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1.
Ochsner J ; 17(3): 292-295, 2017.
Article in English | MEDLINE | ID: mdl-29026366

ABSTRACT

BACKGROUND: Trigeminal trophic syndrome (TTS) is an uncommon disorder of the trigeminal nerve tract and trigeminal brainstem nucleus. The syndrome is characterized by a triad of unilateral crescentic ulcers with anesthesia and paresthesias of the involved trigeminal dermatomes. CASE REPORT: A 24-year-old right-handed black female presented to our emergency department with a 4-week history of rapidly progressive painless desquamation/denudation of skin over her right face and scalp. Four weeks prior, she had been admitted to another institution for seizures and was diagnosed with seizures provoked by synthetic marijuana use. She was afebrile during her initial presentation at our institution. Dermatologic examination revealed denudation of the epidermis and partial dermis over the right frontal, parietal, and temporal scalp with associated alopecia. CONCLUSION: To our knowledge, the association of disorders of the trigeminal nerve pathway, including TTS, with the use of synthetic marijuana has not been previously reported. The long-term neurologic effects of synthetic marijuana are difficult to predict, and the pathologic underpinnings of TTS are largely unknown. Further studies dedicated to exploring the underlying molecular and cellular mechanisms may translate into effective therapies and approaches to halt and reverse the process and prevent tissue destruction and cosmetic disfigurement.

2.
Dermatol Online J ; 20(6)2014 Jun 15.
Article in English | MEDLINE | ID: mdl-24945647

ABSTRACT

We report an uncommon case of a cutaneous infection with Mycobacterium fortuitum arising in a new tattoo. A 29-year-old man presented with a several month history of a non-pruritic papular eruption within a tattoo; the papules developed 1-to-2 weeks after the tattoo procedure. He denied similar symptoms with previous tattoos. He had been treated unsuccessfully with cephalexin. Histopathologic examination revealed perifollicular chronic and granulomatous inflammation, consistent with chronic folliculitis. Acid-fast bacilli culture identified Mycobacterium fortuitum complex. The patient was treated with a 2-month course of oral trimethoprim-sulfamethoxazole (160mg/800mg twice daily) and ciprofloxacin (250 mg twice daily), with clinical improvement at follow up after three weeks of the antibiotic regimen. Rapidly growing mycobacteria have emerged as a cause of tattoo-associated cutaneous infection in recent years. Diagnosis and treatment can be difficult without clinical suspicion. M. fortuitum and other rapidly growing mycobacteria should be considered in the differential diagnosis of tattoo-associated dermatologic complications.


Subject(s)
Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium Infections, Nontuberculous/pathology , Mycobacterium fortuitum/isolation & purification , Tattooing/adverse effects , Adult , Anti-Bacterial Agents/therapeutic use , Cephalexin/therapeutic use , Ciprofloxacin/therapeutic use , Clarithromycin/therapeutic use , Cosmetic Techniques , Drug Therapy, Combination , Humans , Male , Mycobacterium Infections, Nontuberculous/drug therapy , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use
3.
Dermatol Surg ; 36(10): 1529-36, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20698870

ABSTRACT

BACKGROUND: Reported infection rates for Mohs micrographic surgery (MMS) range from less than 1% to 3.5%. OBJECTIVE: To determine whether lower infection rates are possible for MMS with a consistently applied infection-control regimen. METHODS: A series of 832 consecutive patients with 950 tumors undergoing MMS formed the cohort for a retrospective study of infections before and after a program of heightened infection-control practices at a single-surgeon academic Mohs practice. The sterility upgrade included jewelry restrictions, alcohol hand scrub before stages and reconstruction, sterile gloves and (during reconstruction) sterile gowns for staff, and sterile towels and dressings for patients during Mohs stages. RESULTS: Infection rate was 2.5% (9 infections/365 tumors) before the sterility upgrade and 0.9% (5 infections/585 tumors) after, a statistically significant difference (p=.04). CONCLUSION: MMS already has low rates of infection, but this study shows that rigorous infection-control practices can significantly affect infection rates. The authors have indicated no significant interest with commercial supporters.


