scispace - formally typeset
Search or ask a question

Showing papers by "University of Maryland, Baltimore published in 1992"


Posted Content
TL;DR: In this article, the authors examined what is known about axis V and selectively reviewed the literature on measures of social functioning to identify potential alternatives to the Global Assessment of Functioning Scale.
Abstract: Objective: Axis V, which uses the Global Assessment of Functioning Scale in the multiaxial system of DSM-III-R, is under review for DSM-IV. This article examines what is known about axis V and selectively reviews the literature on measures of social functioning to identify potential alternatives to the Global Assessment of Functioning Scale. Method: About 25 studies on the use, reliability, and validity of axis V in DSM-III and DSM-III-R are reviewed. In addition, nearly 30 measures of social functioning are reviewed and analyzed as potential substitutes for the Global Assessment of Functioning Scale. The analysis focuses on the strengths and weaknesses of each measure for assessing functioning on axis V. Results: Axis V measures are modestly reliable and valid but not widely used. The authors identify and discuss two particular limitations on the Global Assessment of Functioning Scale: 1) the combination of measures of symptoms and measures of social functioning on a single axis and 2) the exclusion of physical impairments from the rating of functioning. Conclusions: None of the measures of social functioning reviewed is clearly superior to the Global Assessment of Functioning Scale for use on axis V. A modified version of the Global Assessment of Functioning Scale, separating the measures of social and occupational functioning from the measures of symptoms and psychological functioning, is proposed for field testing, along with a new set of instructions permitting the rating of limitations due to both physical and mental impairments.

1,148 citations


Journal ArticleDOI
TL;DR: In this paper, the authors examined what is known about axis V and selectively reviewed the literature on measures of social functioning to identify potential alternatives to the Global Assessment of Functioning Scale.
Abstract: Objective Axis V, which uses the Global Assessment of Functioning Scale in the multiaxial system of DSM-III-R, is under review for DSM-IV. This article examines what is known about axis V and selectively reviews the literature on measures of social functioning to identify potential alternatives to the Global Assessment of Functioning Scale. Method About 25 studies on the use, reliability, and validity of axis V in DSM-III and DSM-III-R are reviewed. In addition, nearly 30 measures of social functioning are reviewed and analyzed as potential substitutes for the Global Assessment of Functioning Scale. The analysis focuses on the strengths and weaknesses of each measure for assessing functioning on axis V. Results Axis V measures are modestly reliable and valid but not widely used. The authors identify and discuss two particular limitations of the Global Assessment of Functioning Scale: 1) the combination of measures of symptoms and measures of social functioning on a single axis and 2) the exclusion of physical impairments from the rating of functioning. Conclusions None of the measures of social functioning reviewed is clearly superior to the Global Assessment of Functioning Scale for use on axis V. A modified version of the Global Assessment of Functioning Scale, separating the measures of social and occupational functioning from the measures of symptoms and psychological functioning, is proposed for field testing, along with a new set of instructions permitting the rating of limitations due to both physical and mental impairments.

1,125 citations


Journal ArticleDOI
15 Jan 1992-JAMA
TL;DR: There was evidence of publication bias in that for both institutional review boards there was an association between results reported to be significant and publication and contrary to popular opinion, publication bias originates primarily with investigators, not journal editors.
Abstract: Objective. —To investigate factors associated with the publication of research findings, in particular, the association between "significant" results and publication. Design. —Follow-up study. Setting. —Studies approved in 1980 or prior to 1980 by the two institutional review boards that serve The Johns Hopkins Health Institutions—one that serves the School of Medicine and Hospital and the other that serves the School of Hygiene and Public Health. Population. —A total of 737 studies were followed up. Results. —Of the studies for which analyses had been reported as having been performed at the time of interview, 81% from the School of Medicine and Hospital and 66% from the School of Hygiene and Public Health had been published. Publication was not associated with sample size, presence of a comparison group, or type of study (eg, observational study vs clinical trial). External funding and multiple data collection sites were positively associated with publication. There was evidence of publication bias in that for both institutional review boards there was an association between results reported to be significant and publication (adjusted odds ratio, 2.54; 95% confidence interval, 1.63 to 3.94). Contrary to popular opinion, publication bias originates primarily with investigators, not journal editors: only six of the 124 studies not published were reported to have been rejected for publication. Conclusion. —There is a statistically significant association between significant results and publication. (JAMA. 1992;267:374-378)

838 citations


Journal ArticleDOI
TL;DR: Using a spin-trapping technique combined with electron spin resonance spectroscopy, it is reported that brain NOS generates superoxide O2-.

