Eva Halapi | University of Akureyri (original) (raw)

Papers by Eva Halapi

Research paper thumbnail of Kinetics of the T-cell receptor CD4 and CD8 Vβ repertoire in HIV-1 vertically infected infants early treated with HAART

AIDS, 2001

Objectives: To determine the kinetics and the relationship between the T-cell receptor Vâ (TCRBV)... more Objectives: To determine the kinetics and the relationship between the T-cell receptor Vâ (TCRBV) complementary determining region 3 length, the CD4 T-cell count and HIV viral load changes in HIV-1 infected infants treated early with highly active antiretroviral therapy (HAART) during 1 year of follow-up. Design: Two HIV-1 vertically infected infants, two HIV-1 vertically exposed uninfected and two healthy controls were analysed by spectratyping. Evaluation of viral load, CD4 naive and memory cell counts and a proliferation test were also carried out. Methods: Twenty-six families and subfamilies of the TCR on CD4 and CD8 T cells were analyzed by spectratyping. Flow cytometric analysis on peripheral blood mononuclear cells for CD4CD45Ra, CD4CD45Ro, CD8CD38, proliferation tests and plasma viral load measurements were performed at baseline, 1, 6 and after 12 months of therapy. Results: HAART induced a marked reduction of viral load in both HIV-1 infected infants and an increase to normal CD4 T-cell count in the symptomatic infant. At baseline the TCRBV family distribution in the majority of CD8 and a few of the CD4 T cells was highly perturbed, with several TCRBV families showing a monoclonal/ oligoclonal distribution. During HAART a normalization of the TCR repertoire in both CD8 and CD4 subsets occurred. TCR repertoire normalization was associated with a good virological and immunological response. Conclusion: These results suggest that complete and early virus replication control as a result of early HAART leads to a marked reduction of T-cell oligoclonality and is an essential prerequisite to the development of a polyclonal immune response in HIV-1 infected infants.

Research paper thumbnail of Paper: DIVERSE T-CELL RECEPTOR CDR3 LENGTH PATTERNS IN HUMAN CD4 (+) AND CD8 (+) T LYMPHOCYTES FROM NEWBORNS AND ADULTS

Research paper thumbnail of A sequence variant on 17q21 is associated with age at onset and severity of asthma

European Journal of Human Genetics, 2010

A sequence variant (rs7216389-T) near the ORMDL3 gene on chromosome 17q21 was recently found to b... more A sequence variant (rs7216389-T) near the ORMDL3 gene on chromosome 17q21 was recently found to be associated with childhood asthma. We sought to evaluate the effect of rs7216389-T on asthma subphenotypes and its correlation with expression levels of neighboring genes. The association of rs7216389-T with asthma was replicated in six European and one Asian study cohort (N¼4917 cases N¼34 589 controls). In addition, we found that the association of rs7216389-T was confined to cases with early onset of asthma, particularly in early childhood (age: 0-5 years OR¼1.51, P¼6.89. 10 À9) and adolescence (age: 14-17 years OR¼1.71, P¼5.47. 10 À9). A weaker association was observed for onset between 6 and 13 years of age (OR¼1.17, P¼0.035), but none for adult-onset asthma (OR¼1.07, P¼0.12). Cases were further stratified by sex, asthma severity and atopy status. An association with greater asthma severity was observed among early-onset asthma cases (P¼0.0012), but no association with sex or atopy status was observed among the asthma cases. An association between sequence variants and the expression of genes in the 17q21 region was assessed in white blood cell RNA samples collected from Icelandic individuals (n¼743). rs7216389 associated with the expression of GSDMB and ORMDL3 genes. However, other sequence variants showing a weaker association with asthma compared with that of rs7216389 were more strongly associated with the expression of both genes. Thus, the contribution of rs7216389-T to the development of asthma is unlikely to operate only through an impact on the expression of ORMDL3 or GSDMB genes.

