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1.
BMC Public Health ; 22(1): 2448, 2022 12 28.
Article in English | MEDLINE | ID: mdl-36577991

ABSTRACT

BACKGROUND: Income and housing are pervasive social determinants of health. Subsidized housing is a prominent affordability mechanism in Canada; however, waitlists are lengthy. Subsidized rents should provide greater access to residual income, which may theoretically improve health outcomes. However, little is known about the health of tenants who wait for and receive subsidized housing. This is especially problematic for New Brunswick, a Canadian province with low population density, whose inhabitants experience income inequality, social exclusion, and challenges with healthcare access.  METHODS: This study will use a longitudinal, prospective matched cohort design. All 4,750 households on New Brunswick's subsidized housing wait list will be approached to participate. The survey measures various demographic, social and health indicators at six-month intervals for up to 18 months as they wait for subsidized housing. Those who receive housing will join an intervention group and receive surveys for an additional 18 months post-move date. With consent, participants will have their data linked to a provincial administrative database of medical records.  DISCUSSION: Knowledge of housing and health is sparse in Canada. This study will provide stakeholders with a wealth of health information on a population that is historically under-researched and underserved.


Subject(s)
Housing , Public Housing , Humans , Canada , Mental Health , New Brunswick , Prospective Studies , Health Services Accessibility
2.
Neurol Res ; 33(10): 1083-93, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22196762

ABSTRACT

Under appropriate culture conditions, bone marrow (BM)-derived mesenchymal stem cells are capable of differentiating into diverse cell types unrelated to their phenotypical embryonic origin, including neural cells. Here, we report the successful generation of neural stem cell (NSC)-like cells from BM-derived human mesenchymal stem cells (hMSCs). Initially, hMSCs were cultivated in a conditioned medium of human neural stem cells. In this culture system, hMSCs were induced to become NSC-like cells, which proliferate in neurosphere-like structures and express early NSC markers. Like central nervous system-derived NSCs, these BM-derived NSC-like cells were able to differentiate into cells expressing neural markers for neurons, astrocytes, and oligodendrocytes. Whole-cell patch clamp recording revealed that neuron-like cells, differentiated from NSC-like cells, exhibited electrophysiological properties of neurons, including action potentials. Transplantation of NSC-like cells into mouse brain confirmed that these NSC-like cells retained their capability to differentiate into neuronal and glial cells in vivo. Our data show that multipotent NSC-like cells can be efficiently produced from BM-derived hMSCs in culture and that these cells may serve as a useful alternative to human neural stem cells for potential clinical applications such as autologous neuroreplacement therapies.


Subject(s)
Bone Marrow Cells/metabolism , Cell Culture Techniques/methods , Cell Differentiation/physiology , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/metabolism , Neural Stem Cells/metabolism , Animals , Bone Marrow Cells/cytology , Humans , Mesenchymal Stem Cells/cytology , Mice , Mice, Inbred C57BL , Neural Stem Cells/cytology , Primary Cell Culture
3.
Neuroepidemiology ; 29(1-2): 96-100, 2007.
Article in English | MEDLINE | ID: mdl-17925601

ABSTRACT

Studies that accurately identify myocardial infarction (MI) and stroke within populations would provide valuable epidemiological information as well as data on vascular disease prevention. We performed a pilot study to assess the feasibility of adding MI surveillance to an ongoing population-based stroke surveillance study, the Brain Attack Surveillance in Corpus Christi (BASIC) Project. We also tested two screening methods for MI ascertainment: discharge International Classification of Diseases, Ninth Revision (ICD-9) codes and cardiac biomarker screening. This pilot study suggests that the addition of MI surveillance to community-based stroke surveillance studies is feasible. Screening for abnormal cardiac biomarkers to identify potential MI cases may be more accurate and efficient than using ICD-9 codes.


