Biomedical subjects

P Gomes

Publications and source records attributed to P Gomes.

At least 19 recordsLinked to original sources

PubMed2001

Antigenicity modulation upon peptide cyclization: application to the GH loop of foot-and-mouth disease virus strain C1-Barcelona.

Foot-and-mouth disease virus (FMDV) isolate C(1)-Barcelona (or C-S30) includes four replacements within its immunodominant site (GH loop, residues 136-150 of capsid protein VP1, YTTSTRGDLAHVTAT), relative to reference strain C-S8c1 (YTASARGDLAHLTTT). Although one of the mutations in C-S30 (147Leu-->Val) is known to be detrimental for antibody recognition, reactivity of this isolate with the neutralizing monoclonal antibody (mAb) 4C4, raised against FMDV C1-Brescia (GH loop: YTASTRGDLAHLTAT), was indistinguishable from those of strains C-S8c1 or C1-Brescia. A structural interpretation for these somewhat striking findings is available, based on the observation that 15-residue peptides reproducing the C-S30 and C-S8c1 GH loops adopt very similar, quasi-circular, conformations in crystal complexes with 4C4. Nevertheless, surface plasmon resonance (SPR) kinetic analyses of the interactions between these peptides and three anti-GH loop mAbs have now revealed that the linear C-S30 peptides were less antigenic in solution than their C-S8c1 and C1-Brescia counterparts. We have, therefore, tried to modulate peptide antigenicity in solution by cyclization. Functional SPR and structural two dimensional proton nuclear magnetic resonance (2D-1H NMR) studies of both linear and cyclic peptide antigens are discussed here. Conformation seems to have an important role in peptide antigenicity, even when continuous (i.e. linear) antigenic sites are involved.

Amino Acid Sequence↗

PubMed2001

D1-like dopamine receptor activation and natriuresis by nitrocatechol COMT inhibitors.

BACKGROUND: In recent years, several nitrocatechol derivatives (tolcapone, entacapone, and nitecapone) have been developed and found to be highly selective and potent inhibitors of catechol-O-methyltransferase (COMT). More recently, natriuretic properties were described for two of these compounds (entacapone and nitecapone), although this was not accompanied by enhanced urinary excretion of dopamine. We hypothesized that nitrocatechol derivatives stimulate D1-like dopamine receptors. METHODS: Adult male Wistar rats were treated with a nitrocatechol COMT inhibitor (entacapone, tolcapone, or nitecapone, 30 mg/kg, orally), and the urinary excretion of dopamine and sodium was quantitated. The interaction of nitrocatechol derivatives with D1-like receptors was evaluated by their ability to displace [3H]-Sch23390 binding from membranes of rat renal cortex and cAMP production in opossum kidney (OK) cells. RESULTS: Urinary excretion of sodium (micromol/h) was markedly increased by all three nitrocatechol derivatives: vehicle, 55.0 +/- 5.6; entacapone, 98.4 +/- 9.3; tolcapone, 97.5 +/- 9.3; and nitecapone, 120.5 +/- 12.6. Pretreatment with the selective D1 antagonist Sch 23390 (60 microg/kg) completely prevented their natriuretic effects. Nitecapone and tolcapone were equipotent (IC50s of 48 and 42 micromol/L) and more potent than entacapone and dopamine (IC50s of 107 and 279 micromol/L) in displacing [3H]-Sch23390 binding. In OK cells, all three nitrocatechol derivatives significantly increased cAMP accumulation and reduced Na(+)/H(+) exchange and Na(+),K(+)-ATPase activities, this being prevented by a blockade of D1-like receptors. CONCLUSION: Stimulation of D1-like dopamine receptors and inhibition of Na(+)/H(+) exchange and Na(+),K(+)-ATPase activities by nitrocatechol COMT inhibitors may contribute to natriuresis produced by these compounds.

