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At least 919 records · Page 51Linked to original sources
PubMed2001

Some specific human leukocyte antigen (HLA)-DR/DQ haplotypes are more important than individual HLA-DR and -DQ phenotypes for the development of mucocutaneous type of Behçet's disease and for disease shift from recurrent aphthous stomatitis to mucocutaneous type of Behçet's disease.

The phenotype and haplotype frequencies of human leukocyte antigens (HLA)-DR and -DQ in 32 Chinese patients with the mucocutaneous (MC) type of Behçet's disease (BD) were calculated and compared with those in 310 healthy control Chinese and with those in 80 Chinese patients with recurrent aphthous stomatitis (RAS). We found that the phenotype frequency of HLA-DRw8 [corrected P (Pc)<0.005] and the haplotype frequencies of HLA-DRw8/DQw1 (Pc<0.005), -DRw8/DQw5(w1) (Pc<0.0005), -DRw12(5)/DQw1 (Pc<0.005), -DRw12(5)/DQw6(w1) (Pc< 0.0005), and -DRw52/DQw1 (Pc<0.005) in patients with the MC type of BD were significantly greater than those in healthy control subjects. This finding suggests that individual Chinese with HLA-DRw8 antigen and HLA-DRw8/DQw1, -DRw8/DQw5(w1), -DRw12(5)/DQw1, -DRw12(5)/DQw6(w1) and -DRw52/DQw1 haplotypes are more likely to have the MC type of BD. Furthermore, the relative risks (RRs) of HLA-DRw8/DQw1 (5.6), -DRw8/ DQw5 (w1) (10.0), and -DRw12(5)/DQw6(w1) (14.4) haplotypes in patients with the MC type of BD were equal to or higher than the RR of HLA-DRw8 phenotype (5.6), suggesting that some of the HLA-DR/DQ haplotypes may play more important roles than the individual HLA-DR and -DQ phenotypes for the development of the MC type of BD. The phenotype frequencies of HLA-DR5 (Pc<0.01), -DRw8 (Pc<0.005) and -DQw1 (Pc<0.05) as well as the haplotype frequencies of HLA-DR5/DQw1 (P<0.005) and -DRw8/DQw1 (Pc<0.00005) in patients with the MC type of BD were significantly higher than those in patients with RAS. Moreover, the RRs of HLA-DR5/DQw1 (29.1) and -DRw8/DQw1 (47.4) haplotypes were greater than the RRs of HLA-DR5 (10.4), -DRw8 (23.4) and -DQw1 (4.0) antigens. These results suggest that some specific HLA-DR/DQ haplotypes may be more important than the individual HLA-DR and -DQ phenotypes in the disease shift from RAS to the MC type of BD.

Adolescent↗
PubMed1991

Elevated serum levels of Dupan-2 in pancreatic cancer patients negative for Lewis blood group phenotype.

CA19-9, a serum marker for pancreatic cancer, gives false-negative results in patients who are negative for the Lewis blood group phenotype. To determine whether other markers may compensate for this drawback, serum levels of CA50, Span-1, sialyl SSEA-1 and Dupan-2 were assayed and compared with those of CA19-9 in 207 normal subjects and in 200 patients with pancreatic carcinoma whose Lewis blood group phenotypes were confirmed. In normal subjects with the Lewis negative phenotype, the serum levels of CA50 and Span-1, as well as CA19-9, were significantly low, whereas those of sialyl SSEA-1 were independent of the Lewis blood group phenotype. Serum levels of Dupan-2 were significantly higher in normal subjects with the Le (a-b-) phenotype as compared with those with Le(a-b+). The sensitivity for pancreatic carcinoma was 81% for CA19-9, 84% for CA50, 82% for Span-1, 51% for sialyl SSEA-1 and 63% for Dupan-2. Among the 39 CA19-9 negative patients, 13 were determined as being Lewis negative by the serum dot-ELISA technique. Although the positive rates were essentially comparable when each marker was combined with CA19-9, a highly elevated serum level of Dupan-2, which strongly suggested the presence of malignancy, was most frequently encountered in 39 patients who were not diagnosed by CA19-9 assay, especially those with Lewis negative blood groups. With regard to the three other markers, we found few patients with a highly elevated serum level in either the Lewis-negative or -positive groups. We conclude that Dupan-2 tended to be elevated in patients with pancreatic cancer who were negative for the Lewis blood group phenotype.

