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PubMed1996

Confirmational identification of Escherichia coli, a comparison of genotypic and phenotypic assays for glutamate decarboxylase and beta-D-glucuronidase.

Genotypic and phenotypic assays for glutamate decarboxylase (GAD) and beta-D-glucuronidase (GUD) were compared for their abilities to detect various strains of Escherichia coli and to discriminate among other bacterial species. Test strains included nonpathogenic E. coli, three major groups of diarrheagenic E. coli, three other non-coli Escherichia species, and various other gram-negative and -positive bacteria found in water. The genotypic assays were performed with hybridization probes generated by PCR amplification of 670- and 623-bp segments of the gadA/B (GAD) and uidA (GUD) genes, respectively. The GAD enzymes catalyze the alpha-decarboxylation of L-glutamic acid to yield gamma-aminobutyric acid and carbon dioxide, which are detected in the phenotypic assay by a pH-sensitive indicator dye. The phenotypic assay for GUD involves the transformation of 4-methylumbelliferyl-beta-D-glucuronide to the fluorogenic compound 4-methylumbelliferone. The GAD phenotypic assay detected the majority of the E. coli strains tested, whereas a number of these strains, including all representatives of the O157:H7 serotype and several nonpathogenic E. coli strains, gave negative results in the GUD assay. Both phenotypic assays detected some but not all strains from each of the four Shigella species. A strain of Citrobacter freundii was also detected by the GUD assay but not by the GAD assay. All E. coli and Shigella strains were detected with both the gadA/B and uidA probes. A few Escherichia fergusonii strains gave weak hybridization signals in response to both probes at 65 degrees C but not at 68 degrees C. None of the other bacterial species tested were detected by either probe. These results were consistent with previous reports which have indicated that the GAD phenotypic assay detects a wider range of E. coli strains than does the GUD assay and is also somewhat more specific for this species. The genotypic assays for the two enzymes were found to be equivalent in both of these respects and superior to both of the phenotypic assays in terms of the range of E. coli strains and isolates detected.

Base Sequence↗
PubMed1996

Antibody-mediated shift in the profile of glycoprotein A phenotypes observed in a mouse model of Pneumocystis carinii pneumonia.

It is well established that Pneumocystis carinii has the molecular capability for variation of a major surface antigen, glycoprotein A (gpA). However, the extent of expression of gpA variation among P. carinii organisms infecting a single host and whether this variation has any impact on host-parasite immunological interactions is unknown. Using a mouse model of P. carinii pneumonia, we were able to demonstrate the expression of more than one gpA phenotype in a closed population of infected mice. Administration of monoclonal antibody (MAb) 2B5, which is specific for one of the gpA phenotypes, resulted in a marked diminution in the frequency of this particular gpA phenotype in the population of organisms. This effect was due to a loss of trophozoites bearing the specific epitope recognized by MAb 2B5; cysts bearing the same epitope appeared unaffected. Interestingly, P. carinii was unable to introduce a new phenotype into the population to compensate for the loss of trophozoites bearing the epitope recognized by MAb 2B5. Discontinuing administration of MAb 2B5 allowed the MAb 2B5-binding phenotype to reemerge. This finding suggests that the phenotype recognized by MAb 2B5 was continually produced even when MAb 2B5 was present. Thus, although P. carinii exhibited a form of antigenic variation, it did not appear able to rapidly introduce new phenotypes into the population in response to destruction by antibodies.

Animals↗
PubMed1999

Control of white-opaque phenotypic switching in Candida albicans by the Efg1p morphogenetic regulator.

Phenotypic switching in Candida albicans spontaneously generates different cellular morphologies and is manifested in strain WO-1 by the reversible switching between the white and opaque phenotypes. We present evidence that phenotypic switching is regulated by the Efg1 protein, which is known as an essential element of hyphal development (dimorphism). Firstly, EFG1 is expressed specifically in cells of the white but not the opaque phenotype. During mass conversion from the opaque to the white phenotype, the EFG1 transcript level correlates with competence of switching of opaque cells to the white form. Secondly, overexpression of EFG1 by a PCK1p-EFG1 fusion forces opaque-phase cells to switch to the white form with a high level of efficiency. Thirdly, low-level expression of EFG1 in strain CAI-8 generates a cellular phenotype similar to that of opaque cells in that cells bud as short rods, which cannot be induced to form hyphae in standard conditions; such cells (unlike authentic opaque cells) lack typical surface "pimples." Importantly, the opaque-specific OP4 transcript is induced in the opaque-like cells generated by strain CAI8 as a response to low-level expression of EFG1. The results suggest that high EFG1 expression levels induce and maintain the white cell form while low EFG1 expression levels induce and maintain the opaque cell form. It is proposed that changes in EFG1 expression determine or contribute to phenotypic switching events in C. albicans.

