Academic relationships with industry: a new model for biomedical research.
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Academic Medical Centers↗
Biomedical subjects
H Moses
Publications and source records attributed to H Moses.
Hashimoto's encephalopathy: documentation of mesial temporal seizure origin by ictal EEG.
Hashimoto's encephalopathy is a chronic relapsing and remitting encephalopathy associated with antithyroid antibodies. Seizures are a frequent manifestation, but are not well characterized in the literature with respect to their onset. We describe a 48-year-old patient with recurrent encephalopathy and seizures, and elevated antithyroid antibodies. One seizure was documented with video-EEG monitoring using scalp and sphenoidal electrodes. The ictal discharge originated in the left mesial-basal temporal region. MRI showed an increased T2 signal in the white matter of the centrum semiovale, but no temporal pathology. Symptoms resolved after treatment with prednisone and azathioprine. Hashimoto's encephalopathy should be considered in patients with unexplained encephalopathy and seizures, including those originating in the temporal lobe.
Arthritis, Rheumatoid↗
An infectious basis for multiple sclerosis: perspectives on the role of Chlamydia pneumoniae and other agents.
The aetiology of multiple sclerosis (MS) remains unknown. Epidemiological, clinical and pathological data support the theory that MS is a complex disease/syndrome with many factors affecting its development and progression. It may be appropriate to regard MS as a syndrome with differing clinical and pathological features occurring along a spectrum. Patients with MS are more likely to have an affected relative than are individuals without MS, which suggests that there is a genetic component to this illness. Despite this genetic susceptibility, 85% of MS patients do not have an affected relative and only 1 in 3 monozygotic (identical) twins develops MS if the other twin already has it. These data strongly suggest that environmental factors influence the development of MS. Many putative infectious agents have been proposed to be involved in the aetiology of MS. Although research into identifying MS-causative agents dates back for more than 5 decades, no agent has yet emerged with any consensus as the cause of MS. This controversy is due to a number of factors, including lack of specificity of an agent to MS, lack of reproducibility in other laboratories, inappropriate controls, laboratory contamination and lack of a standard and easily reproducible assay system. Chlamydia pneumoniae is a recently described pathogen that may have a role in the pathogenesis of MS. C. pneumoniae is an intracellular bacterial organism that is infectious to humans. It has recently been detected in the cerebrospinal fluid (CSF) of MS patients but not in that of patients with other neurological diseases. There is also a case report of a patient with CNS C. pneumoniae infection and rapidly progressive MS responding to antimicrobial therapy directed against this pathogen. An association between C. pneumoniae in the CSF and MS is now apparent, but its role in the development of MS remains unknown. Further work exploring the role of C. pneumoniae in inflammatory demyelination is required. This may be accomplished either by developing an animal model or in a therapeutic trial in patients with MS.
Chlamydia Infections↗
Interferon beta and the cytokine trail: where are we going?
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Cytokines↗
Sporadic Creutzfeldt-Jakob disease presenting as major depression.
We describe a 68-year-old white woman who initially had symptoms of major depression and was admitted to a psychiatric hospital where she had electroconvulsive therapy. With failure of psychiatric treatment and subsequent rapidly progressive dementia, she had left frontal brain biopsy. The biopsy revealed spongiform changes, the hallmark of Creutzfeldt-Jakob disease (CJD). We report a case of sporadic CJD with unusual initial presentation of psychiatric symptoms.
Aged↗
Role of transforming growth factor (TGF)-beta Type I and TGF-beta type II receptors in the TGF-beta1-regulated gene expression in pituitary prolactin-secreting lactotropes.
