Search PubMed⌕ Search

Biomedical subjects

G Napolitano

Publications and source records attributed to G Napolitano.

At least 37 records · Page 2Linked to original sources
PubMed1999

Zinc sulfate supplementation improves thyroid function in hypozincemic Down children.

In subjects affected by trisomy 21 (Down syndrome), hypothyroidism is the most common endocrinological deficit. Plasma zinc levels, which are commonly detected below the normal range in Down patients, are related to some endocrinological and immunological functions; in fact, zinc deficiency has been shown to impair immune response and growth rate. Aims of this study were to evaluate (1) the role of zinc deficiency in subclinical hypothyroidism and (2) thyroid function changes in Down children cyclically supplemented with zinc sulfate. Inverse correlations have been observed between age and triiodotironine (T3) and between zinc and thyroid-stimulating hormone (TSH); higher TSH levels have been found in hypozincemic patients at the beginning of the study. After 6 mo of supplementation, an improvement of thyroid function (TSH levels: 3.96 +/- 1.84 vs 2.64 +/- 1.33 mUI/mL basally and after 6 mo, respectively) was observed in hypozincemic patients. In the second cycle of supplementation, a similar trend of TSH was observed. At the end of the study, TSH significantly decreased in treated hypozincemic subjects (4.48 +/- 1.93 vs 2.96 +/- 1.20 mUI/mL) and it was no longer different in comparison to normozincemic patients. We suggest zinc supplementation to the diet in hypozincemic Down children as a simple and useful therapeutic tool.

Adolescent↗
PubMed1998

Recruitment of the TATA-binding protein to the HIV-1 promoter is a limiting step for Tat transactivation.

OBJECTIVES: To examine the functional interaction between HIV-1 Tat protein and the TATA-binding protein (TBP). DESIGN: HIV long terminal repeat reporter plasmids were cotransfected into mammalian and Drosophila insect cells with expression vectors encoding Tat and vectors encoding TBP either alone or linked to an heterologous DNA-binding domain. METHODS: The activity of the different reporters was compared in the presence or absence of Tat or TBP, or both, upon cotransfections into human and Drosophila insect cell lines. RESULTS: Tat protein is unable to transactivate enhancerless HIV-1 minimal promoter bearing only the TATA box and TAR. Artificial recruitment of human TBP (hTBP) to the enhancerless HIV minimal promoter was found to trigger gene expression and coexpression of Tat resulted in a marked synergy. Tat protein cooperated with DNA-bound hTBP by inducing high levels of processive viral transcripts. Synergy between Tat and hTBP was also observed when both factors were targeted to a promoter DNA template. The functional cooperation between TBP and Tat was further demonstrated using the Drosophila Schneider SL2 cells. In these cells Tat protein alone was ineffective; however, coexpression of Drosophila TBP and Tat resulted in a trans-activating response region-dependent synergistic transactivation of basal transcription. CONCLUSION: The strong synergy between TBP and Tat in the absence of any DNA-bound activator suggests that Tat stimulates transcription in an activator-independent manner most likely by a functional interaction with general transcription factors that occurs after TBP recruitment. Thus, efficient recruitment of TBP represents a limiting step for Tat transactivation.

Animals↗
PubMed1998

Recruitment of human TBP selectively activates RNA polymerase II TATA-dependent promoters.

An increasing body of evidence suggests that eukaryotic activators stimulate polymerase II transcription by facilitating the assembly of the functional basal machinery at the promoter. Here we describe experiments that provide added support for the idea that recruitment of TATA-binding protein (TBP) is a rate-limiting step for transcription activation in mammalian cells. We found that, in human cell lines, recruitment of TBP to a promoter, as a GAL4-TBP fusion protein, can provide a substantial activation of transcription. Activation mediated by the hTBP, tethered to promoter DNA, is strictly dependent upon the presence of a functional TATA element, and it directs faithful transcription initiation. Interestingly, GAL4-hTBP activation was not observed from initiator (Inr) -dependent TATA-less promoters. These results suggest that TBP binding to DNA is not a rate-limiting step for the initial stages of TFIID recruitment to initiator-dependent TATA-less promoters. Finally, we provide evidence that synergy between GAL4-hTBP and defined transcription domains is restricted to activators, such as VP16 and Tat, which are likely to function at steps subsequent to the TFIID recruitment. These findings strengthen the idea that recruitment of TBP represents an important mechanism of activation of TATA-dependent promoters, and on the other hand, they suggest that TBP-DNA interactions are largely dispensable for specific transcription of initiator dependent TATA-less promoters.