773 citations


Journal ArticleDOI
TL;DR: FLIM is used to create lifetime images of NADH when free in solution and when bound to malate dehydrogenase, and describes am imaging procedure that allows specific decay times to be suppressed, allowing in this case suppression of the emission from either free or bound NADH.
Abstract: We introduce a methodology, fluorescence lifetime imaging (FLIM), in which the contrast depends on the fluorescence lifetime at each point in a two-dimensional image and not on the local concentration and/or intensity of the fluorophore. We used FLIM to create lifetime images of NADH when free in solution and when bound to malate dehydrogenase. This represents a challenging case for lifetime imaging because the NADH decay times are just 0.4 and 1.0 ns in the free and bound states, respectively. In the present apparatus, lifetime images are created from a series of phase-sensitive images obtained with a gain-modulated image intensifier and recorded with a charge-coupled device (CCD) camera. The intensifier gain is modulated at the light-modulation frequency or a harmonic thereof. A series of stationary phase-sensitive images each obtained with various phase shifts of the gain-modulation signal, is used to determine the phase angle or modulation of the emission at each pixel, which is in essence the lifetime image. We also describe am imaging procedure that allows specific decay times to be suppressed, allowing in this case suppression of the emission from either free or bound NADH. Since the fluorescence lifetimes of probes are known to be sensitive to numerous chemical and physical factors such as pH, oxygen, temperature, cations, polarity, and binding to macromolecules, this method allows imaging of the chemical or property of interest in macroscopic and microscopic samples. The concept of FLIM appears to have numerous potential applications in the biosciences.

686 citations


Journal ArticleDOI
TL;DR: The association of serum cholesterol with specific causes of death varies in direction, strength, gradation, and persistence, and further research on the determinants of low serum cholesterol level in populations and long-term follow-up of participants in clinical trials is necessary.
Abstract: Background.— With increased efforts to lower serum cholesterol levels, it is important to quantify associations between serum cholesterol level and causes of death other than coronary heart disease, for which an etiologic relationship has been established. Methods.— For an average of 12 years, 350 977 men aged 35 to 57 years who had been screened for the Multiple Risk Factor Intervention Trial were followed up following a single standardized measurement of serum cholesterol level and other coronary heart disease risk factors; 21 499 deaths were identified. Results.— A strong, positive, graded relationship was evident between serum cholesterol level measured at initial screening and death from coronary heart disease. This relationship persisted over the 12-year follow-up period. No association was noted between serum cholesterol level and stroke. The absence of an association overall was due to different relationships of serum cholesterol level with intracranial hemorrhage and nonhemorrhagic stroke. For the latter, a positive, graded association with serum cholesterol level was evident. For intracranial hemorrhage, cholesterol levels less than 4.14 mmol/L ( Conclusions.— The association of serum cholesterol with specific causes of death varies in direction, strength, gradation, and persistence. Further research on the determinants of low serum cholesterol level in populations and long-term follow-up of participants in clinical trials are necessary to assess whether inverse associations with noncardiovascular disease causes of death are consequences of noncardiovascular disease, whether serum cholesterol level and noncardiovascular disease are both consequences of other factors, or whether these associations are causal. ( Arch Intern Med . 1992;152:1490-1500)

662 citations


Journal ArticleDOI
TL;DR: The relative insensitivity of CT makes formal nodal sampling at the time of mediastinoscopy or thoracotomy essential to detect lymph node metastases.
Abstract: One hundred forty-three patients with bronchogenic carcinoma were studied prospectively with computed tomography (CT) to determine the accuracy of CT in the evaluation of mediastinal nodal metastases. Mediastinal lymph nodes were localized according to the lymph node mapping scheme of the American Thoracic Society and were considered abnormal if they exceeded 1 cm in short-axis diameter. All patients underwent surgical staging, which consisted of either mediastinoscopy alone or mediastinoscopy and thoracotomy. At the time of surgical staging, all accessible nodes were either removed or sampled. The sensitivity of CT for mediastinal nodes on a per-patient basis was 64%, with a specificity of 62%. The sensitivity of CT for individual nodal stations involved with tumor was only 44%. The presence of obstructive pneumonitis did not appreciably alter the sensitivity of CT, but the specificity was lower (43%). The likelihood of metastases increased with lymph node size; however, seven of 19 (37%) lymph nodes that measured 2-4 cm in short-axis diameter were hyperplastic and did not contain metastases. The relative insensitivity of CT makes formal nodal sampling at the time of mediastinoscopy or thoracotomy essential to detect lymph node metastases.