Candida albicans↗
PubMed2002

Phenotypic selection and phase variation occur during alfalfa root colonization by Pseudomonas fluorescens F113.

During colonization of the alfalfa rhizosphere, Pseudomonas fluorescens F113 undergoes phenotypic variation, resulting in the appearance of colonies with different morphology. Among phenotypic variants, three isolates, C, F, and S were selected, with the C variant showing colony morphology identical to that of the inoculated wild-type strain and F and S having a translucent and diffuse morphology. Phenotypic variants F and S were shown to preferentially colonize distal parts of the roots and showed alterations in motility, swimming faster than the C variant and swarming under conditions that did not allow swarming of the C variant. The motility behavior correlated with overproduction of the fliC-encoded protein flagellin but not with hyperflagellation. Flagella of the F and S variants were several times longer than those of the C variant, and overproduction of flagellin was regulated at the transcriptional level. Variant F showed alterations in traits that have been shown to be important for rhizosphere colonization, such as siderophore, cyanide, and exoprotease production, and these phenotypes were complemented by a cloned gacA. Sequence analysis of the gacA alelle in variant F suggested selection of the phenotype in the rhizosphere. Variant F was also affected in other phenotypes, such as lipopolysaccharide structure and flocculation in unshaken liquid medium, which were not complemented by the gacA or gacS gene. Mutation of the F113 sss gene, encoding a site-specific recombinase, showed that most of the phenotypic variation was due to the activity of this recombinase, indicating that phase variation occurs during rhizosphere colonization.

Alleles↗
PubMed1990

T-cell lymphoma lines derived from rat thymomas induced by Moloney murine leukemia virus: phenotypic diversity and its implications.

The phenotype of 27 Moloney murine leukemia virus-induced rat thymic lymphomas and 36 cell lines derived from these tumors was determined by using 18 monoclonal antibodies directed against hematopoietic cell surface determinants. The cell lines and the primary tumors from which they were derived were clonally related as determined by the pattern of provirus integration and the pattern of rearrangement of the T-cell receptor beta and delta and Igh loci. The differentiation phenotype of the primary tumors and the cell lines derived from them were related. The differences observed between the primary tumors and the cell lines could be explained either by the selection of subpopulations of tumor cells during establishment in culture or by the phenotypic instability of the tumor cells. One cell line (LE3Sp) underwent the transition from a CD4+ CD8+ to a CD4+ CD8- phenotype following exposure to interleukin-2 in culture. Both the primary tumors and the cell lines derived from them express a wide range of phenotypes which correspond to multiple stages in T-cell development. This observation suggests that the pleiomorphism of retrovirus-induced lymphomas, which had been suggested previously from the analysis of mouse tumors, is an intrinsic property of the process of oncogenesis and is not due to the transformation of different types of cells by spontaneously arising leukemogenic variants of the inoculated virus. The wide spectrum of phenotypes expressed by these tumors suggests that Moloney murine leukemia virus may infect and transform T cells at various stages of development. Alternatively, the target cells may be immature T-cell precursors which, following transformation, continue to differentiate. A host of early findings, suggesting that the repertoire of target cells is restricted to poorly differentiated hematopoietic progenitors, and the ability of the LE3Sp cell line to differentiate in culture indicate that the latter possibility may be more likely. The data in this report address the extent and mechanism of the phenotypic variability of retrovirus-induced rodent T-cell lymphomas. In addition, they demonstrate the potential usefulness of the T-cell lymphoma lines we have established in studies of oncogenesis and T-cell differentiation.

Animals↗
PubMed2005

A herpes simplex virus type 1 mutant expressing a baculovirus inhibitor of apoptosis gene in place of latency-associated transcript has a wild-type reactivation phenotype in the mouse.