Transforming growth factor beta1 (TGF-beta1) inhibits pituitary lactotrope proliferation and secretion of PRL in an autocrine/paracrine manner. In this study, the role of TGF-beta1 type I (TbetaR-I) and TGF-beta type II (TbetaR-II) receptors in TGF-beta1-regulated gene expression in lactotropes was determined using anterior pituitary cells known to be responsive to TGF-beta1 growth inhibition and using a transformed PR1 cell line known to be nonresponsive to TGF-beta1 growth inhibition. Treatment with TGF-beta1 inhibited cell proliferation and decreased PRL mRNA levels in anterior pituitary cells, but in PR-1 cells, the treatment caused only decreased PRL mRNA levels. Affinity labeling of TGF-beta binding proteins indicated that anterior pituitary cells contain several TGF-beta-binding protein complexes, including the 65 kDa size TbetaR-I and 95 kDa size TbetaR-II. In the PR1 cells, the major complex found was similar to the 65 kDa size of TbetaR-I. Immunocytochemistry identified TbetaR-I and TbetaR-II receptor proteins in lactotropes but detected primarily TbetaR-I receptor protein in PR1 cells. RT-PCR detection of TbetaR-I and TbetaR-II mRNA identified both receptor mRNA transcripts in anterior pituitary cells and in PR1 cells but the levels of TbetaR-II and TbetaR-I mRNA transcripts in PR1 cells was much lower than that in anterior pituitary cells. Determination of the TGF-beta1 gene responses in PR1 cells following TbetaR-I and TbetaR-II gene transfection indicated that PR1 cells transactivate transcription of the TGF-beta-responsive p3TP-Lux reporter in the absence of cotransfected TbetaR-II receptor. The introduction of the TbetaR-II receptor alone or in combination with TbetaR-I confer ligand-independent reporter transactivation in these cells. When only TbetaR-I was introduced along with reporter, a ligand-dependent transactivation was observed. These data suggest for the first time that the TGF-beta1-mediated transcriptional activation response can be distinguished from the growth response in lactotropes. Furthermore, the TGF-beta1 gene-transcription response is less dependent on TbetaR-II receptor expression than is the TGF-beta1 growth-inhibitory response.
Activin Receptors, Type I↗
Opportunities and challenges in academic neurology: report of the Long Range Planning Committee of the American Neurological Association.
By most measures, academic neurology is thriving as never before, yet convening forces are changing the face of academic neurology. This report focuses on changes that academic neurology and the American Neurological Association could undertake to seize new opportunities and resist damaging potential changes. These proposals can be categorized in the following four major goals: (1) enhance the quality of a smaller neurology workforce and augment the recruitment of gifted young neuroscientists into neurology; (2) foster new diversity in neurological investigation, including clinical research in neurology; (3) document the benefits and relative costs of neurological care, in general, and of academic neurology, in particular; and (4) foster the role of neurologists as teachers to medical caregivers at all levels, including medical students, nonneurological house staff, and primary practitioners.
Education, Medical, Graduate↗
Investigation of potential HIV transmission to the patients of an HIV-infected surgeon.
OBJECTIVE: To ascertain if a surgeon infected with the human immunodeficiency virus (HIV) transmitted HIV to patients during invasive surgical procedures. DESIGN: Survey of patients and acquired immunodeficiency syndrome (AIDS) case registries, and laboratory analysis of nucleotide sequence data. SETTING: One surgeon's private and institutional practices within one academic referral hospital. PATIENTS: A total of 1131 persons identified in hospital databases who underwent invasive surgical procedures from 1984 through 1990 and for whom the surgeon was listed as the admitting or operating surgeon. MEASUREMENT: Patients presumed to be living were surveyed by mailed questionnaire. The AIDS case registries were reviewed for all patients having undergone invasive procedures and death certificates were obtained. Person-hours of surgery during which exposure might have occurred were calculated for surgical procedures. RESULTS: Of 1131 patients, 101 were dead, 119 had no address, 413 had test results known, and 498 did not respond to the questionnaire. No study patient name was found in reported AIDS case registries. One newly detected, HIV-seropositive patient was determined (through nucleotide sequencing) to have been most probably infected in 1985 during a transfusion. There was no HIV transmission in 369 person-hours of surgical exposure, indicating that HIV transmission to patients is unlikely to occur more frequently than once per 1000 person-hours of surgical exposure. CONCLUSIONS: If study validity and resources permit, investigation of publicly disclosed, HIV-infected health care workers whose practices involve invasive procedures should be pursued. The risk of HIV transmission during surgery may be so small that it will be quantified only by pooling data from multiple, methodologically similar investigations.
Acquired Immunodeficiency Syndrome↗
Tumor necrosis factor alpha response elements in the HLA-DRA promoter: identification of a tumor necrosis factor alpha-induced DNA-protein complex in astrocytes.