Subject(s)
Infection Control/methods , Infection Control/statistics & numerical data , Mohs Surgery/statistics & numerical data , Neoplasms/surgery , Surgical Wound Infection/epidemiology , Surgical Wound Infection/prevention & control , Antibiotic Prophylaxis/statistics & numerical data , Cohort Studies , Female , Health Care Costs , Humans , Incidence , Infection Control/economics , Male , Middle Aged , Mohs Surgery/adverse effects , Neoplasms/classification , Retrospective Studies , Risk Assessment , Sterilization/methods , Sterilization/statistics & numerical data , Surgical Wound Infection/etiology , United States/epidemiology
6.
Nat Rev Microbiol ; 7(5): 393-400, 2009 May.
Article in English | MEDLINE | ID: mdl-19369954

ABSTRACT

Ebola virus infection is a highly lethal disease for which there are no effective therapeutic or preventive treatments. Several vaccines have provided immune protection in laboratory animals, but because outbreaks occur unpredictably and sporadically, vaccine efficacy cannot be proven in human trials, which is required for traditional regulatory approval. The Food and Drug Administration has introduced the 'animal rule', to allow laboratory animal data to be used to show efficacy when human trials are not logistically feasible. In this Review, we describe immune correlates of vaccine protection against Ebola virus in animals. This research provides a basis for bridging the gap from basic research to human vaccine responses in support of the licensing of vaccines through the animal rule.


Subject(s)
Ebola Vaccines/immunology , Hemorrhagic Fever, Ebola/immunology , Animals , Hemorrhagic Fever, Ebola/prevention & control , Hemorrhagic Fever, Ebola/virology , Humans , United States , United States Food and Drug Administration/legislation & jurisprudence
8.
Vaccine ; 26(50): 6338-43, 2008 Nov 25.
Article in English | MEDLINE | ID: mdl-18824060

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome (SARS) virus is a member of the Coronaviridae (CoV) family that first appeared in the Guangdong Province of China in 2002 and was recognized as an emerging infectious disease in March 2003. Over 8000 cases and 900 deaths occurred during the epidemic. We report the safety and immunogenicity of a SARS DNA vaccine in a Phase I human study. METHODS: A single-plasmid DNA vaccine encoding the Spike (S) glycoprotein was evaluated in 10 healthy adults. Nine subjects completed the 3 dose vaccination schedule and were evaluated for vaccine safety and immune responses. Immune response was assessed by intracellular cytokine staining (ICS), ELISpot, ELISA, and neutralization assays. RESULTS: The vaccine was well tolerated. SARS-CoV-specific antibody was detected by ELISA in 8 of 10 subjects and neutralizing antibody was detected in all subjects who received 3 doses of vaccine. SARS-CoV-specific CD4+ T-cell responses were detected in all vaccinees, and CD8+ T-cell responses in approximately 20% of individuals. CONCLUSIONS: The VRC SARS DNA vaccine was well tolerated and produced cellular immune responses and neutralizing antibody in healthy adults.


Subject(s)
Antibodies, Viral/blood , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Severe Acute Respiratory Syndrome/prevention & control , Severe acute respiratory syndrome-related coronavirus/immunology , Vaccines, DNA , Viral Vaccines , Adolescent , Adult , Female , Humans , Male , Membrane Glycoproteins/genetics , Membrane Glycoproteins/immunology , Middle Aged , Neutralization Tests , Severe acute respiratory syndrome-related coronavirus/genetics , Severe Acute Respiratory Syndrome/immunology , Spike Glycoprotein, Coronavirus , Treatment Outcome , Vaccines, DNA/administration & dosage , Vaccines, DNA/genetics , Vaccines, DNA/immunology , Viral Envelope Proteins/genetics , Viral Envelope Proteins/immunology , Viral Vaccines/administration & dosage , Viral Vaccines/genetics , Viral Vaccines/immunology , Young Adult
9.
PLoS Pathog ; 4(5): e1000060, 2008 May 09.
Article in English | MEDLINE | ID: mdl-18464894

