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Biomedical subjects

J White

Publications and source records attributed to J White.

At least 451 records · Page 25Linked to original sources

Variation in venom constituents within a single isolated population of peninsula tiger snake (Notechis ater niger).

Venom from seven individuals in a homogeneous isolated population of Notechis ater niger on Roxby Island, off the South Australia coast, was subjected to gel filtration liquid chromatography and polyacrylamide gel electrophoresis to determine the extent of homogeneity of the venom constituent profile. The gel filtration chromatograms from six of the specimens were easily equated, while the seventh showed a slight variation. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of the venoms in a native and reduced state showed no detectable difference between six of the seven individuals, the remaining individual showing minor changes only in the native venom.

Chromatography, Gel↗

Modelling the temporal region in patients with temporal lobe epilepsy.

EEG interictal epileptiform discharges in temporal lobe epilepsy are associated with magnetic fields. The maxima of magnetic spikes recorded over the spherical portions of the head appear fairly symmetric, whereas those over the lower temporal region often have irregular shapes. Furthermore, their magnitude is often unequal with the extremum over the lower temporal region usually of lower magnitude than the extremum over the upper temporal region. This lack of symmetry in shape and magnitude may be due to non-sphericity of the skull over the temporal region or to variations in conductivities of intervening tissues. We present our observation in two patients suggesting that the surface contours of the head contribute to the apparent asymmetries of the field pattern but that the head contours alone may not account for the asymmetries seen in the clinical data.

Computer Simulation↗

Clinical and laboratory study of two Caucasian families with hereditary pyropoikilocytosis and hereditary elliptocytosis.

Hereditary pyropoikilocytosis (HPP) is a severe, congenital hemolytic anemia occurring almost exclusively in black persons and characterized by extreme red blood cell anisopoikilocytosis. The authors report two unrelated white females with HPP. Both had severe hemolytic anemia at birth, red blood cell morphologic features characteristic for HPP, and increased thermal sensitivity of the red blood cells. Examination of the red blood cell membranes of both patients showed markedly unstable membrane skeletons when subjected to shear stress, spectrin dimer association defects with increased dimers, and partial spectrin deficiency. Limited tryptic digestion of the spectrin molecule from both patients yielded an abnormal pattern with a decrease in the normal 80,000-dalton alpha I domain and a concomitant increase of an abnormal 74,000-dalton peptide (Sp alpha 1/74). One parent and one sibling of one of the patients with HPP had hereditary elliptocytosis (HE) and the Sp alpha 1/74 defect. The other patient with HPP was different from others reported in that both parents were hematologically and biochemically normal. In addition, her daughter had HE and the Sp alpha 1/74 defect.

Adult↗

Intracranial hemorrhage and cerebral angiopathic changes in a suicidal phenylpropanolamine poisoning.

A 27-year-old man had an intracerebral hemorrhage and angiographic evidence of cerebral vasculitis after suicidal ingestion of 13 nasal decongestant tablets containing phenylpropanolamine (PPA). Toxicology screen and gas chromatography demonstrated PPA in the urine. Phenylpropanolamine is found in many over-the-counter preparations, but physicians should be aware of PPA's side effects and should be cautious about prescribing this potentially hazardous drug to suicidal patients.

Adult↗

The laparoscope.

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Female↗

Characteristics of site variation among clones of the 340-base pair, tandemly repeated EcoR1 family of human DNA.

Twenty-four clones of EcoR1-restricted, 340-base pair (bp) DNA derived from human DNA have been sequenced and compared to a published consensus sequence for this family. No two clones were found to have identical sequences; the clones studied differed from the consensus sequence in as few as 1 or as many as 41 sites. On the average in these clones, a 5.2% divergence from exact homology was found, with 1 of 10 of the site variations being "nonrandom," i.e., cases in which five or more clones had the same nucleotide substitution at that site (viz., 53, 124, 126, 138, 152, and 157). At site 157, for example, 16 of the 24 clones differed from the reference sequence. Positions and their respective changes, as compared to the consensus sequence, are summarized. Variations are discussed with relation to possible functions for these sequences.

