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Biomedical subjects

K D White

Publications and source records attributed to K D White.

At least 19 recordsLinked to original sources

Effects of ayahuasca on binocular rivalry with dichoptic stimulus alternation.

RATIONALE: During binocular rivalry, two incompatible images are presented to each eye and these monocular stimuli compete for perceptual dominance, with one pattern temporarily suppressed from awareness. One variant of stimulus presentation in binocular rivalry experiments is dichoptic stimulus alternation (DSA), when stimuli are applied to the eyes in rapid reversals. There is preliminary report that in contrast with healthy controls, schizophrenic patients can maintain binocular rivalry even at very high DSA rates. OBJECTIVE: The study was undertaken to investigate whether binocular rivalry survives high rates of DSA induced by the South American hallucinogenic beverage ayahuasca. METHODS: Ten individuals who were participating in ayahuasca ceremonials were requested to volunteer for binocular rivalry tests (DSA=0, 3.75, 7.5, 15 and 30 Hz) without and after drinking the brew. RESULTS: Ingestion of ayahuasca increased mean dominance periods both in standard binocular rivalry conditions (no DSA) and tests with DSA. At higher DSA rates (15 and 30 Hz) the total length of dominance periods was longer on the brew. CONCLUSION: It is discussed that ayahuasca-induced survival of binocular rivalry at high DSA rates may be related to slow visual processing and increased mean dominance periods may result from hallucinogen-induced alteration of gamma oscillations in the visual pathways.

Adult↗

Occurrence of aflatoxins and fumonisins in Incaparina from Guatemala.

The occurrence of aflatoxins and fumonisins in Incaparina was investigated. Incaparina is a mixture of corn and cottonseed flour with added vitamins, minerals and a preservative. It has been marketed as a high-protein food supplement, particularly for children on protein-deficient diets. According to estimates, 80% of Guatemalan children in their first year are given Incaparina to provide an adequate diet. Eight samples of Incaparina manufactured in Guatemala were collected. Five were from three different geographical locations in the USA and three were from Guatemala. Seven were examined for fungal contamination and analysed for aflatoxins and fumonisins. Aspergillus flavus was the predominant fungus in all samples purchased in the USA and in one sample purchased from Guatemala, whereas Fusarium verticillioides was present in only two samples (one from the USA and one from Guatemala). All samples contained aflatoxins, ranging from 3 to 214 ng g(-1) and <2 to 32ng g(-1) for aflatoxin B(1) and aflatoxin B(2), respectively; and one sample contained aflatoxin G(1) (7 ng g(-1)). Total aflatoxins present ranged from 3 to 244 ng g(1). All samples contained fumonisins, ranging from 0.2 to 1.7 microg g(-1), <0.1 to 0.6 microg g(-1), and <0.1 to 0.2 microg g(-1) for fumonisins B(1), fumonisin B(2), and fumonisin B(2), respectively. Total fumonisins present ranged from 0.2 to 2.2 microg g(-1). The identity of aflatoxin B(2) was confirmed using both the chemical derivatization method and liquid chromatographic (LC)/mass spectrometric (MS) analysis. Appropriate regulatory action was recommended for the import of Incaparina and has been in effect since 22 December 1998.

Aflatoxins↗

Microbial indicator removal in onsite constructed wetlands for wastewater treatment in the southeastern U.S.

Seven onsite constructed wetlands for wastewater treatment in the coastal plains of Alabama and North Carolina were studied from September 1997 to July 1998. Each site was examined for its ability to remove a range of fecal contamination indicators from settled wastewater. Indicator organisms include total and fecal coliforms, enterococci, Clostridium perfringens, and somatic and male-specific (F+) coliphages. Four identical domestic wastewater treatment sites in Alabama were evaluated. In these sites the Log10 geometric mean reductions ranged between 0.5 and 2.6 for total and fecal coliforms, 0.1 and 1.5 for enterococci, 1.2 to 2.7 for C. perfringens, -0.3 and 1.2 for somatic coliphages, and -0.2 and 2.2 for F+ coliphages. Three unique designs were examined in North Carolina. Log10 geometric mean reductions ranged between 0.8 to 4.2 for total and fecal coliforms, 0.3 to 2.9 for enterococci, 1.6 to 2.9 for C. perfringens, -0.2 and 2.8 for somatic coliphages, and -0.1 and 1.5 for F+ coliphages. Somatic and F+ coliphage detection was highly variable from month to month.

Biodegradation, Environmental↗

Clinical and pathologic findings in hereditary spastic paraparesis with spastin mutation.