544 citations


Journal ArticleDOI
TL;DR: The results suggest that the limbic system, especially the hippocampus, is functionally involved in schizophrenic psychosis and that different manifestations of schizophrenia may involve different neuronal circuits.
Abstract: • A hypothesis of psychosis localization in schizophrenia was derived from studying metabolic alterations in rat brain in response to phencyclidine hydrochloride administration. Since phencyclidine and its selective agonist dizocilpine maleate (MK801) induced overlapping and long-lasting metabolic alterations predominantly in limbic areas, the hypothesis developed that schizophrenic patients with psychosis would evidence functional abnormalities in limbic circuits compared with normal controls. Accordingly, 12 actively psychotic, drug-free patients with schizophrenia and matched normal controls underwent functional brain scans using positron emission tomography and fluorodeoxyglucose. Regions of interest were identified on five matched axial slices in each patient and control subject, and average metabolic rates were calculated. Patients with schizophrenia showed a significantly lower regional cere- bral metabolic rate of glucose in the hippocampus and the anterior cingulate cortex than did normal controls, but not in neocortical areas or in the extrapyramidal system. When the group of schizophrenic patients was divided into deficit and nondeficit types, a preliminary exploratory analysis suggested thalamic, frontal, and parietal cortical hypometabolism in the deficit subgroup, with normal metabolism in the nondeficit patient group in those areas; in contrast, hippocampal and anterior cingulate cortical metabolism was reduced in both deficit and nondeficit subtypes. These results suggest that the limbic system, especially the hippocampus, is functionally involved in schizophrenic psychosis and that different manifestations of schizophrenia may involve different neuronal circuits.

528 citations


Journal ArticleDOI
TL;DR: The right white matter volume in schizophrenic patients was significantly related to right amygdala/hippocampal volume, data that provide preliminary support for a hypothesis of abnormal limbic-cortical connection in schizophrenia.
Abstract: • We used magnetic resonance imaging to examine the morphologic characteristics of the amygdala/hippocampus, prefrontal cortex, and caudate nucleus in 29 healthy volunteers matched for age, gender, and head of household socioeconomic status and 44 patients with chronic schizophrenia. Total volumes of these structures were determined from 3-mm contiguous coronal sections. Schizophrenic patients, compared with healthy controls, had significantly smaller right and left amygdala/hippocampal complex volumes, smaller right and left prefrontal volumes, and larger left caudate volumes. A secondary analysis revealed reductions in the right and left amygdala and the left hippocampus. In addition, prefrontal white matter, but not gray matter, was reduced in the schizophrenic patients. Moreover, the right white matter volume in schizophrenic patients was significantly related to right amygdala/hippocampal volume ( r =.39), data that provide preliminary support for a hypothesis of abnormal limbic-cortical connection in schizophrenia. We studied the implications of these data for the pathophysiology of schizophrenia.

496 citations


Journal ArticleDOI
TL;DR: In the genetically restricted response that follows immunization with (4-hydroxy-3-nitrophenyl)acetyl coupled to protein carriers, two distinct populations of B cells are observed in the spleens of C57BL/6 mice.
Abstract: In the genetically restricted response that follows immunization with (4-hydroxy-3-nitrophenyl)acetyl coupled to protein carriers, two distinct populations of B cells are observed in the spleens of C57BL/6 mice. By 48 h postimmunization, foci of antigen-binding B cells appear along the periphery of the periarteriolar lymphoid sheaths. These foci expand to contain large numbers of antibody-forming cells that neither bind the lectin, peanut agglutinin, nor mutate the rearranged immunoglobulin variable region loci. Germinal centers containing peanut agglutinin-positive B cells can be observed by 96-120 h after immunization. Although specific for the immunizing hapten, these B cells do not produce substantial amounts of antibody, but are the population that undergoes somatic hypermutation and affinity-driven selection. Both focus and germinal center populations are pauciclonal, founded, on average, by three or fewer B lymphocytes. Despite the highly specialized roles of the focus (early antibody production) and germinal center (higher affinity memory cells) B cell populations, analysis of VH to D to JH joins in neighboring foci and germinal centers demonstrate that these B cell populations have a common clonal origin.