DNA↗
PubMed1998

Polymorphism of motilin gene in patients with Crohn's disease.

An increasing body of evidence supports the concept of genetic heterogeneity within inflammatory bowel disease (IBD). In this study, a polymorphism of the motilin gene, which determines an amino acid substitution in the motilin protein, has been investigated in IBD patients. Fifty patients with ulcerative colitis (UC), and 52 with Crohn's disease (CD) were investigated for anti-neutrophil cytoplasmatic antibodies (ANCA) and the polymorphism in the second exon of the motilin gene. Sixty unrelated blood donors served as controls. ANCA were found in 30% of UC and 13% of CD. In controls the DNA polymorphism identified two alleles (1 and 2) at a frequency of 42% and 58%, respectively. Patients with either UC or CD showed a slight increase in the frequency of allele 2 (69% and 60%, respectively; P > 0.05 vs controls). This allele was predominant in ANCA-positive CD patients (86%; P < 0.04) while in UC it did not differ. All ANCA-positive CD patients had the disease confined to the colon. A polymorphism of second exon of the motilin gene, leading to a protein variant, is significantly more frequent in the subset of ANCA-positive CD patients. This subgroup of patients appears to share peculiar genetic and clinical features.

Adult↗
PubMed1998

Long-term effect of a single dose of flunarizine in Huntington's disease.

We report a preliminary pilot study on the clinical efficacy of flunarizine (FNZ), a calcium-entry blocker that causes extrapyramidal side-effects, in 10 patients with Huntington's disease (HD). FNZ (20 mg) administered by the sublingual route resulted in a decrease in choreic movements and improved dexterity in performing several tests. These effects lasted for at least 7 days after a single dose. Therefore, FNZ seems to exert the same effect as a long-acting neuroleptic agent in our HD patients.Copyright Lippincott-Raven Publishers

Journal Article↗
PubMed1998

Regulation of major histocompatibility class II gene expression in FRTL-5 thyrocytes: opposite effects of interferon and methimazole.

Aberrant expression of major histocompatibility complex (MHC) class II antigens is associated with autoimmune thyroid disease; aberrant expression duplicating the autoimmune state can be induced by interferon-gamma (IFNgamma). We have studied IFNgamma-induced human leukocyte antigen (HLA)-DR alpha gene expression in rat FRTL-5 thyroid cells to identify the elements and factors important for aberrant expression. Using an HLA-DR alpha 5'-flanking region construct from -176 to +45 bp coupled to the chloramphenicol acetyltransferase reporter gene, we show that there is no basal class II gene expression in FRTL-5 thyroid cells, that IFNgamma can induce expression, and, as is the case for antigen-presenting cells from the immune system, that IFNgamma-induced expression requires several highly conserved elements on the 5'-flanking region, which, from 5' to 3', are the S, X1, X2, and Y boxes. Methimazole (MMI), a drug used to treat patients with Graves' disease and experimental thyroiditis in rats or mice, can suppress the IFNgamma-induced increase in HLA-DR alpha gene expression as a function of time and concentration; MMI simultaneously decreases IFNgamma-induced endogenous antigen presentation by the cell. Using gel shift assays and the HLA-DR alpha 5'-flanking region from -176 or -137 to +45 bp as radiolabeled probes, we observed the formation of a major protein-DNA complex with extracts from FRTL-5 cells untreated with IFNgamma, termed the basal or constitutive complex, and formation of an additional complex with a slightly faster mobility in extracts from cells treated with IFNgamma. MMI treatment of cells prevents IFNgamma from increasing the formation of this faster migrating complex. Formation of both complexes is specific, as evidenced in competition studies with unlabeled fragments between -137 and -38 bp from the start of transcription; nevertheless, they can be distinguished in such studies. Thus, high concentrations of double stranded oligonucleotides containing the sequence of the Y box, but not S, X1, or X2 box sequences, can prevent formation of the IFNgamma-increased faster migrating complex, but not the basal complex. Both complexes involve multiple proteins and can be distinguished by differences in their protein composition. Thus, using specific antisera, we show that two cAMP response element-binding proteins, activating transcription factor-1 and/or -2, are dominant proteins in the upper or basal complex. The upper or basal complex also includes c-Fos, Fra-2, Ets-2, and Oct-1. A dominant protein that distinguishes the IFNgamma-increased lower complex is CREB-binding protein (CBP), a coactivator of cAMP response element-binding proteins. We, therefore, show that aberrant expression of MHC class II in thyrocytes, induced by IFNgamma, is associated with the induction or increased formation of a novel protein-DNA complex and that its formation as well as aberrant class II expression are suppressed by MMI, a drug used to treat human and experimental autoimmune thyroid disease. Its component proteins differ from those in a major, basal, or constitutive protein-DNA complex formed with the class II 5'-flanking region in cells that are not treated with IFNgamma and that do not express the class II gene.