ABSTRACT

West Nile virions incorporate 180 envelope (E) proteins that orchestrate the process of virus entry and are the primary target of neutralizing antibodies. The E proteins of newly synthesized West Nile virus (WNV) are organized into trimeric spikes composed of pre-membrane (prM) and E protein heterodimers. During egress, immature virions undergo a protease-mediated cleavage of prM that results in a reorganization of E protein into the pseudo-icosahedral arrangement characteristic of mature virions. While cleavage of prM is a required step in the virus life cycle, complete maturation is not required for infectivity and infectious virions may be heterogeneous with respect to the extent of prM cleavage. In this study, we demonstrate that virion maturation impacts the sensitivity of WNV to antibody-mediated neutralization. Complete maturation results in a significant reduction in sensitivity to neutralization by antibodies specific for poorly accessible epitopes that comprise a major component of the human antibody response following WNV infection or vaccination. This reduction in neutralization sensitivity reflects a decrease in the accessibility of epitopes on virions to levels that fall below a threshold required for neutralization. Thus, in addition to a role in facilitating viral entry, changes in E protein arrangement associated with maturation modulate neutralization sensitivity and introduce an additional layer of complexity into humoral immunity against WNV.


Subject(s)
Antibodies, Viral/immunology , Viral Envelope Proteins/immunology , West Nile Fever/immunology , West Nile virus/immunology , Animals , Antibodies, Viral/metabolism , Cell Line , Chlorocebus aethiops , Clinical Trials, Phase I as Topic , Dose-Response Relationship, Immunologic , Humans , Neutralization Tests , Protein Binding , Protein Biosynthesis , Vero Cells , Viral Envelope Proteins/metabolism , Virion/immunology , Virion/metabolism , West Nile virus/growth & development
10.
Vaccine ; 25(20): 4085-92, 2007 May 16.
Article in English | MEDLINE | ID: mdl-17391815

ABSTRACT

Needle-free delivery of a six-plasmid HIV-1 DNA vaccine encoding EnvA, EnvB, EnvC, and subtype B Gag, Pol, and Nef underwent open-label evaluation in 15 subjects; 14 completed the 0, 1, 2 month vaccination schedule. T cell responses to HIV-specific peptide pools were detected by intracellular cytokine staining of CD4(+) [13/14 (93%)] and CD8(+) [5/14 (36%)], and by ELISpot in 11/14 (79%). Ten of 14 (71%) had ELISA antibody responses to Env proteins. Compared to a four-plasmid product, Gag- and Nef-specific T cell responses were improved, while Env-specific responses were maintained. This candidate vaccine has now advanced to Phase II evaluation.


Subject(s)
AIDS Vaccines/administration & dosage , HIV Infections/prevention & control , HIV-1/immunology , Vaccines, DNA/administration & dosage , AIDS Vaccines/adverse effects , AIDS Vaccines/genetics , AIDS Vaccines/immunology , Adolescent , Adult , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Female , Gene Products, env/immunology , Gene Products, gag/immunology , Gene Products, nef/immunology , HIV Antibodies/biosynthesis , HIV Antibodies/immunology , HIV Infections/immunology , HIV Infections/virology , HIV-1/genetics , Humans , Immunity, Cellular/immunology , Male , Plasmids/genetics , Plasmids/immunology , Vaccines, Combined/administration & dosage , Vaccines, Combined/adverse effects , Vaccines, Combined/genetics , Vaccines, Combined/immunology , Vaccines, DNA/adverse effects , Vaccines, DNA/genetics , Vaccines, DNA/immunology , nef Gene Products, Human Immunodeficiency Virus
11.
J Acquir Immune Defic Syndr ; 44(5): 601-5, 2007 Apr 15.
Article in English | MEDLINE | ID: mdl-17325604

