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PubMed2001

Flow cytometric analysis of the human articular chondrocyte phenotype in vitro.

OBJECTIVE: To develop flow cytometry for the study of human articular cartilage cell phenotype and to validate the method on chondrocytes cultured in different in-vitro systems. METHODS: Chondrocyte phenotype was modulated by culturing the cells under different in-vitro conditions: i.e. in monolayer and in suspension culture in gelled agarose. Monolayer cultured chondrocyte phenotype was assayed by immunohistochemical staining with monoclonal antibodies against chondrocyte-specific aggrecan, type II and I collagen. Flow cytometry was used to quantify the proportions of chondrocytes expressing these extracellular matrix molecules in both culture conditions. To exclude the effects of cell-harvesting methods on the presence of cell-bound ECM molecules, non-proteolytic isolation procedures were used to obtain the chondrocytes for flow cytometry. Subconfluent cells from monolayer cultures were detached with EDTA. Chondrocytes cultured in gelled agarose were obtained after the agarose was enzymatically digested with agarase. RESULTS: Immunohistochemical staining showed that monolayer-cultured chondrocytes, in the presence of serum, gradually lost the expression of chondrocyte-specific aggrecan and type II collagen, while type I collagen was increasingly expressed. Flow cytometry allowed monolayer cultured chondrocyte phenotype to be assessed reproducibly. Chondrocyte phenotype was characterized through the cell membrane-associated extracellular matrix antigens. EDTA, used to obtain single cells from monolayer cultures, did not affect the cell-associated matrix. Where the chondrocytes had been cultured in gelled agarose, flow cytometry allowed quantification of the percentages of chondrocytes maintaining or reexpressing their original phenotype. The agarase digestion procedure used to isolate the cells from the agarose gel did not affect the plasma membrane-associated extracellular matrix antigens. CONCLUSION: Flow cytometry allows quantification of cells expressing aggrecan, type II and I collagen in their cell-associated extracellular matrix. A continuously increasing number of specific monoclonal antibodies will broaden the range of applications offered by this method.

Adolescent↗

PubMed1999

Evidence from a novel human cell clone that adult vascular smooth muscle cells can convert reversibly between noncontractile and contractile phenotypes.

Smooth muscle cells (SMCs) perform diverse functions that can be categorized as contractile and synthetic. A traditional model holds that these distinct functions are performed by the same cell, by virtue of its capacity for bidirectional modulation of phenotype. However, this model has been challenged, in part because there is no physiological evidence that an adult synthetic SMC can acquire the ability to contract. We sought evidence for this by cloning adult SMCs from human internal thoracic artery. One clone, HITB5, expressed smooth muscle alpha-actin, smooth myosin heavy chains, heavy caldesmon, and calponin and showed robust calcium transients in response to histamine and angiotensin II, which confirmed intact transmembrane signaling cascades. On serum withdrawal, these cells adopted an elongated and spindle-shaped morphology, random migration slowed, extracellular matrix protein production fell, and cell proliferation and [(3)H]thymidine incorporation fell to near 0. Cell viability was not compromised, however; in fact, apoptosis rate fell significantly. In this state, agonist-induced elevation of cytoplasmic calcium was even more pronounced and was accompanied by SMC contraction. Readdition of 10% serum completely returned HITB5 cells to a noncontractile, proliferative phenotype. Contractile protein expression increased after serum withdrawal, although modestly, which suggested that the switch to contractile function involved reorganization or sensitization of existing contractile structures. To our knowledge, the physiological properties of HITB5 SMCs provide the first direct demonstration that cultured human adult SMCs can convert between a synthetic, noncontracting state and a contracting state. HITB5 cells should be valuable for characterizing the basis of this critical transition.

Adult↗

PubMed2006

Functional signatures of protective antiviral T-cell immunity in human virus infections.

The most common human viruses have different abilities to establish persistent chronic infection. Virus-specific T-cell responses are critical in the control of virus replication and in the prevention of disease in chronic infection. A large number of phenotypic markers and a series of functions have been used to characterize virus-specific CD4+ and CD8+ T-cell responses, and these studies have shown great phenotypic and functional heterogeneity of the T-cell responses against different viruses. The heterogeneity of the T-cell response has been proposed to be specific to each virus. However, over the past 2 years, several studies have provided evidence that the phenotypic and functional heterogeneity of CD4+ and CD8+ T-cell responses is predominantly regulated by the levels of antigen load. The levels of antigen load modulate the phenotypic and functional patterns of the T-cell response within the same virus infection. Furthermore, the functional characterization of virus-specific CD4+ and CD8+ T-cell responses has identified signatures of protective antiviral immunity. Polyfunctional, i.e. interleukin-2 and interferon-gamma (IFN-gamma) secretion and proliferation, and not monofunctional, i.e. IFN-gamma secretion, CD4+ and CD8+ T-cell responses represent correlates of protective antiviral immunity in chronic virus infections.