Base Sequence↗

Purification of Ascaris suum antigen: its allergenic activity in vitro and in vivo.

Crude aqueous extracts of Ascaris suum (CE) have been used widely to study IgE-mediated reactions in various experimental preparations. Because some CE may contain a polypeptide, a mast cell degranulating peptide (MCDP), that degranulates mast cells by nonimmunologic mechanisms, various protocols have been used to ensure that the Ascaris preparation used did not contain MCPD. In general, these protocols have assumed MCDP had been without providing proof. Even protocols designed to isolate the major antigenic determinants from CE have usually been designed to evaluate immunogenic characteristics of the purified Ascaris; thus, few systematic comparisons of CE with purified Ascaris exist concerning mast cell degranulation, and few studies have demonstrated that MCDP has been removed during purification. Since Ascaris has proved to be useful in a variety of studies of IgE-mediated reactions, particularly in large animals (dog and sheep), we have developed a protocol to purify CE and MCDP and characterize their physiochemical and immunologic properties. We compared the allergenic activity of our purified Ascaris to that of CE and MCDP in skin and lung of natively sensitized dogs and in unsensitized rat peritoneal mast cells. Our results indicate that MCDP probably contaminates CE by less than 1.0%. However, the biologic activity of MCDP in dog lung appears insignificant and probably contributes little to CE-induced reactions in doses of CE commonly used (less than or equal to 100 mg injected). If a purified Ascaris preparation is essential, our protocol will yield an Ascaris preparation that has potent IgE-mediated effects in dog preparations with insignificant contamination by MCDP.

Allergens↗

Studies on the mechanism of membrane fusion: site-specific mutagenesis of the hemagglutinin of influenza virus.

Oligonucleotide-directed mutagenesis of a cDNA encoding the hemagglutinin of influenza virus has been used to introduce single base changes into the sequence that codes for the conserved apolar "fusion peptide" at the amino-terminus of the HA2 subunit. The mutant sequences replaced the wild-type gene in SV40-HA recombinant virus vectors, and the altered HA proteins were expressed in simian cells. Three mutants have been constructed that introduce single, nonconservative amino acid changes in the fusion peptide, and three fusion phenotypes were observed: substitution of glutamic acid for the glycine residue at the amino-terminus of HA2 abolished all fusion activity; substitution of glutamic acid for the glycine residue at position 4 in HA2 raised the threshold pH and decreased the efficiency of fusion; and, finally, extension of the hydrophobic stretch by replacement of the glutamic acid at position 11 with glycine yielded a mutant protein that induced fusion of erythrocytes with cells with the same efficiency and pH profile as the wild-type protein. However, the ability of this mutant to induce polykaryon formation was greatly impaired. Nevertheless, all the mutant proteins underwent a pH-dependent conformational change and bound to liposomes. These results are discussed in terms of the mechanism of HA-induced membrane fusion.

Animals↗

Arbovirus infection in a Murray Valley community.

Serum antibodies to Ross River virus and Murray Valley encephalitis virus were measured during 1974-1975 in residents of Echuca, an urban Murray Valley community. A representative group of volunteers was obtained by random selection of households. The prevalence of antibodies to both viruses increased progressively with age. Prevalence was equal in both sexes for both viruses in all age groups, indicating that the risk of infection was mainly determined by geography rather than by personal activities. Antibody levels remained unchanged in the following year when there was no disease activity in the area. The stability of antibody levels permitted retrospective estimates of mean rates of infection. These were approximately 0.4% per annum for both viruses when age was used as the index for years of exposure. With allowance for other factors, the best estimate for both virus infections is probably closer to 1%. The morbidity rate for Ross River virus infection appeared to be low. It is concluded that infection with Ross River virus and with Murray Valley encephalitis-related viruses is endemic in the Murray Valley.

Adolescent↗

Variant influenza virus hemagglutinin that induces fusion at elevated pH.