The latency-associated transcript (LAT) is essential for the wild-type herpes simplex virus type 1 (HSV-1) high-reactivation phenotype since LAT- mutants have a low-reactivation phenotype. We previously reported that LAT can decrease apoptosis and proposed that this activity is involved in LAT's ability to enhance the HSV-1 reactivation phenotype. The first 20% of the primary 8.3-kb LAT transcript is sufficient for enhancing the reactivation phenotype and for decreasing apoptosis, supporting this proposal. For this study, we constructed an HSV-1 LAT- mutant that expresses the baculovirus antiapoptosis gene product cpIAP under control of the LAT promoter and in place of the LAT region mentioned above. Mice were ocularly infected with this mutant, designated dLAT-cpIAP, and the reactivation phenotype was determined using the trigeminal ganglion explant model. dLAT-cpIAP had a reactivation phenotype similar to that of wild-type virus and significantly higher than that of (i) the LAT- mutant dLAT2903; (ii) dLAT1.5, a control virus containing the same LAT deletion as dLAT-cpIAP, but with no insertion of foreign DNA, thereby controlling for potential readthrough transcription past the cpIAP insert; and (iii) dLAT-EGFP, a control virus identical to dLAT-cpIAP except that it contained the enhanced green fluorescent protein open reading frame (ORF) in place of the cpIAP ORF, thereby controlling for expression of a random foreign gene instead of the cpIAP gene. These results show that an antiapoptosis gene with no sequence similarity to LAT can efficiently substitute for the LAT function involved in enhancing the in vitro-induced HSV-1 reactivation phenotype in the mouse.

Animals↗
PubMed1995

Apolipoprotein E phenotypes in patients with gout: relation with hypertriglyceridaemia.

OBJECTIVE: To elucidate the relationship, if any, between lipid abnormalities and apolipoprotein E (apo E) polymorphism, by investigating apo E phenotype and allele frequency. METHODS: Fasting blood samples were taken for determination of apo E phenotype and serum lipids in 221 male patients with gout and 141 control male subjects. Apo E phenotype was determined by one dimensional flat gel isoelectric focusing. RESULTS: Frequencies of apo E phenotypes in gout were apo E3/3 67.9%, E4/3 18.1%, E4/4 2.3%, E4/2 1.8%, E3/2 9.5%, and E2/2 0.5%; those in control male subjects were 74.5%, 15.6%, 0%, 1.4%, 7.1%, and 1.4%, respectively. Frequencies of the e2, e3, and e4 alleles in gout were 0.061, 0.817 and 0.122, compared with the corresponding control frequencies of 0.057, 0.858 and 0.085. These differences in apo E phenotype and allele frequencies between gout and control subjects were not significant. The frequency of apo e4 allele in hyperlipidaemic gout subjects was significantly greater than that in normolipidaemic gout subjects; in contrast, its frequency was not different between hyperlipidaemic and normolipidaemic control subjects. Serum triglyceride, total cholesterol, apo B and E concentrations were significantly greater in gouty patients with the apo E4/3 phenotype than in those with gout having the apo E3/3 phenotype. CONCLUSIONS: These data suggest that gout subjects with hyperlipidaemia (hypertriglyceridaemia, hypercholesterolaemia or both) possess the apo e4 allele with higher frequency than those with normolipidaemia. They also suggest that apo e4 may induce some susceptibility to the development of hyperlipidaemia in gout in addition to that induced by obesity or excessive alcohol consumption, and may contribute to the high prevalence of atherosclerotic diseases in gout patients.

Alleles↗
PubMed1993

GSTM1 null polymorphism at the glutathione S-transferase M1 locus: phenotype and genotype studies in patients with primary biliary cirrhosis.

Studies were carried out to test the hypothesis that the GSTM1 null phenotype at the mu (mu) class glutathione S-transferase 1 locus is associated with an increased predisposition to primary biliary cirrhosis. Starch gel electrophoresis was used to compare the prevalence of GSTM1 null phenotype 0 in patients with end stage primary biliary cirrhosis and a group of controls without evidence of liver disease. The prevalence of GSTM1 null phenotype in the primary biliary cirrhosis and control groups was similar; 39% and 45% respectively. In the primary biliary cirrhosis group all subjects were of the common GSTM1 0, GSTM1 A, GSTM1 B or GSTM1 A, B phenotypes while in the controls, one subject showed an isoform with an anodal mobility compatible with it being a product of the putative GSTM1*3 allele. As the GSTM1 phenotype might be changed by the disease process, the polymerase chain reaction was used to amplify the exon 4-exon 5 region of GSTM1 and show that in 13 control subjects and 11 patients with primary biliary cirrhosis, GSTM1 positive and negative genotypes were associated with corresponding GSTM1 expressing and non-expressing phenotypes respectively. The control subject with GSTM1 3 phenotype showed a positive genotype.