Adult↗
PubMed1994

Dapsone N-acetylation, metoprolol alpha-hydroxylation, and S-mephenytoin 4-hydroxylation polymorphisms in an Indonesian population: a cocktail and extended phenotyping assessment trial.

We examined dapsone N-acetylation and metoprolol alpha-hydroxylation and S-mephenytoin 4-hydroxylation phenotypings using the respective test probes (dapsone and racemic metoprolol and mephenytoin) administered separately and in a cocktail manner to an Indonesian subject group (n = 30). After ascertaining that the separate and cocktail phenotyping tests of the probe drugs correlated with each other (all rs values > 0.84; p < 0.001), the cocktail phenotyping assessment was extended to the other 74 Indonesians. In a total of 104 Indonesians phenotyped with the cocktail test, a visual antimode was apparent only in the dapsone N-acetylation and S-mephenytoin 4-hydroxylation polymorphisms: the frequencies of slow acetylators and poor hydroxylators were 43.3% (95% confidence interval, 33.7% to 52.8%) and 15.4% (95% confidence interval, 8.5% to 22.3%), respectively. The distribution histogram and probit plots of the metabolic ratio of metoprolol gave no clear evidence for bimodality, and therefore no poor alpha-hydroxylator of metoprolol was considered to exist in the present sample size. The findings indicate that the Indonesian subjects have a greater incidence of slow acetylator phenotype compared with Japanese and Chinese, as well as a frequency of poor metabolizer phenotype of S-mephenytoin similar to that of Korean and Chinese subjects. They resemble an African population (Nigerians) in metoprolol alpha-hydroxylation polymorphism, with no apparent antimode derived from white populations.

Acetylation↗
PubMed1993

Apolipoprotein(a) phenotypes and serum lipoprotein(a) levels in maintenance hemodialysis patients with/without diabetes mellitus.

We studied the quantitative and qualitative characteristics of lipoprotein(a) [Lp(a)] as a function of apolipoprotein(a) [apo(a)] phenotypes in 152 patients (123 males, 29 females) undergoing maintenance hemodialysis (HD) with or without diabetes mellitus (DM), in 101 patients with diabetes mellitus without hemodialysis (58 males, 43 females), and in 421 normal controls (333 males, 88 females). Serum Lp(a) levels were significantly (P < 0.01) higher in patients than in controls (26.2 +/- 18.3 mg/dl in HD with DM, 26.4 +/- 22.0 mg/dl in HD without DM, 27.1 +/- 27.3 mg/dl in DM without HD, and 14.9 +/- 13.7 mg/dl in controls, respectively). Apo(a) phenotyping was performed by a sensitive, high resolution technique using SDS-agarose/gradient (3 to 6%) PAGE. In normal controls, the molecular weights of apo(a) isoforms were inversely correlated with plasma Lp(a) levels, and the same tendency was found in patients who were undergoing hemodialysis and/or who had diabetes mellitus. We assumed the differences in apo(a) phenotypes detectable with our method reflected consecutive differences in molecular weights of apo(a). The results of an analysis of covariance and a least square means comparison indicated that the regression lines between serum Lp(a) levels [log Lp(a)] and apo(a) phenotypes in patient groups were significantly (P < 0.01) elevated for every apo(a) phenotype, as compared to the regression line of the control group. Even after the low molecular weight apo(a) phenotypes (A1-A8) were omitted, the same tendency was observed. However, no differences were observed between the patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2022

A multi-omic analysis of MCF10A cells provides a resource for integrative assessment of ligand-mediated molecular and phenotypic responses.

The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods ( synapse.org/LINCS_MCF10A ). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.

Epidermal Growth Factor↗
PubMed2004

Gastric and intestinal phenotypic marker expression in gastric carcinomas and recurrence pattern after surgery-immunohistochemical analysis of 213 lesions.