Research paper thumbnail of Adolescent digital profiles: A process-based typology of highly engaged internet users

Computers in Human Behavior, 2017

Research paper thumbnail of Association of Vitamin D Binding Protein Variants with Chronic Mucus Hypersecretion in Iceland

American Journal of Pharmacogenomics, Dec 31, 2003

Previous studies of vitamin D binding protein (VDBP, also known as group-specific component, Gc, ... more Previous studies of vitamin D binding protein (VDBP, also known as group-specific component, Gc, encoded by the GC gene) have implicated two gene variants, GC*2 and GC*1F, as possible contributors with chronic obstructive pulmonary disease (COPD) protection and susceptibility, respectively. The objective of this study was to examine the association of VDBP to different subtypes of COPD. The association of the various GC genotypes to the COPD phenotype was examined in Icelandic COPD patients who were followed by pulmonary physicians at the University Hospital of Iceland. All patients were genotyped for the known alleles of the GC gene. The single nucleotide polymorphisms (SNPs) were identified by a restriction fragment length polymorphism procedure. Study power was estimated based on allele frequencies of the variants, and risk ratios were calculated from the prevalence of genotypes in the affected group divided by its prevalence in the control population. Statistical analyses were performed using the 2-tailed Fisher's Exact Test and chi(2) test, where appropriate. One hundred and two COPD patients and 183 controls, together with 46 asthma patients and 48 patients with chronic mucous hypersecretion (CMH) were examined. The results demonstrate similar allele and genotype frequencies of GC in COPD patients overall and healthy controls. However, there was a higher prevalence of genotypes carrying a GC*1F allele and lower prevalence of genotypes with a GC*2 allele in the CMH patients than in controls. This difference was most notable in the homozygous form: 8.3% vs 1.1% for the GC*1F/*1F, and 0.0% vs 7.6% for the GC*2/*2 genotypes, respectively. When controlled for smoking, only the non-smoking CMH patients demonstrated a significantly altered frequency of the GC*1F/*1F genotype (p = 0.0001). The prevalence of the GC*2/*2 genotype was also significantly lower in patients with bronchial hypersecretion with airflow obstruction compared with the control group (2.9% vs 7.6%). Taken together, these results demonstrate that the GC*1F and GC*2 alleles are associated with sputum hypersecretion in individuals who are at increased risk of developing COPD.

Research paper thumbnail of Allelic Frequencies and Patterns of Single-nucleotide Polymorphisms in Candidate Genes for Asthma and Atopy in Iceland

Numerous asthma and atopy loci have been reported in studies demonstrating associations of the as... more Numerous asthma and atopy loci have been reported in studies demonstrating associations of the asthma-related phenotypes atopy, elevated IgE levels, and bronchial hyperresponsiveness with alleles of microsatellite markers and single-nucleotide polymorphisms (SNPs) within specific cytokine/chemokine and IgE-regulating genes. Although the studies reporting these observations are compelling, most of them lack statistical power. We assessed the nature, pattern, and frequency of SNPs in 24 candidate genes in Iceland and looked for associations with asthma and atopy. We identified 42 SNPs with an average minor allele frequency of 20.3% (asthma) and 20.7% (control). Twenty SNPs (48%) were within coding sequences and 90% of those led to a predicted change in protein sequence. No differences were detected in the allelic frequencies of SNPs in any of these candidate genes between control subjects and the patients with atopic asthma. Moreover, linkage analysis that included 269 patients with atopic asthma uncovered no evidence of linkage to markers associated with these genes. We conclude that this study has failed to produce evidence in support of the notion that variations within these 24 candidate atopy and asthma genes significantly influence the expression of the atopic asthmatic phenotype or contribute to the susceptibility of atopic asthma.

