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Biomedical subjects

P K Hall

Publications and source records attributed to P K Hall.

16 recordsLinked to original sources
PubMed1992

Methionine oxidation and inactivation of alpha 1-proteinase inhibitor by Cu2+ and glucose.

The effect of glucose/Cu2+ incubation on (a) pure methionine oxidation, (b) the oxidation of active-site methionine in alpha 1-proteinase inhibitor (alpha 1PI) and (c) the resulting activity and structural changes of this inhibitor was investigated. While no methionine was oxidized during a 24 day, 37 degrees C incubation with 0.01 M EDTA and 100 mM glucose, 64.2% oxidation occurred in 6 days when 0.01 mM Cu2+ was added to the 100 mM glucose. The first-order rate constant for oxidation in 10 mM glucose, 0.01 mM Cu2+ was 0.0218 day-1. Oxidation was inhibited by catalase, but accelerated by ascorbate ion. The active-site methionyl residue of alpha 1PI was oxidized 71.3% after a 4 day incubation in 100 mM glucose, 0.01 mM Cu2+ (pH 7.45), 0.1 M phosphate buffer. The elastase and trypsin inhibiting activities were lowered to 3.1 and 1.5% of control samples during this incubation. The inclusion of 1 mM DETAPAC, a transition metal chelator, resulted in a 98 + % retention of activity. Intrinsic fluorescence (350 nm excitation, 415 nm emission) of alpha 1PI increased 576% over control for the sample incubated in 100 mM glucose, 0.01 mM Cu2+ and SDS-PAGE revealed protein fragment molecular weights of 44.4 and 39.8 kDa. These studies suggest that both methionine oxidation and free radical induced fragmentation contribute to loss of alpha 1PI activity during glucose/Cu2+ incubations.

Binding Sites↗
PubMed1991

Fluoride ingestion in children: a review of 87 cases.

All cases of fluoride ingestion in children younger than 12 years old reported to the Rocky Mountain Poison Center between January 1 and December 31, 1986, were retrospectively reviewed. Eighty-seven cases were identified. Eighty-four cases involved accidental ingestion of dental fluoride products in the home (tablets, drops, rinses) in children 8 months to 6 years old. Two older children (8 and 9 years old) became symptomatic after fluoride treatment by a dentist. A 13-month-old child died after ingesting an unknown amount of sodium fluoride insecticide, the only insecticide exposure in our series. Postmortem total serum calcium value was 4.8 mg/dL (normal 8.8 to 10.3). No other patients had serious symptoms or sequelae. Twenty-six (30%) of 87 became symptomatic, with gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain) in 25 patients and drowsiness in 1. Only 3 patients became symptomatic later than 1 hour after ingestion. Analysis of data from 70 cases with sufficient information revealed that as the amount of fluoride ingested increased, the percentage of patients with symptoms increased. Not including the fatal case, 6 patients had serum calcium levels measured, and all were normal. Children who ingested up to 8.4 mg/kg of elemental fluoride in dental products had mild and self-limited symptoms, mostly gastrointestinal.

Accidents↗
PubMed1990

A child with signs of developmental apraxia of speech with whom a palatal lift prosthesis was used to manage palatal dysfunction.

A client is described who exhibited a large number of characteristics consistent with developmental apraxia of speech (DAS). The exhibited symptoms included excessive nasal resonance and nasal emission of air due to velopharyngeal port dysfunction, for which successful management was achieved by use of a palatal lift prosthesis. The results of the client's use of the lift, in conjunction with her speech and language remedial programming, is presented.

Apraxias↗
PubMed1989

Phosphate promotes glycation of antithrombin III which interferes with heparin binding.

Nonenzymatic glycation of antithrombin III has been reported to cause the reduction of heparin-catalyzed thrombin-inhibiting activity in diabetes. The effect of in vitro nonenzymatic glycation of pure antithrombin III on heparin binding and heparin-potentiated activity under a variety of buffers and pH values was studied to further clarify the physiological significance of this reaction. The extent of glycation, measured by the fructosamine assay and [14C]glucose binding, was enhanced by the presence of phosphate ion (pH 7.45, 8.5 and 9.5) and increased linearly with increasing phosphate ion concentration from 0.01 to 0.2 M phosphate. Conversely, the heparin-catalyzed antithrombin activity decreased from 93.1% of controls for 0.01 M phosphate to 73.5% for 0.2 M phosphate as the extent of glycation increased. The increase in intrinsic fluorescence induced by binding of heparin to antithrombin III was also moderated by glycation of antithrombin III in a dose-dependent manner with a negative correlation coefficient of -0.94. Direct measurement of the heparin binding by affinity chromatography showed a decrease in the heparin-binding fraction which correlated with the degree of glycation and the decrease in heparin-catalyzed activity. These studies suggest that nonenzymatic glycation may be responsible for the reduction in antithrombin III activity observed in some diabetics.