Both gastric and intestinal phenotypic markers are known to be expressed in gastric carcinomas, irrespective of their histologic type. In the present study, the relation between gastric and intestinal phenotypic marker expression in gastric carcinomas and the recurrence pattern after surgery was examined. The phenotypic marker expression of the tumour was determined by examining the expression of human gastric mucin (HGM), MUC6, MUC2 and CD10 in 213 advanced gastric carcinomas in 213 patients who had undergone a curative resection (97 died from recurrent gastric carcinoma and 116 were alive without recurrence at the end of the follow-up period). Tumours were classified into gastric (G), gastric and intestinal mixed (GI), intestinal (I) or unclassified (UC) phenotypes according to the immunopositivity of HGM, MUC6, MUC2 and CD10 stainings. The incidence of HGM-positive tumours and MUC2-negative tumours was significantly higher in tumours with peritoneal recurrence than in tumours without recurrence (73.3%, 44 out of 60 cases vs 54.3%, 63 out of 116 (P=0.022); and 70.0%, 42 out of 60 vs 38.8%, 45 out of 116 (P=0.0002), respectively). The incidence of G-phenotype tumours was also significantly higher in tumours with peritoneal recurrence than in tumours without recurrence (58.3%, 35 out of 60 cases vs 28.4%, 33 out of 116 (P=0.0002)). The incidence of MUC2-negative tumours and CD10-positive tumours was significantly higher in tumours with haematogenous recurrence than in tumours without recurrence (62.5%, 20 out of 32 cases vs 38.8%, 45 out of 116 (P=0.028); and 43.8%, 14 out of 32 vs 23.3%, 27 out of 116 (P=0.039); respectively). Our present findings show that the gastric and intestinal phenotypic marker expression of the tumour, determined by immunohistochemical staining for HGM, MUC6, MUC2 and CD10, can be used to predict the pattern of gastric carcinoma recurrence after curative resection.

Aged↗
PubMed2000

An essential SMN interacting protein (SIP1) is not involved in the phenotypic variability of spinal muscular atrophy (SMA).

The survival motor neuron (SMN) protein and the SMN interacting protein 1 (SIP1) are part of a 300 kD protein complex with a crucial role in snRNP biogenesis and pre-mRNA splicing. Both proteins are colocalised in nuclear structures called gems and in the cytoplasm. Approximately 96% of patients with autosomal recessive spinal muscular atrophy (SMA) show mutations in the SMN1 gene, while about 4% fail to show any mutation, despite a typical SMA phenotype. Additionally, sibs with identical 5q13 homologs and homozygous absence of SMN1 can show variable phenotypes which suggest that SMA is modified by other, yet unknown factors. Since both genes, SMN1 and SIP1, belong to the same pathway and are part of the same protein complex, it is obvious to ask whether mutations within SIP1 are responsible for both the phenotypic variability and the appearance of non-SMN mutated SMA patients. First, we identified the chromosomal location of SIP1 and assigned it to chromosomal region 14q13-q21 by fluorescence in situ hybridisation. No SMA related disorder has yet been assigned to this chromosomal region. Next, we determined the exon-intron structure of the SIP1 gene which encompasses 10 exons and identified five transcription isoforms. We sequenced either RT-PCR products or genomic DNA covering the complete coding region from 23 typical SMA patients who had failed to show any SMN1 mutation. No mutation and no polymorphism was found within SIP1. Additionally, we sequenced RT-PCR products or genomic fragments of the entire SIP1 coding region from 26 sibs of 11 SMA families with identical genotypes (delta7SMN/delta7SMN or delta7SMN/other mutation) but different phenotypes and again no mutation was found. Finally, we performed quantitative analysis of RT-PCR products from the same 26 sibs. No difference in expression level of the five isoforms among phenotypically variable sibs was observed. Based on these data, we suggest that neither the phenotypic variability nor the 5q-unlinked SMA are caused by mutations within SIP1.

Alternative Splicing↗
PubMed1998

Phenotypical heterogeneity of CD4+CD8+ double-positive chronic T lymphoid leukemia.

