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Biomedical subjects

W E Brown

Publications and source records attributed to W E Brown.

At least 19 recordsLinked to original sources
PubMed2001

Amygdala and hippocampal volumes in children with Down syndrome: a high-resolution MRI study.

The objective of this study was to use high-resolution MRI techniques to determine whether children with Down syndrome exhibit decreases in hippocampal and amygdala volumes similar to those demonstrated in recent studies of adults with this condition. When corrected for overall brain volumes, amygdala volumes did not differ between groups but hippocampal volumes were significantly smaller in the Down syndrome group. These findings suggest that the hippocampal volume reduction seen in adults with Down syndrome may be primarily due to early developmental differences rather than neurodegenerative changes.

Amygdala↗
PubMed2001

Preliminary evidence of widespread morphological variations of the brain in dyslexia.

The MR images of 16 men with dyslexia and 14 control subjects were compared using a voxel-based analysis. Evidence of decreases in gray matter in dyslexic subjects, most notably in the left temporal lobe and bilaterally in the temporoparietooccipital juncture, but also in the frontal lobe, caudate, thalamus, and cerebellum, was found. Widely distributed morphologic differences affecting several brain regions may contribute to the deficits associated with dyslexia.

Adolescent↗
PubMed1999

Specific IgG response to monomeric and polymeric diphenylmethane diisocyanate conjugates in subjects with respiratory reactions to isocyanates.

BACKGROUND: Isocyanates are a frequent cause of occupational asthma and can also induce hypersensitivity pneumonitis. OBJECTIVES: It is still unclear whether antibodies to diphenylmethane diisocyanate (MDI), which are elicited in some subjects with these conditions, are specific for this type of isocyanate. Moreover, preparation of conjugates to human serum albumin (HSA) with the polymeric formulation rather than monomeric MDI might result in improved detection of antibodies. METHODS: We addressed these issues by testing the sera of 13 subjects with asthma (n = 12) and hypersensitivity pneumonitis (n = 1) induced by MDI (n = 4 or 5, see below) by comparing them with sera obtained from subjects with occupational asthma caused by toluene diisocyanate (TDI; n = 5) and hexamethylene diisocyanate (HDI; n = 2). Conjugate preparations were compared by using SDS-PAGE, absorbance spectral analysis, and isolectric focusing. Immunologic screening was done by ELISA. RESULTS: Specific IgG antibodies that recognize MDI-HSA conjugates were detected in all but 1 of the MDI-exposed workers and could not be found in TDI-exposed and HDI-exposed workers. The levels of specific IgG antibodies were more elevated when tested against the HSA conjugates formed with polymeric MDI compared with the HSA conjugates formed with monomeric MDI. CONCLUSION: This study shows that specific IgG antibodies to MDI appear to be specific for MDI without cross-reactivity with TDI and HDI and higher by use of polymeric rather than monomeric MDI-HSA test antigens.

Adult↗
PubMed1998

Cocaine use as a risk factor for abdominal pregnancy.

Failure to diagnose abdominal pregnancies can have disastrous morbidity/mortality consequences for mother and fetus. To make the diagnosis of abdominal pregnancy requires that the physician have a high index of suspicion and that he or she have a good understanding of the risk factors of abdominal pregnancy. This article presents data suggesting that maternal cocaine use is a risk factor for abdominal pregnancy, reviews the literature on the maternal/fetal effects of maternal cocaine use and the risk factors of abdominal pregnancy, and analyzes 55 cases of abdominal pregnancy. Maternal cocaine use correlated with a 20% rate of increase in the incidence of abdominal pregnancy compared with the 70% rate of decrease in the "before cocaine" time period. Recommendations are offered for management.

Adult↗
PubMed1995

Analysis of the reactivity of [14C]toluene diisocyanate (TDI) in an isolated, perfused lung model.

An isolated, perfused, guinea pig lung model was used to investigate the molecular events which occur when a 14C-labeled TDI vapor reaches the airways. Exposure concentrations of 0.2 and 0.7 ppm were tested. Perfusate composition included: Krebs Ringer buffer only, as well as buffer containing either guinea pig serum albumin, human serum albumin, or diluted guinea pig plasma. Radioactivity was detected in the perfusate within minutes of exposure, and following a delay, increased linearly. The rate of uptake was dependent on TDI concentration and the composition of the perfusate. Biochemical characterization of the state of the 14C-labeled material in the perfusate was performed. The distribution between low and high molecular weight reaction products was determined by molecular sieve fractionation and varied as a function of perfusate composition but no variability was observed as a function of time during the 45 min of exposure. An increase in nucleophile concentration in the perfusate was associated with both a higher percentage of conjugated products (from 15% with buffer only to 45% with diluted guinea pig plasma) and an increase in the rate of TDX uptake (from 0.5 microns Eq/min with buffer alone to 0.1 micrograms Eq/min with diluted GPSA as perfusate at 0.7 ppm). GC-MS analysis of the samples for free TDA, before and after acid hydrolysis, showed that the low molecular weight product(s), which represented from 55-85% of the circulating radioactivity, was composed of hydrolyzable and non-hydrolyzable conjugates and metabolites with approximately 4% of the label associated with free TDA. Although the distribution between high and low molecular weight species varies, this result is analogous to the findings from in vivo studies and suggests that the isolated, perfused lung (IVPL) system may be a useful tool in investigating the molecular mechanisms of isocyanate-induced disease and metabolic activity of the lung.