Research paper thumbnail of Oligoclonal T cells in human cancer

Cancer Immunol Immunother, Dec 1, 1998

Many solid tumors are characterised by the infiltration of lymphocytes and their presence has bee... more Many solid tumors are characterised by the infiltration of lymphocytes and their presence has been correlated with a more favourable prognosis. These tumor-infiltrating lymphocytes (TIL), have been shown to possess specific cytolytic reactivity towards autologous tumours, thus suggesting that tumour cells may express antigens capable of eliciting an immune response. Expression of such tumour-associated antigens (TAA) in combination with appropriate accessory signals would lead to the in vivo accumulation of T cells with anti-tumour specificity. Analysis of the composition of the specific T-cell receptor (TCR) of TIL could thus provide information on the nature of the antigen(s) recognised by TIL. In this review, different aspects of the presence of clonal T cells in patients with cancer are discussed.

Research paper thumbnail of Genetics of obstructive airways disease

Immunol Allergy Clin N Amer, 2002

Cystic fibrosis (CF), the most prevalent of severe autosomal recessive diseases in whites, first ... more Cystic fibrosis (CF), the most prevalent of severe autosomal recessive diseases in whites, first was described over 60 years ago. It has been almost 12 years since the genetic defect of CF was localized to the long arm of chromosome 7. Mutations in the gene that codes for the CF transmembrane conductance regulator (CFTR) protein are responsible for the various phenotypes of CF. Although most organ systems are affected, the principal features of CF include chronic obstructive pulmonary disease, exocrine pancreatic insufficiency, and elevated levels of sodium and chloride in sweat (Fig. 1). Progressive obstructive pulmonary disease, the primary cause of morbidity and mortality in CF, is attributed to impaired mucociliary clearance, abnormal mucous plugging, airway inflammation, and chronic respiratory infections from bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa [1,2]. The most important result of therapeutic advances in CF is the continuing improvement in life expectancy. The median life expectancy in the United States and Europe now exceeds 30 years. Although the acquisition of P. aeruginosa is an important negative prognostic factor, the prognosis in CF is continuing to improve; a newborn infant with CF is projected to have a life expectancy well exceeding 40 years. Individuals with adequate pancreatic function have higher life expectancies, exceeding 50 years [3]. Role of CFTR Cystic fibrosis is one of the most thoroughly understood genetic diseases. It affects approximately 1 in 3000 living individuals [4]. Its carrier gene is estimated

Research paper thumbnail of Restricted T cell receptor V-13 and J-13 usage in T cells from interleukin-2-cultured lymphocytes of ovarian and renal carcinomas

Cancer Immunol Immunother, 1993

Research paper thumbnail of Methods of diagnosis and treatment for asthma, allergic rhinitis and other respiratory diseases based on haplotype association

Research paper thumbnail of Genetics of obstructive airways disease: Cystic fibrosis, α-1 antitrypsin deficiency, and Hermansky-Pudlak syndrome

Immunology and Allergy Clinics of North America, May 1, 2002

ABSTRACT

Research paper thumbnail of Methods of diagnosis and treatment for asthma and other respiratory diseases based on haplotype association

Research paper thumbnail of Analysis of heterogenous viral populations by direct DNA sequencing

Research paper thumbnail of Oligoklonal T cells expressing the TCR V-beta 6 gene product following IL-2 culture of ovarian carcinoma derived lymphocytes

Research paper thumbnail of High expression of Vγ8 is a shared feature of human γδ T cells in the epithelium of the gut and in the inflamed synovial tissue

The Journal of Immunology

ABSTRACT

Research paper thumbnail of Increased frequency of abnormal gamma delta T cells in blood of patients with inflammatory bowel diseases

Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1996

We have previously reported a preferential usage of V delta 1/V gamma 8 on TCR-gamma-delta-bearin... more We have previously reported a preferential usage of V delta 1/V gamma 8 on TCR-gamma-delta-bearing intraepithelial lymphocytes of the normal human intestine as well as in the inflamed synovial tissue of patients with rheumatoid arthritis. The aim of the present study was to analyze V gene segment usage by gamma delta T cells of the intestine and peripheral blood (PB) from patients with inflammatory bowel disease. Freshly isolated lymphocytes were analyzed by flow cytometry using a panel of V gene subset-specific mAbs. The relative proportion of PB TCR-gamma delta+ cells was increased in patients with Crohn's disease as compared with controls. Interestingly, an increased proportion of PB gamma delta T cells of patients with ulcerative colitis or CrD expressed V delta and V gamma genes typically used by intraepithelial lymphocytes. Thus, increased proportions of V delta 1+ and V gamma 8+ cells were found in the PB of both patient groups. The majority of TCR-gamma delta+ intraepith...