Chronic T lymphoid leukemias are defined as leukemias of post-thymic T cells. The CD4+CD8+ double-positive (DP) phenotype is seen in a few cases. Since DP generally occurs in thymic T cells, whether the DP T leukemia cells represent thymic or peripheral T cells has been a matter of controversy. To address this issue, we studied phenotypical features in eight cases of DP T cell leukemia. Thymic DP T cells and peripheral CD8+ T cells have CD8 of alphabeta subunit, while CD8alphaalpha is induced in CD4+ T cells on activation with IL-4. We found that two patients with DP T large granular lymphocyte leukemia (LGLL) showed dim expression of CD8alphaalpha, identical to the phenotype on IL-4-activated DP-T cells. The leukemic cells of these patients expressed IL-4 mRNA and produced high levels of IL-4. These findings suggest that they may be derived from peripheral CD4+ T cells. Three patients with adult T cell leukemia/lymphoma (ATLL) showed CD8alphaalpha, suggestive of an activated peripheral T cell origin. One case expressed CD8alphaalpha dim and IL-4 mRNA, while the other two cases expressed no IL-4 mRNA and showed CD8alphaalpha bright phenotype, features not found in normal T cell populations. Three patients with T-prolymphocytic leukemia (T-PLL) expressed CD8alphabeta. The DP phenotype is relatively common in T-PLL, and CD4+CD8alphabeta+ is characteristic of thymic T cells. The DP T-PLL cells did not express TdT,CD1 or recombination activating gene-1 (RAG-1), which is down-regulated at the late stage of thymic T cell development. On the basis of these findings, we propose a late thymic origin for DP T-PLL. The phenotype of DP T cells differed for each entity and appeared to correlate with minor normal DP T cell population.

Adult↗
PubMed1999

CYP2D6 polymorphism in a Gabonese population: contribution of the CYP2D6*2 and CYP2D6*17 alleles to the high prevalence of the intermediate metabolic phenotype.

AIMS: To determine the molecular basis of the intermediate extensive metaboliser (EM) CYP2D6 phenotype in healthy Gabonese subjects. METHODS: The CYP2D6 phenotype of 154 healthy Gabonese subjects was assessed by giving the subject a single dose of 30 mg dextromethorphan, and collecting their urine for the next 8 h. The CYP2D6 genotype was determined for 50 individuals of the EM phenotypic group by Southern blotting and various PCR-based procedures aimed at identifying different CYP2D6 alleles. RESULTS: We found that in the studied Gabonese population, as compared with a French population, there is significantly higher frequency of intermediate EM phenotype having lower frequency of CYP2D6 PM alleles. To clarify this discrepancy phenotype-genotype relationship was studied. We found that the CYP2D6*17 and CYP2D6*2 alleles, prevalent in this black population, are characterised by their low capacity for dextromethorphan demethylation. Our data also show that the CYP2D6*1 allele is associated with the highest in vivo activity followed by the CYP2D6*2 allele and then the CYP2D6*17 allele. CONCLUSIONS: The higher frequencies of the CYP2D6*2 and CYP2D6*17 alleles than the CYP2D6*1 allele account for the high frequency of the intermediate EM phenotype in this black population. The polymorphism of the CYP2D6 enzyme activity in African populations could have important implications for use of drugs that are substrates for CYP2D6 and have a narrow therapeutic window.

Alleles↗
PubMed2001

Mephenytoin as a probe for CYP2C19 phenotyping:effect of sample storage, intra-individual reproducibility and occurrence of adverse events.

AIMS: To further evaluate mephenytoin as a probe for CYP2C19 phenotyping. METHODS: Healthy subjects (n = 2638) were phenotyped using the urinary (S)-mephenytoin to (R)-mephenytoin ratio. This method was evaluated for (a) the stability of the S/R-ratio following sample storage, (b) the intraindividual reproducibility of the ratio, and (c) the occurrence of adverse events. RESULTS: After prolonged storage, the S/R-ratio of samples from extensive metabolisers (EM) increased up to 85%. In 1.5% of the cases (1 out 66), this led to incorrect classification of phenotype. In EMs, but not in poor metabolisers (PMs), the S/R-ratio increased after acid treatment. The intraindividual reproducibility of the mephenytoin phenotyping procedure was 28%. No major side-effects were observed and there was no relationship between the incidence of side-effects and the phenotype of the subject. CONCLUSIONS: After prolonged storage the S/R-ratio significantly increased in EMs and, although low, the risk of incorrect classification should not be ignored. Our data support the use of mephenytoin as a safe drug for CYP2C19 phenotyping.

Aryl Hydrocarbon Hydroxylases↗
PubMed2001

Lymphomatoid papulosis with a natural killer-cell phenotype.