Animals↗
PubMed1998

Major histocompatibility class II HLA-DR alpha gene expression in thyrocytes: counter regulation by the class II transactivator and the thyroid Y box protein.

Aberrant expression of major histocompatibility complex (MHC) class II proteins on thyrocytes, which is associated with autoimmune thyroid disease, is mimicked by gamma-interferon (gamma-IFN). To define elements and factors that regulate class II gene expression in thyrocytes and that might be involved in aberrant expression, we have studied gamma-IFN-induced HLA-DR alpha gene expression in rat FRTL-5 thyroid cells. The present report shows that class II expression in FRTL-5 thyrocytes is positively regulated by the class II transactivator (CIITA), and that CIITA mimics the action of gamma-IFN. Thus, as is the case for gamma-IFN, several distinct and highly conserved elements on the 5'-flanking region of the HLA-DR alpha gene, the S, X1, X2, and Y boxes between -137 to -65 bp, are required for class II gene expression induced by pCIITA transfection in FRTL-5 thyroid cells. CIITA and gamma-IFN do not cause additive increases in HLA-DR alpha gene expression in FRTL-5 cells, consistent with the possibility that CIITA is an intermediate factor in the gamma-IFN pathway to increased class II gene expression. Additionally, gamma-IFN treatment of FRTL-5 cells induces an endogenous CIITA transcript; pCIITA transfection mimics the ability of gamma-IFN treatment of FRTL-5 thyroid cells to increase the formation of a specific and novel protein/DNA complex containing CBP, a coactivator of CRE binding proteins important for cAMP-induced gene expression; and the action of both gamma-IFN and CIITA to increase class II gene expression and increase complex formation is reduced by cotransfection of a thyroid Y box protein, which suppresses MHC class I gene expression in FRTL-5 thyroid cells and is a homolog of human YB-1, which suppresses MHC class II expression in human glioma cells. We conclude that CIITA and TSH receptor suppressor element binding protein-1 are components of the gamma-IFN-regulated transduction system which, respectively, increase or decrease class II gene expression in thyrocytes and may, therefore, be involved in aberrant class II expression associated with autoimmune thyroid disease.

Animals↗
PubMed1998

Regulation of major histocompatibility (MHC) class II human leukocyte antigen-DR alpha gene expression in thyrocytes by single strand binding protein-1, a transcription factor that also regulates thyrotropin receptor and MHC class I gene expression.