Base Sequence↗
PubMed1999

HLA-DR and -DQ phenotypes in inflammatory bowel disease: a meta-analysis.

BACKGROUND: Susceptibility to inflammatory bowel disease (IBD) is partially genetically determined and the HLA class II genes are candidates for a role in genetic susceptibility to IBD, because their products play a central role in the immune response. Multiple studies have reported associations between HLA-DR or -DQ phenotypes and either ulcerative colitis or Crohn's disease, but much of the data are still controversial. AIMS: To estimate overall associations between HLA class II phenotypes and IBD, and to establish the relative risk conferred by HLA-DR and -DQ phenotypes by meta-analysis. METHODS: Medline was searched for publications reporting on the relation between IBD and HLA class II phenotypes. Raw data were extracted by recalculating the number of phenotypes or the number of alleles of the main antigens. Odds ratios and confidence intervals were calculated according to the Mantel-Haenszel method. RESULTS: DR2, DR9, and DRB1*0103 were positively associated with ulcerative colitis, and a negative association was found for DR4 and ulcerative colitis. For Crohn's disease a positive association was found with DR7, DRB3*0301, and DQ4 and a negative association with DR2 and DR3. CONCLUSIONS: Both ulcerative colitis and Crohn's disease are associated with specific HLA class II phenotypes. Further analysis of these phenotypes and subgroup analysis may elucidate how these alleles contribute to susceptibility to IBD.

Biomarkers↗
PubMed1996

Phenotypic changes in acute myeloid leukaemia: implications in the detection of minimal residual disease.

AIM: To explore the role of phenotypic changes as possible limiting factors in the immunological detection of minimal residual disease in patients with acute myeloid leukaemia (AML). METHODS: 20 relapses were evaluated, with special attention to changes in the criteria used for the definition of a phenotype as "aberrant". In all cases the same monoclonal antibody and fluorochrome were used at diagnosis and in relapse. RESULTS: Six out of the 16 patients showed aberrant phenotypes at diagnosis. At relapse, no changes in the aberrant phenotypes were detected in most of the patients; nevertheless, in two of the four patients with asynchronous antigen expression this aberration disappeared at relapse. At diagnosis in both cases there were already small blast cell subpopulations showing the phenotype of leukaemic cells at relapse. Ten out of the 16 cases analysed showed significant changes in the expression of at least one of the markers analysed. CONCLUSIONS: At relapse in AML the "leukaemic phenotypes" usually remained unaltered, while other phenotypic features--not relevant for distinguishing leukaemic blast cells among normal progenitors--changed frequently; however, they were not a major limitation in the immunological detection of minimal residual disease.

Acute Disease↗
PubMed1997

Gastric mucous neck cell and intestinal goblet cell phenotypes in gastric adenocarcinoma.

AIM: To investigate the phenotype of cells comprising diffuse and intestinal-type gastric cancers using monoclonal antibodies to two antigens. One antigen (designated D10) is characteristic of gastric mucous neck cells, cardiac glands, pyloric glands, and Brunner's glands. The second antigen (designated 17NM) is specific to the mucous vacuole of intestinal goblet cells. METHODS: Thirty two gastrectomy specimens with adenocarcinoma were studied. Serial paraffin sections were stained immunohistochemically for D10 and 17NM and histochemically for acid and neutral mucins. The cancers were classified histologically as of either diffuse or intestinal type according to Lauren. RESULTS: Of 15 diffuse-type gastric carcinomas, 11 showed the majority of cancer cells staining for D10 while four were typical signet ring cell cancers staining predominantly for 17NM; five tumours displayed both phenotypes with the two phenotypes segregated in different areas of the tumours. In contrast, of 16 intestinal-type cancers, six expressed 17NM, three D10, five neither antigen, and two expressed both antigens. One indeterminate-type cancer expressed both antigens. The staining of individual cells for D10 and 17NM was mutually exclusive in both diffuse and intestinal types. In contrast to the diffuse cancers, intestinal-type cancers typically expressed either antigen only in occasional small groups of cells and individual cells. CONCLUSIONS: In disease, the gastric stem cell can assume the capacity of the duodenal stem cell for divergent differentiation into either intestinal goblet cells (for example, as in intestinal metaplasia) or Brunner's gland cells (for example, as in pyloric gland/Brunner's gland metaplasia). With neoplastic transformation, this potential for divergent differentiation is maintained and gives rise to diffuse-type cancers that display either the D10 phenotype, the 17NM phenotype, or the clonal expression of both phenotypes. In the more cell cohesive (intestinal-type) tumours, differentiation for antigen expression is poorly developed and more frequently directed towards the intestinal goblet cell phenotype.

