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K Brown

Publications and source records attributed to K Brown.

At least 235 records · Page 13Linked to original sources
PubMed1996

Critical role for lysines 21 and 22 in signal-induced, ubiquitin-mediated proteolysis of I kappa B-alpha.

The NF-kappa B transcription factor induces rapid transcription of many genes in response to a variety of extracellular signals. NF-kappa B is readily activated from normally inhibited cytoplasmic stores by induced proteolytic degradation of I kappa B-alpha, a principal inhibitor of this transcription factor. Following the inhibitor's degradation, NF-kappa B is free to translocate to the nucleus and induce gene transcription. The I kappa B-alpha inhibitor is targeted for degradation by signal-induced phosphorylation of two closely spaced serines in its NH2 terminus (Ser32 and Ser36). Proteolytic degradation appears to be carried out by proteasomes which can recognize ubiquitinated intermediates of the I kappa B-alpha inhibitor. We provide evidence which supports a ubiquitin-mediated mechanism. Amino acid substitutions of two adjacent potential ubiquitination sites in the NH2 terminus of I kappa B-alpha (Lys21 and Lys22) almost completely block the rapid, signal-induced degradation of the mutant protein, while they do not interfere with induced phosphorylation. The mutant I kappa B-alpha also does not permit signal-induced activation of NF-kappa B bound to it. The data suggest that ubiquitination at either of the two adjacent lysines (21 and 22) is required for degradation following induced phosphorylation at nearby serines 32 and 36. Such dependence on ubiquitination of specific sites for protein degradation is unusual. This mechanism of degradation may also apply to I kappa B-beta, an inhibitor related to and functionally overlapping with I kappa B-alpha, as well as to cactus, an I kappa B homolog of Drosophila.

Amino Acid Sequence↗
PubMed1996

A Novel Technique for Accurate Intensity Calibration of Area X-ray Detectors at Almost Arbitrary Energy.

A novel intensity uniformity calibration method for area X-ray detectors is described. In diffraction experiments, amorphous lithium glass plates, containing doping elements chosen for their K edges just below the energy of the main beam, replace the crystallographic samples for the calibration measurement. The fluorescent emission excited by the X-ray beam is almost isotropic. It has exactly the same geometry as the diffracted radiation, and can be obtained at the same wavelength by proper selection of the element and excitation energy. A sample 2theta scan allows the emission distribution as a function of angle to be characterized with an accuracy of a fraction of a percent. This allows a flat-field correction of similar accuracy. The quality of crystallographic data collected with an X-ray image intensifier/CCD detector was significantly improved by flat-field correction using an Sr-doped lithium tetraborate glass. This technique can be applied to X-ray energies from 5 to 50 KeV; the calibration sample is small, stable and easily handled.

Journal Article↗
PubMed1996

Anisotropy of radiance in tissue phantoms and Dunning R3327 rat tumors: radiance measurements with flat cleaved fiber probes.

BACKGROUND AND OBJECTIVE: The goal of this study is to determine if flat cleaved fiber probes are appropriate for interstitial measurements of radiance in tissue. Flat cleaved probes have the advantage of high responsivity, and they are easy to insert into tissue. Owing to the non-isotropic response of flat cleaved probes, a calibration function is required, taking the anisotropy in the radiance in tissue into account. STUDY DESIGN, MATERIALS AND METHODS: The method used to determine this function consists of radiance measurements in tissue, performed with a flat cleaved fiber probe mounted on a stereotactic stage for insertion into the tissue from different directions. Interstitial irradiation at 630 nm was delivered by a spherical source. RESULTS: We found that the degree of anisotropy in the radiance decreases with increasing distance from the interstitially implanted source in two different tissue phantoms and in the Dunning R3327-AT and R3327-H rat tumor models. CONCLUSION: A position-dependent calibration function is required for interstitially implanted flat cleaved fiber probes. An anisotropy function is presented, which modifies the measurements of radiance with a flat cleaved probe, to account for the change in anisotropy in the radiance. The anisotropy functions for the two tumor models differ substantially.

Animals↗
PubMed1996

Exposures and health effects: an evaluation of workers at a sodium azide production plant.