The single strand binding protein (SSBP-1) is a positive regulator of TSH receptor gene expression and binds to an element with a GXXXXG motif. The S box of the mouse major histocompatibility class II gene has multiple GXXXXG motifs and can also bind SSBP-1. The S box is one of four highly conserved elements on the 5'-flanking region of class II genes that are necessary for interferon-gamma (IFNgamma) to overcome the normally suppressed state of the gene and induce aberrant class II expression. In this report we show that SSBP-1, when overexpressed in FRTL-5 thyroid cells, is a positive regulator of human leukocyte antigen (HLA)-DR alpha class II gene expression, as is IFNgamma or the class II trans-activator (CIITA). This is evidenced by increased exogenous promoter activity, increased endogenous RNA levels, and increased endogenous antigen expression after transfecting full-length SSBP-1 complementary DNA together with a HLA-DR alpha promoter-reporter gene chimera into TSH-treated FRTL-5 thyroid cells whose endogenous SSBP-1 levels are low. IFNgamma reverses the ability of TSH to decrease endogenous SSBP-1 RNA levels. Also, whereas SSBP-1 transfection does not cause any increase in IFNgamma-induced exogenous promoter activity, transfection of SSBP-1 and CIITA additively increases endogenous class II RNA levels to levels measured in cells treated with IFNgamma. Further, competition studies show that SSBP-1 binding is necessary for formation of the double strand protein/DNA complexes that are seen in electrophoretic mobility shift assays when the class II 5'-flanking region is incubated with extracts from IFNgamma-treated FRTL-5 cells and that have been previously associated with IFNgamma-induced aberrant class II expression. These data suggest that SSBP-1 is involved in the action of IFNgamma to overcome the normally suppressed state of the class II gene; it functions together with CIITA, whose expression is independently increased by IFNgamma. The effect of SSBP-1 as a positive regulator of class II promoter activity is lost in cells maintained without TSH, in which endogenous SSBP-1 RNA levels are already high in the absence of aberrant class II gene expression. These data suggest that high levels of endogenous SSBP-1 are insufficient to cause aberrant class II expression, but, rather, TSH or IFNgamma treatment additionally modulates the cell, albeit differently, such that transfected or endogenous SSBP-1, respectively, can express its positive regulatory activity. The effect of TSH is consistent with reports indicating that TSH enhances the ability of IFNgamma to increase class II gene expression despite the fact IFNgamma increases endogenous SSBP-1 to only the same levels as in cells untreated with TSH. Finally, the effect of SSBP-1 as a positive regulator is lost when GXXXXG motifs, which exist on both the coding and noncoding strands of the S box, are mutated. Consistent with this, mutation and oligonucleotide competition studies show that GXXXXG motifs are necessary for either strand of the S box to bind protein/DNA complexes containing SSBP-1 in FRTL-5 cell extracts or to bind to recombinant SSBP-1. They also suggest that the SSBP-1-binding sites on either strand of the HLA-DR alpha S box are functionally distinct. We conclude from these data that the positive regulatory action of SSBP-1 on class II gene expression involves GXXXXG motifs on each strand of the highly conserved S box of the class II 5'-flanking region. As SSBP-1 is modulated by IFNgamma and is involved in class I and TSH receptor as well as class II gene expression in FRTL-5 cells, the sum of the data supports the hypotheses that common transcription factors regulate all three genes, and their altered activities may contribute to the development of autoimmunity.

Animals↗
PubMed1998

Iodide suppression of major histocompatibility class I gene expression in thyroid cells involves enhancer A and the transcription factor NF-kappa B.