The cytokine tumor necrosis factor alpha (TNF-alpha) alone does not induce class II major histocompatibility complex (MHC) expression in most primary cells but can regulate ongoing class II expression in either a positive or negative fashion. The mechanism(s) by which TNF-alpha enhances interferon gamma (IFN-gamma)-induced class II expression was examined in a primary cell type, the astrocyte, by transient transfection of the HLA-DRA promoter linked to a chloramphenicol acetyltransferase reporter gene (DRA-CAT). We show that TNF-alpha, while having no effect on its own, can synergize with IFN-gamma to increase the level of promoter activity of a DRA-CAT construct. Three known sequences--W, X, and Y--are required for TNF-alpha enhancement of IFN-gamma-induced promoter activity. The corollary effect of TNF-alpha on DNA-binding proteins specific for these elements was examined. A previous report described a DNA-binding protein, IFN-gamma-enhanced factor X (IFNEX), which is upregulated by IFN-gamma in astrocytes and is specific for the X box of the DRA promoter. In this study, we found that TNF-alpha alone did not induce any nuclear proteins; however, combined treatment of astrocytes with both IFN-gamma and TNF-alpha induced a DNA-protein complex of slower electrophoretic mobility than IFNEX. The TNF-alpha-induced complex (TIC-X) has specificity for the X element of the DRA promoter. These results suggest a mechanism by which TNF-alpha enhances IFN-gamma-induced class II MHC expression via the formation of TIC-X.
Animals↗
Usage of primary cells to delineate IFN-gamma-responsive DNA elements in the HLA-DRA promoter and to identify a novel IFN-gamma-enhanced nuclear factor.
The IFN-gamma regulation of the HLA-DRA gene was examined in a primary cell type, the astrocyte. Site-specific mutagenesis of the DRA promoter reveals that three known sequences, S, X, and Y, are required for an optimal IFN-gamma response. Specifically for the X sequence, the X1, but not the X2, site is involved in IFN-gamma regulation of HLA-DRA in the astrocyte. Most interesting, a novel IFN-gamma-enhanced protein (IFNEX) with specificity for the X element has consistently been observed in nuclear extracts made from primary astrocytes. The correlation of the functional importance of X1 in IFN-gamma-regulated DRA expression and the enhancement of IFNEX by IFN-gamma strongly suggests that IFNEX may play a crucial role in IFN-gamma-regulated class II MHC gene expression.
Animals↗
Cerebral vasculopathy associated with collateralization resembling moya moya phenomenon and with anti-Ro/SS-A and anti-La/SS-B antibodies.
We describe a 48-year-old, previously healthy, anti-Ro/SS-A and anti-La/SS-B antibody positive black woman with negative risk factors for atherosclerosis, who developed mental status and personality changes over a 6-12-month period, and progressive cortical blindness over a 2-week period. Angiographic and computed axial tomographic studies of the brain demonstrated multiple large areas of infarction correlating with stenosis and occlusions of the internal carotid and posterior cerebral arteries. Moya moya-like findings were prominent radiographically. Results of angiographic, computed tomographic, and magnetic resonance imaging studies were interpreted as being compatible with large, medium, and small vessel disease, most likely a vasculitis.
Angiography↗
Identification of an interferon-gamma-responsive element of a class II major histocompatibility gene in rat type 1 astrocytes.
Interferon-gamma(IFN-gamma) has been shown to induce class II major histocompatibility complex (MHC) antigens on several cell types. Previous analysis of cell lines including a glioblastoma multiforme line by our laboratory has mapped an IFN-gamma-responsive element to the upstream - 141 to - 109 base pair (bp) region of the DRA promoter. Using deletion mutants, this report shows that this same general region (-135 to -109 bp) is important for IFN-gamma induction in two other human glioma lines and more importantly in primary astrocytes. We have confirmed that this regulatory region of the HLA-DRA gene is necessary for IFN-gamma inducibility in astrocytes using a substitution mutant. Sequences beyond -135 bp do not appear to have any additional positive or negative elements.
Animals↗
The yield of cholesterol screening in an urban black community.