Acute Disease↗

PubMed2000

Modulation of the typical multidrug resistance phenotype by targeting the MED-1 region of human MDR1 promoter.

Multidrug resistance of cancer (MDR) is the major cause of failure of chemotherapy. The typical MDR phenotype is due to the overexpression of membrane proteins among which the main representative is P-glycoprotein (Pgp) encoded by the MDR1 gene. Many attempts to modulate MDR by chemosensitizers have been unsuccessful in human therapy due to their intrinsic toxic effects. In an effort to modulate the MDR phenotype efficiently we designed an antisense and a transcriptional decoy strategy targeting the TATA-less human MDR1 gene promoter. The choice of the start point of transcription in a multiple start site window is related to an upstream MED-1 cis-element, the sequence and configuration of which are specific to human MDR1 gene expressed in Pgp-overproducing cancer cells. A 12mer antisense oligodeoxynucleotide (ODN) and a 12mer double-stranded ODN, both containing the MED-1 sequence, were designed and efficiently vectorized into the nucleus with the chimerical MPG peptide. A synthetic cellular model (NIH-EGFP) and highly resistant human CEM/VLB0.45 leukemia cells, significantly responded to transfection with the ODN/MPG complex. The level of EGFP fluorescence in NIH-EGFP cells decreased, and thus its production, and viability of CEM/VLB0.45 cells decreased by 63% in the presence of vinblastine, revealing that their resistance to the anticancer drug was reversed. These results open new insights into transcriptional decoy and anti-gene therapies of MDR cancers that overproduce Pgp. Gene Therapy (2000) 7, 1224-1233.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

The osteoblastic phenotype in calcium-depleted and calcium-repleted rats: a structural and histomorphometric study.

In a previous report we showed that young rats fed a calcium-free diet for 28 days developed severe hypocalcaemia and showed a significant increase in serum alkaline phosphatase activity. The main histological and cytochemical changes exhibited by these animals in bone of the metaphyseal primary spongiosa were: (1) hyperplasia of osteoblasts, (2) an increase in the frequency of tartrate-resistant acid phosphatase (TRAP)-positive osteoblasts apposed to osteoid, and (3) an excessive amount of osteoid tissue. In addition to typical osteoblasts, there was a subpopulation of osteoblast-like cells with coated pits, lysosome-like bodies and large cytoplasmic processes. In the present study, we investigated how the above parameters change when calcium-depleted rats are placed on a normal diet for 7 days. Such a regimen normalized calcium concentration and alkaline phosphatase activity in the serum. The osteoid thickness returned to normal and, in some areas, was fully calcified. Most osteoblasts no longer showed TRAP activity and their ultrastructure was similar to that found in controls. Despite an intense alkaline phosphatase activity, some of them still exhibited a number of macrophagic characteristics. They were TRAP-positive, and showed electron-dense bodies in the cytoplasm facing bone, an abundance of coated pits, calcified spicules impinging on the cell membrane and large processes extending into the mineralized matrix. We concluded that calcium deficiency causes hyperplasia of osteoblasts in primary spongiosa and an increase in expression of TRAP. It also induces changes in their phenotype characterized by the acquisition of macrophagic cellular features. While TRAP activity is normalized by calcium repletion, macrophagic characteristics persist. These results suggest that the osteoblast can modulate its phenotype according to its physiological status.

Acid Phosphatase↗

PubMed2025

Interaction of host gene-gut microbiota in male grading of Macrobrachium rosenbergii.