High concentrations of iodide can induce transient, clinical improvement in patients with autoimmune Graves' disease. Previous work has related this iodide action to the autoregulatory effect of iodide on the growth and function of the thyroid; more recently, we additionally related this to the ability of iodide to suppress major histocompatibility (MHC) class I RNA levels and antigen expression on thyrocytes. In this report, we describe a transcriptional mechanism involved in iodide suppression of class I gene expression, which is potentially relevant to the autoregulatory action of iodide. Transfection experiments in FRTL-5 cells show that iodide decreases class I promoter activity and that this effect can be ascribed to the ability of iodide to modulate the formation of two specific protein/DNA complexes with enhancer A, -180 to -170 bp, of the class 1 5'-flanking region. Thus, iodide decreases the formation of Mod-1, an enhancer A complex involving the p50 subunit of NF-kappa B and a c-fos family member, fra-2, which was previously shown to be important in the suppression of class I levels by hydrocortisone. Unlike hydrocortisone, iodide also increases the formation of a complex with enhancer A, which we show, in antibody shift experiments, is a heterodimer of the p50 and p65 subunits of NF-kappa B. The changes in these complexes are not duplicated by chloride and are related to the action of iodide on class I RNA levels by the following observations. First, FRTL-5 thyroid cells with an aged phenotype coincidentally lose the ability of iodide to decrease MHC class I RNA levels and to induce changes in either complex. Second, the effect of iodide on class I RNA levels and on enhancer A complex formation with Mod-1 and the p50/p65 heterodimer is inhibited by agents that block the inositol phosphate, Ca++, phospholipase A2, arachidonate signal transduction pathway: acetylsalicylate, indomethacin, and 5,8,11,14-eicosatetraynoic acid. Interestingly, iodide can also decrease formation of the Mod-1 complex and increase formation of the complex with the p50/p65 subunits of NF-kappa B when the NF-kappa B enhancer sequence from the Ig kappa light chain, rather than enhancer A, is used as probe; and both actions mimic the action of a phorbol ester. This suggests that iodide may regulate complex formation with NF-kappa B regulatory elements on multiple genes associated with growth and function, providing a potential mechanism relating the autoregulatory action of iodide on thyroid cells and its action on class I gene expression.

Animals↗
PubMed1998

HLA antigens and pANCA define ulcerative colitis as a genetically heterogeneous disorder.

BACKGROUND: Several genetic and subclinical markers have been associated with ulcerative colitis. AIM: To determine whether a significant association with HLA class I and II antigens was present in Italian ulcerative colitis patients considered as a whole population or stratified according to their anti-neutrophil cytoplasmatic antibodies. METHODS: HLA class I and II antigens were studied by serological typing techniques and related to the presence of anti-neutrophil cytoplasmatic antibodies detected by means of indirect immunofluorescence. RESULTS: Patients with ulcerative colitis (n = 45) had a significantly increased frequency of DQ6 (p = 0.04) and DQ7 (p = 0.003) and a decreased frequency of DQ5 (p = 0.03) and DQ8 (p = 0.02) when compared with ethnically matched healthy controls (n = 252 for HLA class I and 173 for HLA class II). No significant difference in HLA I- and DR-antigens was observed. Anti-neutrophil cytoplasmatic antibodies were found in 27/45 (60%) ulcerative colitis patients and in 0/252 controls (p < 0.001). After stratifying ulcerative colitis patients according to their anti-neutrophil cytoplasmatic antibodies status, anti-neutrophil cytoplasmatic antibodies +ve patients had an increased frequency of A19 (p = 0.007), DR2 (p = 0.03), and DR15 (p = 0.006), and a decreased frequency of A1 (p = 0.004) compared with anti-neutrophil cytoplasmatic antibodies -ve ones. CONCLUSIONS: We suggest that specific HLA-class II loci play an important role in the susceptibility to ulcerative colitis in Italy. A subset of ulcerative colitis patients is characterised by the presence of a specific subclinical marker (anti-neutrophil cytoplasmatic antibodies) which seems to be genetically determined as shown by the increased frequencies of HLA-A19 and DR2 observed in anti-neutrophil cytoplasmatic antibodies +ve ulcerative colitis.

Adult↗
PubMed1997

Regulation of major histocompatibility complex class I gene expression in thyroid cells. Role of the cAMP response element-like sequence.