Subject(s)
Brain Ischemia/diagnosis , Mass Screening/methods , Myocardial Infarction/diagnosis , Population Surveillance/methods , Stroke/diagnosis , Aged , Aged, 80 and over , Biomarkers/blood , Brain Ischemia/epidemiology , Cohort Studies , Feasibility Studies , Female , Humans , International Classification of Diseases , Male , Middle Aged , Myocardial Infarction/blood , Myocardial Infarction/epidemiology , Patient Discharge , Pilot Projects , Sensitivity and Specificity , Stroke/epidemiology
4.
Invest Radiol ; 37(7): 363-7, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12068156

ABSTRACT

RATIONALE AND OBJECTIVES: To measure T2 relaxation times of normal white and gray matter using a novel CPMG sequence and investigate if any correlation exists between magnetization transfer ratio (MTR) and T2 relaxation-related parameters. MATERIALS AND METHODS: Seventeen normal volunteers participated on this study. A single-slice 32-echo sequence was used to calculate the T2 relaxation time of frontal and occipital white matter and cortical gray matter. T2 relaxation analysis included monoexponential and biexponential fitting whereas an F test was used to determine if biexponential fitting was statistically more accurate than monoexponential fitting. Short and long T2 constants were calculated as well as the signal fractions of each pool. MTR calculations were based on a three-dimensional gradient echo (3D FFE) proton density weighted sequence with and without an on-resonance composite prepulse. MTR and T2 relaxation times were calculated and linear regression analysis was applied. RESULTS: Biexponential fitting was more accurate comparing with monoexponential fitting in all WM and GM regions (F > 2.47, P < 0.01). Mean values of short T2 constant for frontal white matter (fWM), occipital white matter (oWM) and gray matter (GM) were 8.10, 9.36, and 22.23 milliseconds, respectively, whereas the mean values of long T2 constant were 85.1, 93.02, and 118.72 milliseconds, respectively. Mean restricted water percentages (RWP)-corresponding to the signal fraction of the protons with short T2-for the fWM, oWM, and GM were 22.01%, 23.36%, and 18.7%. Mean free water percentages (FWP)-corresponding to the signal fraction of the protons with long T2-for the fWM, oWM and GM were 77.99%, 76.64%, and 81.3%. Mean MTR values for fWM, oWM and GM were 68.4%, 68.2%, and 61.3%, respectively. No significant correlation was found in fWM and oWM between MTR and RWP, short and long T2 components while a moderate correlation existed in GM between MTR and RWP (r = 0.57; P = 0.02), MTR and short T2 component (r = -0.69; P = 0.004) and MTR and long T2 component (r = -0.62; P = 0.012). CONCLUSIONS: Two proton pools with different T2 decay characteristics can be separated in normal gray and white matter when using a multiecho sequence with short echo spacing. MTR and T2 relaxation times were significantly correlated in gray matter and the combination of both types of measurements may be helpful in studying myelin related disorders.


Subject(s)
Brain/anatomy & histology , Magnetic Resonance Imaging , Adult , Female , Humans , Male
5.
J Vasc Access ; 3(3): 120-6, 2002.
Article in English | MEDLINE | ID: mdl-17639473

ABSTRACT

PURPOSE: To retrospectively determine the incidence and outcome of angioplasty-induced ruptures that occurred during treatment of hemodialysis graft-related stenoses. MATERIALS AND METHODS: During a five year period 1222 patients with dysfunctional or thrombosed polytetrafluoroethylene (PTFE) hemodialysis grafts underwent angioplasty procedures at our institution. Angioplasty-induced vascular ruptures occurred in 24 (2.0%) patients. The locations of these ruptures were: basilic vein (10), venous anastomosis (7), cephalic vein (5), brachial vein (1) and intragraft (1). The mean length of the treated stenoses was 2.4 centimeters. RESULTS: Manual compression was used to treat the vascular rupture in ten patients. One patient was treated with endovascular balloon tamponade and one patient underwent stenting of the rupture site. Despite the rupture, 15 patients had completion of the angioplasty procedure. In nine patients the procedure was abandoned due to persistent stenosis at the rupture site. There were no major complications as a result of these ruptures. Follow-up was available in ten of these patients. All ten underwent at least one successful hemodialysis treatment. In five of these patients the hemodialysis graft failed within 30 days after the rupture. The mean primary patency following rupture in the ten patients with follow-up was 87.5 days (range 5 - 225 days). CONCLUSION: The incidence of angioplasty-induced vascular rupture of hemodialysis-related stenoses is low and despite the injury, the majority (62%) of procedures can be completed. However, in our experience the long-term patency of the vascular access was suboptimal.