UNLABELLED: The giant freshwater prawn (GFP; Macrobrachium rosenbergii), a crustacean of high nutritional and economic value, is crucial for aquaculture. During the same growth cycle, male GFPs develop into three distinct forms: small males, orange claw males, and blue claw males. These morphotypes display varying social behaviors, which severely constrain their industrial development. To address this, this study collected male GFP samples at critical developmental time points (100, 110, and 120 days post-hatching) for phenotypic trait measurement and analysis to obtain external morphological data. Through gut microbiota diversity analysis, we identified key gut bacteria (Lactococcus garvieae and Lactobacillus taiwanensis) influencing male morphotype differentiation. Transcriptomic analysis revealed host Kyoto Encyclopedia of Gene and Genome pathways and key genes (Wnt-6, CTSB, CTSL, PPAE, and TP53) associated with morphotype differentiation. The interactions among phenotypic traits, gut microbiota, and key genes were systematically studied through association analysis. Weighted gene co-expression network analysis was employed to construct co-expression modules, from which critical gene modules influencing phenotypic variation were identified. Through association network analysis, we established an "Achromobacter-CD-TRINITY_DN93139_c0_g2 (calpain clp-1)" interaction model. Our findings provide novel insights into the genetic enhancement of GFPs and offer guidelines for future research regarding gut symbiotic bacteria and breeding initiatives. IMPORTANCE: Male Macrobrachium rosenbergii (giant freshwater prawn [GFP]) in the same growth cycle will develop into small males, orange claw males, and blue claw males. This individual heterogeneity in growth significantly impacts the benefits of aquaculture. However, the factors influencing the differentiation of male GFP morphotype remain unclear. This study analyzed the phenotypic data of various GFP levels, the structure of the intestinal microbiota, and the differential genes within the gonadal transcriptome at critical time points of male GFP-level type differentiation. The aim was to explore the potential role of intestinal microbiota and differential genes in this phenomenon. This study offers new insights into the research on the phenomenon of male GFP-level type differentiation.

Animals↗

PubMed1984

Colonization of the developing murine enteric nervous system and subsequent phenotypic expression by the precursors of peptidergic neurons.

The development of peptidergic neurons was analyzed in the murine bowel. Neurons, detected immunocytochemically with antisera to substance P (SP) and vasoactive intestinal polypeptide (VIP), respectively, were selected for study. Explantation of the primordial bowel with subsequent growth in organotypic tissue culture served as an assay for the presence of neuronal precursor cells within the developing gut. One objective of the study was to determine whether the neural crest population that initially colonizes the mammalian bowel contains the precursors of peptidergic neurons as well as those of neurons that contain small molecule neurotransmitters, or whether peptidergic neurons are derived from a later migration of emigr és to the gut. A second objective was to compare the timing of peptidergic phenotypic expression with that of the small molecule neurotransmitters, acetylcholine (ACh) and serotonin (5-HT). The precursors of peptidergic neurons were found to have colonized the bowel prior to the appearance of recognizable neurons of any type. The immunocytochemical detection of SP and VIP in vivo lagged behind the appearance of cholinergic and serotonergic markers by at least 2 days in the foregut and by greater than 3 days in the hindgut. Peptidergic neurons showed a proximodistal pattern of phenotypic expression. These observations support the hypothesis that the murine bowel is colonized by a single wave of precursor cells that contains the primordia of peptidergic neurons as well as neurons that use small molecule neurotransmitters. Data are consistent with the earlier expression of the small molecule phenotype. The proximodistal sequence of phenotypic expression in the absence of a similar sequence in precursor colonization supports an interaction between the precursors of enteric neurons and the microenvironment of the gut that modulates neuronal phenotypic expression.

Acetylcholine↗

PubMed2004

Selection in modular organisms: is intraclonal variation in macroalgae evolutionarily important?

Theoretical and practical difficulties occur when defining the units of selection in modular organisms that grow by iteration of repeated parts (modules). Modules may become physically autonomous through fragmentation and may vary because of genetic variation arising in somatic cell lineages. Since cells destined for gamete production are not sequestered in early development, heritable variation and selection among asexual progeny are possible. We used the branching red macroalgae Delisea pulchra and Asparagopsis armata to test whether modules fulfill three fundamental criteria for units of selection: that they replicate, that they display heritable variation, and that selective agents distinguish among the variants. We detected significant phenotypic variation among modules for fitness-related traits (growth, secondary metabolite concentrations, and rates of tissue loss to herbivory) in each species and significant heritability estimates for secondary metabolite production and tissue loss to herbivory in D. pulchra. Variation in growth rate among A. armata modules was largely phenotypic with small but important estimates of genetic variation. Our results indicate that selection may indeed act on phenotypic variation among modules within individuals and that this process may effect evolutionary change within asexual lineages given sufficient genetic variation in the traits examined.

Animals↗

PubMed1998

Regulation of periodontal ligament cell functions by interleukin-1beta.