The major histocompatibility complex (MHC) class I gene cAMP response element (CRE)-like site, -107 to -100 base pairs, is a critical component of a previously unrecognized silencer, -127 to -90 bp, important for thyrotropin (TSH)/cAMP-mediated repression in thyrocytes. TSH/cAMP induced-silencer activity is associated with the formation of novel complexes with the 38-base pair silencer, whose appearance requires the CRE and involves ubiquitous and thyroid-specific proteins as follows: the CRE-binding protein, a Y-box protein termed thyrotropin receptor (TSHR) suppressor element protein-1 (TSEP-1); thyroid transcription factor-1 (TTF-1); and Pax-8. TTF-1 is an enhancer of class I promoter activity; Pax-8 and TSEP-1 are suppressors. TSH/cAMP decreases TTF-1 complex formation with the silencer, thereby decreasing maximal class I expression; TSH/cAMP enhance TSEP-1 and Pax-8 complex formation in association with their repressive actions. Oligonucleotides that bind TSEP-1, not Pax-8, prevent formation of the TSH/cAMP-induced complexes associated with TSH-induced class I suppression, i.e. TSEP-1 appears to be the dominant repressor factor associated with TSH/cAMP-decreased class I activity and formation of the novel complexes. TSEP-1, TTF-1, and/or Pax-8 are involved in TSH/cAMP-induced negative regulation of the TSH receptor gene in thyrocytes, suppression of MHC class II, and up-regulation of thyroglobulin. TSH/cAMP coordinate regulation of common transcription factors may, therefore, be the basis for self-tolerance and the absence of autoimmunity in the face of TSHR-mediated increases in gene products that are important for thyroid growth and function but are able to act as autoantigens.

Animals↗
PubMed1997

Gastrointestinal motility disorders in patients with inactive Crohn's disease.

BACKGROUND: Although some symptoms of Crohn's disease may be related to gastrointestinal motility disorders, studies on gastrointestinal motility in inactive Crohn's disease are lacking. METHODS: Fasting and postprandial motor activity (1 h) was recorded in the gastric antrum and upper small intestine of 35 patients with inactive Crohn's disease and 18 controls, using conventional manometry. RESULTS: Motor disorders were observed in 26 of 35 patients. The number of phase-II contractions was reduced (1.3 +/- 0.7/min versus 1.8 +/- 0.6/min in controls; P < 0.02) (mean +/- standard deviation), whereas the incidence of propagated single (2.2 +/- 3.2/h versus 0.5 +/- 0.6/h; P < 0.03) and clustered contractions (3.8 +/- 7/h versus 1.1 +/- 1.4, P < 0.04) was markedly increased. Motor abnormalities were more frequent and severe in patients with Crohn's ileitis than in controls, and in patients with gastrointestinal symptoms than in asymptomatic patients. CONCLUSION: Most patients with inactive, uncomplicated Crohn's disease show marked gastrointestinal motor disorders, characterized either by reduced incidence of small-bowel contractions and increased incidence of single or clustered propagated contractions.

Adolescent↗
PubMed1996

Thyroid function and plasma selenium in chronic uremic patients on hemodialysis treatment.

It has been shown recently that Selenium (Se), an essential trace element for humans, is involved in the regulation of thyroid function, since the enzyme that catalyzes the liver conversion of the thyroid hormone T4 to the more active form T3 is a selenoenzyme. In chronic uremic patients, low blood Se levels as well as thyroid function abnormalities are often found. The present study was carried out to verify whether any correlation exists between Se levels and thyroid function, and to evaluate possible changes in hormonal pattern during Se supplementation in 10 chronic uremic patients on hemodialysis (HD) treatment. Se was supplemented orally as sodium selenite over six consecutive months. Basic plasma Se levels were significantly lower in patients than in normal controls. Right from the start of Se supplementation, plasma Se concentration promptly normalized and leveled off in the normal range throughout the study. Significant increase of FT3 and reduction of TSH levels were detected during Se supplementation. In Se-supplemented patients, a significant direct correlation was also found between reverse T3 (rT3) and TSH, and a significant inverse correlation was found between Se and TSH. Our results suggest that Se deficiency in chronic uremic patients represents a factor influencing the thyroid function and that the Se status should be determined in the evaluation of thyroid metabolism in these patients.

Administration, Oral↗
PubMed1995

Hormonal modulation of major histocompatibility complex class I gene expression involves an enhancer A-binding complex consisting of Fra-2 and the p50 subunit of NF-kappa B.

