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1.
Cureus ; 16(6): e61888, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38975457

ABSTRACT

A 26-year-old male with no significant medical history presented with hematochezia and was diagnosed with ulcerative colitis (UC) accompanied by immune thrombocytopenia (ITP) as an extraintestinal manifestation (EIM) of UC. This case report delves into the uncommon overlap between UC, a subtype of inflammatory bowel disease primarily affecting the colon and rectum, and ITP, an autoimmune condition leading to platelet destruction. The patient's atypical presentation and subsequent positive response to a treatment regimen targeting both UC and ITP underscores the necessity for a thorough and multifaceted diagnostic approach in individuals with UC, especially when faced with non-gastrointestinal symptoms like unexplained thrombocytopenia. The findings from this study enhance the understanding of UC's diverse manifestations and highlight its potential intersection with other autoimmune diseases, advocating for integrated care strategies in managing such intricate clinical cases.

2.
Cureus ; 16(1): e51848, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38327910

ABSTRACT

Introduction Artificial intelligence (AI) integration in healthcare, specifically in gastroenterology, has opened new avenues for enhanced patient care and medical decision-making. This study aims to assess the reliability and accuracy of two prominent AI tools, ChatGPT 4.0 and Google Bard, in answering gastroenterology-related queries, thereby evaluating their potential utility in medical settings. Methods The study employed a structured approach where typical gastroenterology questions were input into ChatGPT 4.0 and Google Bard. Independent reviewers evaluated responses using a Likert scale and cross-referenced them with guidelines from authoritative gastroenterology bodies. Statistical analysis, including the Mann-Whitney U test, was conducted to assess the significance of differences in ratings. Results ChatGPT 4.0 demonstrated higher reliability and accuracy in its responses than Google Bard, as indicated by higher mean ratings and statistically significant p-values in hypothesis testing. However, limitations in the data structure, such as the inability to conduct detailed correlation analysis, were noted. Conclusion The study concludes that ChatGPT 4.0 outperforms Google Bard in providing reliable and accurate responses to gastroenterology-related queries. This finding underscores the potential of AI tools like ChatGPT in enhancing healthcare delivery. However, the study also highlights the need for a broader and more diverse assessment of AI capabilities in healthcare to leverage their potential in clinical practice fully.

3.
Cureus ; 15(4): e37977, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37101799

ABSTRACT

Introduction Upper gastrointestinal bleeding (UGIB) refers to blood loss from a gastrointestinal (GI) source proximal or above the ligament of Treitz. Health equity means giving everyone an equal chance to achieve optimal health by addressing injustices, overcoming barriers, and eliminating health disparities. Healthcare providers must analyze racial and ethnic disparities in UGIB management to ensure all patients receive equal care. Identifying risk factors in specific populations leads to tailored interventions that improve outcomes. Our study aims to examine trends and identify disparities in upper gastrointestinal bleeding across races and ethnicities to promote health equity. Methods Retrospective data on upper gastrointestinal bleeding from June 2009 to June 2022 were collected and categorized into five groups based on race. The baseline characteristics of each group were matched to ensure equitable comparison. A joinpoint regression model was used to compare incidence trends, identifying potential healthcare disparities for different racial/ethnic groups over time. Patients aged 18-75 who suffered from upper gastrointestinal bleeding at Nassau University Medical Center in New York from 2010 to 2021 were selected, excluding those with incomplete baseline comorbidity information. Results This study examined 5103 cases of upper gastrointestinal bleeding, with 41.9% female. The cohort was diverse, with 29.4% African American, 15.6% Hispanic, 45.3% White, 6.8% Asian, and 2.9% of other races. Data were split into two groups; 49.9% occurred between 2009 and 2015 and 50.1% between 2016 and 2022. Findings showed increased UGIB among Hispanics and decreased bleeding among Asians during 2016-2021 compared to 2009-2015. However, no significant difference was found for African Americans, Whites, and other races. In addition, Hispanics had a rise in the annual percentage change (APC) rate, whereas Asians had a decrease. Conclusion Our study examined trends in upper gastrointestinal bleeding and potential healthcare disparities across races and ethnicities. Our findings highlight an increased incidence of UGIB in Hispanics and a decreased incidence in Asians. Additionally, we identified a significant increase in the annual percentage change rate in Hispanics and a decrease in Asians over time. Our study underscores the importance of identifying and addressing disparities in UGIB management to promote health equity. Future research can build on these findings to develop tailored interventions that improve patient outcomes.