Animals↗

PubMed2001

Identification of T-cell epitopes in nonstructural proteins of foot-and-mouth disease virus.

Porcine T-cell recognition of foot-and-mouth disease virus (FMDV) nonstructural proteins (NSP) was tested using in vitro lymphoproliferative responses. Lymphocytes were obtained from outbred pigs experimentally infected with FMDV. Of the different NSP, polypeptides 3A, 3B, and 3C gave the highest stimulations in the in vitro assays. The use of overlapping synthetic peptides allowed the identification of amino acid regions within these proteins that were efficiently recognized by the lymphocytes. The sequences of some of these antigenic peptides were highly conserved among different FMDV serotypes. They elicited major histocompatibility complex-restricted responses with lymphocytes from pigs infected with either a type C virus or reinfected with a heterologous FMDV. A tandem peptide containing the T-cell peptide 3A[21-35] and the B-cell antigenic site VP1[137-156] also efficiently stimulated lymphocytes from infected animals in vitro. Furthermore, this tandem peptide elicited significant levels of serotype-specific antiviral activity, a result consistent with the induction of anti-FMDV antibodies. Thus, inclusion in the peptide formulation of a T-cell epitope derived from the NSP 3A possessing the capacity to induce T helper activity can allow cooperative induction of anti-FMDV antibodies by B cells.

Amino Acid Sequence↗

PubMed2001

Ouabain-insensitive acidification by dopamine in renal OK cells: primary control of the Na(+)/H(+) exchanger.

The present study was aimed at evaluating the role of D(1)- and D(2)-like receptors and investigating whether inhibition of Na(+) transepithelial flux by dopamine is primarily dependent on inhibition of the apical Na(+)/H(+) exchanger, inhibition of the basolateral Na(+)-K(+)-ATPase, or both. The data presented here show that opossum kidney cells are endowed with D(1)- and D(2)-like receptors, the activation of the former, but not the latter, accompanied by stimulation of adenylyl cyclase (EC(50) = 220 +/- 2 nM), marked intracellular acidification (IC(50) = 58 +/- 2 nM), and attenuation of amphotericin B-induced decreases in short-circuit current (28.6 +/- 4.5% reduction) without affecting intracellular pH recovery after CO(2) removal. These results agree with the view that dopamine, through the activation of D(1)- but not D(2)-like receptors, inhibits both the Na(+)/H(+) exchanger (0.001933 +/- 0.000121 vs. 0.000887 +/- 0.000073 pH unit/s) and Na(+)-K(+)-ATPase without interfering with the Na(+)-independent HCO transporter. It is concluded that dopamine, through the action of D(1)-like receptors, inhibits both the Na(+)/H(+) exchanger and Na(+)-K(+)-ATPase, but its marked acidifying effects result from inhibition of the Na(+)/H(+) exchanger only, without interfering with the Na(+)-independent HCO transporter and Na(+)-K(+)-ATPase.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2000

Importance of handling organic atmospheric pollutants for assessing air quality.

Volatile organic compounds (VOCs) are the main precursors of tropospheric ozone production, playing an important role in photochemical pollution of the atmosphere and, consequently, in the degradation of air quality. Air quality photochemical models require a specific VOC profile for each different main source, based on the most important group compounds. Chromatographic techniques have been used to identify and measure VOC in Portugal. These measured values were used to simulate photochemical pollution, and modelling results were compared with those from another simulation using VOC class distributions from the literature. Ozone concentration values estimated via both simulations indicate the importance of using VOC data from Portugal instead of those obtained in different conditions.

Air↗

PubMed2000

Direct single-step surface plasmon resonance analysis of interactions between small peptides and immobilized monoclonal antibodies.

Surface plasmon resonance (SPR) methods have been optimized to permit direct kinetic analysis of the antigenic peptide analytes interacting with immobilized monoclonal antibodies (mAbs). High reproducibility and a significant correlation between SPR and previous ELISA data on the same set of antibodies and peptides were observed. The kinetic data obtained provide further insight into the structure of the main antigenic site of foot-and-mouth disease virus (FMDV).