Periodontal ligament (PDL) cells maintain the attachment of the tooth to alveolar bone. These cells reside at a site in which they are challenged frequently by bacterial products and proinflammatory cytokines, such as interleukin-1beta (IL-1beta), during infections. In our initial studies we observed that IL-1beta down-regulates the osteoblast-like characteristics of PDL cells in vitro. Therefore, we examined the functional significance of the loss of the PDL cell's osteoblast-like characteristics during inflammation. In this report we show that, during inflammation, IL-1beta can modulate the phenotypic characteristics of PDL cells to a more functionally significant lipopolysaccharide (LPS)-responsive phenotype. In a healthy periodontium PDL cells exhibit an osteoblast-like phenotype and are unresponsive to gram-negative bacterial LPS. Treatment of PDL cells with IL-1beta inhibits the expression of their osteoblast-like characteristics, as assessed by the failure to express transforming growth factor beta1 (TGF-beta1) and proteins associated with mineralization, such as alkaline phosphatase and osteocalcin. As a consequence of this IL-1beta-induced phenotypic change, PDL cells become responsive to LPS and synthesize proinflammatory cytokines. The IL-1beta-induced phenotypic changes in PDL cells were transient, as removal of IL-1beta from PDL cell cultures resulted in reacquisition of their osteoblast-like characteristics and lack of LPS responsiveness. The IL-1beta-induced phenotypic changes occurred at concentrations that are frequently observed in tissue exudates during periodontal inflammation (0.05 to 5 ng/ml). The results suggest that, during inflammation in vivo, IL-1beta may modulate PDL cell functions, allowing PDL cells to participate directly in the disease process by assuming LPS responsiveness at the expense of their normal structural properties and functions.

Adult↗

PubMed2002

Dietary intake of Lactobacillus rhamnosus HNOO1 enhances production of both Th1 and Th2 cytokines in antigen-primed mice.

Probiotic lactobacilli have been proposed as a potential oral bacteriotherapeutic means of modulating immune phenotype expression in vivo, via their ability to promote cytokine production. This study investigated the ability of a known interferon (IFN)gamma-promoting probiotic (Lactobacillus rhamnosus HNOOI) to modulate cytokine production in mice expressing an on-going Th2-type immune response. BALB/c mice were primed to ovalbumin in alum adjuvant to invoke antigen-specific Th2 cytokine-secreting cell populations. Mice that were fed Lb. rhamnosus HN001 during antigen sensitization produced higher levels of lymphocyte-derived IFNgamma, but also interleukin (IL)-4 and IL-5, in comparison to control animals. Although HN001 was additionally shown to induce pro-IFNgamma monokine (IL-12, IL-18) secretion in macrophages in vitro, its ability to invoke mixed lymphocyte cytokine production during an on-going Th2-type immune response in vivo suggests that this probiotic is a general immunostimulatory agent, in contrast to the pro-Th1/anti-Th2 immunoregulation reported for some strains of IFNgamma-promoting lactobacilli.

Adjuvants, Immunologic↗

PubMed1996

Biological and clinical significance of haptoglobin polymorphism in humans.

Haptoglobin is a hemoglobin-binding protein expressed by a genetic polymorphism as three major phenotypes: 1-1, 2-1, and 2-2. Most attention has been paid to determining haptoglobin phenotype as a genetic fingerprint used in forensic medicine. More recently, several functional differences between haptoglobin phenotypes have been demonstrated that appear to have important biological and clinical consequences. Haptoglobin polymorphism is associated with the prevalence and clinical evolution of many inflammatory diseases, including infections, atherosclerosis, and autoimmune disorders. These effects are explained by a phenotype-dependent modulation of oxidative stress and prostaglandin synthesis. Recent evidence is growing that haptoglobin is involved in the immune response as well. The strong genetic pressure favoring the 2-2 phenotype suggests an important role of haptoglobin in human pathology.

Chemistry, Clinical↗

PubMed2006

Multiple repressor pathways contribute to phenotypic switching of vascular smooth muscle cells.

Smooth muscle cell (SMC) differentiation is an essential component of vascular development and these cells perform biosynthetic, proliferative, and contractile roles in the vessel wall. SMCs are not terminally differentiated and possess the ability to modulate their phenotype in response to changing local environmental cues. The focus of this review is to provide an overview of the current state of knowledge of molecular mechanisms involved in controlling phenotypic switching of SMC with particular focus on examination of processes that contribute to the repression of SMC marker genes. We discuss the environmental cues which actively regulate SMC phenotypic switching, such as platelet-derived growth factor-BB, as well as several important regulatory mechanisms required for suppressing expression of SMC-specific/selective marker genes in vivo, including those dependent on conserved G/C-repressive elements, and/or highly conserved degenerate CArG elements found in the promoters of many of these marker genes. Finally, we present evidence indicating that SMC phenotypic switching involves multiple active repressor pathways, including Krüppel-like zinc finger type 4, HERP, and ERK-dependent phosphorylation of Elk-1 that act in a complementary fashion.