6.
Dig Dis Sci ; 46(11): 2360-6, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11713936

ABSTRACT

Ascitic fluid infection probably results from repeated episodes of bacteremia and seeding of ascitic fluid. The outcome of these episodes of colonization is probably a function of serum and ascitic fluid defense mechanisms and the virulence of the organism. Patients who develop spontaneous bacterial peritonitis may have serum and ascitic fluid characteristics that are different from those who do not develop infection. We prospectively collected serum and ascitic fluid specimens at the time of admission from patients with sterile cirrhotic ascites, and tested these specimens for interleukin-6, tumor necrosis factor-alpha, and nitric oxide and compared these results as well as other characteristics of patients who did not develop infection to those who did. An elevated baseline serum tumor necrosis factor-alpha as well as an increased proportion of polymorphonuclear leukocytes in sterile ascitic fluid from patients who subsequently developed infection probably represent a subclinical activation of defense mechanisms from prior silent colonizations with bacteria.


Subject(s)
Ascitic Fluid/chemistry , Interleukin-6/metabolism , Liver Cirrhosis/metabolism , Nitric Oxide/metabolism , Peritonitis/microbiology , Tumor Necrosis Factor-alpha/metabolism , Adult , Ascitic Fluid/microbiology , Bacterial Translocation , Case-Control Studies , Female , Humans , Liver Cirrhosis/microbiology , Male , Middle Aged , Peritonitis/metabolism , Prospective Studies
7.
Altern Ther Health Med ; 7(1): 38-47, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11191041

ABSTRACT

CONTEXT: Drum circles have been part of healing rituals in many cultures throughout the world since antiquity. Although drum circles are gaining increased interest as a complementary therapeutic strategy in the traditional medical arena, limited scientific data documenting biological benefits associated with percussion activities exist. OBJECTIVE: To determine the role of group-drumming music therapy as a composite activity with potential for alteration of stress-related hormones and enhancement of specific immunologic measures associated with natural killer cell activity and cell-mediated immunity. DESIGN: A single trial experimental intervention with control groups. SETTING: The Mind-Body Wellness Center, an outpatient medical facility in Meadville, Pa. PARTICIPANTS: A total of 111 age- and sex-matched volunteer subjects (55 men and 56 women, with a mean age of 30.4 years) were recruited. INTERVENTION: Six preliminary supervised groups were studied using various control and experimental paradigms designed to separate drumming components for the ultimate determination of a single experimental model, including 2 control groups (resting and listening) as well as 4 group-drumming experimental models (basic, impact, shamanic, and composite). The composite drumming group using a music therapy protocol was selected based on preliminary statistical analysis, which demonstrated immune modulation in a direction opposite to that expected with the classical stress response. The final experimental design included the original composite drumming group plus 50 additional age- and sex-matched volunteer subjects who were randomly assigned to participate in group drumming or control sessions. MAIN OUTCOME MEASURES: Pre- and postintervention measurements of plasma cortisol, plasma dehydroepiandrosterone, plasma dehydroepiandrosterone-to-cortisol ratio, natural killer cell activity, lymphokine-activated killer cell activity, plasma interleukin-2, plasma interferon-gamma, the Beck Anxiety Inventory, and the Beck Depression Inventory II. RESULTS: Group drumming resulted in increased dehydroepiandrosterone-to-cortisol ratios, increased natural killer cell activity, and increased lymphokine-activated killer cell activity without alteration in plasma interleukin 2 or interferon-gamma, or in the Beck Anxiety Inventory and the Beck Depression Inventory II. CONCLUSIONS: Drumming is a complex composite intervention with the potential to modulate specific neuroendocrine and neuroimmune parameters in a direction opposite to that expected with the classic stress response.


Subject(s)
Anxiety/therapy , Immune System , Music Therapy , Neurosecretory Systems , Adult , Dehydroepiandrosterone/blood , Female , Humans , Hydrocortisone/blood , Killer Cells, Lymphokine-Activated/metabolism , Male , Reference Values
8.
Radiology ; 217(1): 213-4, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11012446
9.
Psychol Rep ; 86(3 Pt 1): 807-18, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10876328

ABSTRACT

Transference, the extent to which consumers transfer their opinions of a parent brand to a new extension, is critical to the success of any brand-extension strategy. Past research has shown that transference is a complex process that varies among persons depending upon an implicit personality theory, entity versus incremental. In a laboratory experiment analysis of ratings for 100 21-yr.-old undergraduates of attitude, perceived fit and risk, prior product involvement, and implicit personality theory (entity versus incremental) the influence of consumers' implicit personality theory on transference was considered within the brand-extension context. As expected, the amount of transference differed between those espousing entity and incremental theories. "Entity theorists" were much more likely to transfer feelings associated with the parent brand to the new extension than were "incremental theorists" who did not rely on prior brand information when forming evaluations of a new extension. This effect did not occur when perceived fit between the parent brand and the extension was high.