4.
Ir J Psychol Med ; 40(3): 369-377, 2023 09.
Article in English | MEDLINE | ID: mdl-33455597

ABSTRACT

OBJECTIVES: Delirium, which is associated with adverse health outcomes, is poorly detected in hospital settings. This study aimed to determine delirium occurrence among older medical inpatients and to capture associated risk factors. METHODS: This prospective cohort study was performed at an Irish University Hospital. Medical inpatients 70 years and over were included. Baseline assessments within 72 hours of admission included delirium status and severity as determined by the Revised Delirium Rating Scale (DRS-R-98), cognition, physical illness severity and physical functioning. Pre-existing cognitive impairment was determined with Short Informant Questionnaire on Cognitive Decline (IQCODE). Serial assessment of delirium status, cognition and the physical illness severity were undertaken every 3 (±1) days during participants' hospital admission. RESULTS: Of 198 study participants, 92 (46.5%) were women and mean age was 80.6 years (s.d. 6.81; range 70-97). Using DRS-R-98, 17.7% (n = 35) had delirium on admission and 11.6% (n = 23) had new-onset delirium during admission. In regression analysis, older age, impaired cognition and lower functional ability at admission were associated with a significant likelihood of delirium. CONCLUSIONS: In this study, almost one-third of older medical inpatients in an acute hospital had delirium during admission. Findings that increasing age, impaired cognition and lower functional ability at admission were associated with increased delirium risk suggest target groups for enhanced delirium detection and prevention strategies. This may improve clinical outcomes.


Subject(s)
Delirium , Humans , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Male , Prospective Studies , Delirium/diagnosis , Delirium/epidemiology , Hospitalization , Inpatients , Hospitals
5.
PeerJ ; 7: e6366, 2019.
Article in English | MEDLINE | ID: mdl-30775173

ABSTRACT

The reported Agrobacterium radiobacter DSM 30174T genome is highly fragmented, hindering robust comparative genomics and genome-based taxonomic analysis. We re-sequenced the Agrobacterium radiobacter type strain, generating a dramatically improved genome with high contiguity. In addition, we sequenced the genome of Agrobacterium tumefaciens B6T, enabling for the first time, a proper comparative genomics of these contentious Agrobacterium species. We provide concrete evidence that the previously reported Agrobacterium radiobacter type strain genome (Accession Number: ASXY01) is contaminated which explains its abnormally large genome size and fragmented assembly. We propose that Agrobacterium tumefaciens be reclassified as Agrobacterium radiobacter subsp. tumefaciens and that Agrobacterium radiobacter retains it species status with the proposed name of Agrobacterium radiobacter subsp. radiobacter. This proposal is based, first on the high pairwise genome-scale average nucleotide identity supporting the amalgamation of both Agrobacterium radiobacter and Agrobacterium tumefaciens into a single species. Second, maximum likelihood tree construction based on the concatenated alignment of shared genes (core genes) among related strains indicates that Agrobacterium radiobacter NCPPB3001 is sufficiently divergent from Agrobacterium tumefaciens to propose two independent sub-clades. Third, Agrobacterium tumefaciens demonstrates the genomic potential to synthesize the L configuration of fucose in its lipid polysaccharide, fostering its ability to colonize plant cells more effectively than Agrobacterium radiobacter.

6.
Health Sciences Journal ; : 101-107, 2019.
Article in English | WPRIM (Western Pacific) | ID: wpr-961165

ABSTRACT

INTRODUCTION@#Despite establishing immunization as an effective approach, the number of deaths from immunizable diseases among 0 to 14 years old remained high in 2012. This prompted the researchers to determine the knowledge, attitude and practices of mothers/caregivers regarding the immunization of their children. @*METHODS@#The research utilized a descriptive cross-sectional design. An interviewer-guided validated questionnaire was administered to mothers and caregivers with at least one child 12 months or younger who was eligible for immunization. @*RESULTS@#Around half of the 211 respondents were aged 20-35 years old, married and living in their own home. A large percentage were unemployed, and the highest educational attainment was high school. Most respondents had one child in care undergoing immunization, mostly in a health center. Results showed that all respondents scored below the MPL for knowledge. For attitude, all scored above the MPL. Only 45.02% of mothers/caregivers scored above the MPL for practices.@*CONCLUSION@#Despite poor knowledge, mothers and caregivers displayed good attitude towards immunization, however this did not translate into bringing their children for vaccination.