Adenocarcinoma↗
PubMed2005

Phenotype of triploid embryos.

The phenotypes of triploid fetuses and placentae are now well established and known to correlate with parental origin of the extra haploid set of chromosomes. In fetuses, it is not clear whether there is a direct parent of origin effect on the fetus itself or if the phenotypes are the result of growth differences influenced by abnormalities in growth and function of the placenta. Examining the phenotype of triploid embryos at an earlier stage in gestation, when the placenta effects may be less pronounced, could help clarify this question. A phenotype characteristic of triploidy in the embryonic period has been described; however, parental origin was not determined in these embryonic cases. In the present study, a population of triploid embryos is assessed to determine if there is a correlation between parental origin and phenotype. Parental origin was determined in 27 first trimester miscarriages. Digyny accounted for 19 cases and diandry for eight cases. Assessment of embryonic phenotype with parental origin showed no correlation between the phenotype of the embryo and parental origin of the extra haploid set. While there may be subtle effects of imprinting on embryonic development, they are not as obvious as they are in the mouse, consistent with the general trend of fewer imprinted genes in human beings compared with the mouse.

Congenital Abnormalities↗
PubMed1994

ANG II receptor expression and function during phenotypic modulation of rat aortic smooth muscle cells.

Angiotensin II (ANG II) receptors were investigated in primary cultured rat aortic smooth muscle cells (SMC) that expressed either a proliferative phenotype (during the growth phase) or a contractile phenotype (at postconfluence). For each phenotype, alpha-smooth muscle actin expression, 125I-labeled ANG II specific binding, D-myo-inositol 1,4,5-triphosphate [Ins(1,4,5)P3] production, and ANG II-mediated increases in intracellular calcium (Cai2+) were studied. In both phenotypes, 1) ANG II-specific high-affinity binding (KD 0.5 +/- 0.1 nM and Bmax 196 +/- 106 pmol/mg protein in proliferative state, KD 1.5 +/- 0.3 nM and Bmax 560 +/- 299 pmol/mg protein in postconfluent state) was entirely inhibited by the selective AT1-antagonist losartan as well as by [Sar1,Ala8]ANG II and ANG III; 2) the AT2-antagonist CGP 42112A was ineffective, except at very high concentrations (> or = 10 microM); 3) the specific binding of ANG II was inhibited by guanosine 5'-[gamma-thio]triphosphate; and 4) ANG II induced a losartan-sensitive increase in Ins(1,4,5)P3. In postconfluent cultures, ANG II elicited a rapid biphasic elevation in Cai2+, which was abolished by losartan, whereas in growing cultures, this response was either absent or greatly attenuated. It is concluded that AT1-receptors coupled to phospholipase C via a G protein are expressed in the proliferative as well as in the contractile SMC phenotype and that their coupling to Cai2+ release is impaired in the proliferative phenotype. No evidence for AT2-receptor expression during phenotypic modulation of SMC was found.

Actins↗
PubMed2001

PKCepsilon activation induces dichotomous cardiac phenotypes and modulates PKCepsilon-RACK interactions and RACK expression.