Animals↗
PubMed1995

The mouse angiogenin gene family: structures of an angiogenin-related protein gene and two pseudogenes.

Angiogenin, a homologue of pancreatic ribonuclease, is a potent inducer of blood vessel formation. As an initial step toward investigating the in vivo functional role of this protein via gene disruption, we undertook the isolation of the angiogenin gene (Ang) from the 129 strain mouse, which will be used for generating targeting constructs. Unexpectedly, screening of a genomic library with an Ang gene probe obtained previously from the BALB/c strain yielded two new genes closely similar to Ang rather than Ang itself. One of these encodes a protein with 78% sequence identity to angiogenin and is designated "Angrp" for "angiogenin-related protein." The ribonucleolytic active site of angiogenin, which is critical for angiogenic activity, is completely conserved in Angrp, whereas a second essential site, thought to bind cellular receptors, is considerably different. Thus, the Angrp product may have a function distinct from that of angiogenin. The second gene obtained by library screening is a pseudogene, designated "Ang-ps1," that contains a frameshift mutation in the early part of the coding region. Although the Ang gene was not isolated from this library, it was possible to amplify this gene from 129 mouse genomic DNA by the polymerase chain reaction (PCR). Sequence analysis showed that the 129 strain Ang gene is identical to the BALB/c gene throughout the coding region. PCR cloning also yielded a second Ang-like pseudogene, designated "Ang-ps2." Southern blotting of genomic DNA confirmed the presence of Ang, Angrp, and at least one of the pseudogenes in an individual mouse and suggested that the mouse Ang gene family may contain more than the four members identified here.

Amino Acid Sequence↗
PubMed1995

Fate of the upper urinary tract in multiple sclerosis.

Urologic problems are a major source of morbidity for patients with multiple sclerosis (MS). Fifty-four to 78% of patients experience bladder symptoms which are due to spinal lesions interrupting neural pathways that control micturition. MS patients could have upper or lower motor neuron lesion type bladders. Both obstructive and irritative symptoms may be present. Although lower urinary tract dysfunction has been well described in MS, few studies have investigated the fate of the upper urinary tract. Thirty-two patients with MS were referred for urodynamic evaluation. Twenty-six of the 32 patients had upper urinary tract studies performed. Only 1 of the 26 patients had evidence of upper urinary tract deterioration. It is our impression that upper tract deterioration occurs infrequently in these patients. We discuss clinical clues that may predict deterioration.

Adult↗
PubMed1995

Matrilysin: expression, purification, and characterization.

The expression vector pGEX-2T under the control of the IPTG-inducible tac promotor is effective for the production of a fusion protein of glutathione transferase (GST, 26 kDa) and promatrilysin (28 kDa) separated from the C-terminus of GST by a thrombin cleavage site. Zwittergen (palmityl sulfobetaine), 2%, solubilizes the fusion protein that is found associated with inclusion bodies. The solubilized fusion protein is purified by affinity chromatography on GSH agarose. Promatrilysin is obtained by thrombin cleavage either on the column or after GSH elution of the fusion protein. Mono S chromatography of the recovered protein yields homogeneous promatrilysin. The zinc content of promatrilysin and its activated enzyme product is slightly greater than 2 mol of zinc per mole of protein. The results indicate that the matrix metalloproteinases (MMPs) contain two metal-binding sites at which zinc is firmly bound and possibly a third site at which it is weakly bound. Primary sequence alignments for all the MMPs have a sequence homologous to the zinc-binding site of astacin, HExxHxxGxxH, suggesting one of the zinc sites is a catalytic one, in agreement with the known inhibition of these enzymes by chelators. However, the other zinc-binding site(s) likely reflect the different ways that astacin and the MMP subfamilies are stabilized, i.e., disulfides in astacin and metal ions in the MMPs.

Base Sequence↗
PubMed1995

Mu1-related transposable elements of maize preferentially insert into low copy number DNA.