ABSTRACT

OBJECTIVE: To evaluate the safety and immunogenicity of a candidate HIV DNA vaccine administered using a needle-free device. DESIGN: In this phase 1, dose escalation, double-blind, placebo-controlled clinical trial, 21 healthy adults were randomized to receive placebo or 0.5, 1.5, or 4 mg of a single plasmid expressing a Gag/Pol fusion protein. Each participant received repeat immunizations at days 28 and 56 after the first inoculation. Safety and immunogenicity data were collected. RESULTS: The vaccine was well tolerated, with most adverse events being mild injection site reactions, including pain, tenderness, and erythema. No dose-limiting toxicities occurred. HIV-specific antibody response was not detected in any vaccinee by enzyme-linked immunosorbent assay. HIV-specific T-cell responses to Gag or Pol as measured by enzyme-linked immunospot assay and intracellular cytokine staining were of low frequency and magnitude. CONCLUSIONS: This candidate HIV DNA vaccine was safe and well tolerated. No HIV-specific antibody responses were detected, and only low-magnitude HIV-specific T-cell responses were detected in 8 (53%) of 15 vaccinees. This initial product led to the development of a 4-plasmid multiclade HIV DNA Vaccine Research Center vaccine candidate in which envelope genes expressing Env from clades A, B, and C and a Nef gene from clade B have been added.


Subject(s)
AIDS Vaccines/administration & dosage , HIV Seronegativity/immunology , HIV-1/immunology , AIDS Vaccines/adverse effects , AIDS Vaccines/immunology , Adult , Double-Blind Method , Female , Genes, gag , Genes, pol , HIV Antibodies/biosynthesis , HIV Infections/immunology , HIV Infections/prevention & control , HIV-1/genetics , Humans , Immunity, Cellular , Male , Middle Aged , Safety , T-Lymphocytes/immunology , Vaccines, DNA/administration & dosage , Vaccines, DNA/adverse effects , Vaccines, DNA/immunology
12.
Virology ; 362(2): 314-9, 2007 Jun 05.
Article in English | MEDLINE | ID: mdl-17275872

ABSTRACT

CD8+ cytotoxic T lymphocytes are key effectors of adaptive immunity for the control of virus infections. Epitope-specific responses are hierarchical and the rules for dominance are not well defined. Here we show that the H2-Kd-restricted RSV M2(82-90) (KdM2(82-90)) epitope dominates the H2-Db-restricted RSV M187-195 (DbM187-195) epitope and influences epitope-specific effector function in the acute and memory phases of the immune response to primary RSV infection in H-2b/d hybrid mice. The hybrid mouse model provides a system to define rules of epitope hierarchy and better understand how antigen presentation and epitope competition affect the phenotype of effector and memory T cells.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Epitopes, T-Lymphocyte/immunology , Immunodominant Epitopes/immunology , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Viruses/immunology , Animals , Cell Line , Crosses, Genetic , Cytokines/immunology , Disease Models, Animal , Female , Humans , Hybridization, Genetic/immunology , Immunologic Memory , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Specific Pathogen-Free Organisms
13.
J Infect Dis ; 196(12): 1732-40, 2007 Dec 15.
Article in English | MEDLINE | ID: mdl-18190252

ABSTRACT

BACKGROUND: West Nile virus (WNV) is a mosquito-borne flavivirus that can cause severe meningitis and encephalitis in infected individuals. We report the safety and immunogenicity of a WNV DNA vaccine in its first phase 1 human study. METHODS: A single-plasmid DNA vaccine encoding the premembrane and the envelope glycoproteins of the NY99 strain of WNV was evaluated in an open-label study in 15 healthy adults. Twelve subjects completed the 3-dose vaccination schedule, and all subjects completed 32 weeks of evaluation for safety and immunogenicity. The development of a vaccine-induced immune response was assessed by enzyme-linked immunosorbant assay, neutralization assays, intracelluar cytokine staining, and enzyme-linked immunospot assay. RESULTS: The vaccine was safe and well tolerated, with no significant adverse events. Vaccine-induced T cell and antibody responses were detected in the majority of subjects. Neutralizing antibody to WNV was detected in all subjects who completed the 3-dose vaccination schedule, at levels shown to be protective in studies of horses, an incidental natural host for WNV. CONCLUSIONS: Further assessment of this DNA platform for human immunization against WNV is warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00106769 .