484 citations


Journal ArticleDOI
TL;DR: A new fluorescence imaging methodology in which the image contrast is derived from the fluorescence lifetime at each point in a two-dimensional image and not the local concentration and/or intensity of the fluorophore is described.


Journal ArticleDOI
TL;DR: It is suggested that localized physiological changes in postsynaptic [Ca2+]i potently modulate synaptic GABAA inputs and that this modulation may be an important regulatory mechanism in mammalian brain.
Abstract: Using intracellular recording techniques in CA1 cells in the hippocampal slice, we studied the responses of cells to synaptically released and iontophoretically applied GABA. With high-resistance, Cl(- )-filled electrodes, which inverted and enlarged the responses at normal resting potentials, we examined spontaneous GABA-mediated IPSPs. Usually we recorded the spontaneous events in the presence of carbachol (10–25 microM), which significantly increased IPSP frequency and blocked potentially confounding K+ conductances. Following a train of action potentials, spontaneous IPSPs were transiently suppressed. This suppression could not be accounted for by membrane conductance changes following the train or activation of a recurrent circuit. Whole-cell voltage-clamp recordings in the slice indicated that the amplitudes of the spontaneous GABAA inhibitory postsynaptic currents (IPSCs) were also diminished following the action potential train. In some cases BAY K 8644, a Ca2+ channel agonist, enhanced the suppression of IPSPs, while buffering changes in [Ca2+]i with EGTA or BAPTA prevented it. The monosynaptically evoked IPSC in the presence of 6-cyano-7- nitroquinoxaline-2,3-dione (CNQX) and dl-2-amino-5-phosphonovaleric acid (APN) was also diminished following a train of action potentials; however, iontophoretically applied GABA responses did not change significantly. These studies suggest that localized physiological changes in postsynaptic [Ca2+]i potently modulate synaptic GABAA inputs and that this modulation may be an important regulatory mechanism in mammalian brain.

Journal ArticleDOI
TL;DR: An accurate yet simple method to determine the apex of deformity and the type of correction required is based on the joint reference lines of the hip, knee, and ankle, and the individual mechanical axis lines of each bone segment.
Abstract: Angular deformities of the tibia or femur in the frontal plane lead to mechanical axis deviation of the lower limb and malorientation of the joints above and below the level of deformity. Accurate correction of the malalignment and of the joint orientation is important for function and to prevent joint degeneration. An accurate yet simple method to determine the apex of deformity and the type of correction required is based on the joint reference lines of the hip, knee, and ankle, and the individual mechanical axis lines of each bone segment. If the osteotomy is performed at the level of the apex of the deformity, then the only correction needed is angulation. If the osteotomy is performed at a level proximal or distal to the apex, then translation in addition to angulation is necessary to accurately correct the deformity.

Journal ArticleDOI
TL;DR: The eae gene from enterohaemorrhagic E. coli (EHEC) which, in addition to producing Shiga‐like cytotoxins, also produces the attaching and effacing effect of EPEC infections is cloned.
Abstract: The eae (Escherichia coli attaching and effacing) gene from enteropathogenic Escherichia coli (EPEC) was previously shown to be essential for production of the 'attaching and effacing' histopathology characteristic of EPEC infections (Jerse et al., 1990). We have now cloned the eae gene from enterohaemorrhagic E. coli (EHEC) which, in addition to producing Shiga-like cytotoxins, also produces the attaching and effacing effect. The sequence homology between the EPEC and EHEC sequences was 86% and 83% at the nucleotide and amino acid levels, respectively. The predicted amino acid sequence of the EHEC eae gene shared 31% identity and 51% similarity with invasin of Yersinia pseudotuberculosis. Alignment of the EPEC and EHEC Eae proteins and the Y. pseudotuberculosis and Y. enterocolitica invasins shows striking regions of identity with the greatest divergence at the C-terminal end, the putative receptor-binding portion of invasin.