Sodium azide is the principal gas-generating agent used to inflate automobile supplemental restraint systems, more commonly called airbags. Although sodium azide is known to affect the cardiovascular system by causing peripheral vasodilation, there is no published literature describing occupational exposures to sodium azide in the rapidly growing automobile airbag industry. In 1994-1995, the National Institute for Occupational Safety and Health (NIOSH) conducted a cross-sectional study of health complaints reported by sodium azide production workers at the only continuous sodium azide production facility in the United States. The NIOSH evaluation consisted of a plant industrial hygiene survey, a symptom questionnaire, ambulatory blood pressure monitoring, and blood azide analysis. Personal breathing zone air monitoring revealed exposures to sodium azide and hydrazoic acid (a reactant product) at levels greater than the NIOSH Recommended Exposure Limits (RELs). In some cases, exposures exceeded the REL despite the use of air-supplied respirators. The questionnaire revealed that most workers reported headache (10 of 11 [91%]), episodes of low blood pressure (9 of 11 [82%]), and palpitations (8 of 11 [73%]) occurring in the production areas within the 6 months preceding the study. Mild headache (4 of 11 [36%]) was the only symptom reported during our 24-hr medical survey. Ambulatory blood pressure monitoring revealed one asymptomatic employee with a drop in blood pressure (defined as a drop in systolic [at least 20 mm Hg] and diastolic [at least 10 mm Hg] blood pressure) during a period of exposure to sodium azide at a level five times the NIOSH REL. Improvements in plant engineering controls, increased attention to employee hygiene practices, and a more comprehensive respiratory protection program were recommendations made by NIOSH to reduce exposures at the plant. All facilities handling sodium azide should be aware of the potential toxicity of sodium azide and hydrazoic acid.

Adult↗
PubMed1996

A low-temperature-responsive gene from barley encodes a protein with single-stranded nucleic acid-binding activity which is phosphorylated in vitro.

A low-temperature-responsive gene, blt 801, isolated from a winter barley (Hordeum vulgare L.) cDNA library prepared from leaf meristematic tissue, was sequenced. The deduced amino acid sequence predicts a glycine-rich RNA-binding protein (GR-RNP) which was homology to stress-responsive GR-RNPs from several other plant species. BLT 801 is a two-domain protein, the amino-terminal domain comprises a consensus RNA-binding domain similar to that found in many eukaryotic genes and the carboxy-terminal domain is extremely glycine-rich (68.5% glycine). Blt 801 mRNA also accumulates in response to the phytohormone abscisic acid. The protein encoded by blt 801 has been produced as a recombinant fusion protein using a bacterial expression vector. The fusion protein, a chimaera of glutathione S-transferase and BLT 801, has been used in studies to determine nucleic acid binding and other characteristics. Binding studies with single-stranded nucleic acids show that BLT 801 has affinity for homoribopolymers G, A and U but not C, it also binds to single-stranded DNA and selects RNA molecules containing open loop structures enriched in adenine but low in cytosine. Blt 801 has a consensus motif for phosphorylation by cAMP protein kinase (PKA) at the junction between the two domains which can be phosphorylated by PKA in vitro and which, by analogy to animal studies, may have significance for controlling enzyme function.

Amino Acid Sequence↗
PubMed1996

A revised teacher rating scale for reactive and proactive aggression.

A teacher rating scale of reactive aggression, proactive aggression, and covert antisocial behavior was evaluated in a normative sample of third- to fifth-grade predominantly white lower middle class boys (N = 186). Factor analysis revealed independent and internally consistent Reactive Aggression (six reactive items), and Proactive Aggression (five proactive items, five covert items) factors. Although the factors were intercorrelated (r = .67), and each factor was significantly correlated with negative peer social status (r = .26 for each, controlling for grade), the independence of the factors was supported by the unique relation of Reactive Aggression with in-school detentions (r = .31), controlling for Proactive Aggression and grade. These results supported the reliability and validity of Reactive and Proactive Aggression as rated by teachers, which should facilitate further research of these constructs.

Aggression↗
PubMed1996

Delayed embryo implantation following in vitro fertilization and embryo transfer (IVFET).

PURPOSE: Our goal was to compare serum human chorionic gonadotropin (hCG) levels in singleton pregnancies achieved following IVFET with those achieved following spontaneous conception. RESULTS: The mean serum hCG level of patients who became pregnant following IVFET lagged 1.5 days behind that of patients who became pregnant spontaneously. CONCLUSIONS: The use of gonadotropin releasing hormone analogue as part of the stimulation protocol leading to egg retrieval and IVFET results in a delay in embryo implantation.

Adult↗
PubMed1996

Hypocrellins as photosensitizers for photodynamic therapy: a screening evaluation and pharmacokinetic study.