Animals↗

PubMed1984

Effects of transposable element insertions on RNA encoded by the white gene of Drosophila.

We have examined the manner in which transposable element insertions affect the expression of the white gene of Drosophila by analyzing polyadenylated RNA of flies with each of nine insertions in or near the gene. In five mutants having insertions in the transcribed sequences of white, transcripts initiating at the white promoter are truncated within the insertions. Two insertions in the 3 kb intron of white alter neither the amount nor the structure of the mature white RNA. An insertion near the 5' end of the gene blocks the accumulation of any white transcripts. Another insertion, located 1.2 kb upstream from the transcribed region of the gene, causes a mutant phenotype yet surprisingly has no obvious effect on the structure or abundance of the major white RNA. We also show that a mutation at each of two other loci that modulate the phenotype of the white-apricot insertion mutant are correlated with small but significant changes in the pattern of white transcripts.

Animals↗

PubMed1997

JURL-MK1 (c-kit(high)/CD30-/CD40-) and JURL-MK2 (c-kit(low)/CD30+/CD40+) cell lines: 'two-sided' model for investigating leukemic megakaryocytopoiesis.

Two novel cell lines (JURL-MK1 and JURL-MK2) have been established from the peripheral blood of a patient in the blastic phase of chronic myelogenous leukemia. The cells grow in a single cell suspension with doubling times of 48 h (JURL-MK1) and 72 h (JURL-MK2). Cytogenetic analysis has shown that JURL-MK1 is hypodiploid whereas JURL-MK2 is near triploid and that both cell lines retain t(9;22). Moreover, JURL-MK1 and JURL-MK2 have a bcr/abl-fused gene with the same junction found in the patient's fresh cells, and both cell lines express the b3/a2 type of hybrid bcr/abl mRNA. The morphology and immunophenotype of these cell lines are reminiscent of megakaryoblasts. In both lines, a limited but consistent percentage of cells expresses gpIIbIIIa (CD41a), gpIIIa (CD61) and CD36, with no expression of gplb (CD42b), glycophorin A, hemoglobin and CD34. Both cell lines are clearly positive for CD33, CD43, CD45RO and CD63, while CD13, CD44, CD54, CD30 and CD40 are specific features of JURL-MK2. Among cytokine receptors, CD117/SCF-R is strongly displayed by a large fraction of JURL-MK1 cells but is hardly detectable on about 20% JURL-MK2 cells. Both cell lines are clearly positive for CD25/IL2R alpha, while a marked expression of CD116/GM-CSF-R and CDw123/IL3R alpha is restricted to JURL-MK2. Induction of cell differentiation in vitro has demonstrated that TPA is able to modulate the JURL-MK1 phenotype, causing an increased expression of platelet-associated antigens. The JURL-MK2 phenotype is easily modulated by both TPA and DMSO, which cause an increased expression of CD41a and CD117 accompanied by a decreased expression of CD30. Proliferation studies demonstrated that JURL-MK1 cell growth is enhanced by stem cell factor, while JURL-MK2 proliferation is unaffected by this cytokine. JURL-MK1 and JURL-MK2 are two novel cell lines with divergent biological features, representing a 'two-sided' model for investigating new aspects of megakaryocytopoiesis.

Antigens, Surface↗

PubMed1997

Mortality from hereditary cerebral haemorrhage with amyloidosis--Dutch type. The impact of sex, parental transmission and year of birth.