Research paper thumbnail of Diverse effect of cytokine treatment of tumor cells on specific versus non-specific cytotoxicity

Medical oncology and tumor pharmacotherapy, 1992

The effect of IFN-gamma and TNF-alpha treatment of an ovarian carcinoma line on the sensitivity t... more The effect of IFN-gamma and TNF-alpha treatment of an ovarian carcinoma line on the sensitivity to lysis by specific CTL clones and non-specific Tumor Associated Lymphocytes (TAL), isolated from the ascites fluid, was analyzed. The in vitro established TAL line displayed a non-specific lytic activity against the autologous tumor as well as against several allogeneic tumor lines. Pretreatment with IFN-gamma alone, or in combination with TNF-alpha, rendered the carcinoma line less susceptible to lysis by the autologous TAL line. Conversely, susceptibility to lysis by tumor specific T cell clones, isolated from the TAL line, was increased as a result of cytokine pretreatment. Several TCR-alpha/beta+, CD8+ T-cell clones showing a more specific pattern of lysis against the autologous tumor were isolated. Lysis of the autologous tumor by these clones involved the TCR-alpha/beta via a MHC-class I restricted mechanism dependent on the adhesion molecules ICAM-1 and LFA-3, as inferred from an...

Research paper thumbnail of Genetic analysis of V3 domain sequences obtained from Uruguayan HIV type 1-infected individuals

AIDS research and human retroviruses, Jan 10, 1996

Research paper thumbnail of Analysis of heterogeneous viral populations by direct DNA sequencing

BioTechniques, 1993

The ability of direct PCR sequencing to detect and quantify sequence polymorphisms was investigat... more The ability of direct PCR sequencing to detect and quantify sequence polymorphisms was investigated using samples containing mixed populations of HIV-1. A part of the genome encoding the polymorphic variable region 3 of the envelope was directly sequenced to yield a consensus sequence of the virus population. The results were compared with sequences obtained by analysis of multiple clones derived from the same clinical samples. The results of five patients suggested that the direct-sequencing method can be used as a rapid tool to analyze and quantify heterogeneous viral populations. Reconstitution experiments using cloned material demonstrated that it was possible to detect and quantify minor sequence variants present in as little as 10% of the total virus population. The use of the method for molecular diagnosis is discussed.

Research paper thumbnail of High expression of V gamma 8 is a shared feature of human gamma delta T cells in the epithelium of the gut and in the inflamed synovial tissue

Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1994

We have analyzed the V-gene usage in gamma delta T cells of the human gut and joint by using a ne... more We have analyzed the V-gene usage in gamma delta T cells of the human gut and joint by using a new mAb (B18) specific for V gamma 8 of human TCR-gamma delta+ T cells. The B18+ population constituted a minor subset of the gamma delta T cells in peripheral blood (PB) of healthy persons (6 +/- 5%) and only 1 of 35 gamma delta T cell clones analyzed was positive. In contrast, the B18+ subset was a dominant gamma delta T cell population among intraepithelial lymphocytes (IEL) derived from the human intestine (74 +/- 29, p < 0.002), and two of three IEL clones from patients with coeliac disease were B18+. Interestingly, a higher proportion of B18+ gamma delta T cells was found in the synovial fluid of patients with rheumatoid arthritis (RA) (21 +/- 18%, 0.02 < p < 0.05) compared with normal PB. Furthermore, the B18+ subset was more frequent among IL-2-expanded gamma delta T cells (42 +/- 20%) derived from synovial tissue than among IL-2-expanded cells derived from synovial fluid ...