Subject(s)
Immunization
7.
Clin Pediatr (Phila) ; 56(8): 737-743, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28589764

ABSTRACT

Male human papillomavirus (HPV) vaccination rates remain very low. The study objective was to gain an understanding of the perceptions of HPV disease and acceptance/barriers to HPV vaccine by parents of boys aged 9 to 18 years. An anonymous, written survey was administered from January 1, 2011 to September 30, 2013 in private pediatric offices (PPOs) and public health clinics (PHCs) in Chicago, Illinois. A total of 230 PPO parents (PPOPs) and 286 PHC parents (PHCPs) completed the survey. Despite significant differences ( P < .0001) in education level, socioeconomic status, and HPV disease and vaccine knowledge/awareness between the PPOP and PHCP, there was no difference between PPOP and PHCP who would vaccinate their sons with HPV vaccine. For both groups, health care provider recommendation was the primary influence for vaccination. The major barrier to vaccination was lack of information on HPV disease/vaccine. Health care providers need to proactively discuss and use HPV vaccine in male patients.


Subject(s)
Health Knowledge, Attitudes, Practice , Papillomavirus Infections/prevention & control , Papillomavirus Vaccines/therapeutic use , Parents/psychology , Patient Acceptance of Health Care/psychology , Patient Acceptance of Health Care/statistics & numerical data , Adolescent , Awareness , Chicago , Child , Humans , Male , Papillomavirus Infections/psychology
8.
Obstet Gynecol ; 122(2 Pt 1): 370-373, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23969807

ABSTRACT

In the United States, major epidemics of pertussis or whooping cough have occurred in the last 5 years making this disease a major public health issue. The adolescent and adult populations are the major transmitters of disease to the community. However, these epidemics have had the greatest effect on the young infant population resulting in high rates of hospitalizations and complications and accounting for 100% of the mortality. Optimization of vaccine recommendations is a strategy that is critically important as a method to control the disease burden and decrease the transmission of disease to the young infant population. Immunization that is focused on the close contacts of these young infants (the cocoon strategy) is felt to be one of the main cornerstones to vaccine optimization with the immunization of pregnant women being critical. Transmission studies have shown that adolescent and adult close contacts, especially new mothers, are the source of disease transmission to their young infants in more than 50% of the cases. The Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists strongly recommend that the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis booster vaccine be given to pregnant women during each pregnancy between 27 weeks and 36 weeks of gestation to protect their infant against pertussis disease.


Subject(s)
Diphtheria-Tetanus-acellular Pertussis Vaccines/administration & dosage , Whooping Cough/prevention & control , Female , Humans , Infant , Mass Vaccination , Pregnancy
9.
J Reprod Med ; 56(7-8): 301-7, 2011.
Article in English | MEDLINE | ID: mdl-21838159

ABSTRACT

OBJECTIVE: To examine the awareness, knowledge, barriers to usage and acceptance of recommended adult vaccines among obstetrician/gynecologists (OB/GYNs) compared to other adult primary care providers (APCPs). STUDY DESIGN: A self-administered survey was sent to 1,000 OB/GYN, 1,000 family practice and 1,000 internal medicine physicians nationwide. RESULTS: Of 3,000 mailed surveys, 733 (24.8%) were returned. Of those, 617 (84.18%) reported providing primary care to adults. Only 53.04% of APCPs reported having a vaccine record on > 50% of their primary care patients, with 33.15% of OB/GYNs having no record. This absence of a record was significantly greater for OB/GYNs vs. other APCPs. OB/GYNs were also significantly less likely to routinely discuss the importance of vaccines and offer any vaccines. With the exception of HPV vaccine, other providers were significantly more likely to provide Td, Tdap, influenza, hepatitis B and MMR compared to OB/GYNs. Overall 58.24% of APCPs administered vaccines to pregnant women: 4.86% administered MMR and 2.86% administered HPV vaccine, vaccines not recommended during pregnancy. Poor reimbursement and lack of knowledge and training in vaccine use were major factors that prevented APCPs from offering vaccines. The greatest perceived barriers to patient vaccine acceptance included concern about adverse effects, perceived lack of disease risk, distrust of vaccines, lack of disease awareness and cost. CONCLUSION: Intensive programs aimed at familiarizing APCPs with vaccine-preventable diseases and the importance of using vaccines are needed in order to improve vaccination rates.