Amino Acid Sequence↗

PubMed2000

Molecular analysis of peptides from the GH loop of foot-and-mouth disease virus C-S30 using surface plasmon resonance: a role for kinetic rate constants.

A foot-and-mouth disease virus (FMDV) field variant, isolate C-S30 (also named C(1)-Barcelona), is known to contain four changes within the main antigenic site A (GH loop of capsid protein VP1, residues 136-150), at least one of which (Leu147-->Val) involves a highly conserved position, critical for antibody recognition in the reference strain C-S8c1. However, immunoenzymatic analysis of FMDV C-S30 showed it was recognised by 4C4, a monoclonal antibody that specifically targets site A. This remarkable behaviour has led us to analyse the individual and combined contributions of the four mutations to the antigenicity of C-S30, by surface plasmon resonance (SPR) and enzyme-linked immunosorbent assay (ELISA) studies of pentadecapeptides displaying all possible combinations of the four replacements. Analysis of this family of C-S30-derived analogues shows a certain level of antibody recognition by SPR. In addition, SPR data suggest that kinetic rate constants provide an indirect measure, on the one hand, of paratope accessibility (association rate constant) and, on the other hand, of peptide fitness to the same paratope (dissociation rate constant).

Amino Acid Sequence↗

PubMed2000

A multiply substituted G-H loop from foot-and-mouth disease virus in complex with a neutralizing antibody: a role for water molecules.

The crystal structure of a 15 amino acid synthetic peptide, corresponding to the sequence of the major antigenic site A (G-H loop of VP1) from a multiple variant of foot-and-mouth disease virus (FMDV), has been determined at 2.3 A resolution. The variant peptide includes four amino acid substitutions in the loop relative to the previously studied peptide representing FMDV C-S8c1 and corresponds to the loop of a natural FMDV isolate of subtype C(1). The peptide was complexed with the Fab fragment of the neutralizing monoclonal antibody 4C4. The peptide adopts a compact fold with a nearly cyclic conformation and a disposition of the receptor-recognition motif Arg-Gly-Asp that is closely related to the previously determined structure for the viral loop, as part of the virion, and for unsubstituted synthetic peptide antigen bound to neutralizing antibodies. New structural findings include the observation that well-defined solvent molecules appear to play a major role in stabilizing the conformation of the peptide and its interactions with the antibody. Structural results are supported by molecular-dynamic simulations. The multiply substituted peptide developed compensatory mechanisms to bind the antibody with a conformation very similar to that of its unsubstituted counterpart. One water molecule, which for steric reasons could not occupy the same position in the unsubstituted antigen, establishes hydrogen bonds with three peptide amino acids. The constancy of the structure of an antigenic domain despite multiple amino acid substitutions has implications for vaccine design.

Amino Acid Substitution↗

PubMed2000

Human immunodeficiency virus type 2 (HIV-2) in Portugal: clinical spectrum, circulating subtypes, virus isolation, and plasma viral load.