Antithrombin III↗
PubMed1989

The occurrence of developmental apraxia of speech in a mild articulation disorder: a case study.

Although Developmental Apraxia of Speech (DAS) often is considered a severe communication disorder, speech-language pathology literature supports the idea that DAS also can be exhibited in children with mildly disordered articulation. The case study is that of an elementary age client with a seemingly mild "r" articulation problem but who also presented characteristics consistent with DAS. Awareness of the possible presence of DAS when assessing and planning remediation for clients exhibiting mild articulation problems could increase the effectiveness of our professional services to these children.

Apraxias↗
PubMed1989

Hydrofluoric acid dermal exposure.

A retrospective review of 237 consecutive cases of dermal exposure to dilute (6-11%) hydrofluoric acid (HF)- containing rust stain remover consumer products reported to the Rocky Mountain Poison and Drug Center during 1986 was done to evaluate the toxicity of these agents and the efficacy of topical treatment with calcium gluconate gel. In 148 cases (62%), failure to follow manufacturers' recommended safety procedures was the likely cause of exposure. 219 patients developed the following symptoms: dermal swelling, redness, or both (131, 55%); blistering (12, 5%); black discoloration under fingernails (12, 5%); or pain without reported dermal changes (64, 27%). Local complications were noted in 7 cases (3%) (infection, 4 cases; fingertip dermal necrosis, 3 cases). No systemic toxicity was noted. 116 patients (49%) received treatment with topical calcium gluconate gel; 53 were followed until complete resolution of symptoms. There appeared to be a relationship between earlier initial gel application and more rapid resolution of signs and symptoms. Some degree of dermal injury may be quite common following exposure to dilute (6-11%) HF-containing rust stain remover consumer products. Failure to follow manufacturers' recommended safety procedures may be responsible for many exposures. Treatment with topical calcium gluconate gel may be effective, and more rapid resolution of signs and symptoms may occur with earlier initiation of this therapy.

Calcium Gluconate↗
PubMed1986

Reduced trypsin binding capacity of alpha 2-macroglobulin in diabetes.

The plasma proteinase inhibitor, alpha 2-macroglobulin, is usually elevated in diabetes. The trypsin binding capacity and the concentration of alpha 2-macroglobulin in 90 diabetics sera were compared with 30 age- and sex-matched normal sera. The mean alpha 2-macroglobulin concentration determined by radial immunodiffusion was 313 mg/dl for the diabetics as compared to 240 mg/dl for the healthy subjects (significantly higher, p less than 0.01). The mean of the ratio, mol trypsin bound/mol alpha 2-macroglobulin (molar binding ratio) for the Type I diabetics (n = 54), 0.82, was significantly lower than the mean of the healthy subjects, 0.87, or the mean of the Type II diabetics, 0.87. No relationship between the molar binding ratios and the levels of glycosylated hemoglobin was found. The alpha 2-macroglobulin was isolated from the plasma of 11 Type I diabetics and 7 normals. The maximum molar trypsin binding capacities of the diabetic alpha 2-macroglobulin were significantly lower. The mean for the diabetic alpha 2-macroglobulin was 1.72 vs. 1.97 for the normal alpha 2-macroglobulin. These results indicate that the trypsin binding function of alpha 2-macroglobulin is moderately impaired in diabetes. No differences were found in the extent of proteolytic cleavage of the 'bait region' of diabetic alpha 2-macroglobulin, autolytic cleavage or the methylamine reaction at the thiolester site between diabetic and normal alpha 2-macroglobulin. Nonenzymatic glucosylation of normal alpha 2-macroglobulin did not lower the trypsin binding capacity. The nature of the modification of alpha 2-macroglobulin leading to reduced trypsin binding capacity or the physiological significance is not yet known.

Adult↗
PubMed1982

Comparison of the structure and aspects of the proteinase-binding properties of cystic fibrotic alpha-macroglobulin with normal alpha 2-macroglobulin.

