associated IRIS and other cases of IRI... [more] Objectives The aim of the study was to determine whether immune reconstitution inflammatory syndrome (IRIS) associated with herpes zoster occurs on a different time frame from other instances of IRIS. Methods Statistical analysis of onset times of herpes zoster-associated IRIS and other cases of IRIS was carried out in a retrospective cohort starting antiretroviral therapy at advanced stages of HIV infection. Results Herpes zoster-associated IRIS was significantly more frequent after the first 3 months of successful highly active antiretroviral therapy (HAART), than other instances of IRIS (IRIS associated with tuberculosis, Mycobacterium avium complex, Kaposi's sarcoma, etc.) which mainly occurred during the first 3 months of treatment. Conclusions The characteristic onset time pattern of herpes zoster-associated IRIS, coincident with the second phase of immune recovery under HAART, suggests that the immune recovery events underlying herpes zoster-associated IRIS are different from those underlying other types of IRIS. Our findings may be useful in improving the follow-up of individuals who start HAART at an advanced stage of HIV infection.
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4.11Impact points
APOBEC3G mRNA expression in exposed seronegative and early stage HIV infected individuals decreases with removal of exposure and with disease progression.
Retrovirology. 02/2009; 6:23.
BACKGROUND: APOBEC3G is an antiretroviral factor that acts by inducing G to A mutations. In this study, we examined the expression of APOBEC3G in uninfected HIV-1 exposed individuals at the time of their partner's diagnosis and one year later. We then compared this expression with that of infect... [more] BACKGROUND: APOBEC3G is an antiretroviral factor that acts by inducing G to A mutations. In this study, we examined the expression of APOBEC3G in uninfected HIV-1 exposed individuals at the time of their partner's diagnosis and one year later. We then compared this expression with that of infected individuals at different disease stages. APOBEC3G mRNA was measured in PBMCs from three groups: healthy controls with no known risk factor to HIV infection (n = 26), exposed uninfected individuals who had unprotected sex with their HIV+ partners for at least 3 months (n = 37), and HIV infected patients at various disease stages (n = 45), including 8 patients with low HIV viral loads < 10,000 copies/mL (LVL) for at least 3 years. Additionally, we obtained sequences from the env, gag, pol, nef, vif and the LTR of the patients' virus. RESULTS: Exposed uninfected individuals expressed higher APOBEC3G than healthy controls (3.86 vs. 1.69 relative expression units), and their expression significantly decreased after a year from the HIV diagnosis and subsequent treatment of their partners. Infected individuals showed a positive correlation (Rho = 0.57, p = 0.00006) of APOBEC3G expression with CD4+ T cell count, and a negative correlation with HIV viremia (Rho = -0.54, p = 0.00004). The percentage of G to A mutations had a positive correlation (Rho = 0.43, p = 0.0226) with APOBEC3G expression, and it was higher in LVL individuals than in the other patients (IQR 8.27 to 9.64 vs. 7.06 to 8.1, p = 0.0084). Out of 8 LVLs, 3 had hypermutations, and 4 had premature stop codons only in viral vif. CONCLUSION: The results suggest that exposure to HIV may trigger APOBEC3G expression in PBMCs, in the absence of infection. Additionally, cessation of exposure or advanced disease is associated with decreased APOBEC3G expression.
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APOBEC3G mRNA expression in exposed seronegative and early stage HIV infected individuals decreases with removal of exposure and with disease progression
Retrovirology. 01/2009;
Abstract Background APOBEC3G is an antiretroviral factor that acts by inducing G to A mutations. In this study, we examined the expression of APOBEC3G in uninfected HIV-1 exposed individuals at the time of their partner's diagnosis and one year later. We then compared this expression with that... [more] Abstract Background APOBEC3G is an antiretroviral factor that acts by inducing G to A mutations. In this study, we examined the expression of APOBEC3G in uninfected HIV-1 exposed individuals at the time of their partner's diagnosis and one year later. We then compared this expression with that of infected individuals at different disease stages. APOBEC3G mRNA was measured in PBMCs from three groups: healthy controls with no known risk factor to HIV infection (n = 26), exposed uninfected individuals who had unprotected sex with their HIV+ partners for at least 3 months (n = 37), and HIV infected patients at various disease stages (n = 45), including 8 patients with low HIV viral loads < 10,000 copies/mL (LVL) for at least 3 years. Additionally, we obtained sequences from the env, gag, pol, nef, vif and the LTR of the patients' virus. Results Exposed uninfected individuals expressed higher APOBEC3G than healthy controls (3.86 vs. 1.69 relative expression units), and their expression significantly decreased after a year from the HIV diagnosis and subsequent treatment of their partners. Infected individuals showed a positive correlation (Rho = 0.57, p = 0.00006) of APOBEC3G expression with CD4+ T cell count, and a negative correlation with HIV viremia (Rho = -0.54, p = 0.00004). The percentage of G to A mutations had a positive correlation (Rho = 0.43, p = 0.0226) with APOBEC3G expression, and it was higher in LVL individuals than in the other patients (IQR 8.27 to 9.64 vs. 7.06 to 8.1, p = 0.0084). Out of 8 LVLs, 3 had hypermutations, and 4 had premature stop codons only in viral vif . Conclusion The results suggest that exposure to HIV may trigger APOBEC3G expression in PBMCs, in the absence of infection. Additionally, cessation of exposure or advanced disease is associated with decreased APOBEC3G expression.