Receptors for activated C kinase (RACKs) have been shown to facilitate activation of protein kinase C (PKC). However, it is unknown whether PKC activation modulates RACK protein expression and PKC-RACK interactions. This issue was studied in two PKCepsilon transgenic lines exhibiting dichotomous cardiac phenotypes: one exhibits increased resistance to myocardial ischemia (cardioprotected phenotype) induced by a modest increase in PKCepsilon activity (228 +/- 23% of control), whereas the other exhibits cardiac hypertrophy and failure (hypertrophied phenotype) induced by a marked increase in PKCepsilon activity (452 +/- 28% of control). Our data demonstrate that activation of PKC modulates the expression of RACK isotypes and PKC-RACK interactions in a PKCepsilon activity- and dosage-dependent fashion. We found that, in mice displaying the cardioprotected phenotype, activation of PKCepsilon enhanced RACK2 expression (178 +/- 13% of control) and particulate PKCepsilon-RACK2 protein-protein interactions (178 +/- 18% of control). In contrast, in mice displaying the hypertrophied phenotype, there was not only an increase in RACK2 expression (330 +/- 33% of control) and particulate PKCepsilon-RACK2 interactions (154 +/- 14% of control) but also in RACK1 protein expression (174 +/- 10% of control). Most notably, PKCepsilon-RACK1 interactions were identified in this line. With the use of transgenic mice expressing a dominant negative PKCepsilon, we found that the changes in RACK expression as well as the attending cardiac phenotypes were dependent on PKCepsilon activity. Our observations demonstrate that RACK expression is dynamically regulated by PKCepsilon and suggest that differential patterns of PKCepsilon-RACK interactions may be important determinants of PKCepsilon-dependent cardiac phenotypes.

Amino Acid Sequence↗
PubMed1996

Two temporally overlapping "delayed-rectifiers" determine the voltage-dependent potassium current phenotype in cultured hippocampal interneurons.

1. Whole cell voltage-clamp recordings were used to characterize the calcium-independent "delayed-rectifier" potassium currents of gamma-aminobutyric acid (GABA)-positive stratum radiatum-lacunosum-moleculare (st. L-M) interneurons in primary culture derived from neonate rats [postnatal day 5-7 (P5-P7)]. 2. Two distinct current phenotypes were observed, which we termed "sustained" and "slowly inactivating." Despite possessing similar voltage-dependent activation properties, current differed in their time-dependent inactivation properties and their kinetics of activation and deactivation. The phenotypes of the observed currents did not change during the time in vitro. The total current phenotype observed in any cell likely resulted from the temporal overlap of the two current components expressed in different relative proportions. 3. Externally applied 4-aminopyridine (4-AP) selectively blocked the slowly inactivating current component, by a use-dependent, but voltage-independent mechanism, suggesting that channel activation is required for 4-AP to interact with its binding site. In contrast, the sustained current component was unaffected by 4-AP. 4. Both the slowly inactivating and sustained current phenotypes were sensitive to externally applied tetraethylammonium (TEA). The IC50 of block by TEA was lower in cells expressing predominantly the sustained current components. 5. Currents recorded in the presence of internally applied TEA were of a slowly inactivating phenotype, suggesting that [TEA]i preferentially blocked the sustained current component. 6. When test pulses were preceded by a prepulse to -100 mV, a transient A-type current component was observed, but in contrast to pyramidal neurons and other interneuron types, this transient current contributed only a minor component to the total initial peak current. 7. In conclusion, two distinct, temporally overlapping potassium current phenotypes were observed on st. L-M interneurons. The overall phenotype was determined by the relative proportion of each current component. The absence of a prominent transient current suggests that the two delayed-rectifier currents play a critical role in determining the firing characteristics of these interneurons.

4-Aminopyridine↗
PubMed1992

The involvement of the intestinal microflora in the expansion of CD4+ T cells with a naive phenotype in the periphery.

