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Neil Brown

Publications and source records attributed to Neil Brown.

6 recordsLinked to original sources
PubMed2005

CcbP, a calcium-binding protein from Anabaena sp. PCC 7120, provides evidence that calcium ions regulate heterocyst differentiation.

Although it is known that calcium is a very important messenger involved in many eukaryotic cellular processes, much less is known about calcium's role in bacteria. CcbP, a Ca(2+)-binding protein, was isolated from the heterocystous cyanobacterium Anabaena sp. PCC 7120, and the ccbP gene was cloned and inactivated. In the absence of combined nitrogen, inactivation of ccbP resulted in multiple contiguous heterocysts, whereas overexpression of ccbP suppressed heterocyst formation. Calmodulin, which is not present in Anabaena species, could also suppress heterocyst formation in both Anabaena sp. PCC 7120 and Anabaena variabilis. HetR induction upon nitrogen step-down was slow in the strain overexpressing ccbP. The Ca(2+) reporter protein obelin was used to show that mature heterocysts had a high intracellular free Ca(2+)concentration {[Ca(2+)](i)}, and immunoblotting showed that CcbP was absent from heterocysts. A regular pattern of cells with higher [Ca(2+)](i) was established during heterocyst differentiation before the appearance of proheterocysts. A rapid increase of [Ca(2+)](i) could be detected 4 h after the removal of combined nitrogen, and this increase was suppressed by excessive CcbP. These results suggest that Ca(2+) ions play very important roles in hetR induction and heterocyst differentiation.

Anabaena↗
PubMed2004

Silverstein MicroWick.

Using the MicroWick to deliver otic medication to the inner ear fluids isa new, unique, effective, safe, efficient, and inexpensive method to treat inner ear disease. This self-treatment method using otic medication represents a major breakthrough in the treatment of inner ear disease. It allows the otologist to treat inner ear disease much as the ophthalmologist treats eye disease using eye drops. In the future, new drugs and medications will likely be developed that will relieve vertigo attacks, improve certain types of sensorineural hearing loss, and reduce tinnitus. The MicroWick will be available for patients to self-administer these medications to the inner ear through the round window membrane.

Administration, Topical↗
PubMed2002

Differential effects of short-chain fatty acids on head and neck squamous carcinoma cells.

OBJECTIVES/HYPOTHESIS: Head and neck squamous cell carcinoma (HNSCC) is a major cause of mortality. Despite advances in therapeutic modalities, recurrences and second primaries are commonly observed. Biological agents that can suppress growth of tumors that are otherwise difficult to treat are greatly needed. The present study examined the effects of short-chain fatty acids on HNSCC cell lines. STUDY DESIGN: The effects of short-chain fatty acids on HNSCC cells was examined using tissue culture and immunoblotting techniques. METHODS: The effects of four short-chain fatty acids, arginine butyrate, alpha-methyl hydrocinnamic acid, 2,2-dimethylbutyrate, and alpha-lipoic acid, were evaluated on four HNSCC cell lines (FaDu, SCC9, SCC25, and Detroit-562). Proliferation assays were performed by means of spectrophotometric techniques. Histone deacetylase activity was assessed by identifying the amount of acetylated histone H4. Involucrin expression was determined to assess cellular differentiation. RESULTS: Inhibition of cellular proliferation was determined after 5 days of incubation with increasing doses with short-chain fatty acids. Arginine butyrate and alpha-lipoic acid were most effective in suppressing growth. Arginine butyrate demonstrated strong histone deacetylase inhibition in FaDu cells, while not inducing cellular differentiation. The short-chain fatty acid alpha-lipoic acid demonstrated weak histone deacetylase inhibition but was the only short-chain fatty acid that induced involucrin expression in at least two of the cell lines. Histone deacetylase inhibitory activity or induction of involucrin expression correlated with suppression of cell growth. CONCLUSIONS: Short-chain fatty acids have variable effects on HNSCC cells. Arginine butyrate and alpha-lipoic acid are the most effective in suppressing growth and appear to do so through different biochemical mechanisms. These compounds warrant further research as chemotherapeutic or chemopreventive agents in HNSCC.

Blotting, Western↗
PubMedDate not supplied

Combination antibiotic susceptibility testing to treat exacerbations of cystic fibrosis associated with multiresistant bacteria: a randomised, double-blind, controlled clinical trial.

BACKGROUND: We did a randomised, double-blind, controlled clinical trial to prospectively assess whether use of combination antibiotic susceptibility testing improved clinical outcomes in patients with acute pulmonary exacerbations of cystic fibrosis who were infected with multiresistant bacteria. METHODS: 251 patients with cystic fibrosis who were chronically infected with multiresistant gram negative bacteria gave sputum at 3-month intervals for conventional culture and sensitivity tests and for combination antibiotic susceptibility tests using multiple combination bactericidal antibiotic testing (MCBT). Patients who developed an exacerbation of pulmonary disease were randomised to receive a 14-day course of any two blinded intravenous antibiotics chosen on the basis of either results from conventional sputum culture and sensitivity testing or the result of MCBT. The primary outcome was time from randomisation until the patient's next pulmonary exacerbation. Analysis was by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN60187870. FINDINGS: 132 patients had a pulmonary exacerbation and were randomised during the 4.5-year study period. The time to next pulmonary exacerbation was not prolonged in the MCBT-treated group (hazard ratio 0.86 in favour of the conventionally-treated group, 95% CI 0.60-1.23, p=0.40). There was no difference between the groups in treatment failure rate. After 14 days of intravenous antibiotic therapy, changes in lung function, dyspnoea, and sputum bacterial density were similar in both groups. INTERPRETATION: Antibiotic therapy directed by combination antibiotic susceptibility testing did not result in better clinical and bacteriological outcomes compared with therapy directed by standard culture and sensitivity techniques. The non-bactericidal effects of antibiotic therapy might play an important part in determining improvement in patients with cystic fibrosis pulmonary exacerbations.

Acute Disease↗
PubMedDate not supplied

Changes in protein secondary structure during gluten deformation studied by dynamic fourier transform infrared spectroscopy.

Fourier transform infrared (FT-IR) spectroscopy was used to monitor changes in the secondary structure of wheat prolamins, the main components of gluten, during mechanical deformation in a series of cycles of extension and relaxation. A sample derived from protein bodies isolated from developing grain showed a buildup of persistent beta-sheet structure. In gluten, the ratio of beta-sheet to random and beta-turn structures changed on extension. After the applied force was released, the sample recovered some of its original shape and structure, but the material became stiffer in consecutive extension cycles. The relationship between gluten structure and mechanical properties is discussed in terms of a model in which conversion of beta-turn to beta-sheet structure is a response to extension and a means by which elastic energy is stored in the system.

Glutens↗