Subject(s)
Antibodies, Viral/biosynthesis , Vaccines, DNA/therapeutic use , West Nile Fever/prevention & control , West Nile Virus Vaccines/therapeutic use , West Nile virus/immunology , Adolescent , Adult , Antibodies, Viral/immunology , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Male , Middle Aged , T-Lymphocytes/immunology , Vaccines, DNA/genetics , Vaccines, DNA/immunology , Vaccines, DNA/virology , West Nile Fever/virology , West Nile Virus Vaccines/genetics , West Nile Virus Vaccines/immunology , West Nile virus/genetics
14.
J Infect Dis ; 194(12): 1638-49, 2006 Dec 15.
Article in English | MEDLINE | ID: mdl-17109335

ABSTRACT

BACKGROUND: The development of an effective human immunodeficiency virus (HIV) vaccine is a high global priority. Here, we report the safety, tolerability, and immunogenicity of a replication-defective recombinant adenovirus serotype 5 (rAd5) vector HIV-1 candidate vaccine. METHODS: The vaccine is a mixture of 4 rAd5 vectors that express HIV-1 subtype B Gag-Pol fusion protein and envelope (Env) from subtypes A, B, and C. Healthy, uninfected adults were randomized to receive 1 intramuscular injection of placebo (n=6) or vaccine at dose levels of 10(9) (n=10), 10(10) (n=10), or 10(11) (n=10) particle units and were followed for 24 weeks to assess immunogenicity and safety. RESULTS: The vaccine was well tolerated but was associated with more reactogenicity at the highest dose. At week 4, vaccine antigen-specific T cell responses were detected in 28 (93.3%) and 18 (60%) of 30 vaccine recipients for CD4(+) and CD8(+) T cells, respectively, by intracellular cytokine staining assay and in 22 (73%) of 30 vaccine recipients by enzyme-linked immunospot assay. Env-specific antibody responses were detected in 15 (50%) of 30 vaccine recipients by enzyme-linked immunosorbant assay and in 28 (93.3%) of 30 vaccine recipients by immunoprecipitation followed by Western blotting. No neutralizing antibody was detected. CONCLUSIONS: A single injection induced HIV-1 antigen-specific CD4(+) T cell, CD8(+) T cell, and antibody responses in the majority of vaccine recipients. This multiclade rAd5 HIV-1 vaccine is now being evaluated in combination with a multiclade HIV-1 DNA plasmid vaccine.


Subject(s)
AIDS Vaccines/adverse effects , AIDS Vaccines/immunology , Antibodies, Viral/blood , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , HIV Infections/immunology , HIV-1/immunology , Nausea/etiology , Vaccination , AIDS Vaccines/administration & dosage , Adenoviruses, Human/genetics , Adolescent , Adult , Antibody Specificity , Blotting, Western , Cytokines/analysis , Cytokines/biosynthesis , Dose-Response Relationship, Immunologic , Double-Blind Method , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Fusion Proteins, gag-pol/immunology , Gene Products, env/immunology , Genetic Vectors , Humans , Injections, Intramuscular , Male , Recombination, Genetic , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology , env Gene Products, Human Immunodeficiency Virus
15.
J Infect Dis ; 194(12): 1650-60, 2006 Dec 15.
Article in English | MEDLINE | ID: mdl-17109336

ABSTRACT

BACKGROUND: Gene-based vaccine delivery is an important strategy in the development of a preventive vaccine for acquired immunodeficiency syndrome (AIDS). Vaccine Research Center (VRC) 004 is the first phase 1 dose-escalation study of a multiclade HIV-1 DNA vaccine. METHODS: VRC-HIVDNA009-00-VP is a 4-plasmid mixture encoding subtype B Gag-Pol-Nef fusion protein and modified envelope (Env) constructs from subtypes A, B, and C. Fifty healthy, uninfected adults were randomized to receive either placebo (n=10) or study vaccine at 2 mg (n=5), 4 mg (n=20), or 8 mg (n=15) by needle-free intramuscular injection. Humoral responses (measured by enzyme-linked immunosorbant assay, Western blotting, and neutralization assay) and T cell responses (measured by enzyme-linked immunospot assay and intracellular cytokine staining after stimulation with antigen-specific peptide pools) were measured. RESULTS: The vaccine was well tolerated and induced cellular and humoral responses. The maximal CD4(+) and CD8(+) T cell responses occurred after 3 injections and were in response to Env peptide pools. The pattern of cytokine expression by vaccine-induced HIV-specific T cells evolved over time, with a diminished frequency of interferon- gamma -producing T cells and an increased frequency of interleukin-2-producing T cells at 1 year. CONCLUSIONS: DNA vaccination induced antibody to and T cell responses against 3 major HIV-1 subtypes and will be further evaluated as a potential component of a preventive AIDS vaccine regimen.