It is well known that immune reactivity declines with age. Recently, we demonstrated that the age-related decrease in IL-2 production by CD4+ T cells was accompanied by an increased production of IL-4 and interferon-gamma (IFN-gamma). This age-related shift in the profile of lymphokine production was related to phenotypic changes within the CD4+ T-cell subset, that is, a decrease in the percentage of CD45RB++ CD4+ T cells and an increase in the percentage of Pgp-1+ CD4+ T cells. To study whether these age-related changes were due to previous antigenic exposure, we performed a phenotypic and functional analysis on splenic CD4+ T cells isolated from individual germ-free (GF), specific pathogen-free (SPF), and clean conventional (CC) mice. Interestingly, the total number of splenic CD4+ T cells in GF mice was twofold lower as compared to age-matched SPF or CC mice, regardless whether mice were analyzed at young (10 weeks) or at advanced age (13-14 months). Unexpectedly, the phenotypic composition of the CD4+ T-cell subset was comparable in the GF, SPF, and CC mice as determined by the expression of CD45RB and Pgp-1, indicating that CD4+ T cells with a naive phenotype (CD45RB++ Pgp-1-) were not enriched in GF mice. Moreover, at an age of 13-14 months, CD4+ T cells from GF mice frequently produced more IL-4 and IFN-gamma than their CC counterparts. These lymphokine data showed, therefore, that a relatively high proportion of CD4+ T cells with a memory phenotype can also be defined in GF mice on the basis of their function. The contamination of GF mice with a colonization resistant factor (CRF flora) resulted in twofold higher numbers of splenic CD4+ T cells. Surprisingly, not only CD4+ T cells with a memory phenotype (CD45RB-/+ Pgp-1++) had expanded, but also CD4+ T cells with a naive (CD45RB++ Pgp-1-) phenotype. Our results, therefore, strongly suggest that the expansion of naive CD4+ T cells in the periphery is mediated by the intestinal microflora.

Animals↗
PubMed2000

Relationship of lipoprotein(a) and its phenotypes with the albumin excretion rate in diabetic patients: a multivariate analysis.

BACKGROUND/AIM: The possible association between lipoprotein(a) [Lp(a)] and albumin excretion rate (AER) is a topic that has generated conflicting views. The aim of this study was to determine the relationship between serum Lp(a) concentrations and AER in diabetic patients, taking into account Lp(a) phenotypes in a multivariate analysis. METHODS: For this purpose 191 consecutive diabetic patients (69 type 1 and 122 type 2) were included in the study. Lp(a) was determined by ELISA and its phenotypes by SDS-PAGE followed by immunoblotting. Lp(a) phenotypes were grouped by size in small (F, B, S1, S2), big (S3, S4) and null. RESULTS: Diabetic patients with an AER >20 microg/min presented higher Lp(a) concentrations than patients with an AER <20 microg/min: median 19 mg/dl versus 5 mg/dl (p < 0.0001). The differences remained at a significant level when the type of diabetes was considered. A linear correlation was observed between Lp(a) concentration and AER (type 1: r = 0.32, p = 0.01; type 2: r = 0.25, p < 0.05). The AER was independently correlated with Lp(a) concentrations in a multiple regression analysis (p < 0.01), and Lp(a) was independently associated with the presence of diabetic nephropathy in the logistic regression analysis. The overall frequency distribution of Lp(a) phenotypes differed significantly between patients with or without microalbuminuria (p < 0.05). In addition, the AER (microg/min) was different among the Lp(a) phenotypes: small 55 +/- 122 (median 4.9), big 58 +/- 123 (median 5.7) and null 3 +/- 2 (median 2.3); p = 0.01. The significant difference mainly resulted from low AER (<10 microg/min) detected in all patients with the null phenotype. CONCLUSIONS: In diabetic patients the serum Lp(a) concentration is associated with AER. Thus, the elevated cardiovascular risk observed in diabetic patients with a high AER could be related to the Lp(a) concentration. Finally, patients with the null Lp(a) phenotype can be considered as a group at low risk of the development of diabetic nephropathy.

Adult↗
PubMed1981

Protease inhibitor phenotypes and pulmonary disease in patients with Sjögren's syndrome.

The incidence of pulmonary emphysema in patients with alpha-1-antitrypsin (alpha-1-AT) deficiency associated with the protease inhibitor (Pi) phenotype ZZ is increased. To determine whether less severe deficiency states of alpha-1-AT (i.e. Pi phenotypes other than ZZ and MM) might predispose to the development of pulmonary disease, Pi phenotypes were determined in a group of patients in whom the incidence of chronic pulmonary disease is high. The proportion of 52 patients with Sjögren's syndrome who had Pi phenotypes other than ZZ and MM was not significantly greater than that for populations of normal subjects. Mean values for tests of pulmonary function, including estimates of both restrictive lung disease and airway obstruction in patients with the MM phenotype were not significantly different from corresponding means for patients with non-MM phenotypes. These findings suggest that the increased susceptibility of patients with Sjögren's syndrome to develop chronic obstructive pulmonary disease is not attributable to an abnormally high frequency of non-MM phenotypes and associated moderately reduced serum levels of alpha-1-AT.

Adult↗