OBJECTIVE: To describe a family with chromosome 2p-linked hereditary spastic paraparesis (HSP) associated with dementia and illustrate the cerebral pathology associated with this disorder. BACKGROUND: HSP comprises a heterogeneous group of inherited disorders in which the main clinical feature is severe, progressive lower limb spasticity. Nongenetic classification relies on characteristics such as mode of inheritance, age at onset, and the presence or absence of additional neurologic features. Several loci have been identified for autosomal dominant pure HSP. The most common form, which links to chromosome 2p (SPG4), has recently been shown to be due to mutations in spastin, the gene encoding a novel AAA-containing protein. RESULTS: The authors report four generations of a British family with autosomal dominant HSP in whom haplotype analysis indicates linkage to chromosome 2p. In addition, a missense mutation has been identified in exon 10 of the spastin gene (A1395G). Dementia was documented clinically in one member of the family, two other affected family members were reported to have had late onset memory loss, and a younger affected individual showed evidence of memory disturbance and learning difficulties. Autopsy of the demented patient confirmed changes in the spinal cord typical of HSP and also demonstrated specific cortical pathology. There was neuronal depletion and tau-immunoreactive neurofibrillary tangles in the hippocampus and tau-immunoreactive balloon cells were seen in the limbic and neocortex. The substantia nigra showed Lewy body formation. The pathologic findings are not typical of known tauopathies. CONCLUSIONS: The authors confirm that chromosome 2p-linked HSP can be associated with dementia and that this phenotype may be associated with a specific and unusual cortical pathology.

Adenosine Triphosphatases↗

Mutation analysis of the spastin gene (SPG4) in patients with hereditary spastic paraparesis.

BACKGROUND: Hereditary spastic paraparesis is a genetically heterogeneous condition. Recently, mutations in the spastin gene were reported in families linked to the common SPG4 locus on chromosome 2p21-22. OBJECTIVES: To study a population of patients with hereditary spastic paraparesis for mutations in the spastin gene (SPG4) on chromosome 2p21-22. METHODS: DNA from 32 patients (12 from families known to be linked to SPG4) was analysed for mutations in the spastin gene by single strand conformational polymorphism analysis and sequencing. All patients were also examined clinically. RESULTS: Thirteen SPG4 mutations were identified, 11 of which are novel. These mutations include missense, nonsense, frameshift, and splice site mutations, the majority of which affect the AAA cassette. We also describe a nucleotide substitution outside this conserved region which appears to behave as a recessive mutation. CONCLUSIONS: Recurrent mutations in the spastin gene are uncommon. This reduces the ease of mutation detection as a part of the diagnostic work up of patients with hereditary spastic paraparesis. Our findings have important implications for the presumed function of spastin and schemes for mutation detection in HSP patients.

Adenosine Triphosphatases↗

A human immunoglobulin (Ig)A calpha3 domain motif directs polymeric Ig receptor-mediated secretion.

Polymeric immunoglobulins provide immunological protection at mucosal surfaces to which they are specifically transported by the polymeric immunoglobulin receptor (pIgR). Using a panel of human IgA1/IgG1 constant region "domain swap" mutants, the binding site for the pIgR on dimeric IgA (dIgA) was localized to the Calpha3 domain. Selection of random peptides for pIgR binding and comparison with the IgA sequence suggested amino acids 402-410 (QEPSQGTTT), in a predicted exposed loop of the Calpha3 domain, as a potential binding site. Alanine substitution of two groups of amino acids in this area abrogated the binding of dIgA to pIgR, whereas adjacent substitutions in a beta-strand immediately NH2-terminal to this loop had no effect. All pIgR binding IgA sequences contain a conserved three amino acid insertion, not present in IgG, at this position. These data localize the pIgR binding site on dimeric human IgA to this loop structure in the Calpha3 domain, which directs mucosal secretion of polymeric antibodies. We propose that it may be possible to use a pIgR binding motif to deliver antigen-specific dIgA and small-molecule drugs to mucosal epithelia for therapy.

Amino Acid Sequence↗

Determination of the diglycidyl ether of bisphenol A and its derivatives in canned foods.

Migration of the diglycidyl ether of bisphenol A (DGEBA) to food from can enamels and can pull-top seals is reported. Derivatives of DGEBA are also determined in some foods. Levels of DGEBA in the foods surveyed in this study range from nondetected (<0.3 ppb) to 50 mg/kg as determined by liquid-liquid extraction or solid-phase extraction coupled with high-pressure liquid chromatography using fluorescence detection. Confirmation of the analytes is by gas and/or liquid chromatography with mass spectral analysis. Fourier transform infrared spectroscopy with 30 degrees specular reflectance/transmittance is used to characterize the coated food contact surfaces. Stability studies with DGEBA in water, acid, and saline solutions show conversion to the hydrolysis products and chloro adducts occurs readily. The presence of DGEBA derivatives in food demonstrates that analysis for DGEBA migration alone is not a good indicator of total migration from can coatings to foods.