Lymphomatoid papulosis (LyP) is defined as a recurrent self-healing papulonodular eruption with the histological features of a (CD30+) cutaneous T-cell lymphoma. The atypical cells usually have a CD3+/-, CD4+/-, CD8-, CD30+, CD56- T-cell phenotype. We report an unusual case of LyP, in which the atypical cells expressed a CD3-, CD4-, CD8-, CD30+, CD56+ phenotype. Detailed phenotypic and genotypic analysis confirmed that these cells had a natural killer (NK)-cell phenotype. Lymphomas with an NK-cell phenotype usually have a poor prognosis. However, the waxing and waning of papular lesions for more than 20 years and the excellent response to low-dose oral methotrexate in this patient suggest similar clinical behaviour to LyP cases with a T-cell phenotype.

CD56 Antigen↗
PubMed1997

Long-term clinical outcome of B-cell chronic lymphocytic leukaemia patients in clinical remission phase evaluated at phenotypic level.

This retrospective study aimed to evaluate the long-term prognostic impact of phenotypic remission in B-cell chronic lymphocytic leukaemia (CLL) patients who have achieved clinical, haematological and bone-marrow complete remission (CR) after conventional chemotherapy. The clinical and phenotypic data of 77 CLL patients in CR with a median follow-up from CR achievement of 54 months (range 5-127) were analysed. 32 patients (42%) displayed a normalized phenotype as evaluated by k:lambda ratio or by CD5+/CD19+ cell numbers. Patients with normalized phenotype demonstrated a significantly higher incidence of female sex, a lower relapse rate, a trend for higher prevalence of stage A and a lower occurrence of CLL-related deaths. The relapse-free survival of patients with normalized phenotype was significantly longer (P = 0.02), whereas no difference in overall survival was found between the two groups. Interestingly, Binet's stage at diagnosis was highly predictive of the overall survival following CR achievement. From the results of the present study we conclude that a phenotype normalization at CR obtained with conventional chemotherapy indicates a higher probability of a longer CR but it does not translate into prolonged survival. Clinical features at diagnosis, such as stage distribution, are apparently stronger predictors of the final outcome. These results emphasize, however, the need for a routine assessment of the quality of response since this information could be crucial in designing therapeutic strategies for young patients suffering from advanced CLL.

Adult↗
PubMed2003

Characterization of wheezing phenotypes in the first 10 years of life.

BACKGROUND: Childhood wheezing illnesses are characterized into different phenotypes. However, severity of the disease associated with these phenotypes has not been extensively studied. OBJECTIVES: To determine characteristics of childhood wheezing phenotypes in the first decade of life using health outcomes plus measurements of atopy, lung function and bronchial hyper-responsiveness. METHODS: A whole population birth cohort (n = 1456) was prospectively studied to examine the natural history of childhood wheezing. Children were seen at 1, 2, 4 and 10 years for questionnaire completion and prospectively collected data used to define wheezing phenotypes. Assessment was made of adverse health outcomes plus spirometry, bronchial hyper-responsiveness, serum IgE measurement at 10 years and skin test sensitization at both 4 and 10 years for wheezing phenotypes. RESULTS: Phenotypic analysis identified that 37% early life wheezers (symptom onset by age 4 years) still wheezed at 10 years. These persistent wheezers showed significantly more physician-diagnosed asthma in early life (P < 0.005 at 2 years) than early transient wheezers (wheezing transiently with onset by age 4 years). Overall they experienced greater multiple hospital admissions (P = 0.024), specialist referral (P = 0.009) and use of inhaled (P < 0.001) and oral steroids (P < 0.001) than early transient wheezers. They also demonstrated enhanced bronchial hyper-responsiveness compared with early transient wheezers (P < 0.001). However, both groups of early life wheezers showed impairment of baseline lung function at 10 years in comparison with non-wheezers: FEV1 (P < 0.029) and FEV1/FVC ratio (P < 0.001) with persistent wheeze and PEF (P = 0.036) with early transient wheeze. Late-onset wheezers (onset from 5 years onwards) had similar BHR to persistent wheezers but maintained normal lung function at age 10 and had lower cumulative prevalence of adverse health outcomes than persistent wheezers. CONCLUSIONS: Persistent wheezing with early childhood onset is associated with substantial morbidity in the first decade of life in association with high levels of atopy, bronchial hyper-responsiveness and impaired lung function at 10 years of age. Late-onset wheezing in the first decade of life could harbour potential for similarly significant disease subsequently.