Research paper thumbnail of Kinetics of the T-cell receptor CD4 and CD8 Vβ repertoire in HIV-1 vertically infected infants early treated with HAART

AIDS, 2001

Objectives: To determine the kinetics and the relationship between the T-cell receptor Vâ (TCRBV)... more Objectives: To determine the kinetics and the relationship between the T-cell receptor Vâ (TCRBV) complementary determining region 3 length, the CD4 T-cell count and HIV viral load changes in HIV-1 infected infants treated early with highly active antiretroviral therapy (HAART) during 1 year of follow-up. Design: Two HIV-1 vertically infected infants, two HIV-1 vertically exposed uninfected and two healthy controls were analysed by spectratyping. Evaluation of viral load, CD4 naive and memory cell counts and a proliferation test were also carried out. Methods: Twenty-six families and subfamilies of the TCR on CD4 and CD8 T cells were analyzed by spectratyping. Flow cytometric analysis on peripheral blood mononuclear cells for CD4CD45Ra, CD4CD45Ro, CD8CD38, proliferation tests and plasma viral load measurements were performed at baseline, 1, 6 and after 12 months of therapy. Results: HAART induced a marked reduction of viral load in both HIV-1 infected infants and an increase to normal CD4 T-cell count in the symptomatic infant. At baseline the TCRBV family distribution in the majority of CD8 and a few of the CD4 T cells was highly perturbed, with several TCRBV families showing a monoclonal/ oligoclonal distribution. During HAART a normalization of the TCR repertoire in both CD8 and CD4 subsets occurred. TCR repertoire normalization was associated with a good virological and immunological response. Conclusion: These results suggest that complete and early virus replication control as a result of early HAART leads to a marked reduction of T-cell oligoclonality and is an essential prerequisite to the development of a polyclonal immune response in HIV-1 infected infants.

Research paper thumbnail of Paper: DIVERSE T-CELL RECEPTOR CDR3 LENGTH PATTERNS IN HUMAN CD4 (+) AND CD8 (+) T LYMPHOCYTES FROM NEWBORNS AND ADULTS

Research paper thumbnail of A sequence variant on 17q21 is associated with age at onset and severity of asthma

European Journal of Human Genetics, 2010

A sequence variant (rs7216389-T) near the ORMDL3 gene on chromosome 17q21 was recently found to b... more A sequence variant (rs7216389-T) near the ORMDL3 gene on chromosome 17q21 was recently found to be associated with childhood asthma. We sought to evaluate the effect of rs7216389-T on asthma subphenotypes and its correlation with expression levels of neighboring genes. The association of rs7216389-T with asthma was replicated in six European and one Asian study cohort (N¼4917 cases N¼34 589 controls). In addition, we found that the association of rs7216389-T was confined to cases with early onset of asthma, particularly in early childhood (age: 0-5 years OR¼1.51, P¼6.89. 10 À9) and adolescence (age: 14-17 years OR¼1.71, P¼5.47. 10 À9). A weaker association was observed for onset between 6 and 13 years of age (OR¼1.17, P¼0.035), but none for adult-onset asthma (OR¼1.07, P¼0.12). Cases were further stratified by sex, asthma severity and atopy status. An association with greater asthma severity was observed among early-onset asthma cases (P¼0.0012), but no association with sex or atopy status was observed among the asthma cases. An association between sequence variants and the expression of genes in the 17q21 region was assessed in white blood cell RNA samples collected from Icelandic individuals (n¼743). rs7216389 associated with the expression of GSDMB and ORMDL3 genes. However, other sequence variants showing a weaker association with asthma compared with that of rs7216389 were more strongly associated with the expression of both genes. Thus, the contribution of rs7216389-T to the development of asthma is unlikely to operate only through an impact on the expression of ORMDL3 or GSDMB genes.