Subject(s)
Attitude of Health Personnel , Physicians, Primary Care/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Primary Health Care/statistics & numerical data , Vaccination/statistics & numerical data , Vaccines/therapeutic use , Adult , Aged , Family Practice/statistics & numerical data , Female , Gynecology/statistics & numerical data , Health Knowledge, Attitudes, Practice , Humans , Internal Medicine/statistics & numerical data , Male , Middle Aged , Obstetrics/statistics & numerical data , Physician-Patient Relations , United States
10.
Jt Comm J Qual Patient Saf ; 36(4): 173-8, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20402374

ABSTRACT

BACKGROUND: Despite the availability of pediatric vaccines against pertussis ("whooping cough"), the disease is poorly controlled. Adolescents and adults with waning immunity, especially immediate family members, are responsible for 76%-83% of pertussis transmission to infants. Adolescent/adult tetanus, diphtheria, and acellular pertussis (Tdap) booster vaccines were licensed in the United States in 2005, but their use has been low and hospitals' implementation of immunization recommendations suboptimal. Efforts were implemented at two hospitals in Chicago to increase postpartum use of Tdap vaccine and to replace the tetanus and diphtheria toxoids (Td) booster with Tdap vaccine in emergency department (ED) settings. Postpartum Pertussis Vaccination Program at Prentice Women's Hospital: In the program's first 18 months (June 2008-November 2009) 9,540 doses of Tdap vaccine were administered to 78.87% of the postpartum patients. Children's Memorial Hospital: Tdap Use in Emergency Settings: In 2007, uptake of Tdap was slow. During 2008, of 43 ED patients receiving a tetanus toxoid-containing vaccine as part of wound management, 10 were given Tdap (20 had previously received a dose of Tdap vaccine). CONCLUSIONS: Hospital-based Tdap initiatives in postpartum and ED settings can be successfully implemented, provided that support is obtained not only from key decision makers at the hospital but also the health care providers who will be directly involved in implementing those initiatives. It is imperative that hospitals implement programs that increase the use of Tdap vaccine among postpartum women, in emergency settings, and among health care personnel.


Subject(s)
Diphtheria-Tetanus-acellular Pertussis Vaccines/therapeutic use , Emergency Service, Hospital , Postnatal Care , Safety Management , Vaccination , Whooping Cough/prevention & control , Adolescent , Adult , Chicago , Child , Female , Humans , Immunization, Secondary , Infant , Infant, Newborn , Pilot Projects , Program Evaluation , Tetanus/prevention & control , Whooping Cough/transmission
11.
Toxicol Sci ; 113(1): 77-84, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19805410

ABSTRACT

The yeast target of rapamycin (Tor) kinases, Tor1 and Tor2, belong to the phosphatidylinositol 3-kinase-related family of proteins, which are involved in the cellular response to DNA damage and changes in nutrient conditions. In contrast to yeast, many eukaryotes possess a single Tor kinase. Regardless of the number of Tor kinases in an organism, two distinct complexes involving Tor proteins exist in eukaryotes, TORC1 and TORC2. The yeast TORC1, containing Tor1 or Tor2, is sensitive to the antibiotic rapamycin. The yeast TORC2 is insensitive to rapamycin. We examined the influence of rapamycin treatment upon yeast transcription-coupled nucleotide excision repair in a gene transcribed by RNA polymerase II. We also examined tor mutants for their ability to perform transcription-coupled repair in the absence or presence of rapamycin. Ostensibly lacking TORC1 and TORC2 function, a tor1tor2(ts) mutant grown at the nonpermissive temperature exhibited similar rates of repair as the wild-type strain. However, repair of both strands in genes decreases in the wild-type strain and the tor1tor2(ts) mutant exposed to rapamycin. Rapamycin may be inhibiting DNA repair independently of the Tor kinases. In yeast, FPR1 encodes the rapamycin-binding protein Fpr1 that inhibits the TORC1 kinase in the presence of rapamycin. Fap1 competes with rapamycin for Fpr1 binding. Deletion of the FPR1 or FAP1 gene abolishes the inhibitory effect of rapamycin on repair. Thus, the decreased repair observed following rapamycin treatment is independent of TORC1/2 function and likely due to a function of Fap1. We suggest that Fap1 and peptidyl-prolyl isomerases, particularly Fpr1, function in the cellular response to genotoxic stress. Our findings have clinical implications for genetic toxicities associated with genotoxic agents when coadministered with rapamycin.