Subject(s)
Marketing of Health Services , Personality , Transference, Psychology , Adult , Consumer Behavior , Female , Generalization, Psychological , Humans , Male , Students/psychology
10.
Radiology ; 215(3): 897-9, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10831718

ABSTRACT

PURPOSE: To determine whether the use of multisection helical computed tomography (CT) can decrease the need for sedation compared with single-section helical CT. MATERIALS AND METHODS: The number of children who required sedation to undergo body CT with a multisection helical scanner was recorded. The authors noted the type of examination and whether contrast material was used. The children were categorized according to age (< or = 17 years, < or = 6 years, < or = 1 year). RESULTS: In 219 CT examinations, only three children required sedation (1.4%). The sedation rate was 3% (three of 90) for children aged 6 years or younger and 8% (three of 37) for those aged 1 year or younger. Examinations were of the chest, abdomen, and pelvis in 68 patients, of the abdomen and pelvis in 112, and of the chest alone in 39. Contrast material was intravenously administered in 186 (85%) examinations. All scans were of diagnostic quality. CONCLUSION: The rate of sedation was reduced threefold with multisection helical CT compared with standard helical CT, and the need for sedation was eliminated in some age groups.


Subject(s)
Conscious Sedation/statistics & numerical data , Tomography, X-Ray Computed/methods , Adolescent , Child , Child, Preschool , Contrast Media/administration & dosage , Humans , Infant , North Carolina , Retrospective Studies , Tomography, X-Ray Computed/statistics & numerical data
11.
FASEB J ; 14(9): 1224-32, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10834944

ABSTRACT

The retinoid receptors (RARs and RXRs) are mediators of the multiple effects of retinoic acid. Of these, the retinoic acid receptor beta2 (RARbeta2) has frequently been shown to be the principal mediator of the growth and tumor suppressive effects of retinoic acid; this gene is inactivated in many epithelial tumors and their derived cell lines. We have searched for genes that are regulated by this isoform and are potentially involved in tumor suppression. Using the Atlas human cDNA array I, we identified 27 genes (not counting RARbeta itself) that are regulated, directly or indirectly, by RARbeta2 when it is transfected into Calu-1, a lung tumor-derived line that does not normally express RARbeta. Several of the affected genes code for proteins whose functions would augment the process of apoptosis and/or the host's immune response. The latter group included ICAM-1 and MHC class I heavy chain, whose protein products play particularly important roles in the mounting of an effective anti-tumor response. We then confirmed by flow cytometry that the observed increases in message levels were reflected in increased cell surface protein levels for ICAM-1 and MHC class I in RARbeta2 transfectants of two RARbeta-deficient lines, Calu-1 and the epidermoid lung cancer-derived line SK-MES. Finally, we showed that RARbeta2 transfection of Calu-1 cells enhanced the heterologous CTL response in both the induction and the effector phases by up to threefold. These results support the hypothesis that down-regulation of these genes (and possibly others) in RARbeta-deficient tumor cells contributes to immune system evasion, and suggest a novel therapeutic approach for this disease.


Subject(s)
Gene Expression Profiling , Gene Expression Regulation, Neoplastic/genetics , Lung Neoplasms/genetics , Lung Neoplasms/immunology , Oligonucleotide Array Sequence Analysis , Receptors, Retinoic Acid/metabolism , Apoptosis/genetics , Cell Membrane/metabolism , Cells, Cultured , Coculture Techniques , Down-Regulation/genetics , Flow Cytometry , Genes, Tumor Suppressor/genetics , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/metabolism , Humans , Intercellular Adhesion Molecule-1/genetics , Intercellular Adhesion Molecule-1/metabolism , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Protein Isoforms/genetics , Protein Isoforms/metabolism , RNA, Messenger/analysis , RNA, Messenger/genetics , Receptors, Retinoic Acid/genetics , T-Lymphocytes, Cytotoxic/cytology , T-Lymphocytes, Cytotoxic/immunology , Transfection , Tumor Cells, Cultured , Up-Regulation/genetics
12.
AJR Am J Roentgenol ; 173(5): 1357-9, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10541118

ABSTRACT

OBJECTIVE: We investigated an indirect radiographic means of predicting proper endotracheal tube placement on underexposed portable chest radiographs. CONCLUSION: When an endotracheal tube is 3.4-5.0 cm above the tangent line of the aortic arch, it is in proper position 95% of the time.