Research paper thumbnail of Adolescent digital profiles: A process-based typology of highly engaged internet users

Computers in Human Behavior, 2017

Research paper thumbnail of Association of Vitamin D Binding Protein Variants with Chronic Mucus Hypersecretion in Iceland

American Journal of Pharmacogenomics, Dec 31, 2003

Previous studies of vitamin D binding protein (VDBP, also known as group-specific component, Gc, ... more Previous studies of vitamin D binding protein (VDBP, also known as group-specific component, Gc, encoded by the GC gene) have implicated two gene variants, GC*2 and GC*1F, as possible contributors with chronic obstructive pulmonary disease (COPD) protection and susceptibility, respectively. The objective of this study was to examine the association of VDBP to different subtypes of COPD. The association of the various GC genotypes to the COPD phenotype was examined in Icelandic COPD patients who were followed by pulmonary physicians at the University Hospital of Iceland. All patients were genotyped for the known alleles of the GC gene. The single nucleotide polymorphisms (SNPs) were identified by a restriction fragment length polymorphism procedure. Study power was estimated based on allele frequencies of the variants, and risk ratios were calculated from the prevalence of genotypes in the affected group divided by its prevalence in the control population. Statistical analyses were performed using the 2-tailed Fisher&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Exact Test and chi(2) test, where appropriate. One hundred and two COPD patients and 183 controls, together with 46 asthma patients and 48 patients with chronic mucous hypersecretion (CMH) were examined. The results demonstrate similar allele and genotype frequencies of GC in COPD patients overall and healthy controls. However, there was a higher prevalence of genotypes carrying a GC*1F allele and lower prevalence of genotypes with a GC*2 allele in the CMH patients than in controls. This difference was most notable in the homozygous form: 8.3% vs 1.1% for the GC*1F/*1F, and 0.0% vs 7.6% for the GC*2/*2 genotypes, respectively. When controlled for smoking, only the non-smoking CMH patients demonstrated a significantly altered frequency of the GC*1F/*1F genotype (p = 0.0001). The prevalence of the GC*2/*2 genotype was also significantly lower in patients with bronchial hypersecretion with airflow obstruction compared with the control group (2.9% vs 7.6%). Taken together, these results demonstrate that the GC*1F and GC*2 alleles are associated with sputum hypersecretion in individuals who are at increased risk of developing COPD.

Research paper thumbnail of Allelic Frequencies and Patterns of Single-nucleotide Polymorphisms in Candidate Genes for Asthma and Atopy in Iceland

Numerous asthma and atopy loci have been reported in studies demonstrating associations of the as... more Numerous asthma and atopy loci have been reported in studies demonstrating associations of the asthma-related phenotypes atopy, elevated IgE levels, and bronchial hyperresponsiveness with alleles of microsatellite markers and single-nucleotide polymorphisms (SNPs) within specific cytokine/chemokine and IgE-regulating genes. Although the studies reporting these observations are compelling, most of them lack statistical power. We assessed the nature, pattern, and frequency of SNPs in 24 candidate genes in Iceland and looked for associations with asthma and atopy. We identified 42 SNPs with an average minor allele frequency of 20.3% (asthma) and 20.7% (control). Twenty SNPs (48%) were within coding sequences and 90% of those led to a predicted change in protein sequence. No differences were detected in the allelic frequencies of SNPs in any of these candidate genes between control subjects and the patients with atopic asthma. Moreover, linkage analysis that included 269 patients with atopic asthma uncovered no evidence of linkage to markers associated with these genes. We conclude that this study has failed to produce evidence in support of the notion that variations within these 24 candidate atopy and asthma genes significantly influence the expression of the atopic asthmatic phenotype or contribute to the susceptibility of atopic asthma.