Subject(s)
Cell Cycle Proteins/metabolism , DNA Repair/drug effects , DNA, Fungal/metabolism , Mutagens/toxicity , Phosphatidylinositol 3-Kinases/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/drug effects , Signal Transduction/drug effects , Sirolimus/toxicity , Cell Cycle Proteins/antagonists & inhibitors , Cell Cycle Proteins/genetics , DNA Damage , DNA Repair/radiation effects , Mutation , Peptidylprolyl Isomerase/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphoinositide-3 Kinase Inhibitors , Protein Kinase Inhibitors/toxicity , RNA Polymerase II/metabolism , Repressor Proteins/metabolism , Saccharomyces cerevisiae/enzymology , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/radiation effects , Saccharomyces cerevisiae Proteins/antagonists & inhibitors , Saccharomyces cerevisiae Proteins/genetics , Temperature , Time Factors , Transcription, Genetic/drug effects , Ultraviolet Rays
12.
Obstet Gynecol ; 113(2 Pt 1): 399-401, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19155912

ABSTRACT

Pertussis, or whooping cough, is a major public health problem in the United States, with the incidence of disease and its associated complications having significantly increased in the adolescent and adult populations. These populations serve as the major transmission source of the disease to young infants, a group that is at the highest risk of severe morbidity and mortality from the disease. Studies have shown that new parents, especially mothers, are the source of disease transmission in more than 50% of the cases. Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis booster vaccines (Tdap) are licensed for use in adolescent and adult populations. The Centers for Disease Control and Prevention (CDC) recommends that the Tdap vaccine be given to postpartum women as soon as possible after delivery and before hospital discharge to protect them and their newborns against pertussis disease. The American College of Obstetricians and Gynecologists recommends that its membership follow the CDC recommendations. This article includes a further discussion of the rationale for this recommendation and provides possible strategies for vaccine implementation.


Subject(s)
Diphtheria-Tetanus-acellular Pertussis Vaccines/therapeutic use , Infectious Disease Transmission, Vertical/prevention & control , Puerperal Disorders/immunology , Whooping Cough/transmission , Adolescent , Adult , Female , Humans , Infant , Mass Vaccination , Postpartum Period/immunology , Practice Guidelines as Topic , Pregnancy , United States , Young Adult
13.
Environ Sci Technol ; 42(14): 5229-34, 2008 Jul 15.
Article in English | MEDLINE | ID: mdl-18754373

ABSTRACT

We designed and tested real-time PCR probe/primer sets to detect and quantify Cytochrome b sequences of mitochondrial DNA (mtDNA) from nine vertebrate species of pet (dog), farm (cow, chicken, sheep, horse, pig), wildlife (Canada goose, white-tailed deer), and human. Linear ranges of the assays were from 10(1) to 10(8) copies/microl. To formally test the performance of the assays, twenty blinded fecal suspension samples were analyzed by real-time PCR to identify the source of the feces. Sixteen of the twenty samples were correctly and unambiguously identified. Average sensitivity was calculated to be 0.850, while average specificity was found to be 0.994. One beef cow sample was not detected, but mtDNA from 11 other beef cattle of both sexes and varying physiological states was found in concentrations similar (3.45 x 10(7) copies/g) to thatfound in human feces (1.1 x 10(7) copies/g). Thus, environmental conditions and sample handling are probably important factors for successful detection of fecal mtDNA. When sewage samples were analyzed, only human mtDNA (7.2 x 10(4) copies/ 100 mL) was detected. With a detection threshold of 250 copies/reaction, an efficient concentration and purification method resulted in a final detection limit for human feces of 1.8 mg/ 100 mL water.