Subject(s)
AIDS Vaccines/adverse effects , AIDS Vaccines/immunology , Genetic Vectors , HIV Infections/immunology , HIV-1/immunology , Immunization Schedule , Neutralization Tests , Plasmids , Vaccination , AIDS Vaccines/administration & dosage , Adolescent , Adult , Antibodies, Viral/blood , Antibody Specificity , Blotting, Western , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cytokines/analysis , Cytokines/biosynthesis , Double-Blind Method , Enzyme-Linked Immunosorbent Assay , Female , Fusion Proteins, gag-pol/genetics , Fusion Proteins, gag-pol/immunology , Gene Products, nef/genetics , Gene Products, nef/immunology , HIV Infections/blood , Humans , Injections, Intramuscular , Male , Vaccines, DNA/administration & dosage , Vaccines, DNA/adverse effects , Vaccines, DNA/immunology , Viral Envelope Proteins/genetics , Viral Envelope Proteins/immunology , nef Gene Products, Human Immunodeficiency Virus
16.
Clin Vaccine Immunol ; 13(11): 1267-77, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16988008

ABSTRACT

Ebola viruses represent a class of filoviruses that causes severe hemorrhagic fever with high mortality. Recognized first in 1976 in the Democratic Republic of Congo, outbreaks continue to occur in equatorial Africa. A safe and effective Ebola virus vaccine is needed because of its continued emergence and its potential for use for biodefense. We report the safety and immunogenicity of an Ebola virus vaccine in its first phase I human study. A three-plasmid DNA vaccine encoding the envelope glycoproteins (GP) from the Zaire and Sudan/Gulu species as well as the nucleoprotein was evaluated in a randomized, placebo-controlled, double-blinded, dose escalation study. Healthy adults, ages 18 to 44 years, were randomized to receive three injections of vaccine at 2 mg (n = 5), 4 mg (n = 8), or 8 mg (n = 8) or placebo (n = 6). Immunogenicity was assessed by enzyme-linked immunosorbent assay (ELISA), immunoprecipitation-Western blotting, intracellular cytokine staining (ICS), and enzyme-linked immunospot assay. The vaccine was well-tolerated, with no significant adverse events or coagulation abnormalities. Specific antibody responses to at least one of the three antigens encoded by the vaccine as assessed by ELISA and CD4(+) T-cell GP-specific responses as assessed by ICS were detected in 20/20 vaccinees. CD8(+) T-cell GP-specific responses were detected by ICS assay in 6/20 vaccinees. This Ebola virus DNA vaccine was safe and immunogenic in humans. Further assessment of the DNA platform alone and in combination with replication-defective adenoviral vector vaccines, in concert with challenge and immune data from nonhuman primates, will facilitate evaluation and potential licensure of an Ebola virus vaccine under the Animal Rule.


Subject(s)
Ebola Vaccines/immunology , Ebolavirus/immunology , Hemorrhagic Fever, Ebola/prevention & control , Vaccines, DNA/immunology , Adolescent , Adult , Antibodies, Viral/biosynthesis , Dose-Response Relationship, Immunologic , Ebola Vaccines/administration & dosage , Ebola Vaccines/adverse effects , Female , Hemorrhagic Fever, Ebola/immunology , Humans , Injections, Intramuscular , Male , Vaccines, DNA/administration & dosage , Vaccines, DNA/adverse effects
17.
Clin Infect Dis ; 38(12): 1749-53, 2004 Jun 15.
Article in English | MEDLINE | ID: mdl-15227622

ABSTRACT

Despite the declaration of smallpox eradication in 1980, the existence of variola stockpiles and the threat of bioterrorism demand that immunity to smallpox through vaccination be maintained. Although the currently available vaccine was used for the most successful medical intervention ever accomplished, it also is associated with side effects that are difficult to accept in a vaccine for a disease that has not been present for >25 years. Herein, we review alternative approaches to maintaining immunity to smallpox through vaccination with attenuated poxviruses, and we suggest modified vaccinia Ankara (MVA) as a leading candidate for an alternative smallpox vaccine.