Research paper thumbnail of Oligoclonal T cells in human cancer

Cancer Immunol Immunother, Dec 1, 1998

Many solid tumors are characterised by the infiltration of lymphocytes and their presence has bee... more Many solid tumors are characterised by the infiltration of lymphocytes and their presence has been correlated with a more favourable prognosis. These tumor-infiltrating lymphocytes (TIL), have been shown to possess specific cytolytic reactivity towards autologous tumours, thus suggesting that tumour cells may express antigens capable of eliciting an immune response. Expression of such tumour-associated antigens (TAA) in combination with appropriate accessory signals would lead to the in vivo accumulation of T cells with anti-tumour specificity. Analysis of the composition of the specific T-cell receptor (TCR) of TIL could thus provide information on the nature of the antigen(s) recognised by TIL. In this review, different aspects of the presence of clonal T cells in patients with cancer are discussed.

Research paper thumbnail of Genetics of obstructive airways disease

Immunol Allergy Clin N Amer, 2002

Cystic fibrosis (CF), the most prevalent of severe autosomal recessive diseases in whites, first ... more Cystic fibrosis (CF), the most prevalent of severe autosomal recessive diseases in whites, first was described over 60 years ago. It has been almost 12 years since the genetic defect of CF was localized to the long arm of chromosome 7. Mutations in the gene that codes for the CF transmembrane conductance regulator (CFTR) protein are responsible for the various phenotypes of CF. Although most organ systems are affected, the principal features of CF include chronic obstructive pulmonary disease, exocrine pancreatic insufficiency, and elevated levels of sodium and chloride in sweat (Fig. 1). Progressive obstructive pulmonary disease, the primary cause of morbidity and mortality in CF, is attributed to impaired mucociliary clearance, abnormal mucous plugging, airway inflammation, and chronic respiratory infections from bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa [1,2]. The most important result of therapeutic advances in CF is the continuing improvement in life expectancy. The median life expectancy in the United States and Europe now exceeds 30 years. Although the acquisition of P. aeruginosa is an important negative prognostic factor, the prognosis in CF is continuing to improve; a newborn infant with CF is projected to have a life expectancy well exceeding 40 years. Individuals with adequate pancreatic function have higher life expectancies, exceeding 50 years [3]. Role of CFTR Cystic fibrosis is one of the most thoroughly understood genetic diseases. It affects approximately 1 in 3000 living individuals [4]. Its carrier gene is estimated

Research paper thumbnail of Restricted T cell receptor V-13 and J-13 usage in T cells from interleukin-2-cultured lymphocytes of ovarian and renal carcinomas

Cancer Immunol Immunother, 1993

Research paper thumbnail of Methods of diagnosis and treatment for asthma, allergic rhinitis and other respiratory diseases based on haplotype association

Research paper thumbnail of Genetics of obstructive airways disease: Cystic fibrosis, α-1 antitrypsin deficiency, and Hermansky-Pudlak syndrome

Immunology and Allergy Clinics of North America, May 1, 2002

ABSTRACT

Research paper thumbnail of Methods of diagnosis and treatment for asthma and other respiratory diseases based on haplotype association

Research paper thumbnail of Analysis of heterogenous viral populations by direct DNA sequencing

Research paper thumbnail of Oligoklonal T cells expressing the TCR V-beta 6 gene product following IL-2 culture of ovarian carcinoma derived lymphocytes

Research paper thumbnail of High expression of Vγ8 is a shared feature of human γδ T cells in the epithelium of the gut and in the inflamed synovial tissue

The Journal of Immunology

ABSTRACT

Research paper thumbnail of Increased frequency of abnormal gamma delta T cells in blood of patients with inflammatory bowel diseases

Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1996

We have previously reported a preferential usage of V delta 1/V gamma 8 on TCR-gamma-delta-bearin... more We have previously reported a preferential usage of V delta 1/V gamma 8 on TCR-gamma-delta-bearing intraepithelial lymphocytes of the normal human intestine as well as in the inflamed synovial tissue of patients with rheumatoid arthritis. The aim of the present study was to analyze V gene segment usage by gamma delta T cells of the intestine and peripheral blood (PB) from patients with inflammatory bowel disease. Freshly isolated lymphocytes were analyzed by flow cytometry using a panel of V gene subset-specific mAbs. The relative proportion of PB TCR-gamma delta+ cells was increased in patients with Crohn's disease as compared with controls. Interestingly, an increased proportion of PB gamma delta T cells of patients with ulcerative colitis or CrD expressed V delta and V gamma genes typically used by intraepithelial lymphocytes. Thus, increased proportions of V delta 1+ and V gamma 8+ cells were found in the PB of both patient groups. The majority of TCR-gamma delta+ intraepith...