Subject(s)
Cytochromes b/genetics , DNA, Mitochondrial/analysis , Feces/chemistry , Polymerase Chain Reaction , Animals , Cattle , Female , Genetic Markers , Humans , Male , Polymerase Chain Reaction/methods , Reproducibility of Results , Sensitivity and Specificity , Sequence Analysis, DNA/methods , Sewage/chemistry
14.
Environ Sci Technol ; 38(22): 6109-17, 2004 Nov 15.
Article in English | MEDLINE | ID: mdl-15573614

ABSTRACT

Microbial source tracking (MST) uses various approaches to classify fecal-indicator microorganisms to source hosts. Reproducibility, accuracy, and robustness of seven phenotypic and genotypic MST protocols were evaluated by use of Escherichia coli from an eight-host library of known-source isolates and a separate, blinded challenge library. In reproducibility tests, measuring each protocol's ability to reclassify blinded replicates, only one (pulsed-field gel electrophoresis; PFGE) correctly classified all test replicates to host species; three protocols classified 48-62% correctly, and the remaining three classified fewer than 25% correctly. In accuracy tests, measuring each protocol's ability to correctly classify new isolates, ribotyping with EcoRI and PvuII approached 100% correctclassification but only 6% of isolates were classified; four of the other six protocols (antibiotic resistance analysis, PFGE, and two repetitive-element PCR protocols) achieved better than random accuracy rates when 30-100% of challenge isolates were classified. In robustness tests, measuring each protocol's ability to recognize isolates from nonlibrary


Subject(s)
Escherichia coli/classification , Feces/microbiology , Water Microbiology , Animals , Escherichia coli/isolation & purification , False Positive Reactions , Gene Library , Genotype , Humans , Phenotype , Reproducibility of Results , Ribotyping , Sensitivity and Specificity
16.
Steroids ; 64(9): 576-86, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10503712

ABSTRACT

To directly activate specific gene expression, the progesterone receptor must bind to specific hormone response elements in target promoters. We have previously reported that progesterone receptor requires a nuclear factor, high mobility group 1 or 2 (HMG-1/-2) for high-affinity interaction with DNA in vitro and for full transcriptional activity in vivo. We have also observed that HMG-1/-2 selectively influences the activity of the steroid hormone class of nuclear receptors but does not affect other classes of nuclear receptors. This report is a summary of our published and unpublished studies to determine the effects of HMG-1/-2 on a broad range of nuclear receptor supergene family members and to define the mechanism for the specific effect of HMG-1/-2 on the steroid class of receptors. Our studies and available structural data suggest a model where the DNA binding domains of nonsteroid nuclear receptors contain a minor groove DNA interface, termed the C-terminal extension, that contributes to high-affinity DNA binding. Steroid receptors lack such a minor groove interface and therefore require an additional protein, HMG-1/-2, that functionally substitutes for the C-terminal extension to facilitate high-affinity interactions with DNA.


Subject(s)
High Mobility Group Proteins/physiology , Receptors, Steroid/physiology , Base Sequence , DNA/metabolism , DNA Probes , Protein Binding , Receptors, Calcitriol/physiology , Recombinant Proteins/metabolism , Transcription, Genetic
17.
Mol Cell Biol ; 18(8): 4471-87, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9671457

