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Biomedical subjects

H M Brown

Publications and source records attributed to H M Brown.

At least 55 records · Page 3Linked to original sources

Detection of an IgM antiglobulin in the sera of atopic patients using insolubilized IgG4, and its capacity to release histamine from leucocytes.

ELISA plates coated with highly pure IgG4 were employed to detect IgM antiglobulin in atopic sera. The use of IgG4, rather than whole IgG, on the solid-phase was to provide direct evidence for the IgG4 reactivity of the antiglobulin. Bound IgM was shown to be antiglobulin in that binding can be inhibited by pre-absorption of serum with IgG. Some 75% of asthmatic patients and 29% of eczema patients were found to have significantly raised level of IgM antiglobulin. This antiglobulin resembles rheumatoid factor in that it appears to be directed against antigenic determinants common to human and rabbit IgG. Isolated antiglobulin-enriched IgM fractions released histamine from leucocytes of 7 out of 12 atopic patients. The histamine-releasing capacity of the IgM antiglobulin was shown to be operating via basophil-bound IgG in that the process can be blocked by pre-absorption of the antiglobulin with IgG. Furthermore, heating the antiglobulin-enriched IgM fraction did not affect its histamine-releasing capacity. We conclude that the IgM antiglobulin detectable in our atopic patients may contribute to the pathological changes in them.

Adolescent↗

IgE and IgG4 antibodies to bovine milk fat globule membrane in atopic eczema patients: a study of their occurrence, relevance and antigenic specificity.

IgE and IgG4 antibodies to bovine milk fat globule membrane (FGM) were measured in atopic eczema patients to determine whether their presence would account for allergy to milk in cases where whole or individual milk protein-specific antibodies are not detectable. The study demonstrates that the measurements of IgE and IgG4 antibodies to FGM do not offer any additional diagnostic value in milk exacerbated cases of atopic eczema. Furthermore, cross-inhibition studies with four milk proteins showed that these FGM-reactive IgE and IgG4 antibodies are directed against alpha-casein.

Adolescent↗

The isolation and characterization of the human helper inducer T cell subset.

Monoclonal antibody anti-4B4 was produced by fusing NS1 myeloma with spleen cells of a mouse immunized with Saguinus oedipus lymphocyte. This anti-4B4 antibody defines a 135-KD cell surface protein that is widely distributed throughout the hematopoietic system. More importantly, anti-4B4 is reactive with functionally unique human T cell subsets. Anti-4B4 antibody was reactive with approximately 41% of unfractionated T cells, 41% of T4+ inducer cells, and approximately 43% of T8+ cytotoxic/suppressor population. This antibody subdivided peripheral blood T4+ cells into two functionally distinct populations. The T4+4B4+ subset proliferates relatively poorly upon stimulation with Con A and autologous cell antigens (AMLR) but well on exposure to soluble antigens, and it provides a good helper signal for PWM-induced Ig synthesis. The T4+4B4- subset, in contrast, proliferates well to Con A stimulation and autologous cell antigen (AMLR) but relatively poorly to soluble antigen stimulation, and provides little help to B cells for PWM-induced Ig synthesis. The T4+4B4- subset is largely 2H4+ and functions as the inducer of the T8+ suppressor cells. Thus, the present results suggest that one can divide the human T4 population into two major subsets that are phenotypically and functionally distinct, the human helper inducer subset (T4+4B4+/H.I.) and its reciprocal population defined by anti-2H4, the suppressor inducer subset (T4+2H4+/S.I.).

Animals↗

Relevance of milk- and egg-specific IgG4 in atopic eczema.

In a substantial proportion of atopic eczema patients clinical sensitivity to food is not confirmable by either skin prick test or IgE RAST. The diagnosis of provocative food factors in this condition is, therefore, highly dependent on dietary manipulations which are time consuming and sometimes dangerous. In an attempt to find an alternative laboratory procedure we have questioned the clinical relevance of specific IgG4 measurement in the sera of these patients in the light of previous reports demonstrating raised total serum IgG4 in patients with atopic eczema. Thus, a highly reliable ELISA was developed to measure IgG4 specific to 3 cow's milk proteins and 2 hen's egg proteins in the sera of milk- and egg-allergic eczema patients and non-eczematous controls. The study provides clear evidence showing that the detection of milk- and egg-specific IgG4 in atopic eczema patients has no clinical value.

Adolescent↗

Effects of priming flash parameters and dark interval on red-induced afterpotential in Balanus photoreceptors.

The sequence (a) priming flash, (b) dark interval, and (c) red light induces a long-lasting afterdepolarization (PDA) in Balanus photoreceptors. The inward flow of membrane current associated with the decay of PDA was independent of red test flashes, provided that PDA had plateaued at a particular intensity. The influence of wavelength and duration of the priming flash and their interaction with the dark interval were investigated. Increasing the duration of the priming flash produced a systematic increase in PDA duration. The dark interval plays a crucial role in PDA induction. The priming flash duration and the dark interval were reciprocally related, i.e, short flashes followed by long dark intervals induced as much PDA as long priming flashes followed by short dark intervals. The action spectrum for the priming flash was found to correspond to that of the primary photopigment (VP537).

Animals↗

Isolation of a stable enzyme.14CO2.Mg2+.carboxyarabinitol bisphosphate complex with ribulosebisphosphate carboxylase from Chromatium vinosum.