Journal ArticleDOI
TL;DR: In this article, the authors derived solutions for planar rigid body collisions using Routh's impact process diagrams for both Newtonian and Poisson restitution for both rigid and non-rigid body collisions.
Abstract: This paper derives solutions for frictional planar rigid body collisions, using Routh's impact process diagrams, for both Newtonian and Poisson restitution.

Journal ArticleDOI
TL;DR: An EPEC plasmid‐encoded fimbrial gene, a candidate for the elusive EPEC adherence factor responsible for localized adherence, is described.
Abstract: Summary Enteropathogenic Escherichia coli (EPEC) form adherent microcolonies on the surface of tissue culture cells in a pattern termed localized adherence. Localized adherence requires the presence of a large EPEC adherence factor (EAF) plasmid. Recently a bundle-forming pilus has been described in EPEC possessing the EAF plasmid. An analysis of 22 non-invasive EPEC TnphoA mutants revealed that seven have insertions in the EAF plasmid and are incapable of localized adherence. We report here the mapping of the TnphoA insertions in these mutants. The nucleotide sequence of the gene interrupted in these TnphoA mutants (bfpA) was determined and found to correspond to the N-terminal amino acid sequence of the major structural protein of the bundle-forming pilus. The bfpA gene bears sequence similarities to members of the type IV fimbrial gene family and encodes a potential site for processing by a prepilin peptidase. A plasmid containing bfpA as the only open reading frame directs the synthesis of a protein recognized by antiserum raised against the bundle-forming pilus. TnphoA mutants at this locus are unable to synthesize BfpA, but synthesis is restored by introduction of a plasmid containing the cloned gene. The minimum fragment of DNA required to restore localized adherence is considerably greater than that required to restore BfpA synthesis. BfpA expression, as assessed by alkaline phophatase activity in bfpA::TnphoA mutants, is affected by temperature and growth medium. These studies describe an EPEC plasmid-encoded fimbrial gene, a candidate for the elusive EPEC adherence factor responsible for localized adherence.

Journal ArticleDOI
TL;DR: IL-2, IL-4, and IL-6 may be among the cytokines that contribute to the disease process in scleroderma patients, and this is the first report of elevated serum IL- 4 levels in human disease.
Abstract: Objective To determine whether interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-4, interferon-gamma (IFN gamma), IL-6, and tumor necrosis factor alpha (TNF alpha) are detected more frequently in sera from scleroderma patients than in sera from controls. Methods Serum concentrations of these cytokines were measured in 78 scleroderma patients and 73 controls, using enzyme-linked immunosorbent assay, radioimmunoassay, and bioassay techniques. Results IL-2, IL-4, and IL-6 were each detected more frequently in sera from scleroderma patients than in sera from controls. TNF alpha and IL-1 alpha were found with equal frequency in patient and control sera. IL-1 beta and IFN gamma were not detected in any sera. Conclusion IL-2, IL-4, and IL-6 may be among the cytokines that contribute to the disease process in scleroderma patients. To our knowledge, this is the first report of elevated serum IL-4 levels in human disease.

Journal ArticleDOI
TL;DR: Cl cloning of the AA determinant from EAggEC strain 17-2 into the 21.5-kb cosmid vector pCVD301 is reported and is termed the cloned bundle-forming fimbriae aggregative adherence fimbRIae I (AAF/I); positivity with a previously describedEAggEC probe and human erythrocyte HA appear to correlate with the presence of AAF/I.
Abstract: Strains of enteroaggregative Escherichia coli (EAggEC) have been implicated in several studies as important agents of persistent diarrhea among infants in the developing world. We have previously shown that the aggregative adherence (AA) property of EAggEC is associated with the presence of a 60-MDa plasmid which confers AA when introduced into E. coli HB101. Here, we report the cloning of the AA determinant from EAggEC strain 17-2 into the 21.5-kb cosmid vector pCVD301. TnphoA mutagenesis of the AA cosmid clone pJPN31 implicated an AA region of approximately 12 kb. Transmission electron microscopy of HB101 (pJPN31) revealed the presence of bundle-forming fimbriae, which were absent in AA- TnphoA insertion mutants. The presence of these fimbriae, AA, and hemagglutination (HA) of human erythrocytes were all concurrently lost by single-insertion mutations. A 14-kDa protein was seen on polyacrylamide gel electrophoresis and Western blotting (immunoblotting) of surface shear preparations from fimbriated clones. Twelve of nineteen volunteers fed EAggEC 17-2 developed rises in antibodies to the 14-kDa protein as determined by Western blot. We have termed the cloned bundle-forming fimbriae aggregative adherence fimbriae I (AAF/I); positivity with a previously described EAggEC probe and human erythrocyte HA appear to correlate with the presence of AAF/I.