Hypocrellin compounds were selected as potential photosensitizers for photodynamic therapy (PDT) owing to their high quantum yields of singlet oxygen (1O2), and facility for site-directed chemical modification to enhance phototoxicity, pharmacokinetics, solubility, and light absorption in the red spectral region, among other properties. Parent hypocrellins A and B share an absorption peak at 658 nm. These molecules may therefore be considered useful progenitors of derivatives which absorb more strongly in the red, considering that the ideal sensitizer should absorb in the 650-800 nm range, beyond the absorption range of hemoglobin and melanin, and where light penetration in tissues is maximized through reduced scattering. A series of pure, monomeric hypocrellin derivatives was tested for properties of dark cytotoxicity and photosensitizing potential by clonogenic assay in monolayer cultures of EMT6/Ed murine tumor cells. Their respective toxicities are reported on a molar basis. The in vitro screening assay has, to date, resulted in the selection of four hypocrellin derivatives for further development as photosensitizers for PDT. Cellular uptake for photosensitizing doses of selected compounds was determined by fluorimetry. Dose escalation studies in rodents indicate that potentially photosensitizing doses promote no demonstrable systemic toxicity.

Animals↗
PubMed1996

Photosensitization by anticancer agents 21: new perylene- and aminonaphthoquinones.

Hypocrellins are under intensive investigation as photosensitizing agents for photodynamic therapy (PDT). A recent advance in the synthesis of hypocrellin congeners resulted in the production of an amino-substituted hypocrellin-B, and its "half chromophore." Both compounds exhibit stronger red light absorption than previously reported hypocrellins, and, therefore, merit investigation as photosensitizers.

Animals↗
PubMed1996

Drainage is unnecessary after elective liver resection.

PURPOSE: A prospective, randomized trial was performed to determine if intra-abdominal drainage catheters are necessary after elective liver resection. PATIENTS AND METHODS: Between April 1992 and April 1994, 120 patients subjected to liver resection, stratified by extent of resection and by surgeon, were randomized to receive or not receive operative closed-suction drainage. Operative blood loss was not an exclusion criteria, and no patient who consented to the study was excluded. RESULTS: Eighty-seven patients (73%) had resection of one hepatic lobe or more (27 lobectomies, 54 trisegmentectomies, and 6 bilobar atypical resections) and 33 had less than a lobectomy (8 wedge resections or enucleations, 9 segmentectomies, and 16 bisegmentectomies). Eighty-four patients (70%) had metastatic cancer and 36 patients (30%) had primary liver pathology. There were no differences in outcome, including length of hospital stay (no drain, 13.4 +/- 0.9 days; drain, 13.1 +/- 0.8 days; P = not significant [NS]), mortality (no drain, 3.3%; drain, 3.3%), complication rate (no drain, 43%; drain, 48%; P = NS), or requirement for subsequent percutaneous drainage (no drain, 18%; drain, 8%; P = NS). All infected collections (n = 3) occurred in operatively drained patients. Two other complications were directly related to the operatively placed drains. One patient developed a subcutaneous abscess at the drain site, and a second developed a subcutaneous drain tract tumor recurrence as the only current site of recurrence. CONCLUSION: In the first 50 consecutive resections performed since the conclusion of this trial, only 4 patients (8%) have required subsequent percutaneous drainage. We conclude that abdominal drainage is unnecessary after elective liver resection.

Abdomen↗
PubMed1996

Pneumococcal meningitis in the North East Thames Region UK: epidemiology and molecular analysis of isolates.

One hundred and fourteen cases of pneumococcal meningitis were identified by prospective laboratory based surveillance during 1990-3 in the North East Thames Region. Higher rates of disease were seen in Asians (2.1/100000) than Caucasians (0.8/100000) (P = 0.002). The incidence of meningitis was higher in children than adults, while mortality rates were highest in adults over the age of 60 (48%). In 72 cases, both blood and CSF were culture positive. Serotyping of 65 isolates collected identified 22 serotypes (and one non-typable) causing disease, the most common being serotype 6 (13 cases) and serotype 14 (11 cases). Overall, 90% of serotype antigens identified were represented in the 23 valent vaccine. Ribotyping of 62 isolates identified 35 different patterns, of which 26 were single types. Different ribotypes were found among isolates of the same serotypes, with the exception of serotype 14, where 9 of 11 isolates had the same ribotype pattern. Four percent of isolates had reduced susceptibility to penicillin, but no high level penicillin resistance was found.