Age of Onset↗
PubMed2002

Paradoxical hyperfibrinolysis is associated with a more intensely haemorrhagic phenotype in severe congenital haemophilia.

To elucidate potential causes for differing bleeding phenotypes of haemophilic patients of identical degree of coagulation factor deficiency, we investigated 21 male patients with severe haemophilia. Median annual coagulation factor demand and the extent of haemophilic arthropathy were used to discriminate between intensely and less intensely haemorrhagic phenotypes. Haemophiliacs with a median annual coagulation factor demand of 800 IU per kg bodyweight or more and with three or more joints affected by haemophilic arthropathy represented the intensely haemorrhagic phenotype group; all other patients comprised the less intense group. The discriminator values represent the respective medians of the overall group. The results of activated partial thromboplastin time, endogenous thrombin potential, pro- and anticoagulant factor analysis did not differ between the two groups. Median tissue-type plasminogen activator concentration (TPA) was elevated significantly in haemophiliacs with an intensely haemorrhagic phenotype, as was the activity of the thrombin-activatable fibrinolysis inhibitor. Median activity of the plasminogen activator inhibitor 1 (PAI 1) and the concentration of TPA-PAI 1 complexes were increased to approximately double those in nonsevere haemophiliacs. Coexistent congenital thrombophilia was found significantly more often in the less intensely haemorrhagic group. Thus, increased stimulation of the fibrinolytic system was associated with a more intensely haemorrhagic phenotype in our patients. We hypothesize that ineffective haemophilic haemostasis in response to trauma evokes a protracted stimulation of the entire haemostatic system, including costimulation of fibrinolysis. The absence of coexistent congenital thrombophilia predisposes to excess stimulation of fibrinolysis, which cannot be downregulated effectively due to the dysfunctional intrinsic pathway. The association of a more intensely haemorrhagic phenotype with a paradoxical hyperstimulation of the fibrinolytic system resembles a vicious circle, where bleeding seems to cause predisposition to more bleeding.

Adolescent↗
PubMed1999

Genotypic and phenotypic alterations in Epstein-Barr virus-associated lymphoma.

AIMS: Epstein-Barr virus (EBV) is associated with numerous reactive and neoplastic lymphoproliferative disorders. In vitro, EBV infection can transform B-lymphocytes and induce phenotypic alterations. This study presents the clinicopathological features of four cases with malignant lymphoma, which showed phenotypic and/or genotypic alterations during the course of the disease. METHODS AND RESULTS: To determine the type of EBV genotype, we performed polymerase chain reaction (PCR) for lymphocyte-defined membrane antigen (LYDMA) of EBV, subtype A/B and latent membrane protein (LMP)-1 deletion. In addition, we analysed the terminal repeat (TR) band of EBV and receptor genes (T-cell receptor gene, TCR; immunoglobulin gene heavy chain, IgH) for EBV-infected cell clonality. Double staining of cell markers (B, T-lymphocytes; histiocytes), and in-situ hybridization (ISH) for EBV were performed using tissues obtained during the course of the disease. The first case showed genotypic and phenotypic alterations of T-cell type to B-cell type. The first TCR rearrangement and T-cell markers (CD3+, CD4+, CD8-) were lost and IgH rearrangement and B-cell markers (CD19+, CD20+) were identified. During the course of the disease, EBV-TR bands changed in size; however, the EBV genotype type B, LMP1 deletion type, and single LYDMA band remained the same. The initial T-cell lymphoma clone was considered to be different from the latter B-cell lymphoma clone. The second case showed phenotypic alterations. The first B-cell marker (CD19+, CD20+, CD68-) changed to histiocytic markers (CD19-, CD20-, CD68+). However, IgH rearrangement and EBV-TR bands remained the same throughout the course of the disease and EBV genotype type A, LMP1 deletion type, and single LYDMA band remained unchanged. The third case showed phenotypic alterations. The B-cell marker (CD20+) was lost; however, IgH rearrangement of PCR and EBV genotype remained the same. In the second and third cases, the initial lymphoma clones were considered to be same as the latter clones. The last case showed lineage alterations from Hodgkin's disease to natural killer (NK) cell leukaemia. However, EBV genotype did not change. The second case and Hodgkin's disease showed LMP expression, but the first and third cases showed no LMP, and EBNA2 was not detected in all cases. CONCLUSIONS: We report the genotypic and/or phenotypic alterations in four patients with EBV-associated lymphoma/leukaemia. However, EBV genotype did not change in all four. These findings suggest that EBV might induce the cell marker and lineage alteration in vivo, as in vitro.