The Mutator transposable element system of maize was originally identified through its induction of mutations at an exceptionally high frequency and at a wide variety of loci. The Mu1 subfamily of transposable elements within this system are responsible for the majority of Mutator-induced mutations. Mu 1-related elements were isolated from active Mutator plants and their flanking DNA was characterized. Sequence analyses revealed perfect nine base target duplications directly flanking the insert for 13 of the 14 elements studied. Hybridizational studies indicated that Mu1-like elements insert primarily into regions of the maize genome that are of low copy number. This preferential selection of low copy number DNA as targets for Mu element insertion was not directed by any specific secondary structure(s) that could be detected in this study, but the 9-bp target duplications exhibited a discernibly higher than random match with the consensus sequence 5'-G-T-T-G-G/C-A-G-G/A-G-3'.

Chromosome Mapping↗
PubMed1994

Zinc content of promatrilysin, matrilysin and the stromelysin catalytic domain.

Promatrilysin expressed in Escherichia coli and Chinese hamster ovary cells contains 2.36 +/- 0.19 and 2.13 +/- 0.39 moles of zinc per mole of protein, respectively, while the activated enzyme contains 2.22 +/- 0.21. The catalytic domain of stromelysin-1 expressed in E. coli contains 2.22 +/- 0.11. Thus these matrix metalloproteinases contain two metal binding sites at which zinc is bound firmly and possibly a third site at which it is bound weakly. Promatrilysin and matrilysin do not contain significant amounts of Fe, Cu, Mn, or Ni. All known matrix metalloproteinases have a sequence homologous to the zinc binding site of astacin, HExxHxxGxxH, suggesting that one of the zinc sites is catalytic in agreement with the known inhibition of these enzymes by chelators.

Amino Acid Sequence↗
PubMed1994

Physicochemical properties of calcific deposits isolated from porcine bioprosthetic heart valves removed from patients following 2-13 years function.

The purpose of this study was to characterize the physicochemical properties of calcific deposits that cause the failure of tissue-derived heart valve bioprostheses. This was done in an effort to understand the mechanism of pathologic biomineralization in the cardiovascular system and potentially prevent deterioration of bioprostheses. Calcific deposits taken from 10 failed bioprosthetic valves that had been implanted in patients for 2-13 years were characterized by chemical analysis, x-ray diffraction, FTIR spectroscopy, scanning electron microscopy, polarized light microscopy, and solubility measurements. The combined results identified the biomineral as an apatitic calcium phosphate salt with substantial incorporation of sodium, magnesium and carbonate. The average Ca/PO4 ratio for this "young" pathologic biomineral was approximately 1.3, considerably lower than approximately 1.7 found in mature atherosclerotic plaque biomineral and mature skeletal biomineral, both of which approximate hydroxyapatite in composition. Deproteinated calcific deposits from bioprostheses had thermodynamic solubilities comparable to those of both atherosclerotic plaque, typical pathologic biomineral and hydrolyzed octacalcium phosphate (OCP, Ca4H(PO4)3 x 2.5 H2O), a proposed precursor phase to biomineral apatite. This later finding, together with chemical composition and structural details of the bioprosthetic deposits themselves, supports a mechanism of cardiovascular calcification in which OCP plays a crucial role in the formation of the final apatitic phase. This suggests an approach toward prevention of bioprosthetic tissue calcification through control of the formation of the kinetically favored OCP precursor and/or its transformation into bioapatite.

Bioprosthesis↗
PubMed1994

Distribution and reactivity of inhaled 14C-labeled toluene diisocyanate (TDI) in rats.

Inhalation exposure to toluene diisocyanate (TDI) can result in a variety of airway diseases. Concern has been expressed that a putative carcinogenic potential of TDI exists as a result of the formation of toluenediamine (TDA) by hydrolysis of the isocyanate in the body. Results from long-term bioassays (TDI inhalation versus gavage in rats and mice) are contradictory and discrepancies do exist concerning the interpretation of adverse effects. This study was performed to analyze the distribution and reactivity of radioactively-labeled TDI using vapor exposure in a rat model system. Rats were exposed to 14C-TDI vapors at concentrations ranging from 0.026 to 0.821 ppm for 4 h. All tissues examined showed detectable quantities of radioactivity, with the airways, gastrointestinal system and blood having the highest levels which increased with exposure concentration. The concentration of radioactivity in the bloodstream after exposure was linear with respect to dose. The majority (74-87%) of the label associated with the blood was recovered in the plasma, and of this, 97-100% of the 14C existed in the form of biomolecular conjugates. Analysis of stomach contents shows that the majority of the label is also associated with high (> 10 kDa) molecular weight species. While a larger percentage (28%) of the label is found in the low molecular weight fraction relative to blood, this low molecular weight labeled material represents at least eight different components. Thus, over the vapor exposure concentrations and time tested, it appears that conjugation is the predominant reaction and that free TDA is not a primary in vivo reaction product under the conditions tested.