Adolescent↗
PubMed1996

Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancer.

The lifetime risk of breast cancer may approach 80-90% in women who have germline mutations of either of two genes, BRCA1 or BRCA2. A single BRCA1 mutation, 185delAG, has been noted in approximately 20% of Ashkenazi Jewish women with early onset breast cancer and in 0.9% of the Ashkenazi population. We recently detected a 6174delT frameshift mutation in BRCA2 in an hereditary breast cancer kindred of Ashkenazi Jewish ancestry. Here, we investigated the frequency of this mutation in 200 women with early-onset breast cancer. Six of 80 Ashkenazi Jewish women (8%) diagnosed with breast cancer before the age of 42, wer heterozygous for the 6174delT mutation, compared to none of 93 non-Jewish women diagnosed with breast cancer at the same age (P = .005). These cases were ascertained without regard to family history. Two of 27 (7%) additional Jewish families in which the proband was diagnosed with breast cancer at age 42 to 50 and had a family history of breast or ovarian cancer had germline 6174delT mutations. The results of this report suggest that a recurrent mutation of BRCA1 and a recurrent mutation BRCA2 together may account for over a quarter of all early-onset breast cancer in the setting of a personal or family history of ovarian cancer in Ashkenazi Jewish women.

Adult↗
PubMed1996

Effect of platelet phospholipid exposure on activated protein C resistance: implications for thrombophilia screening.

The effect of platelet contamination and freeze-thawing on the activated protein C sensitivity ratio (APCsr) was determined. With increasing platelet count there was a progressive reduction in the ratio. Filtration of samples through a 0.2 microm filter before or after freeze-thawing abolished the development of resistance to the addition of activated protein C indicating that the phenomenon is due to the presence of a particulate factor. Contamination of normal plasma with platelets from a patient with homozygous factor V (FV) deficiency was also associated with the same development of resistance to activated protein C, indicating that the phenomenon was not due to exposure of platelet-derived factor V that might be inaccessible to APC. 82% (96/117) of FVQ506 and 32% (138/430) of FVR506 individuals had APC resistance on analysis of unfiltered plasma. However, 85% (42/50) of FVQ506 individuals had APC resistance on analysis of filtered plasma, whilst only 1/50 FV R506 individuals had APC resistance after filtration. For the purpose of identifying individuals at increased risk of venous thromboembolism due to the presence of the FVQ506 and associated APC resistance a PCR-based genotypic analysis is recommended.

Base Sequence↗
PubMed1996

Ataxia-telangiectasia: founder effect among north African Jews.

The ATM gene is responsible for the autosomal recessive disorder ataxia-telangiectasia (A-T), characterized by cerebellar degeneration, immunodeficiency and cancer predisposition. A-T carriers were reported to be moderately cancer-prone. A wide variety of A-T mutations, most of which are unique to single families, were identified in various ethnic groups, precluding carrier screening with mutation-specific assays. However, a single mutation was observed in 32/33 defective ATM alleles in Jewish A-T families of North African origin, coming from various regions of Morocco and Tunisia. This mutation, 103C-->T, results in a stop codon at position 35 of the ATM protein. In keeping with the nature of this mutation, various antibodies directed against the ATM protein failed to defect this protein in patient cells. A rapid carrier detection assay detected this mutation in three out of 488 ATM alleles of Jewish Moroccan or Tunisian origin. This founder effect provides a unique opportunity for population-based screening for A-T carriers in a large Jewish community.

Africa, Northern↗
PubMed1996

Integrated multimedia timeline of medical images and data for thoracic oncology patients.

A prototype multimedia medical database has been developed to provide image and textual data for thoracic oncology patients undergoing treatment of advanced malignancies. The database integrates image data from the hospital picture archiving and communication system with textual reports from the radiology information system, alphanumeric data contained in the hospital information system, and other electronic medical data. The database presents information in a timeline format and also contains visualization programs that permit the user to view and annotate radiographic measurements in tabular or graphic form. The database provides an efficient and intuitive display of the changing status of oncology patients. The ability to integrate, manage, and access relevant multimedia information may substantially enhance communication among distributed multidisciplinary health care providers and may ensure greater consistency and completeness of patient-related data.

Databases, Factual↗
PubMed1996

Vaccine cuisine.

Explore the source record for details and available documents.

Fruit↗