Considerable attention has been focused recently on alpha 2-macroglobulin (alpha 2M), a major endopeptidase inhibitor in blood plasma, as a possible source of the primary defect in cystic fibrosis (CF). We report here studies designed to compare the structure of CF alpha 2M with normal alpha 2M to determine if there is a difference. The physicochemical properties of purified alpha 2M as revealed by various electrophoretic techniques, covalent proteinase binding properties, and primary structural studies on a variety of partial hydrolyzates of CF alpha 2M and normal alpha 2M are compared. These studies were carried out on eight different individual isolates of CF alpha 2M and three age-matched normal alpha 2M preparations and alpha 2M isolated from fetal cord blood. Three properties of CF alpha 2M were studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE): (1) the existence of four identically-sized subunits in the native molecule (10), (2) the cleavage of this subunit into fragments of approximately 100,000 daltons upon interaction with proteinases (10), and (3) the cleavage of an alkaline/heat sensitive bond to produce 120,000 and 60,000 dalton fragments (11). Both CF and normal alpha 2M were cleaved to the extent of 79-87%, CF alpha 2M behaves identically with normal alpha 2M with regard to all these properties. Salvesen and Barrett (24) have demonstrated that varying proportions of several [125I]-labeled proteinases form SDS-stable, non-reducible links to normal alpha 2M. Two of the CF alpha 2M preparations were studied to determine if similar covalent binding of proteinases occurred. The positions of the labeled and % of proteinase bound bands in SDS/reduced PAGE system were identical for normal alpha 2M and CF alpha 2M. These results indicate that CF alpha 2M behaves normally with regard to covalent binding of proteinases. Qualitative comparison of the peptide fragments separated by SDS-PAGE or isoelectric focusing of CF and normal alpha 2M produced by partial proteolysis with trypsin, chymotrypsin or Staphylococcus aureus V-8 proteinase did not reveal any difference unique to CF alpha 2M. The cyanogen bromide fragmentation studies and the cysteine cleavage studies also indicated that no major change in the positions of methionyl residues or cysteinyl/cystinyl residues has occurred in CF alpha 2M. The failure of all these different studies and those reported by others to demonstrate any differences between CF and normal alpha 2M makes it highly unlikely that there is a primary defect in alpha 2M in CF.

Adolescent↗
PubMed1980

Human alpha-2-macroglobulin. Studies on the electrophoretic heterogeneity.

Purified alpha-2-macroglobulin may be resolved into as many as five electrophoretic bands on selected polyacrylamide gel systems. The microheterogeneity does not result from prior proteolytic attack but appears to correspond to different conformational states of the inhibitor. Trypsin binding capacity and the extent of subunit cleavage into 120,000 and 70,000 dalton fragments by mild alkaline treatment are related to the proportion of fast and slow electrophoretic forms. Study of proteinase binding after electrophoretic separation by special zymogram techniques confirms that the fastest electrophoretic form has very low binding capacity. No electrophoretic differences conld be observed in alpha-2-macroglobulin derived from cystic fibrosis plasma relative to control alpha-2-macroglobulin. Alpha-2-macroglobulin appears to exist as a simple, slow electrophoretic form in fresh plasma but converts into faster forms upon aging the plasma or during purification. Characterization of the electrophoretic microhetergeneity of alpha-2-macroglobulin preparations should be a prerequisite for the study of its proteinase binding properties.

Cystic Fibrosis↗
PubMed1978

Physical and chemical properties of human plasma alpha2-macroglobulin.

Alpha2-M (alpha2-macroglobulin) was purified from human plasma by two different procedures. As well as having no detectable impurities by the usual criteria for testing the homogeneity of protein preparations, these alpha2M preparations showed a single component, after reduction in urea, of 185000 daltons by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. The molecular weight of the alpha2M was found to be 718000 by sedimentation equilibrium experiments using the gravimetrically determined -v of 0.731 ml/g. The interaction of several proteinases with alpha2M was studied by using a novel discontinuous polyacrylamide-gel system, which showed clear separation of the enzyme-complexed alpha2M from the free alpha2M. These studies indicated that urokinase, as well as trypsin, chymotrypsin, plasmin and thrombin forms complexes with alphaM. The cleavage of the 185000-dalton subunit to a 85000-dalton species on interaction of trypsin with alpha2M was demonstrated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis after reduction of the alpha2M-trypsin complex in urea. The amino acid composition, carbohydrate content, absorption coefficient at 280 nm, the specific refractive increment and the sedimentation coefficient for these alpha2M preparations were measured. The stability of the trypsin-binding activity of the alpha2M preparations was also studied under several storage situations.

Amino Acids↗
PubMed1978

A follow-up study of children with articulation and language disorders.

Thirty-six subjects, 18 language-impaired and 18 articulation-impaired children, were followed up with respect to communication skills and educational performance 13 to 20 years after their initial contact with the Speech and Hearing Clinic. According to their parents, nine language-impaired subjects continued to exhibit communication problems as adults, compared to only one of the articulation-impaired subjects. Standardized educational testing conducted while the subjects were in elementary and secondary schools indicated that the language-impaired group consistently achieved at a lower level than the articulation-impaired group, particularly in reading. Differences between the groups were also exhibited in the types of postsecondary education attempted by the subjects. Clinical, educational, and research implications of these results are discussed.

Achievement↗