Animals↗

Allium chemistry: identification of organosulfur compounds in ramp (Allium tricoccum) homogenates.

Supercritical fluid (SF) extracts of homogenized ramp (Allium tricoccum Ait.) were separated and characterized with liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometric identification. The profiles of SF extracts of aqueous homogenates of ramp bulbs from three different seasons and growing regions revealed that the thiosulfinates were major components. In addition, some of the cepaenes (alpha-sulfinyldisulfides) found in extracts of onion juice, as well as allyl containing cepaenes (2-propenyl l-(2-propenylsulfinyl)propyl disulfide), are present in the ramp extracts. The amount of allicin in ramp bulb homogenates ranged from approximately 10% to 50% of that found in extracts of aqueous garlic homogenates. The greater amount of the methyl 1-propenyl thiosulfinates in the ramp extracts relative to that found in the garlic extracts correlates with the flavor characteristics of ramp bulbs.

Allium↗

Ig N-glycan orientation can influence interactions with the complement system.

This study was prompted by the paradoxical observation that a pair of dinitrophenyl-specific murine monoclonal IgG2a Abs had similar monosaccharide content and yet differed in their binding to lectins. The differential lectin-binding properties were lost when the Abs were denatured, suggesting that variations in lectin binding reflected the conformational accessibility of the N-glycans rather than intrinsic differences in the lectin binding capacity of the glycans themselves. This hypothesis was supported by experiments indicating that the degree to which the N-glycans on the Abs were reactive with beta-1,4-galactosyltransferase or susceptible to peptide N-glycosidase F corresponded directly to their relative accessibility to lectins. Moreover, the relative susceptibility to these enzymes and accessibility to lectins was inversely related to the capacity of the Abs to activate the classical pathway, suggesting that the orientation of the more accessible N-glycan might inhibit C1q binding. This hypothesis was supported by evidence that enzymatic cleavage of the more accessible N-glycan resulted in enhanced Clq, C4b, and C3b deposition. Conversely, removal of the less accessible N-glycan expressed by the other Ab inhibited C1q, C4b, and C3b deposition. The respective increase or decrease in C3b deposition on the two deglycosylated Abs was magnified when complement activation was performed in factor B-depleted serum, suggesting that N-glycan conformation primarily affects the classical pathway. Collectively, these data suggest that the orientation of the N-glycan expressed on Igs can profoundly influence interaction with the complement system.

Amidohydrolases↗

Effect of immunoglobulin variable region structure on C3b and C4b deposition.

Many of the biological activities of immunoglobulins, including interaction with the complement system, are attributed to the structure of the heavy chain constant domains. However, previous studies indicated that immune complexes formed with independently derived isotype-matched pairs of monoclonal antibodies vary with respect to their capacity to activate complement and to serve as targets for C3b and C4b deposition. The goal of the present study was to provide a structural basis for explaining how variable domains influence C3b and C4b deposition on immunoglobulins. Heavy and light chain variable domains from a pair of IgG2a antibodies previously shown to differ in terms of complement activation and C3b and C4b deposition were cloned and sequenced. The two clones utilize distinct heavy and light variable region genes and the translated amino acid sequence reveals several residues that could serve as potential targets for complement deposition which differs between the two antibodies. Molecular modeling suggests that many of the relevant differences between the two antibodies are located in solvent exposed portions of the heavy and light chain variable domains and that some of the relevant sites are located within the complementarity determining regions. Differences in antibody affinity do not provide an explanation for the previously observed role of variable domains on interactions with the complement system. These data suggest that sequence variations within solvent-exposed variable domain residues may play a key role in C3b and C4b deposition on immunoglobulins.

Amino Acid Sequence↗

Hypothermia in multiple sclerosis.

Five patients with clinically definite multiple sclerosis are reported who presented with acute relapses associated with hypothermia. Repeated episodes of hypothermia were seen in four. Thrombocytopenia was associated with the hypothermia in four patients. Further investigation disclosed a tendency to chronic hypothermia and suggested an altered thermoregulatory set point in one patient, when MRI, endocrine, and autonomic studies failed to localise a lesion in the hypothalamus, but subsequent necropsy showed hypothalamic lesions. In such patients a predisposition to altered thermoregulation may occur due to direct involvement of the hypothalamus or from combined lesions affecting hypothalamic outflow to the brainstem and spinal cord.

Adult↗

Improved stability in oral delivery of albuterol provides less variability in bronchodilation in adults with asthma.

