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Biomedical subjects

H Moses

Publications and source records attributed to H Moses.

At least 19 recordsLinked to original sources

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

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

Transforming growth factor type beta in normal human urine.

TGF beta has been identified in normal human urine specimens from five individuals studied for five consecutive days. The peptide was extracted from urine using Sepralyte C1 beads. Detectable levels of [125I]TGF beta competing activity as measured by radioreceptor assay was found in about half of the specimens studied. The protein isolated from urine using C1 Sepralyte beads was further purified using Biogel P-60 column chromatography. Fractions were tested for TGF beta and EGF competing activity using radioreceptor assays. TGF beta and EGF extracted from urine are clearly separated by column chromatography. Two distinct EGF peaks and a single TGF beta peak were observed. Fractions having [125I]TGF beta competing activity were pooled and further purified using reverse-phase HPLC. HPLC fractions having [125I]TGF beta competing activity were tested for bioactivity using a soft agar assay. The fractions were capable of stimulating soft agar growth of AKR-2B (clone 84A) cells and cross reacted with a TGF beta antibody in a radioimmunoassay. The presence of TGF beta in normal human urine was also demonstrated by immunoblotting. These results also suggest that C1 bead extraction of urine specimens can be used as a rapid first step in purification of TGF beta.

Biological Assay

Intraoperative CT monitoring during stereotactic brain surgery.

This paper reports our experience in performing the entire stereotactic surgical procedure with a CT scanner, which shows that target shifting can occur as the probe approaches the target. Therefore, when sampling of small targets or specific sites within larger targets is desired. CT confirmation of the probe's position ensures that the specific area seen on CT is biopsied.

Adolescent

Response of cranial nerve abnormalities in nasopharyngeal carcinoma to radiation therapy.

Eighteen of 36 patients (50%) with the diagnosis of nasopharyngeal carcinoma had cranial nerve deficits before definitive radiotherapy. Within this group of 18 patients, there were 34 cranial nerve abnormalities and four Horner's syndromes. Overall, 62% of cranial nerve deficits recovered completely (CR) and 32% recovered partially (PR), for a total response rate of 94% to definitive radiotherapy. The magnitude of response (complete versus partial) depended upon the individual cranial nerve and the pretreatment duration of the abnormality. All of the responses except one occurred within 1 month after the completion of therapy. Complete responses were not obtained when deficits had existed longer than 2 months. However, PRs were obtainable. Seven of seven cases of posttreatment new or recurrent cranial nerve deficits were caused by recurrent tumor. The actuarial 5-year disease-free survival for this group of 18 patients was 31%. The results indicate that patients with cranial nerve deficits will respond to definitive radiotherapy and long-term disease-free survival can be achieved in some patients.

Adolescent

Profiles of physician practice and patient severity of illness.

We report on a study that examined physician practice profiles using two methods of patient classification: the Severity of Illness Index and diagnosis-related groups (DRGs). When used together with conventional management information and DRGs, the Severity of Illness Index permitted useful comparisons to be made among physicians; differences in both case-mix and severity could be estimated. In 37 per cent of the physicians studied, we found differences of more than $10,000 in the apparent impact of a physician on the hospital's financial position, depending on whether one controlled for severity or not. The extent to which these differences in impact could be due to quality of care differences is an area for future research. However, the findings that 37 per cent of the physicians in the study may be wrongly identified as over- or under-utilizers suggest long-term public health consequences of preparing physician profiles based on unadjusted DRGs.

Cost Control

Adult onset of the Dandy-Walker syndrome.

Two patients with the Dandy-Walker malformation first developed neurologic symptoms in adult life. In both patients there was normal motor and intellectual development during childhood, but as adults they had gradual evolution of brain stem and cerebellar signs and obstructive hydrocephalus. Following resection of the fourth ventricular cyst, both patients recovered. A review of the literature disclosed seven additional patients in whom the Dandy-Walker syndrome was first diagnosed in adult life. These cases illustrate that this congenital brain malformation may not only first become symptomatic later in life, but that it is possible for patients to remain asymptomatic.

Adult

Levodopa-induced psychosis: a kindling phenomenon.

Of 88 patients with idiopathic Parkinson's disease, without prior psychotic symptoms, and without significant dementia, nearly half had experienced vivid dreams, hallucinations, illusions, and nonconfusional as well as confusional psychoses as side effects of chronic levodopa therapy within the previous year of treatment. It was found that 61.3% of all hallucinations were associated with preexistent or concurrent vivid dream phenomena, that all psychotic states were associated with preexistent or concurrent vivid dreams and/or hallucinations, and that nonconfusional psychotic states tended to become confusional. These findings raise the possibility that chronic levodopa therapy may result in dopaminergic kindling and support the hypothesis that chronic dopaminergic agonism may, via such a kindling mechanism, play a role in the development of some types of psychoses.

Adult

Ocular involvement in wound botulism.

A 7-year-old girl developed bilateral ptosis, total ophthalmoplegia, and fixed, dilated pupils associated with bulbar paralysis and generalized weakness six days after she sustained a compound supracondylar fracture of the right humerus. Nerve conduction studies showed a facilitated muscle action potential after repetitive nerve stimulation. Blood cultures were negative. Although the wound site appeared noninfected, the wound was explored. Clostridium botulinum, type B, grew from cultures taken from the depths of the wound. The patient recovered fully with supportive care, and EEG abnormalities present during the acute phase of the illness disappeared.

Adolescent