Subject(s)
Smallpox/prevention & control , Vaccinia virus/immunology , Viral Vaccines , Humans , Immunity, Active , Smallpox/immunology , Smallpox Vaccine , Vaccination , Vaccines, Attenuated , Viral Vaccines/immunology
18.
Am J Med Genet A ; 125A(2): 145-51, 2004 Mar 01.
Article in English | MEDLINE | ID: mdl-14981714

ABSTRACT

We report a family with five of six siblings (including identical male twins) with a novel constellation of immunologic and neurologic impairments. Affected subjects experienced severe dermatitis starting around 9 months of age, Stevens-Johnson syndrome in early childhood, and extreme elevations of IgE (9,400-43,000 IU/ml). The oldest sibling died at age 27 of respiratory failure following recurrent, severe pneumonias. All four surviving affected siblings have had chronic sinusitis or otitis, cutaneous vasculitis, and recurrent bacterial pneumonias leading to bronchiectasis. Neurologic features in all five siblings included oral motor deficits, dysarthria, low average IQ (70-80), and essential myoclonus. Four had documented ataxia and/or mild sensory loss with increased patellar but diminished ankle reflexes. The nonconsanguineous parents and one sibling had none of the above findings, consistent with autosomal recessive inheritance. This primary immunodeficiency with distinctive neurological impairments represents a new syndrome. Published 2003 Wiley-Liss, Inc.


Subject(s)
Cognition Disorders/genetics , Dermatitis/genetics , Diseases in Twins/genetics , Immunologic Deficiency Syndromes/genetics , Myoclonus/genetics , Vasculitis/genetics , Adult , Cognition Disorders/pathology , Dermatitis/pathology , Female , Genes, Recessive , Humans , Immunologic Deficiency Syndromes/pathology , Male , Myoclonus/pathology , Pedigree , Siblings , Syndrome , Vasculitis/pathology
19.
Cancer Epidemiol Biomarkers Prev ; 11(11): 1405-12, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12433719

ABSTRACT

Elevated mortality rates of lung cancer in the Mississippi River corridor in Louisiana have been clearly documented for the past half-century and rank among the highest in the nation. A population-based case-control study of lung cancer termed Lower Mississippi River Interagency Cancer Study was conducted in southern Louisiana. Lung tumor specimens were collected, isolated by laser capture microdissection, subjected to PCR to amplify KRAS, and sequenced to confirm mutation status and specificity. Of the 116 lung tumors analyzed to date, 32 (27.6%) contained mutations in either codon 12 or 13 of KRAS. This frequency is comparable to that reported in the literature; however, the mutation spectrum was strikingly different. Of the 32 mutations observed, 21 (65.6%) resulted in the inappropriate insertion of cysteine, 6 (18.8%) resulted in the insertion of serine, 3 (9.4%) resulted in the insertion of valine, and 1 (3.1%) each resulted in the insertion of aspartate and alanine. These data indicate that an abnormally high proportion of cysteine (P = 0.010) and serine (P = 0.002) mutations was observed in our sample group versus lung cancers reported in the literature. KRAS mutations were more common in African Americans with an odds ratio of 2.4 (P = 0.048), as were serine mutations, although the latter did not reach statistical significance (odds ratio, 2.6; P = 0.373). No association was found between the observed mutation spectrum and known lung cancer risk factors.


Subject(s)
Black People , Carcinogens/toxicity , Environmental Exposure/adverse effects , Lung Neoplasms/chemically induced , Lung Neoplasms/ethnology , Occupational Exposure/adverse effects , Point Mutation/drug effects , Proto-Oncogene Proteins/drug effects , White People , Adult , Aged , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Case-Control Studies , Codon/drug effects , Codon/genetics , Evidence-Based Medicine , Female , Humans , Louisiana/ethnology , Lung Neoplasms/genetics , Male , Middle Aged , Point Mutation/genetics , Polymerase Chain Reaction , Polymorphism, Genetic/drug effects , Polymorphism, Genetic/genetics , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins p21(ras) , Sequence Analysis, DNA , Spectrum Analysis , ras Proteins
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