Adult↗
PubMed2003

Identification of campylobacteria isolated from Danish broilers by phenotypic tests and species-specific PCR assays.

AIMS: To validate a phenotypic Campylobacter species identification method employed to identify campylobacters in broilers by comparison with campylobacterial species identification using various species-specific PCR analyses. METHODS AND RESULTS: From a collection of 2733 phenotypically identified campylobacterial cultures, 108 Campylobacter jejuni cultures and 351 campylobacterial cultures other than Camp. jejuni were subjected to various species-specific PCR assays. On the basis of the genotypic tests, it was demonstrated that Camp. jejuni and Camp. coli constituted approx. 99% of all cultures, while other species identified were Helicobacter pullorum, Camp. lari and Camp. upsaliensis. However, 29% of the 309 Camp. coli cultures identified by phenotypic tests were hippurate-variable or negative Camp. jejuni cultures, whereas some Camp. lari cultures and unspeciated campylobacter cultures belonged to H. pullorum. It was also notable that 2-6% of the cultures were, in fact, mixed cultures. CONCLUSIONS: The phenotypic identification scheme employed failed to appropriately differentiate Campylobacter species and particularly to identify the closely related species, H. pullorum. SIGNIFICANCE AND IMPACT OF THE STUDY: Future phenotypic test schemes should be designed to allow a more accurate differentiation of Campylobacter and related species. Preferably, the phenotypic tests should be supplemented with a genotypic strategy to disclose the true campylobacterial species diversity in broilers.

Animals↗
PubMed2003

Polymorphism of a complex resistance gene candidate family in wild populations of common bean (Phaseolus vulgaris) in Argentina: comparison with phenotypic resistance polymorphism.

Fifteen populations of wild bean (Phaseolus vulgaris), located in three provinces in Argentina, were analysed for their polymorphism for a complex resistance gene candidate (RGC) family clustered on the genome and for resistance phenotypes to strains of Colletotrichum lindemuthianum. Results indicate that RGC polymorphism is high. Population structure obtained for markers related to resistance was compared to population structure obtained for RAPD markers in order to infer the evolutionary forces driving polymorphism for resistance in wild populations at both molecular and phenotypic levels. Hierarchical analysis of differentiation showed that, within provinces, populations were differentiated for RAPD as well as for molecular and phenotypic markers of resistance. In contrast, provinces were differentiated only for RAPD and RGC markers and not for resistance phenotypes. The discrepancies found between diversity structures for molecular markers (RAPD and RGCs) and for resistance phenotypes suggest an effect of selection and indicate that diversity for resistance may not be driven by the same selective forces at the molecular and phenotypic levels. We further discuss whether specific selective forces are exerted on RGC markers and underline the importance of spatial scale of analysis for demonstrating an impact of selection.

Argentina↗
PubMed1998

Heterogeneity of the blood group Ax allele: genetic recombination of common alleles can result in the Ax phenotype.

The Ax phenotype is an important subgroup of the ABO blood group system. Its inheritance does not always follow Mendelian rules and recent studies suggested that different alleles can result in this phenotype. This suggestion has been explored by cloning and sequencing exons 6 and 7 of the ABO gene and the intervening intron from members of six unrelated families expressing the Ax phenotype. Two families showed the previously described T646A 'Ax' mutation as the only deviation from the consensus A1 allele. In two other families the Ax phenotype was inherited as two different recombinational gene products. Combination of exon 6 derived from A or B/O2 alleles with exon 7 from the O1v allele created two novel alleles that have four O1v-characteristic nucleotide substitutions in exon 7, including T646A. Sequencing and analysis of polymorphisms in intron 6 defined the crossing-over zones of these hybrid alleles. Southern blot confirmed the hybrid formation by detecting ABO-related polymorphisms approximately 1.35 kb downstream from the ABO reading frame. The remaining two families expressed the Ax phenotype via an allele having A2-specific mutations. Thus, a heterogeneous molecular background leads to the serologically defined Ax phenotype and may well explain the different modes of inheritance observed.

ABO Blood-Group System↗