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Biomedical subjects

K G Hardy

Publications and source records attributed to K G Hardy.

17 recordsLinked to original sources
PubMed1998

Genetic dissection of Alzheimer's disease and related dementias: amyloid and its relationship to tau.

Molecular genetic analysis is revealing the etiologies of Alzheimer's disease (AD) and related dementias. Here we review genetic and molecular biological evidence suggesting that the peptide A beta 42 is central to the etiology of AD. Recent data also suggests that dysfunction in the cytoskeletal protein tau is on the pathway that leads to neurodegeneration and dementia. Tau is produced either indirectly, by A beta 42, or directly, in some forms of frontotemporal dementia by mutations in tau itself. These data support are refine the amyloid cascade hypothesis for AD and suggest that understanding the causes and consequences of tau dysfunction is an important priority for dementia research.

Alzheimer Disease↗
PubMed1998

Sensitivity of aerosol bolus behavior to methacholine-induced bronchoconstriction.

STUDY OBJECTIVES: Airway narrowing causes alterations in the shape of an exhaled aerosol bolus that can serve as indexes of airway changes during bronchoprovocation. We compared the sensitivities of aerosol bolus behavior and specific airway conductance (SGaw) during bronchoprovocation in normal subjects. DESIGN AND PARTICIPANTS: Fifteen normal, nonsmoking subjects were studied. Doubling methacholine (MCh) concentrations were delivered during tidal breathing. After each dose, SGaw was determined followed by inhalation of narrow pulses of 1-microm particles introduced into 1-L breaths. Inhaled and exhaled particle concentrations were measured with light scattering photometry. Using plots of concentration vs volume, the exhaled bolus was compared with the inhaled bolus for measurements of volumetric change in mode location (modal shift), particle deposition, and dispersion. To determine baseline intrasubject variability, sham studies using buffer solution were performed on five subjects. RESULTS: MCh caused a proximal modal shift, and increased dispersion and deposition of the exhaled bolus. At most doses, a greater percentage of subjects showed significant change (p<0.05) from baseline for modal shift and deposition than for SGaw. Aerosol bolus behavior displayed less intrasubject variability than did SGaw during sham studies. CONCLUSION: Aerosol bolus behavior is at least as sensitive as SGaw in detecting MCh-induced airway constriction in normal subjects and exhibits less intrasubject variability.

Administration, Inhalation↗
PubMed1994

Detection of small airway dysfunction in asymptomatic smokers using aerosol bolus behavior.

Tests using inhaled particles assess ventilatory nonuniformities and may be sensitive to early changes in the small airways of cigarette smokers. We measured aerosol bolus behavior in 20 asymptomatic smokers and 20 age- and sex-matched nonsmokers for comparison with pulmonary function parameters including the single-breath nitrogen test. Narrow boluses containing 1-micron particles were introduced into 1-I breaths and inhaled to varying lung depths. We examined changes in bolus shape between inhalation and exhalation using plots of aerosol concentration versus respired volume for measurement of bolus dispersion, volumetric change in mean location (mean shift), and quantitative particle deposition. We found exhaled bolus dispersion to be significantly increased in smokers compared with nonsmokers. Volumetric mean shift was significantly different in smokers at shallow lung depths, with the center of bolus mass occurring later in exhalation. FEV1/FVC in smokers was significantly inversely correlated with dispersion at deeper lung depths and with mean shift at all lung depths. Smokers with abnormal spirometry (n = 4) or an abnormal single-breath nitrogen test (n = 7) had significantly increased dispersion compared with smokers with normal pulmonary function tests. We conclude that aerosol bolus dispersion is a useful tool for examination of small airway function in asymptomatic smokers.

Adult↗
PubMed1988

Conversion of Glucose to 2-Keto-l-Gulonate, an Intermediate in l-Ascorbate Synthesis, by a Recombinant Strain of Erwinia citreus.

A gene for 2,5-diketo-d-gluconate (25DKG) reductase, which encodes an enzyme composed of 277 amino acid residues catalyzing the reduction of 25DKG to 2-keto-l-gulonate (2KLG), was cloned from Corynebacterium sp. strain SHS752001 and expressed in Erwinia citreus SHS2003, a strain which oxidizes glucose to 25DKG. The recombinant microorganism converted glucose to 2KLG, a compound which can be readily converted to l-ascorbate (vitamin C). Improvements in the yield of 2KLG were obtained by changing fermentation conditions, using the p(l) promoter of bacteriophage lambda to express the reductase, and selecting a mutant of E. citreus which could use neither 25DKG nor 2KLG as a sole carbon source for growth. When a culture of the recombinant strain was fed with glucose to a total of 40 g/liter, 49.4% of the glucose was converted to 2KLG during a 72-h fermentation.

Journal Article↗
PubMed1981

Colicin V production by clinical isolates of Escherichia coli.

Strains of Escherichia coli isolated from random fecal samples, urines of hospitalized and nonhospitalized patients who had urinary tract infections, and blood of patients with septicemia were examined for colicin V production. The percentage of ColV+ strains isolated from blood (31.6%) or from urines of hospitalized patients with urinary tract infections (26.2%) was significantly greater (P less than 0.01) than the percentage isolated from feces (13.6%). The colicin V immunity determinant of ColV,I-K94 conferred immunity to 26% of the type V colicins produced by clinical isolates. Of the ColV+ strains studied, 63.6% produced at least one other type of colicin.

Bacteriuria↗
PubMed1979

Cloned fragments of the plasmid ColV,I-K94 specifying virulence and serum resistance.

A cloned BamH1-generated fragment of ColV,I-K94 increased the virulence of Escherichia coli, causing an approximately 100-fold reduction in LD50 for chicks. A genetic determinant for resistance to the bactericidal effects of serum was mapped to a 5,300 base-pair sequence within the fragment. Neither colicin V nor immunity to colicin V affected the pathogenicity of E. coli for chicks.

Animals↗