Subject(s)
Aorta, Thoracic/diagnostic imaging , Intubation, Intratracheal/instrumentation , Point-of-Care Systems , Radiography, Thoracic , Technology, Radiologic , Adult , Aged , Critical Care , Female , Humans , Male , Middle Aged , Retrospective Studies
13.
Lung Cancer ; 20(1): 1-16, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9699182

ABSTRACT

Hepatocyte growth factor (HGF)/scatter factor (SF) is a multifunctional factor that stimulates epithelial cell motility, invasion and morphogenesis. Its receptor is a transmembrane tyrosine kinase encoded by the Met proto-oncogene. Several studies have suggested a possible role for HGF/Met in tumor development and progression. To investigate the potential roles of Met in human lung cancer biology, we have studied the mRNA and protein expression of Met in normal lung tissue, primary non-small cell lung carcinoma (NSCLC), and NSCLC cell lines. The results indicated a differential pattern of Met expression among various subtypes of NSCLC. The majority of squamous cell carcinoma (SQCC), either in vivo or in vitro, expressed Met mRNA and its protein product at levels much lower than or similar to normal lung tissue or bronchial epithelium. Moreover, SQCC characteristically over-expressed a variant Met mRNA which corresponds to a 5' partially deleted transcript produced by alternative splicing. In contrast, the expression of Met mRNA and its protein product in adenocarcinoma (ADC) and large cell undifferentiated carcinoma were more heterogeneous. Overexpression was demonstrated in approximately 35% and 20% of these subtypes of NSCLC, respectively. Among ADC, intermediate to high levels of Met immunoreactivity correlated with greater degree of tumor differentiation. Furthermore, an accentuation of Met immunoreactivity was often noted in cancer cells at the advancing edge of tumors. These findings support a role for Met in lung cancer cell invasion and differentiation in vivo, but its expression and functions may be modified by the differentiation phenotype of the tumor cells.


Subject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/metabolism , Proto-Oncogene Proteins c-met/metabolism , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Blotting, Northern , Blotting, Western , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , DNA Probes , Humans , Immunohistochemistry , Lung Neoplasms/pathology , Phenotype , Polymerase Chain Reaction , Precipitin Tests , Proto-Oncogene Mas , RNA, Messenger/isolation & purification , Statistics, Nonparametric , Tumor Cells, Cultured
14.
J Nurs Care Qual ; 12(5): 30-40, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9610012

ABSTRACT

Nursing Interventions Classification (NIC) and Nursing Outcomes Classification (NOC) are recognized examples of standardized nursing languages used to describe the contribution nursing makes to patient care. Columbus Regional Hospital nursing leadership recognized the need to use standardized nursing interventions and nursing-sensitive patient outcomes to describe the unique contribution nursing makes to patient education. In collaboration with the University of Iowa, NIC/NOC languages were implemented in the development of a patient education plan for a clinical pathway population.


Subject(s)
Critical Pathways/standards , Nursing Service, Hospital/classification , Nursing Service, Hospital/standards , Outcome Assessment, Health Care/classification , Patient Education as Topic/standards , Terminology as Topic , Vocabulary, Controlled , Humans , Indiana , Nursing Evaluation Research , Program Development , Program Evaluation , Referral and Consultation , Respiration Disorders/nursing
15.
Hematopathol Mol Hematol ; 11(2): 73-88, 1998.
Article in English | MEDLINE | ID: mdl-9608356