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4.91Impact points
Life-threatening exacerbation of Kaposi's sarcoma after prednisone treatment for immune reconstitution inflammatory syndrome.
AIDS (London, England). 04/2008; 22(5):663-5.
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3.58Impact points
Unexpected immunoresponse to Gal and APA antigens in diabetic type 1 patients receiving neonatal pig islets after 6 years.
Journal of clinical immunology. 06/2007; 27(3):266-74.
Cotransplantation of porcine islets and Sertoli cells into preimplanted subcutaneous devices improve metabolic control in type 1 diabetic patients, and survive grafted for more than 4 years. We report here, further assessment of the endocrine and porcine nature of the surviving cells and the immune ... [more] Cotransplantation of porcine islets and Sertoli cells into preimplanted subcutaneous devices improve metabolic control in type 1 diabetic patients, and survive grafted for more than 4 years. We report here, further assessment of the endocrine and porcine nature of the surviving cells and the immune responses elicited toward Gal alpha(1,3)-Gal beta(1,4)-GlcNAc (Gal) antigen in patients who received a second and third transplants. No immunosuppressive drugs were administered. We were able to immunostain insulin- and glucagon-positive cells in all biopsies of patients and Sertoli cell markers in 60.9% of biopsies. Additionally, all biopsies tested, amplified the porcine COII gene. Patients demonstrated an increase in antipig antibodies in response to the first transplant with a decreasing response toward the second and third transplants. In all transplants, the IgG levels promptly returned to basal values after 3-4 months. The long-term survival of porcine cells and the reduced humoral immune response to multiple transplants indicate a form of tolerance. We have not been able to find CD25-positive cells, indicating that it is probably an immune accommodation of the graft.
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2.71Impact points
Method for evaluating quality of cultured neonatal pig Sertoli cells.
Xenotransplantation. 08/2005; 12(4):316-23.
BACKGROUND: Sertoli cells (SC) in the testis secrete factors that nourish and immunoprotect developing spermatozoa, which have made them the focus of studies that aim to generate localized tolerance, particularly for transplantation and perhaps autoimmunity. Several methods have been described to is... [more] BACKGROUND: Sertoli cells (SC) in the testis secrete factors that nourish and immunoprotect developing spermatozoa, which have made them the focus of studies that aim to generate localized tolerance, particularly for transplantation and perhaps autoimmunity. Several methods have been described to isolate these cells, which include a two-step enzymatic digestion with limited assessment of the culture. Here we describe a one-step method, and a series of tests for determining purity, viability, and function of the cultured cells. METHODS: We isolated SC from neonatal pigs using Liberase HI digestion. Viability and apoptosis of cultured cells were measured by flow cytometry with propidium iodide and annexin, respectively. Specific identification of the Sertoli type was made by immunodetection of Sox9, vimentin, and Mullerian inhibiting substance. Moreover, for functionality we were able to detect clusterin in the cultured cells by Western blot. RESULTS: Our isolation method had a yield and purity similar to previous reports measured with two-step methods. Viability was 95.22 +/- 0.57% and apoptotic cells were 10.5 +/- 0.32% after 48 h in culture. At 7 days, practically all cells expressed Sox9, Mullerian inhibiting substance, clusterin, and vimentin. CONCLUSIONS: We describe an alternative strategy for preparing and identifying cultured SC for further assays of metabolic activity or in transplantation models. Establishing a one-step Liberase-digestion method for isolation, evaluating viability and apoptosis by more sensitive methods, and detecting specific markers in culture can help to evaluate the quality of cultured cells. Specific cell markers for identifying SC may be critical when identifying SC outside the testis, in contrast with vimentin which is useful only for in situ cells.
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2.71Impact points
Improved method for isolation of porcine neonatal pancreatic cell clusters.
Xenotransplantation. 05/2005; 12(3):240-4.
Based on the described methods for the isolation of neonatal pancreatic cell clusters (NPCCs), we have developed modifications in order to improve their quality, functionality, and process reproducibility in the isolation technique, for potential use in research. In addition, we indicate techniques ... [more] Based on the described methods for the isolation of neonatal pancreatic cell clusters (NPCCs), we have developed modifications in order to improve their quality, functionality, and process reproducibility in the isolation technique, for potential use in research. In addition, we indicate techniques for describing yield, functionality, viability and purity of the NPCCs. METHODS: Purity of the NPCCs was determined through dithizone staining and subjected to image analysis. Viability and apoptosis was measured through flow cytometry with propidium iodide and annexin, respectively. NPCC functionality was measured through a static glucose stimulation test. RESULTS: We developed a high-yield reproducible technique that had 81 279.55 +/- 18 257.05 IEQ/g of pancreas at 4 days of culture, with a 94% viability and an 88 +/- 2.73% purity. Stimulation index from the glucose stimulation test was >10. CONCLUSION: The technique allowed us to obtain NPCC with optimal viability, functionality, purity, and endurance for use in research.
Following (6)
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Joaquin Zuñiga
Instituto Nacional de Enfermedades Respiratorias -
Enrique Espinosa
Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico -
Esmeralda Juarez
Instituto Nacional de Enfermedades Respiratorias -
Scott F Sieg
Case Western Reserve University -
Klintsy Torres
Heinrich-Heine-Universität Düsseldorf