Hereditary cerebral haemorrhage with amyloidosis--Dutch type (HCHWA-D) is an autosomal dominant disorder, caused by a single base mutation in the amyloid beta precursor protein (beta PP) gene located on chromosome 21, resulting in recurrent haemorrhagic strokes and dementia. Though HCHWA-D is caused by a dominant mutation, the phenotypic expression varies widely, suggesting modulation of the phenotypic expression by additional factors. In this study we investigated the influence of sex, parental transmission and year of birth on mortality from HCHWA-D. Since the early sixties, clinical and genealogical data of patients with HCHWA-D have been collected. The standardized mortality rate (relative to the general population) was calculated to compare the mortality within the pedigrees with the mortality in the Dutch population. The influence of sex, parental transmission and year of birth on survival were studied using Cox's proportional hazard model. By December 1, 1995, a total of 187 cases were identified belonging to four large families. Mortality rate in affected individuals was fourfold increased compared with the Dutch population (relative mortality 4.0; 95% confidence interval 3.4-4.7) and higher in females than in males (relative mortality risk 8.0 and 2.6, respectively). Mortality rate was lower when HCHWA-D was maternally transmitted (mortality relative to paternal transmission 0.7; 95% confidence interval 0.5-1.0). Year of birth had no effect on the mortality of the affected individuals. Survival of HCHWA-D has not yet increased, in spite of higher standards of general medicine, i.e. the mortality rate did not decline over the years. Female sex was a major factor increasing mortality rate in HCHWA-D. Paternal transmission had a just significant effect on mortality rate in HCHWA-D. The possible mechanisms behind these phenomena remain unexplained by this clinical study.

Amyloid beta-Protein Precursor↗

PubMed1982

The H-2 haplotype of a thymus graft influences the Ir gene regulated IgG3, IgG1, IgG2b, and IgG2a anti-(T,G)-A--L antibody responses of high-responder F1.nude mice.

In order to examine whether the H-2 haplotype of a thymus graft influences the levels of IgG3, IgG1, IgG2b, and IgG2a antibodies produced in an in vivo response to antigens under immune response (Ir) gene control, genotypic high-responder (H-2b X H-2k)F1.nude mice were grafted with thymuses from irradiated, neonatal low-responder (H-2k) or high-responder (H-2b or (H-2k X H-2b)F1) mice and immunized with (T,G)-A--L. All IgG antibody responses to (T,G)-A--L in high-responder mice were shown to be thymus dependent. The majority of F1.nude mice grafted with thymuses from high-responder haplotype donors produced high-responder levels of IgG anti-(T,G)-A--L antibodies. Conversely, the majority of F1.nude mice grafted with thymuses from low-responder haplotype donors gave low-responder phenotypic patterns. The modulation of the Ir gene phenotype was not restricted to a particular IgG isotype, but affected IgG3, IgG1, IgG2b, and IgG2a. The F1 . nude mice grafted with low-responder haplotype thymuses were able to produce IgG1, IgG3, and IgG2b antibodies to sheep erythrocytes, a thymus-dependent (TD) antigen not under overt Ir gene control. Circulating peripheral T cells were shown to be of host origin. By these criteria, the thymus grafts did enable F1.nude mice to respond to a TD antigen. These results support the concept that thymic H-2 determinants are involved in at least the selection of H-2 restricted T cell subsets, if not also the derivation of the T cell receptor repertoire for self and/or antigen recognition.

Animals↗

PubMedDate not supplied

Phenotypic stability of B16-BL6 melanoma exposed to low levels of tyrosine and phenylalanine.

We previously demonstrated that tyrosine (Tyr) and phenylalanine (Phe) restriction suppresses metastatic heterogeneity of B16-BL6 (BL6) melanoma and selects for tumor variants with decreased metastatic potential. In this study, we investigate stability of this Tyr- and Phe-modulated tumor phenotype by sequentially transplanting BL6 in vivo into mice fed Low Tyr and Phe Diet. Metastatic potential of BL6 is suppressed after one subcutaneous passage. Suppression is unlikely to result from inhibition of tumor growth, since growth in vitro is significantly increased. The metastatic potential of the Tyr- and Phe-modulated tumor is unstable after in vivo passage, and lung colonizing ability is regenerated after ten in vivo passages. Conversely, the antimetastatic effect of Tyr and Phe restriction is stable after prolonged in vitro passage. The metastatic potential of tumors from mice fed Normal Diet is unstable after long-term in vitro culture. Sensitivity to adriamycin of BL6 from mice fed Low Tyr and Phe Diet is increased and is not altered by change in metastatic potential.

Animals↗

PubMed2006

Molecular basis of worm-induced immunomodulation.

Long-term infection with parasitic worms is generally associated with an immunological phenotype that is Th2-like and anti-inflammatory. This phenotype is probably an unintentional consequence of molecular characteristics of worms (as free-living worms also express polarising molecules) in combination with deliberate attempts by the parasites, via molecular secretions, to modulate the phenotype. This review is concerned with the identity of immunomodulatory worm products, the receptors that they interact with and the signal transduction pathways that they activate. It hopes to indicate how knowledge of these factors can explain the changes in gene expression that result in the characteristic worm-induced immunological phenotype.

Animals↗