Higher plant-type ribulosebisphoshate carboxylase from Chromatium vinosum formed a stable, nonexchangeable complex with activator 14CO2 in the presence of Mg2+ and 2-carboxyarabinitol bisphosphate, an analog of the proposed transition-state intermediate. The response of the procaryotic enzyme to this analog was indistinguishable from that of the higher-plant carboxylase, which should permit comparative analysis of the activator site amino acid sequence in the two proteins.

Binding Sites↗

Arsenazo III-Ca2+. Effect of pH, ionic strength, and arsenazo III concentration on equilibrium binding evaluated with Ca2+ ion-sensitive electrodes and absorbance measurements.

Equilibrium binding properties of the metallochromic indicator Arsenazo III (AIII) were characterized by Ca2+ and acid/base titration. Free calcium was measured directly with Ca2+ ion-sensitive electrodes. Absorbance changes were measured by both a conventional scanning spectrophotometer and a dual wavelength spectrophotometer. Acid/base titration of AIII in conjunction with Ca2+ ion-sensitive electrode measurement and absorbance changes indicate that pH can change AIII absorbance through a change of the K(D) for Ca-AIII formation, and, in addition, that there is a pH-specific component that is not dependent on Ca-AIII formation. THe dissociation constant (K(D)) of AIII varied not only with pH, but with ionic strength and AIII concentration. Studies conducted to examine AIII-Ca stoichiometry resulted in different initial conclusions, depending on the method of analysis. Log delta A-log AIII relations were in accord with previously published results, which indicate that more than one AII binds to one Ca2+ ion. But Job plots. Scatchard analysis, and Hill plots all indicated 1:1 binding. THe method of absorbance measurement, i.e., scanning or dual wavelength did not influence the results. these findings were reconciled on the basis of changes in K(D) with AIII concentration and ionic strength. In 200 mM KCl, K(D) of AIII-Ca varies by a factor of 7 between 10(-4.3) and 10(-3) M AIII. Thus, a disproportionately large amount of Ca-AIII is formed as AIII concentration is increased, which results in slopes greater than unity for log delta A-log AIII relations.

Arsenazo III↗

Prick testing for allergens standardized by using a precision needle.

A new standardized precision needle which virtually removes operator variation from skin prick testing with allergens is described. The instrument is simple and robust, and the results of its use are demonstrated. The most important finding was that the use of strong pollen extracts produced very inconsistent and irregular weals, but when suitably diluted, or used on mildly sensitive skins, reproducibility of the response was excellent and it is therefore ideal for titration of skin sensitivity and biological assessment of the potency of allergens. The standard needle was also compared with two other methods of skin prick testing. Results were similar but the standard needle showed the least variation.

Humans↗

A comparative trial of flunisolide and sodium cromoglycate nasal sprays in the treatment of seasonal allergic rhinitis.

A trial of flunisolide nasal spray and sodium cromoglycate nasal spray in the treatment of hay fever was carried out during the summer of 1978. Sixty-seven patients all suffering from grass-pollen hay fever were given either flunisolide or sodium cromoglycate nasal sprays for 7 weeks. Patients were seen at 0, 3 and 7 weeks and they also kept a daily record of symptoms. Overall assessment of symptom control and the patients daily records of sneezing showed flunisolide to be significantly superior to sodium cromoglycate. Patients records of symptoms correlated well with daily pollen counts. Side-effects were similar in both treatment groups and consisted mainly of mild naso-pharyngeal irritations.

Administration, Intranasal↗

Inhibition of ribulose-1,5-bisphosphate carboxylase-oxygenase activities by hydroxylamine.

Hydroxylamine directly and reversibly inhibits both activities of homogeneous ribulose-1,5-bisphosphate carboxylase-oxygenase (3-phospho-D-glycerate carboxy-lyase (dimerizing), EC 4.1.1.39) isolated from diverse sources. NH2OH is an uncompetitive inhibitor of carboxylase activity with respect to ribulose-bisphosph ate. This reagent also reacts non-enzymically with ribulosebisphosphate to deplete this substrate. Contrary to previous reports, these results indicate that hydroxylamine directly and indirectly inhibits both activities of this bifunctional enzyme.

Carboxy-Lyases↗

Indoleacetaldehyde Reductase of Cucumis sativus L: KINETIC PROPERTIES AND ROLE IN AUXIN BIOSYNTHESIS.

Indoleacetaldehyde reductase catalyzes the conversion of indoleacetaldehyde to indole ethanol in extracts of Cucumis sativus L., with reduced pyridine nucleotide required as co-substrate. NADH and NADPH result in markedly different enzyme behavior, as reflected in reaction kinetics and in responses to inhibitors and activators. It is not yet clear whether there are two separate enzymes, one specific for NADH and the other for NADPH, or whether there is a single enzyme differentially influenced by the two co-substrates.In the presence of NADH, the indoleacetaldehyde reductase activity was inhibited by NaCl and displayed hyperbolic kinetics under all conditions tested. However, in the presence of NADPH the enzyme was activated by NaCl at concentrations up to 0.1 molar. Under certain conditions with NADPH as co-substrate, the enzyme showed kinetics sigmoidal with respect to indoleacetaldehyde concentration and was strongly inhibited by high concentrations of NADPH. It is possible that this substrate inhibition of the NADPH-linked indoleacetaldehyde reductase activity by NADPH, as well as the sigmoidicity with respect to indoleacetaldehyde concentration, may function in the regulation of auxin biosynthesis.

Journal Article↗