The hemagglutinin (HA) glycoprotein of influenza virus performs two critical roles during infection: it binds virus to cell surface sialic acids, and under mildly acidic conditions it induces fusion of the virion with intracellular membranes, liberating the genome into the cytoplasm. The pH dependence of fusion varies for different influenza virus strains. Here we report the isolation and characterization of a naturally occurring variant of the X31 strain that fuses at a pH 0.2 units higher than the parent strain does and that is less sensitive to the effects of ammonium chloride, a compound known to elevate endosomal pH. The bromelain-solubilized ectodomain of the variant HA displayed a corresponding shift in the pH at which it changed conformation and bound to liposomes. Cloning and sequencing of the variant HA gene revealed amino acid substitutions at three positions in the polypeptide. Two substitutions were in antigenic determinants in the globular region of HA1, and the third occurred in HA2 near the base of the molecule. By using chimeric HA molecules expressed in CV-1 cells from simian virus 40-based vectors, we demonstrated that the change in HA2 was solely responsible for the altered fusion phenotype. This substitution, asparagine for aspartic acid at position 132, disrupted a highly conserved interchain salt bridge between adjacent HA2 subunits. The apparent role of this residue in stabilizing the HA trimer is consistent with the idea that the trimer dissociates at low pH. Furthermore, the results demonstrate that influenza virus populations contain fusion variants, raising the possibility that such variants may play a role in the evolution of the virus.

Amino Acid Sequence↗

Salivary androgens in hirsutism: are they of use in routine evaluation?

In the biochemical evaluation of hirsutism, 50% or less of patients have an elevated total serum testosterone. Recent work has suggested that measuring salivary testosterone or a derived serum 'free testosterone index' may be of use in the evaluation of hyperandrogenism. We have measured serum total, derived serum free indices and salivary concentrations of testosterone and 5 alpha-dihydrotestosterone in an unselected group of hirsute patients in order to assess their value in the routine evaluation of hirsutism. The assays were performed using a novel oxidation procedure to overcome the need for chromatographic separation. The 'free testosterone index' gave the best discrimination. Salivary androgen concentrations were comparatively poor and cannot be recommended for routine use.

Adult↗

Pathobiochemistry of sepsis: role of proteinases, proteinase inhibitors and oxidizing agents.

Degradation of structural elements and excessive consumption of humoral factors, especially of plasma proteinase inhibitors, by proteolysis and/or oxidation is a major cause of multiple organ failure in sepsis or septic shock. Such pathobiochemical reactions seem to be induced primarily by extracellularly liberated lysosomal proteins from PMN granulocytes (e.g. elastase, cathepsin G, myeloperoxidase, lactoferrin) as well as oxygen radicals produced during extensive phagocytosis. In clinical studies on septicemia and septic shock the consumption of plasma proteins including proteinase inhibitors was inversely correlated to the liberation of lysosomal factors, especially the granulocytic elastase. Administration of relatively specific elastase-cathepsin G-inhibitors (Bowman-Birk inhibitor, eglin) in experimental septicemia proved to be a promising therapeutic approach to reduce consumption of plasma proteinase inhibitors and development of interstitial lung edema in severe inflammation.

Animals↗

Tranylcypromine: patterns and predictors of response.

Data on 58 patients with major depressive episodes treated with tranylcypromine in the course of two controlled, 4-week trials were examined for clinical predictors of favorable response and patterns of symptom improvement and side effects. Predictors of positive outcome with tranylcypromine were associated with greater initial severity on the Hamilton Rating Scale for Depression (HAM-D) ratings of depressed mood, psychomotor retardation, and weight loss, and with lower initial severity on ratings of middle and late insomnia. Distinct quality of depressed mood predicted poorer response; endogenicity, as defined by Research Diagnostic Criteria or the Nies-Robinson Diagnostic Index, failed to predict outcome. Analysis of improvement on individual symptom items of the HAM-D and Zung Self-Rating Depression Scale indicated a generalized patholysis except in a few areas such as appetite/weight loss and insomnia, which may reflect specific side effects of tranylcypromine.

Adult↗