BACKGROUND: While the distribution of cholesterol levels have been well studied in the general population, little is known about cholesterol and other cardiovascular disease risk factors in screenings held in an urban Black community. This study was designed to determine the yield of cholesterol screening in this community. METHODS: Screening took place in eight community sites. Serum total cholesterol was measured using a rapid capillary technique. Blood pressure was taken according to national guidelines and the average of two to three measurements were used. Standard interviews were used to determine the presence of cardiovascular risk factors by history. RESULTS: Of the 562 individuals screened, 44.9 percent had cholesterol levels requiring referral for follow-up care. Of those with total cholesterol greater than or equal to 6.21 mmol/L, 66.4 percent were previously undetected and more than half also had blood pressure levels greater than or equal to 140/90 mmHg on screening; 45 percent of all participants had blood pressure greater than or equal to 140/90 on screenings. Of those with a history of elevated total cholesterol levels, none had levels below 5.17 mmol/L at the time of screening. CONCLUSIONS: Multiple risk factors are highly prevalent in the urban Black community during cholesterol screening programs. Findings suggest the need for cholesterol programs incorporating blood pressure screening in the urban Black community.
Adult↗
Ending smoking at the Johns Hopkins Medical Institutions. An evaluation of smoking prevalence and indoor air pollution.
An empiric evaluation of a policy ending smoking in a large urban medical center was conducted. The study included a prospective cohort tracking of employees to measure changes in smoking behavior, environmental fires, smoking-related litter, and environmental tobacco pollution exposure. A 25% decrease in employee smoking prevalence was found (21.7% vs 16.2% before vs after policy implementation, respectively). The daily number of cigarettes reportedly smoked by employees who continued smoking and the total number smoked at work decreased across all occupational categories by an average of 25%. Significant reductions were noted in the level of public smoking and the amount of cigarette remnants. Nicotine vapor concentrations decreased significantly in all areas except restrooms. These findings suggest that visible smoking and environmental tobacco smoke exposure can be markedly decreased by instituting a policy eliminating smoking in a large medical center.
Air Pollutants, Occupational↗
Characterization of the activation of latent TGF-beta by co-cultures of endothelial cells and pericytes or smooth muscle cells: a self-regulating system.
The conversion of latent transforming growth factor beta (LTGF-beta) to the active species, transforming growth factor beta (TGF-beta), has been characterized in heterotypic cultures of bovine aortic endothelial (BAE) cells and bovine smooth muscle cells (SMCs). The formation of TGF-beta in co-cultures of BAE cells and SMCs was documented by a specific radioreceptor competition assay, while medium from homotypic cultures of BAE cells or SMCs contained no active TGF-beta as determined by this assay. The concentration of TGF-beta in the conditioned medium of heterotypic co-cultures was estimated to be 400-1,200 pg/ml using the inhibition of BAE cell migration as an assay. Northern blotting of poly A+ RNA extracted from both homotypic and heterotypic cultures of BAE cells and SMCs revealed that BAE cells produced both TGF-beta 1 and TGF-beta 2, while SMCs produced primarily TGF-beta 1. No change in the expression of these two forms of TGF-beta was apparent after 24 h in heterotypic cultures. Time course studies on the appearance of TGF-beta indicated that most of the active TGF-beta was generated within the first 12 h after the establishment of co-cultures. The generation of TGF-beta in co-cultures stimulated the production of the protease inhibitor plasminogen activator inhibitor-1 (PAI-1). The inclusion of neutralizing antibodies to TGF-beta in the co-culture medium blocked the observed increase in PAI-1 levels. The increased expression of PAI-1 subsequent to TGF-beta formation blocked the activation of the protease required for conversion of LTGF-beta to TGF-beta as the inclusion of neutralizing antibodies to PAI-1 in the co-culture medium resulted in prolonged production of TGF-beta. This effect was lost upon removal of the PAI-1 antibodies. Thus, the activation of LTGF-beta appears to be a self-regulating system.
Animals↗
Cervical spondylosis: a therapeutic update.
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Adolescent↗
Active and latent forms of transforming growth factor beta activity in synovial effusions.
We have evaluated the possible involvement of TGF-beta in rheumatoid arthritis by assay of 16 cell-free synovial fluids for the presence of its active and "latent" forms. Evidence has been obtained for TGF-beta-like activity in synovial effusions by four criteria: (a) TGF-beta receptor competition, (b) soft-agar colony formation of AKR-2B and NRK-49F indicator cells, (c) immunological neutralization of the biological activity, and (d) biochemical activation of a latent form.
Antigen-Antibody Reactions↗
Dural scrofula.
A middle-aged woman presenting with multiple cranial neuropathies, hemiparesis, and CSF pleocytosis had tuberculous infection of the cranial dura mater at autopsy. This is the first description of dural scrofula in modern medical literature.
Autopsy↗