Administration, Inhalation↗
PubMed1994

Active maize genes are unmodified and flanked by diverse classes of modified, highly repetitive DNA.

We have characterized the copy number, organization, and genomic modification of DNA sequences within and flanking several maize genes. We found that highly repetitive DNA sequences were tightly linked to most of these genes. The highly repetitive sequences were not found within the coding regions but could be found within 6 kb either 3' or 5' to the structural genes. These highly repetitive regions were each composed of unique combinations of different short repetitive sequences. Highly repetitive DNA blocks were not interrupted by any detected single copy DNA. The 13 classes of highly repetitive DNA identified were found to vary little between diverse Zea isolates. The level of DNA methylation in and near these genes was determined by scoring the digestibility of 63 recognition/cleavage sites with restriction enzymes that were sensitive to 5-methylation of cytosines in the sequences 5'-CG-3' and 5'-CNG-3'. All but four of these sites were digestible in chromosomal DNA. The four undigested sites were localized to extragenic DNA within or near highly repetitive DNA, while the other 59 sites were in low copy number DNAs. Pulsed field gel analysis indicated that the majority of cytosine modified tracts range from 20 to 200 kb in size. Single copy sequences hybridized to the unmodified domains, while highly repetitive sequences hybridized to the modified regions. Middle repetitive sequences were found in both domains.

Chromosome Mapping↗
PubMed1994

Animal models for brain tumors: historical perspectives and future directions.

The scientific understanding of the biology of human brain tumors has advanced in large part through the use of animal models. For most of this century, investigators have been evaluating the inciting factors in brain tumor development, and applying this knowledge to direct tumor growth in laboratory animals. Virus-induced, carcinogen-induced, and transplant-based models have been vigorously investigated. As knowledge of the molecular biology of neoplasia has advanced, transgenic technology has been introduced. The authors review the development of animal models for brain tumor, and focus on the role of transgenic models in elucidating the complex process of central nervous system neoplasia.

Animals↗
PubMed1993

Cross-reactivity between murine melanoma antigen B700 and a human melanoma-associated antigen (M-66) recognized by autologous antibody: evidence suggesting shared epitopes.

We have previously reported the purification and partial characterization of a human melanoma-associated antigen (M-66) recognized by autologous antibody. This antigen was found to be an unusually acidic 66 kDa glycoprotein. In studies of murine melanoma, a 67-kDa albumin-like melanoma-associated antigen (MAA) isolated from B16 melanoma cells has also been reported by our laboratories. Because the murine MAA, B700, has a molecular weight that is nearly the same as M-66, we sought to determine what similarities and differences existed between these two antigens. Human sera S150, which is known to recognize M-66, was found to bind to murine melanoma cell line B16. The addition of purified M-66 inhibited binding of S150 to B16 cells. Binding by S150 was not noted against murine melanoma cell line S91, which is known not to express cell surface B700. Conversely, reactivity of S150 against Y-Mel 84:420, known to express M-66, could be inhibited by preincubation with B16 cells. Four monoclonal antibodies known to recognize B700 were evaluated for-binding against murine B16 and human melanoma cell line Y-Mel 84:420. Binding was noted against both B16 and Y-Mel 84:420 which could be inhibited by the addition of M-66. Binding of S150 was also noted against purified B700 as tested by ELISA. While a comparison of the amino acid composition of the two antigens revealed similarities, M-66 contained 2.8 times as much serine and 0.4 times as much proline as B700. B700 has been reported to be related to serum albumin, which is not the case for M-66.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Isolation and purification of a squamous cell carcinoma of the head and neck-associated antigen identified by autologous antibody.

We have previously shown that detection of autologous antibody activity to squamous cell carcinoma of the head and neck may be augmented by dissociation of immune complexes. Western blot analysis with autologous antibody has identified a 60 kDa squamous cell carcinoma of the head and neck-associated antigen in spent media and immune complex-dissociated serum ultrafiltrate not recognized by normal human sera. Antigen-containing fractions of spent media were eluted from anion exchange columns immediately after serum albumin indicating that the antigen has an acidic pI < 4. Preparative purification of the squamous cell carcinoma antigen was accomplished by anion exchange of concentrated spent media (protein concentration 300 mg/ml) followed by lectin affinity chromatography with a Triticum vulgaris column. A single 60 kDa band was detected by silver stain and Western blot in antigen-containing fractions eluted following lectin affinity chromatography and SDS-PAGE. Final concentration of the antigen was determined to be 1 microgram/ml of protein with relative activity increased 1600 x over unfractionated spent media. We conclude that a squamous cell carcinoma of the head and neck-associated antigen, detected by autologous antibody, is an acidic 60 kDa glycoprotein.

Antibodies↗