Hydrocortisone decreases major histocompatibility complex (MHC) class I gene expression in rat thyroid cells and counteracts increases induced by interferons. Using FRTL-5 cells transfected with class I promoter-reporter gene chimeras, we show that hydrocortisone action is transcriptional and mediated by an element located between 180 and 170 base pairs upstream of the start of transcription. Gel shift assays reveal that hydrocortisone causes the decrease of a specific protein-DNA complex; this same complex, referred to as Mod-1, is increased by interferon. Oligonucleotide competition assays reveal that the Mod-1 complex is associated with enhancer A of the class I gene, -180 to -170 base pairs (5'-GGGGAGTCCCC-3'), immediately upstream of the interferon response element. Antibodies to fra-2, a fos family member, and to the p50, but not the p65, subunit of NF-kappa B supershift the Mod-1 complex. We suggest that hydrocortisone decreases MHC class I gene expression by reducing the formation of Mod-1, which contains both p50 and fra-2; interferon reverses the hydrocortisone effect and increases Mod-1 formation. These observations are relevant to the molecular basis of hydrocortisone therapy in autoimmune thyroid disease and to the actions of interferon to exacerbate or induce autoimmune disease.

Animals↗
PubMed1995

The thyrotropin receptor.

This chapter has outlined the complex process required for thyroid growth and function. Both events are regulated by TSHR via a multiplicity of signals, with the aid of and requirement for a multiplicity of hormones that regulate the TSHR via receptor cross-talk: insulin, IGF-I, adrenergic receptors, and purinergic receptors. Cross-talk appears to regulate G-protein interactions or activities induced by TSH as well as TSHR gene expression. The TSHR structure and its mechanism of signal transduction is being rapidly unraveled in several laboratories, since the recent cloning of the receptor. In addition, the epitopes for autoantibodies against the receptor that can subvert the normal regulated synthesis and secretion of thyroid hormones, causing hyper- or hypofunction, have been defined. Studies of regulation of the TSHR minimal promotor have uncovered a better understanding of the mechanisms by which TSH regulates both growth and function of the thyroid cell. A key novel component of this phenomenon involves TSH AMP positive and negative regulation of the TSHR. Negative transcriptional regulation is a common feature of MHC class I genes in the thyroid. Subversion of negative regulation or too little negative regulation is suggested to result in autoimmune disease. Methimazole and iodide at autoregulatory levels may be important in reversing this process and returning thyroid function to normal. Their action appears to involve factors that react with the IREs on both the TSHR and the TG promoter. Too much negative regulation, as in the case of ras transformation, results in abnormal growth without function. TTF-1 is implicated as a critical autoregulatory component in both positive and negative regulation of the TSHR and appears to be the link between TSH, the TSHR, TSHR-mediated signals, TG and TPO biosynthesis, and thyroid hormone formation. Differentially regulated expression of the TSHR and TG by cAMP and insulin depend on differences in the specificity of the TTF-1 site, that is, the lack of Pax-8 interactions with the TSHR, and the IRE sites. Single-strand binding proteins will become important in determining how TSHR transcription is controlled mechanistically.

Amino Acid Sequence↗
PubMed1995

Gastric emptying of solids in patients with nonobstructive Crohn's disease is sometimes delayed.

To date, only a few studies of gastric emptying in Crohn's disease have been published in the literature. This might be clinically important because slow-release drug formulations are increasingly available for treatment. Studies in children with gastric involvement suggest that gastric emptying may be delayed in this condition. We studied the scintigraphic gastric emptying of 21 adult patients with nonobstructive Crohn's disease and without gastric or duodenal involvement by the disease, compared with that of 20 healthy volunteers. Overall, no significant differences were found, but subgroup analysis showed that symptomatic patients [half-time (t1/2) 133 +/- 75.9] and those with colonic involvement (t1/2 127.2 +/- 64) had a significantly (p < 0.01) delayed gastric emptying over controls (t1/2 85.5 +/- 15.4). Such a difference was also observed between symptomatic and asymptomatic patients (p < 0.05). We conclude that gastric emptying is slowed in symptomatic patients with nonobstructive Crohn's disease and in those with colonic involvement. This may have therapeutic implications.

Adult↗
PubMed1994

[Osteoarticular manifestations during liver and gastrointestinal diseases].

The most important osteoarticular complications occurring during gastrointestinal and liver diseases are reviewed. Although etiopathogenesis of these disorders is not yet fully understood, their knowledge is required to gastroenterologists for two main reasons: to establish a correct diagnosis and to start an appropriate therapy.

Bone Diseases↗