The objective of this randomized, single-blind, parallel group study was to determine whether a more constant rate of albuterol delivery from tablets provides less variability in bronchodilation. Thirty-eight adult patients were enrolled with FEV1 between 40% to 80% of predicted normal and greater than or equal to 15% reversibility. Eighteen patients received Volmax, 8 mg bid, and 20 patients received Proventil Repetabs, 8 mg (as two 4-mg tablets) bid. The magnitude and duration of bronchodilation were determined after the first dose and at steady state on treatment day 7 by measuring serial values of pulmonary function for 12 hours on each day. Interpatient variability in bronchodilation was calculated for each study day did not differ significantly between treatments, the interpatient variability in bronchodilation with Volmax was, on average, one-half of that experienced with Proventil Repetabs. Adverse events, mainly headache and tremor, were comparable between Volmax and Proventil Repetabs. This study demonstrates that Volmax achieves less variable bronchodilation through a more constant rate of drug delivery from the onset of therapy.

Administration, Oral↗

Adolescents' compliance-resistance: effects of parents' compliance strategy and gender.

This investigation determined choice of compliance-resisting behaviors on the basis of compliance-gaining strategy, gender of parent, and gender of adolescent. One hundred and eighteen 9th- through 12th-grade students identified resistance strategies they would use when confronted with five compliance-gaining attempts: manipulation, nonnegotiation, emotional appeal, personal rejection, and empathic understanding. Each compliance-gaining attempt was associated with a specific parent and a specific compliance-gaining strategy. The results demonstrate significant differences in resistance strategy selected on the basis of parent's gender, adolescent's gender, and compliance-gaining strategy. When mothers employed personal rejection or empathic understanding, the adolescent was most likely to use nonnegotiation. When the mother used an emotional appeal, adolescents used identity management. Fathers who employed manipulation by using an emotional appeal were resisted with justification. When fathers used nonnegotiation or personal rejection, adolescents used nonnegotiation. The father's use of empathic understanding was countered with identity management. Adolescents are more likely to use identity management with their mothers and justification with their fathers. Female adolescents are more likely to use identity management than are male adolescents, while males are more likely to use nonnegotiation and negotiation than are females. Nonnegotiation occurs most often from son to mother, followed by son to father, daughter to father, and daughter to mother.

Adolescent↗

Preparation of inositol phosphates from sodium phytate by enzymatic and nonenzymatic hydrolysis.

Procedures for preparing myo-inositol bis-, tris-, tetrakis-, and pentakisphosphates from sodium phytate were established. Hydrolysis was achieved by autoclaving or enzymatic treatment; the inositol phosphates were separated by anion-exchange chromatography and were identified by fast atom bombardment-mass spectrometry. Enzymatic hydrolysis was more specific than autoclaving for isomer formation, whereas autoclaving was more efficient for producing the bis- and trisphosphates, which did not accumulate in significant amounts under the conditions of enzymatic hydrolysis. Sodium salts of the inositol phosphates were more powdery and less hygroscopic than the potassium salts. The procedures were satisfactory for producing gram quantities of each inositol phosphate, amounts adequate for animal studies of effects on mineral bioavailability.

6-Phytase↗

Highly purified human growth hormone fails to stimulate lipolysis in rabbit adipocytes in vitro or in rabbits in vivo.

To determine whether the rapid lipolytic effect observed with human growth hormone (hGH) preparations in rabbits and rabbit adipose tissue is an intrinsic property of the hormone, we examined the lipolytic effects in vivo and in vitro of clinical grade preparations, hGH purified by DEAE cellulose chromatography, and hGH prepared by recombinant DNA techniques. Using isolated rabbit perirenal adipocytes, ACTH and clinical-grade hGH preparations both stimulated glycerol release to the same maximal rate with half-maximal hGH effects observed between 8 and 50 micrograms/mL. Purification of the most potent lipolytic preparation of clinical grade hGH by DEAE cellulose chromatography yielded a preparation (2 IU/mg of growth activity that retained insulinlike effects on rat fat pad [U-14C] glucose metabolism) that, at concentrations up to 0.2 mg/mL, failed to stimulate lipolysis by adipocytes incubated for one or four hours in the presence or absence of dexamethasone or trypsin inhibitor or when preincubated for three hours prior to addition of hGH. Recombinant DNA-derived hGH did not stimulate glycerol release at 0.1 mg/mL. While antiserum to purified hGH blocked the increase in glucose oxidation in rat fat pads produced by clinical grade hGH, it did not inhibit its lipolytic effect using rabbit adipocytes. Purified hGH (0.1 mg/kg IV) was also unable to elicit a rise in serum free fatty acid (FFA) levels of conscious rabbits while, at the same dose, clinical grade hGH increased FFA levels to 900 microEq/L over basal. Rapid lipolytic stimulation in rabbit adipocytes by hGH preparations could not be attributed to the 20,000 molecular weight variant of hGH (hGH20K) or the peptide corresponding to positions 32 to 46 of hGH (deletion peptide).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