The human immunodeficiency virus type 2 (HIV-2) is responsible for 4. 5% of AIDS cases in Portugal. Six HIV-2 subtypes have been described so far, subtype A being proposed as more pathogenic than the rest. The relationship between the clinical status and levels of both cellular and plasma HIV-2 viraemia is not well known, nor their modifications under antiretroviral therapy. Thirty-two consecutive HIV-2 infected persons (17 men, 15 women) attending two different hospitals in Lisbon in 1997 were enrolled prospectively in the study. All but 4 individuals most likely acquired the infection through heterosexual contact. More than half of the study population was of African origin, mainly from Guinea-Bissau. Eleven (34.4%) patients had developed clinical manifestations included within the B or C groups of the CDC classification system for HIV infection, with the rest being asymptomatic. Half of the population was undergoing antiretroviral treatment at the time of the study. HIV-2 subtypes were investigated using a new Nef-based restriction fragment length polymorphism (RFLP) method that allows differentiation of the main two variants, A and B. Plasma viral load was quantified using a new quantitative competitive reverse transcriptase polymerase chain reaction (QcRT-PCR) procedure as well as the Amp-RT assay. Virus isolation was attempted from peripheral blood mononuclear cells. All but one person carried HIV-2 subtype A. Plasma viraemia examined by QcRT-PCR was measurable in 15 (50%) of 30 subjects, yielding in all instances values below 20,000 HIV-2 RNA copies per ml. Plasma RT activity could be detected in only 10 (33%) of 30 subjects, a rate much lower than that seen in HIV-1 infection. Virus was isolated from 16 (53.3%) of 30 patients. A significant correlation was found between CD4+ counts, clinical status, rate of virus isolation, and plasma viral load by both QcRT-PCR and Amp-RT. In conclusion, HIV-2 subtype A is the predominant variant circulating in Portugal among both natives and immigrants. A lower cellular and plasma viral load with respect to HIV-1 was seen in persons without immunosuppression, from whom the rate of virus recovery was extremely low.

Female↗

PubMed1999

L-DOPA transport properties in an immortalised cell line of rat capillary cerebral endothelial cells, RBE 4.

The present study aimed to determine the kinetics of L-3, 4-dihydroxyphenylalanine (L-DOPA) uptake in an immortalised cell line of rat capillary cerebral endothelial cells (clones RBE 4 and RBE 4B), to define the type of inhibition produced by L-5-hydroxytryptophan (L-5-HTP), 2-aminobicyclo(2,2,1)-heptane-2-carboxylic acid (BHC) and N-(methylamino)-isobutyric acid (MeAlB) and its sodium dependence. Non-linear analysis of the saturation curves for L-DOPA and L-5-HTP revealed in RBE 4 cells Km values (in microM) of 72 and 102 and in RBE 4B cells Km values (in microM) of 60 and 118, respectively. IC50 values for L-5-HTP (RBE 4, 1026 microM; RBE 4B, 831 microM) obtained in the presence of a nearly saturating (250 microM) concentration of L-DOPA were almost 5-fold those obtained when non-saturating (25 microM) concentrations of L-DOPA were used. IC50 values for BHC obtained in the presence of a nearly saturating (250 microM) concentration of L-DOPA were also 6- to 5-fold those obtained when non-saturating (25 microM) concentrations of L-DOPA were used. MeAlB (up to 2.5 mM) was found not to interfere with the uptake of L-DOPA. In RBE 4 cells, Vmax values for L-DOPA uptake were identical in the absence and the presence of 150 microM L-5-HTP or 150 microM BHC, but Km values (microM) were significantly greater (P<0.05) when L-DOPA uptake was studied in the presence of L-5-HTP or BHC. Similar findings were observed when RBE 4B cells were used. Uptake of (250 microM) L-DOPA in the absence of sodium in the incubation medium was similar to that observed in the presence of increasing concentrations of sodium (20 to 140 mM). It is concluded that RBE 4 and RBE 4B cells are endowed with the L-type amino acid transporter through which L-DOPA and L-5-HTP can be taken up, and suggested that this immortalised cell line of rat capillary cerebral endothelium might constitute an interesting in vitro model for the study of BBB mechanisms, namely those concerning solute and nutrient transfer across the brain capillary endothelium.

Animals↗

PubMed1999

Interaction between L-DOPA and 3-O-methyl-L-DOPA for transport in immortalised rat capillary cerebral endothelial cells.