ABSTRACT

We employed the nonpalindromic adaptor-PCR (NPA-PCR) method to amplify T-cell receptor (TCR) alpha- and beta-chain transcripts from the spleen of normal SJL mice. The NPA-PCR method has been specifically designed for the amplification of transcripts with variable or unknown 5' ends, such as TCRs and immunoglobulins (Ig). This method has certain distinct advantages over existing two-sided PCR methods for the amplification of TCR transcripts. Two NPA-PCR amplifications are sufficient to amplify all the TCR transcripts (one for the alpha-chain and another one for the beta-chain). Amplification of TCR transcripts by classical two-sided PCR requires a minimum of 45 amplification reactions for the murine TCR (20 for the V alpha families and 25 for the V beta families), using 45 different V-family-specific amplification primers. cDNA was synthesized from spleen RNA, using oligonucleotides complementary to sequences of either the murine TCR C alpha or C beta regions. The NotI restriction site was conjugated to these primers and therefore, a NotI restriction site was incorporated at the 3' end of the cDNA. A double-stranded nonpalindromic adaptor (EcoRI-XmnI strand and XmnI G strand, which are complementary to each other) was ligated onto both ends of the double-stranded cDNA. The adaptor was removed from the 3' end by NotI nuclease digestion whereas the adaptor was retained at the 5' end. Two rounds of PCR amplification were carried out. In the first, the EcoRI-XmnI adaptor was used as 5' end amplification primer; an antisense C region primer, designated mC alpha 2 or mC beta 2 (for the alpha- and beta-chain, respectively), was used as 3' amplification primer. In the second round of PCR amplification the same 5' end primer and a 3' end antisense primer, designated mC alpha 1 or mC beta 1, were used. These mC alpha 1 and mC beta 1 primers are located 5' to the mC alpha 2/mC beta 2 primers that were used for the first amplification. The amplified transcripts were cloned. Colonies were screened using a 32P-labeled probe, either C alpha or C beta, located 5' to those used for the last amplification and many positive clones were isolated and sequenced. All clones were unique when compared to each other, as anticipated for polyclonal T-cell populations. Comparison of the sequences obtained to those in the GENBANK/EMBL database revealed that they were typical of mouse alpha- or beta-chain TCR. With the exception of two beta-chain TCR transcripts, all the sequences shown here (36 alpha-chain and 20 beta-beta chain) have not been previously reported to the GENBANK/EMBL database.


Subject(s)
Polymerase Chain Reaction/methods , Receptors, Antigen, T-Cell, alpha-beta/genetics , T-Lymphocyte Subsets/metabolism , Transcription, Genetic , Amino Acid Sequence , Animals , Base Sequence , Female , Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor/genetics , Gene Rearrangement, beta-Chain T-Cell Antigen Receptor/genetics , Mice , Mice, Inbred Strains , Molecular Sequence Data , RNA, Messenger/metabolism , Spleen/cytology , T-Lymphocyte Subsets/chemistry
16.
Am J Hum Genet ; 62(4): 855-64, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9529340

ABSTRACT

The DAX1 protein is an orphan nuclear hormone receptor based on sequence similarity in the putative ligand-binding domain (LBD). DAX1 mutations result in X-linked adrenal hypoplasia congenita (AHC). Our objective was to identify DAX1 mutations in a series of families, to determine the types of mutations resulting in AHC and to locate single-amino-acid changes in a DAX1 structural model. The 14 new mutations identified among our 17 families with AHC brought the total number of families with AHC to 48 and the number of reported mutations to 42; 1 family showed gonadal mosaicism. These mutations included 23 frameshift, 12 nonsense, and six missense mutations and one single-codon deletion. We mapped the seven single-amino-acid changes to a homology model constructed by use of the three-dimensional crystal structures of the thyroid-hormone receptor and retinoid X receptor alpha. All single-amino-acid changes mapped to the C-terminal half of the DAX1 protein, in the conserved hydrophobic core of the putative LBD, and none affected residues expected to interact directly with a ligand. We conclude that most genetic alterations in DAX1 are frameshift or nonsense mutations and speculate that the codon deletion and missense mutations give insight into the structure and function of DAX1.