Research paper thumbnail of Diverse effect of cytokine treatment of tumor cells on specific versus non-specific cytotoxicity

Medical oncology and tumor pharmacotherapy, 1992

The effect of IFN-gamma and TNF-alpha treatment of an ovarian carcinoma line on the sensitivity t... more The effect of IFN-gamma and TNF-alpha treatment of an ovarian carcinoma line on the sensitivity to lysis by specific CTL clones and non-specific Tumor Associated Lymphocytes (TAL), isolated from the ascites fluid, was analyzed. The in vitro established TAL line displayed a non-specific lytic activity against the autologous tumor as well as against several allogeneic tumor lines. Pretreatment with IFN-gamma alone, or in combination with TNF-alpha, rendered the carcinoma line less susceptible to lysis by the autologous TAL line. Conversely, susceptibility to lysis by tumor specific T cell clones, isolated from the TAL line, was increased as a result of cytokine pretreatment. Several TCR-alpha/beta+, CD8+ T-cell clones showing a more specific pattern of lysis against the autologous tumor were isolated. Lysis of the autologous tumor by these clones involved the TCR-alpha/beta via a MHC-class I restricted mechanism dependent on the adhesion molecules ICAM-1 and LFA-3, as inferred from an...

Research paper thumbnail of Genetic analysis of V3 domain sequences obtained from Uruguayan HIV type 1-infected individuals

AIDS research and human retroviruses, Jan 10, 1996

Research paper thumbnail of Analysis of heterogeneous viral populations by direct DNA sequencing

BioTechniques, 1993

The ability of direct PCR sequencing to detect and quantify sequence polymorphisms was investigat... more The ability of direct PCR sequencing to detect and quantify sequence polymorphisms was investigated using samples containing mixed populations of HIV-1. A part of the genome encoding the polymorphic variable region 3 of the envelope was directly sequenced to yield a consensus sequence of the virus population. The results were compared with sequences obtained by analysis of multiple clones derived from the same clinical samples. The results of five patients suggested that the direct-sequencing method can be used as a rapid tool to analyze and quantify heterogeneous viral populations. Reconstitution experiments using cloned material demonstrated that it was possible to detect and quantify minor sequence variants present in as little as 10% of the total virus population. The use of the method for molecular diagnosis is discussed.

Research paper thumbnail of High expression of V gamma 8 is a shared feature of human gamma delta T cells in the epithelium of the gut and in the inflamed synovial tissue

Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1994

We have analyzed the V-gene usage in gamma delta T cells of the human gut and joint by using a ne... more We have analyzed the V-gene usage in gamma delta T cells of the human gut and joint by using a new mAb (B18) specific for V gamma 8 of human TCR-gamma delta+ T cells. The B18+ population constituted a minor subset of the gamma delta T cells in peripheral blood (PB) of healthy persons (6 +/- 5%) and only 1 of 35 gamma delta T cell clones analyzed was positive. In contrast, the B18+ subset was a dominant gamma delta T cell population among intraepithelial lymphocytes (IEL) derived from the human intestine (74 +/- 29, p < 0.002), and two of three IEL clones from patients with coeliac disease were B18+. Interestingly, a higher proportion of B18+ gamma delta T cells was found in the synovial fluid of patients with rheumatoid arthritis (RA) (21 +/- 18%, 0.02 < p < 0.05) compared with normal PB. Furthermore, the B18+ subset was more frequent among IL-2-expanded gamma delta T cells (42 +/- 20%) derived from synovial tissue than among IL-2-expanded cells derived from synovial fluid ...