The present study aimed to determine the kinetics of L-3,4-dihydroxyphenylalanine (L-DOPA) uptake in an immortalised cell line of rat capillary cerebral endothelial cells (clones RBE 4 and RBE 4B), to define the type of interaction with 3-O-methyl-L-DOPA (3-OM-L-DOPA), sensitivity to 2-aminobicyclo(2,2,1)-heptane-2-carboxylic acid (BHC), N-(methylamino)-isobutyric acid (MeAIB) and sodium. Non-linear analysis of the saturation curves for L-DOPA and 3-OM-L-DOPA revealed in RBE 4 cells Km values (in microM) of 72 (53, 91) and 40 (25, 57) and in RBE 4B cells Km values (in microM) of 60 (46, 74) and 44 (13, 75), respectively. IC50 values for 3-OM-L-DOPA (RBE 4, 642 [542, 759] microM; RBE 4B, 482 [475, 489] microM) obtained in the presence of a nearly saturating (250 microM) concentration of L-DOPA were greater than the corresponding Ki values (RBE 4, 143 [121, 170] microM; RBE 4B, 93 [92, 95] microM) obtained in the presence of a nearly saturating (250 microM) concentration of 3-OM-L-DOPA; this is compatible with a competitive type of interaction between L-DOPA and 3-OM-L-DOPA. Uptake of both L-DOPA and 3-OM-L-DOPA in RBE 4 and RBE 4B cells was sensitive to BHC with similar IC50 values. MeAIB (up to 2.5 mM) was found not to interfere with the uptake of both L-DOPA and 3-OM-L-DOPA. Uptake of (250 microM) L-DOPA and 3-OM-L-DOPA in the absence of sodium in the incubation medium was similar to that observed in the presence of increasing concentrations of sodium (20-140 mM). Homogenates of both cell lines were endowed with considerable COMT activity. Incubation of RBE 4 and RBE 4B cells with L-DOPA (25 microM) in the presence of a methyl donor (S-adenosyl-L-methionine) resulted in the formation of 3-OM-L-DOPA; this was abolished by 1 microM tolcapone. The fractional outflow of intracellular L-DOPA through the luminal and abluminal cell side was not affected by the presence of intracellular 3-OM-L-DOPA. The fractional outflow of exogenous 3-OM-L-DOPA applied from the luminal cell border was similar to that observed for 3-OM-L-DOPA with origin in L-DOPA. It is concluded that RBE 4 and RBE 4B cells are endowed with the L-type amino acid transporter through which L-DOPA and 3-OM-L-DOPA can be taken up, and 3-OM-L-DOPA behaves as a competitive inhibitor for the uptake of L-DOPA. This, however, only occurs for luminal cell inward movement but not for abluminal cell outward movement of the substrates.

Amino Acids↗

PubMed1999

Surface plasmon resonance screening of synthetic peptides mimicking the immunodominant region of C-S8c1 foot-and-mouth disease virus.

The main antigenic site (site A) of foot-and-mouth disease virus (FMDV, strain C-S8c1) may be adequately reproduced by a 15-peptide with the amino acid sequence H-YTASARGDLAHLTTT-NH(2) (A15), corresponding to the residues 136-150 of the viral protein VP1. The effect of amino acid substitutions within A15 on its antigenicity towards monoclonal antibodies (MAb) raised against antigenic site A, has been studied by means of BIAcore technology, based on surface plasmon resonance (SPR). Although these antigenicities have previously been determined from enzyme-linked immunosorbent assays (ELISA), the SPR-based technique is superior in that it allows a fast and straightforward screening of antigens while simultaneously providing kinetic data of the antigen-antibody interaction. With a view to screening fairly large libraries of individual peptides, we have inverted the typical SPR experiment by immobilizing the MAb on the sensor surface and using peptides as soluble analytes. We report the validation of this approach through the screening of 44 site A peptides, with results generally in good agreement with the relative antigenicities previously determined by competition ELISA.

Amino Acid Sequence↗

PubMed1999

Quantitation of human immunodeficiency virus type 2 DNA in peripheral blood mononuclear cells by using a quantitative-competitive PCR assay.