Journal ArticleDOI
TL;DR: A significant increase in the incidence of epidural abscess after June 1988 is reported, and surgical drainage with sustained intravenous antibiotic treatment remains the cornerstone of therapy.

Journal ArticleDOI
TL;DR: The cholinergic receptor agonist, carbamylcholine (carbachol), depressed evoked excitatory postsynaptic potentials (EPSPs), but enhanced small spontaneously occurring membrane potential fluctuations that resembled IPSPs, and it is concluded that GABAergic inhibitory interneurons possess muscarinic receptors, that activation of these receptors increases the excitability of the interneurs and that synaptically released ACh increases interneURonal activity.
Abstract: 1. Intracellular recordings were made from CA1 pyramidal cells in the rat hippocampal slice to study the cholinergic modulation of GABAergic inhibition. The cholinergic receptor agonist, carbamylcholine (carbachol), depressed evoked excitatory postsynaptic potentials (EPSPs) and evoked inhibitory postsynaptic potentials (IPSPs), but enhanced small spontaneously occurring membrane potential fluctuations that resembled IPSPs. Both atropine (1 microM) and picrotoxin (25-60 microM) abolished the small fluctuations. 2. Recording from cells with potassium or caesium chloride (KCl or CsCl)-filled microelectrodes enhanced and inverted spontaneous Cl(-)-dependent GABAA-mediated IPSPs. These events appeared to result from the spontaneous firing of GABAergic interneurons since they could be inhibited by picrotoxin or bicuculline and nearly eliminated by tetrodotoxin. 3. Muscarinic acetylcholine (ACh) receptor activation significantly increased the frequency of spontaneous-activity-dependent IPSPs from 1.7 +/- 0.4 s (mean +/- S.E.M.) in control saline to 7.0 +/- 1.1 s in carbachol (10-50 microM)-containing saline, although evoked IPSPs were inhibited. All effects of carbachol were completely reversed by atropine. 4. The increase in frequency of spontaneous IPSPs observed in carbachol was not secondary to changes in the postsynaptic cell and was not blocked by high doses of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5-10 microM) and 2-amino-5-phosphonovaleric acid (APV, 10-20 microM), which abolished evoked excitatory transmission. Amplitude histograms showed an increase in mean size as well as of frequency of spontaneous IPSCs in carbachol. 5. Stimulation of cholinergic afferents in stratum oriens in the presence of the acetylcholinesterase inhibitor eserine (1 microM) also increased spontaneous IPSP frequency, and the time course of this response was similar to that of the muscarinic slow EPSP. Postsynaptic factors or the activation of glutamatergic excitatory pathways could not account for this effect. 6. Evoked monosynaptic IPSCs in CNQX and APV were diminished by carbachol. 7. We conclude that GABAergic inhibitory interneurons possess muscarinic receptors, that activation of these receptors increases the excitability of the interneurons and that synaptically released ACh increases interneuronal activity. Cholinergic reduction of the monosynaptic IPSC may point to additional complexity in cholinergic regulation of the GABA system.

Journal ArticleDOI
28 Aug 1992-Science
TL;DR: It was shown that Met is expressed in cells bordering lumen-like structures that resemble ducts in the human mammary cell line T47D, and reduced expression of Met could be related to the extent of tumor cell differentiation.
Abstract: The met proto-oncogene product (Met) and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), have been implicated in cell mitogenic response, cell motility, and the promotion of the ordered spatial arrangement of tissue. By means of confocal laser-scanning microscopy, it was shown that Met is expressed in cells bordering lumen-like structures that resemble ducts in the human mammary cell line T47D. In human breast tissue biopsies, Met staining was intense in normal cells bordering mammary ducts but was reduced in adjacent tumor tissue. Met staining in lumen-forming organs colocalizes with staining of antibody to phosphotyrosine, which suggests that the Met receptor and its substrates may be activated in lumen structures or ducts. HGF/SF treatment of human epithelial carcinoma cell lines resulted in the formation of lumen-like structures in vitro. Reduced expression of Met could be related to the extent of tumor cell differentiation.