ABSTRACT

We previously reported that the chromatin high-mobility group protein 1 (HMG-1) enhances the sequence-specific DNA binding activity of progesterone receptor (PR) in vitro, thus providing the first evidence that HMG-1 may have a coregulatory role in steroid receptor-mediated gene transcription. Here we show that HMG-1 and the highly related HMG-2 stimulate DNA binding by other steroid receptors, including estrogen, androgen, and glucocorticoid receptors, but have no effect on DNA binding by several nonsteroid nuclear receptors, including retinoid acid receptor (RAR), retinoic X receptor (RXR), and vitamin D receptor (VDR). As highly purified recombinant full-length proteins, all steroid receptors tested exhibited weak binding affinity for their optimal palindromic hormone response elements (HREs), and the addition of purified HMG-1 or -2 substantially increased their affinity for HREs. Purified RAR, RXR, and VDR also exhibited little to no detectable binding to their cognate direct repeat HREs but, in contrast to results with steroid receptors, the addition of HMG-1 or HMG-2 had no stimulatory effect. Instead, the addition of purified RXR enhanced RAR and VDR DNA binding through a heterodimerization mechanism and HMG-1 or HMG-2 had no further effect on DNA binding by RXR-RAR or RXR-VDR heterodimers. HMG-1 and HMG-2 (HMG-1/-2) themselves do not bind to progesterone response elements, but in the presence of PR they were detected as part of an HMG-PR-DNA ternary complex. HMG-1/-2 can also interact transiently in vitro with PR in the absence of DNA; however, no direct protein interaction was detected with VDR. These results, taken together with the fact that PR can bend its target DNA and that HMG-1/-2 are non-sequence-specific DNA binding proteins that recognize DNA structure, suggest that HMG-1/-2 are recruited to the PR-DNA complex by the combined effect of transient protein interaction and DNA bending. In transient-transfection assays, coexpression of HMG-1 or HMG-2 increased PR-mediated transcription in mammalian cells by as much as 7- to 10-fold without altering the basal promoter activity of target reporter genes. This increase in PR-mediated gene activation by coexpression of HMG-1/-2 was observed in different cell types and with different target promoters, suggesting a generality to the functional interaction between HMG-1/-2 and PR in vivo. Cotransfection of HMG-1 also increased reporter gene activation mediated by other steroid receptors, including glucocorticoid and androgen receptors, but it had a minimal influence on VDR-dependent transcription in vivo. These results support the conclusion that HMG-1/-2 are coregulatory proteins that increase the DNA binding and transcriptional activity of the steroid hormone class of receptors but that do not functionally interact with certain nonsteroid classes of nuclear receptors.


Subject(s)
DNA/metabolism , High Mobility Group Proteins/metabolism , Receptors, Steroid/metabolism , Transcription, Genetic , Animals , COS Cells , Chloramphenicol O-Acetyltransferase/genetics , Genes, Reporter , High Mobility Group Proteins/genetics , Humans , Mammals , Receptors, Androgen/metabolism , Receptors, Calcitriol/metabolism , Receptors, Glucocorticoid/metabolism , Receptors, Progesterone/genetics , Receptors, Progesterone/metabolism , Receptors, Steroid/genetics , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/isolation & purification , Recombinant Fusion Proteins/metabolism , Repetitive Sequences, Nucleic Acid , Transcriptional Activation
18.
Environ Res ; 50(1): 140-56, 1989 Oct.
Article in English | MEDLINE | ID: mdl-2792056

ABSTRACT

Coturnix coturnix japonica, selected for large adult weight (Fatty), were 40% heavier than random-bred controls (RB). Given dietary lead (50 or 500 mg/kg) from hatching, fatty (10%) showed a smaller decrease in body weight than did RB (22%) at 6 weeks. Egg production was lower in Fatty, and lead (500 mg/kg) caused a greater suppression in Fatty. Lead added to the diet of Fatty and RB control diets at 7 weeks into egg production caused a 15% decrease in RB production but only a transitory decrease in Fatty. Removal of lead from the diets at 7 weeks into production allowed RB to increase egg production 6-7 weeks later but no change was seen in Fatty. Plasma calcium was reduced in lead-exposed Fatty and RB, and removal of lead from the diets allowed only a small increase in calcium. After 15 weeks production, plasma calcium in lead-treated Fatty was approaching control levels. Femur weight was greater in Fatty, but lead caused an increase in both RB and Fatty femur weight. Removal of lead from the diet allowed only minimal recovery of femur weight. Male and female Fatty responses to dietary lead were parallel. These data indicate that Fatty was less sensitive to dietary lead than RB even though more lead per unit of metabolic mass was consumed.


Subject(s)
Body Weight/drug effects , Coturnix/physiology , Lead/toxicity , Quail/physiology , Animal Feed/adverse effects , Animal Feed/analysis , Animals , Female , Femur/anatomy & histology , Femur/drug effects , Lead/administration & dosage , Lead/adverse effects , Lead/analysis
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