A new quantitative-competitive PCR-based human immunodeficiency virus type 2 (HIV-2) proviral DNA assay (QC-PCR) was developed and used to determine the proviral load in HIV-2-infected individuals. Proviral load varied considerably, with means of 1,831 copies per 10(6) peripheral blood mononuclear cells for asymptomatic subjects (n = 19) and 2,587 for AIDS patients (n = 2). HIV-2 viral and proviral loads also varied significantly over time in asymptomatic patients. These data suggest that a high level of virus replication occurs throughout the asymptomatic phase of HIV-2 infection.

Adolescent↗

PubMed1998

L-3,4-dihydroxyphenylalanine and L-5-hydroxytryptophan share the same transporter in Opossum kidney cells.

Opossum kidney (OK) cells, which have the ability to synthesise dopamine and 5-HT, have been used as an in vitro model for the study of renal actions of dopamine and 5-hydroxytryptamine (5-HT). The present study reports on the uptake of their immediate precursors L-3,4-dihydroxyphenylalanine (L-DOPA) and L-5-hydroxytryptophan (L-5-HTP). IC50 values for L-5-HTP (1569 microM) obtained in the presence of a nearly saturating (250 microM) concentration of L-DOPA were 6-fold those obtained when using non-saturating (0.25 and 25 microM) concentrations of L-DOPA (251 and 266). Vmax values (in nmol mg protein-1 6 min-1) for L-DOPA uptake are identical in the absence (13.6) and the presence of 250 microM L-5-HTP (13.3), but K(m) values (microM) are significantly greater (P < 0.05) when L-DOPA uptake was studied in the presence of L-5-HTP (90 vs 1.79). IC50 values for L-DOPA (679 microM) obtained in the presence of a near saturating (250 microM) concentration of L-5-HTP were almost 3-fold those obtained when non-saturating (0.25 and 25 microM) concentrations of L-5-HTP were used (254 and 220). Vmax values (in nmol mg protein-1 6 min-1) for L-5-HTP uptake are identical in the absence (11.2) and the presence of 250 microM L-DOPA (11.7), but K(m) values (microM) are significantly greater (P < 0.05) when L-5-HTP uptake was studied in the presence of L-DOPA (103 vs 220). It is concluded that L-DOPA and L-5-HTP share the same transporter(s) and each compound exerts a competitive type of inhibition upon the other.

5-Hydroxytryptophan↗

PubMed1997

Competitive and non-competitive inhibition of L-3, 4-dihydroxyphenylalanine uptake in Opossum kidney cells.

The present study aimed to determine the kinetics of L-3,4-dihydroxyphenylalanine (L-DOPA) uptake in Opossum kidney (OK) cells and to define the type of inhibition produced by L-5-hydroxytryptophan (L-5-HTP), cyanine 863 and 3,3'-diethyloxacarbocyanine (3,3'-DOC). Non-linear analysis of the saturation curves revealed for L-DOPA a Km (in microM) of 129 (114, 145) and a Vmax (in nmol/mg protein per 6 min) of 30.0 +/- 0.4 IC50 values for L-5-HTP (1454 microM) obtained in the presence of a nearly saturating (250 microM) concentration of L-DOPA were almost 4-fold those obtained when non-saturating (25 microM) concentrations of L-DOPA were used (330). IC50 values for cyanine 863 and 3,3'-DOC (638 and 353 microM) obtained in the presence of a nearly saturating (250 microM) concentration of L-DOPA were similar to those obtained when non-saturating (25 microM) concentrations of L-DOPA were used (654 and 339 microM). Vmax values (in nmol/mg protein per 6 min) for L-DOPA uptake were identical in the absence (36.4 +/- 0.7) and the presence of L-5-HTP (39.2 +/- 1.3), but Km values (microM) were significantly greater (P < 0.05) when L-DOPA uptake was studied in the presence of L-5-HTP (121 (100, 142) versus 318 (237, 399)). In contrast, the effect of cyanine 863 and 3,3'-DOC was to cause a significant reduction in Vmax values without significant changes in Km values. It is concluded that L-5-HTP exerts a competitive type of inhibition of L-DOPA uptake in cultured OK cells, whereas both cyanine 863, an organic cation transport inhibitor and 3,3'-DOC behave as non-competitive inhibitors.