Journal Article
Abstract: Methyllycaconitine, a toxin isolated from the seeds of Delphinium brownii, inhibited acetylcholine- and anatoxin-induced whole-cell currents in cultured fetal rat hippocampal neurons, at picomolar concentrations. This antagonism was specific, concentration dependent, reversible, and voltage independent. Furthermore, methyllycaconitine inhibited 125I-alpha-bungarotoxin binding to adult rat hippocampal membranes, protected against the alpha-bungarotoxin-induced pseudoirreversible blockade of nicotinic currents, and shifted the concentration-response curve of acetylcholine to the right in fetal rat hippocampal neurons, suggesting a possible competitive mode of action for this toxin. Remarkably low concentrations of methyllycaconitine (1-1000 fM) decreased the frequency of anatoxin-induced single-channel openings, with no detectable decrease in the mean channel open time. These actions of methyllycaconitine commend this neurotoxin for the characterization of the alpha-bungarotoxin-sensitive subclass of neuronal nicotinic receptors, which has hitherto eluded functional demonstration.

Journal ArticleDOI
01 Sep 1992-Medicine
TL;DR: Whether these known risk factors are sufficient in and of themselves to explain the high frequency of CAD in the Hopkins Lupus Cohort or whether they are "enabling" factors acting upon endothelium damaged by immune-complex disease cannot be addressed by this study.

Journal ArticleDOI
TL;DR: The ability of human neutrophils and monocytes to generate hydroxyl radical through a myeloperoxidase-dependent mechanism is supported.

Journal ArticleDOI
TL;DR: Data suggest that loss of heterozygosity of regions on 5q including the APC and MCC genetic loci is involved in the development and/or progression of most human esophageal cancers, implying that inactivation of APC, MCC, and/ or a linked gene on chromosome 5q plays a role in the pathogenesis of some cancers of the upper gastrointestinal tract.
Abstract: The tumor suppressor gene APC was recently identified, and the cDNA was cloned from chromosome 5q21. Point mutations affecting APC are seen in the hereditary syndrome familial adenomatous polyposis, and point mutations in APC and a closely linked gene, MCC, as well as loss of heterozygosity involving chromosome 5q have been reported in sporadic colon cancer. To our knowledge, loss of heterozygosity involving APC or MCC or both has not yet been described in any other human cancer besides lung cancer. We used the polymerase chain reaction and DNA content flow cytometric nuclear sorting to examine 30 primary human esophageal cancers for loss of heterozygosity of APC or MCC or both. Loss of one allele was detected in 77% of 26 informative cases. These data suggest that loss of heterozygosity of regions on 5q including the APC and MCC genetic loci is involved in the development and/or progression of most human esophageal cancers. They imply that inactivation of APC, MCC, and/or a linked gene on chromosome 5q plays a role in the pathogenesis of some cancers of the upper gastrointestinal tract, as well as in colon cancer and familial adenomatous polyposis.

Journal ArticleDOI
TL;DR: It is concluded that defined mutations in the aromatic biosynthetic pathway and in the cyclic AMP global regulatory system attenuate S. typhi lipopolysaccharide after vaccination with no statistically significant differences in the rate of seroconversion among volunteers in the three groups.
Abstract: Three attenuated Salmonella typhi strains have been constructed by introducing deletions in aroC and aroD or deletions in cya and crp into one of two wild-type parent strains, Ty2 or ISP1820. These mutant strains were designated CVD 906 (ISP1820 delta aroC delta aroD), CVD 908 (Ty2 delta aroC delta aroD), and chi 3927 (Ty2 delta cya delta crp). Two studies were conducted with 36 healthy adult inpatient volunteers to determine in a double-blind fashion the safety and immunogenicity of approximately 5 x 10(4) and 5 x 10(5) CFU of each of these three vaccine candidates given as a single dose. No statistically significant difference in the incidence of reactions among vaccinees was observed. Fever (oral temperature greater than or equal to 38.2 degrees C) occurred in 2 of 12 volunteers who received CVD 906, in 0 of 12 who received CVD 908, and in 1 of 12 who received chi 3927. Vaccine bacteremia without symptoms occurred in 1 of 12 vaccinees who received CVD 906, in 0 of 12 who received CVD 908, and in 2 of 12 who received chi 3927. Overall, 19 (53%) of 36 vaccinees developed immunoglobulin G antibody to S. typhi lipopolysaccharide after vaccination, with no statistically significant differences in the rate of seroconversion among volunteers in the three groups. We conclude that defined mutations in the aromatic biosynthetic pathway and in the cyclic AMP global regulatory system attenuate S. typhi. Mutant strains CVD 906, CVD 908, and chi 3927 are highly (and approximately equally) immunogenic but possibly differ in their propensity to induce fever. Further studies are needed to document the apparent relative safety of CVD 908 as a typhoid vaccine and as a vaccine carrier of foreign antigens.