Subject(s)
DNA-Binding Proteins/chemistry , DNA-Binding Proteins/genetics , Mutation , Receptors, Retinoic Acid/chemistry , Receptors, Retinoic Acid/genetics , Repressor Proteins , Transcription Factors/chemistry , Transcription Factors/genetics , X Chromosome , Adrenal Glands/abnormalities , Amino Acid Sequence , DAX-1 Orphan Nuclear Receptor , Genetic Linkage , Humans , Hypogonadism/genetics , Molecular Sequence Data , Sequence Analysis , Structure-Activity Relationship
17.
Abdom Imaging ; 23(1): 91-5, 1998.
Article in English | MEDLINE | ID: mdl-9437072

ABSTRACT

We present three patients with peritoneal metastases from transitional cell carcinoma of the urinary tract. CT scan in one patient showed massive ascites with subtle peritoneal thickening and infiltration of omental fat. We had the opportunity to study the other patients with both CT and MR. Both examinations showed numerous large and small peritoneal implants in the abdomen and pelvis, mostly in the greater omentum.


Subject(s)
Carcinoma, Transitional Cell/secondary , Kidney Neoplasms/pathology , Magnetic Resonance Imaging , Peritoneal Neoplasms/secondary , Tomography, X-Ray Computed , Urinary Bladder Neoplasms/pathology , Adult , Carcinoma, Transitional Cell/diagnosis , Carcinoma, Transitional Cell/therapy , Combined Modality Therapy , Fatal Outcome , Follow-Up Studies , Humans , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/therapy , Male , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/therapy , Urinary Bladder Neoplasms/diagnostic imaging , Urinary Bladder Neoplasms/therapy
18.
Proc AMIA Symp ; : 210-4, 1998.
Article in English | MEDLINE | ID: mdl-9929212

ABSTRACT

A robust software architecture is necessary to support a large-scale multi-tier clinical information system. This paper describes our mechanism for enterprise distribution of applications and support files, the consolidation of data-access functions and system utilities stored on the data access tier, and an application framework which implements a coherent clinical computing environment. The software architecture and systems described in this paper have been robust through pilot testing of our applications at Massachusetts General Hospital.


Subject(s)
Hospital Information Systems/organization & administration , Software , Computer Security , Pilot Projects , Programming Languages , Software Design
19.
Nat Med ; 3(9): 984-9, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9288724

ABSTRACT

Patients with B-cell chronic lymphocytic leukemia (CLL) acquire an immunodeficiency with many characteristics similar to those of persons with inherited defects in the gene encoding the CD40-ligand (CD154). We found that the blood and splenic CD4+ T cells of patients with CLL failed to express surface CD154 after CD3 ligation. However, using an enzyme-linked immunosorbent assay (ELISA)-based quantitative competitive polymerase chain reaction (PCR), we noted that CD3 ligation could induce such T cells to express CD154 messenger RNA at levels similar to that of CD3-activated T cells from normal donors. Moreover, addition of increasing numbers of CLL B cells to activated normal donor T cells rapidly resulted in progressively greater down-modulation of CD154. Such down-modulation of CD154 could be blocked by addition of CD40 monoclonal antibody to cultures in vitro. We propose that leukemia cell-mediated down-modulation of CD154 on activated T cells accounts for some of the acquired immune defects of patients with CLL.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Membrane Glycoproteins/deficiency , Base Sequence , CD3 Complex/metabolism , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , CD40 Antigens/metabolism , CD40 Ligand , DNA Primers/genetics , Down-Regulation , Humans , In Vitro Techniques , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Ligands , Lymphocyte Activation , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Polymerase Chain Reaction , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Neoplasm/genetics , RNA, Neoplasm/metabolism , Solubility
20.
Eur J Radiol ; 25(1): 2-8, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9248790

ABSTRACT

OBJECTIVE: To describe the computed tomography (CT) and magnetic resonance (MR) features of corpus callosum (CC) infarctions. METHODS: We reviewed retrospectively 352 consecutive cranial CT and MR scans showing cerebral infarcts. Involvement of the CC was identified in 28 patients. RESULTS: Infarctions of the CC were diffuse (n = 3) or focal (n = 25). The former were seen in the setting of diffuse cerebral ischemia secondary to cardiopulmonary arrest or status epilepticus. The latter were divided into those affecting predominantly the genu, body or splenium. The most common location of the insult was the splenium (n = 13), followed by the body (n = 6) and genu (n = 3). In the remaining three patients combined genu/body infarctions were seen. CONCLUSION: Infarction of the CC may be more common than previously thought and is most often the result of cerebral embolism. MR is better suited than CT for the detection of vascular lesions of the CC.


Subject(s)
Cerebral Infarction/diagnosis , Corpus Callosum/blood supply , Corpus Callosum/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed
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