Animals↗

PubMed1997

Opossum kidney cells take up L-DOPA through an organic cation potential-dependent and proton-independent transporter.

The present work was aimed at studying the kinetics and nature of the L-DOPA transporter in opossum kidney (OK) cells. Saturation experiments were performed in OK cells incubated for 6 min with increasing concentrations of L-DOPA (10 to 2500 microM); non-linear analysis of the saturation curve revealed for L-DOPA a K(m) of 129 microM (114, 145) and Vmax of 30.0 +/- 0.4 nmol mg protein-1 6 min-1. The uptake of L-DOPA (250 microM) was inhibited in a concentration-dependent manner by cyanine 863, an organic cation inhibitor, with a Ki value of 638 (430, 947) microM; the organic anion inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS), was devoid of effect upon the uptake of L-DOPA. The uptake of L-DOPA (250 microM) was significantly (P < 0.02) decreased (25% reduction) when cells were incubated in the presence of 137 mM K+ plus 5 mM Na+, when compared with the control condition (137 mM Na+ plus 5 mM K+); substitution of NaCl by choline chloride (137 mM) did not affect L-DOPA uptake. Similarly, inwardly or outwardly directed proton gradients of 0.5 pH units (7.9, 7.4, 6.9, 6.4 and 5.9) were found not to change L-DOPA uptake. In conclusion, the L-DOPA uptake system in OK cells has the characteristics of an organic cation potential-dependent and proton-independent transporter.

Animals↗

PubMed1996

Inhibitory effects of activin on the growth and morpholgenesis of primary and transformed mammary epithelial cells.

Activin is a member of the transforming growth factor beta superfamily, which is known to have activities involved in regulating differentiation and development. By using reverse transcription-PCR analysis on immunoaffinity-purified human breast cells, we have found that activin beta a and activin type II receptor are expressed by myoepithelial cells, whereas no expression was detected in other breast cell types. In examining 15 breast cell lines, we have found only four (HBL-100, MCF10-A, PMC-42, and BT 20) to be positive for activin beta a mRNA, whereas all expressed the activin type II receptor. Furthermore, we have found activin A to be a potent growth inhibitor of MCF- 7 cells (at 2 ng/ml), where it causes an arrest in G(1). Activin A does not appear to have an effect on the cell cycle of primary myoepithelial or luminal cells. However, we demonstrate that activin is an inhibitor of tubule formation by human mammary organoids in vitro. These are the first observations of activin and activin receptor in the normal human breast and in human breast cell lines and suggest a role for activin in mammary cell growth and morphogenesis.

Activins↗

PubMed1995

Cytogenetic findings in 31 papillary thyroid carcinomas.

Chromosome studies performed on 31 papillary thyroid carcinomas (PTCs) revealed clonal numerical and structural abnormalities in 12 tumors. The numerical clonal aberrations found were trisomy 2, trisomy 7, and loss of the Y chromosome. A nonrandom telomeric association, tas(15;16)(p13;p13), was observed in one carcinoma. Structural alterations with a breakpoint at 10q11.2 were detected in two tumors. Other chromosomes involved in rearrangements were chromosomes 1, 2, 3, 5, 7, 9, 11, 12, and 14. The observation of clonal changes of chromosome 2 [i(2)(q10) and trisomy 2] in two tumors, which were both histologically classified as tall-cell PTC variants, suggests that gain of 2q may be important in the development of this morphological variant.

Adolescent↗