Journal ArticleDOI
TL;DR: The results indicated that specialized brain systems for short-term storage of phonological and visuo-spatial information could be identified on the basis of marked differences between the topographies and morphologies of the ERP components elicited during these two types of short- term memory.

Journal ArticleDOI
TL;DR: It is discussed the possibility that dystrophin and spectrin, along with vinculin, may function to link the contractile apparatus to the sarcolemma of normal skeletal muscle.
Abstract: Duchenne's muscular dystrophy (DMD) is caused by the absence or drastic decrease of the structural protein, dystrophin, and is characterized by sarcolemmal lesions in skeletal muscle due to the stress of contraction. Dystrophin has been localized to the sarcolemma, but its organization there is not known. We report immunofluorescence studies which show that dystrophin is concentrated, along with the major muscle isoform of beta-spectrin, in three distinct domains at the sarcolemma: in elements overlying both I bands and M lines, and in occasional strands running along the longitudinal axis of the myofiber. Vinculin, which has previously been found at the sarcolemma overlying the I bands and in longitudinal strands, was present in the same three structures as spectrin and dystrophin. Controls demonstrated that the labeling was intracellular. Comparison to labeling of the lipid bilayer and of the extracellular matrix showed that the labeling for spectrin and dystrophin is associated with the intact sarcolemma and is not a result of processing artifacts. Dystrophin is not required for this lattice-like organization, as similar domains containing spectrin but not dystrophin are present in muscle from the mdx mouse and from humans with Duchenne's muscular dystrophy. We discuss the possibility that dystrophin and spectrin, along with vinculin, may function to link the contractile apparatus to the sarcolemma of normal skeletal muscle.

Journal Article
TL;DR: The data suggest that allelic deletions including these tumor suppressor genes are important in the formation and/or progression of most esophageal cancers; (b) allelic deletion involving MCC may not occur independently of deletions involving other tumor suppressing genes; and (c) the accumulation of multiple allelic deleting involving specific tumor suppresser genes may be important in most esphageal tumorigenesis or tumor evolution.
Abstract: Loss of heterozygosity occurring on various chromosomes has been described in the majority of human tumors. The targets of frequent or consistent subchromosomal deletions are believed to be tumor suppressor genes. We examined 72 esophageal tumors (46 squamous cell carcinomas and 26 adenocarcinomas) for loss of heterozygosity at the p53, Rb, APC, MCC, and DCC loci. Inclusion of these tumor suppressor genes in the allelic deletions was directly ascertained by performing polymerase chain reaction at polymorphic sites within the genes. Loss of heterozygosity occurred in 55% of informative cases at p53, in 48% of informative cases at Rb, in 66% at APC, in 63% at MCC, and in 24% at DCC. Ninety-three % of tumors informative at all loci (fully informative) lost heterozygosity of at least one locus. A high percentage of fully informative tumors (71%) also lost heterozygosity at more than one locus. There were no significant differences among histological types in the prevalence of loss of heterozygosity at any locus. There were correlations of losses involving MCC versus DCC, Rb, and p53. These data suggest that (a) allelic deletions including these tumor suppressor genes are important in the formation and/or progression of most esophageal cancers; (b) allelic deletions involving MCC may not occur independently of deletions involving other tumor suppressor genes; and (c) the accumulation of multiple allelic deletions involving specific tumor suppressor genes may be important in most esophageal tumorigenesis or tumor evolution.