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Biomedical subjects

M Edwards

Publications and source records attributed to M Edwards.

At least 73 records · Page 4Linked to original sources

Antigenic analysis of gonococcal pili using monoclonal antibodies.

A bank of mouse monoclonal antibodies has been produced with reactivity to gonococcal pili to investigate epitopes of the pilus structural protein, pilin. Pili of Neisseria gonorrhoeae strains R10 and MS11 were used as immunogens to elicit 19 monoclonal antibodies reactive with the homologous pili type in ELISA. Of the 19 antibodies, 16 demonstrated type-specific reactivity and 3 were cross-reactive with heterologous pili. Reactivity of the antibodies with the carboxyterminal, cyanogen bromide fragment (CB-3) of R10 pilin allowed their classification into three groups. The first group (10 antibodies) were R10 specific and equally reactive with the R10 CB-3 fragment. The second group (6) were also type specific but demonstrated poor reactivity with the CB-3 fragment. This suggested that the epitopes of the first group are linear, and those of the second group, nonlinear. The third group (3), consisting of the cross-reactive antibodies, were not reactive with the CB-3 fragment. Two of the antibodies in group 3 were examined in detail to localize their epitopes. The epitope of one, 9B9/H5, was shown to be a linear determinant. This antibody was reactive with a fragment of MS11 pilin (residues 31-111) and to a synthetic peptide representing residues 69-84 in MS11 pilin. The epitope was more finely mapped, with shorter synthetic peptides conjugated to bovine serum albumin, to an eight amino acid segment (residues 69-76). The epitope of 1E8/G8, a strongly reactive antibody, proved elusive to this type of analysis and probably results from conformational restraints. The significance of species-specific epitopes in the pilin protein is discussed.

Amino Acid Sequence

Does trypsin extract soluble antigen meet the criteria of immunogenicity without allergenicity?

We were unable to confirm the finding of Crowle that TESA possesses the attribute of immunogenicity and absence of allergenicity which are desired in a non-living antituberculosis vaccine. This disagreement could be a function of the particular lot of TESA examined and/or differences in the animal test systems used for the assay of protective potency. The relative contribution of these two possibilities could be determined by the simultaneous assay of a potent TESA product in different laboratories using different animal models.

Animals

Architectonic and hodological organization of the cerebellum in reeler mutant mice.

The architectonic and hodologic organization of the reeler cerebellum has been studied by means of immunohistochemistry, general cell and fiber stains and by horseradish peroxidase and autoradiographic tracing methods. Malposition of Purkinje cells, which varies in degree, is the most salient architectonic anomaly of the mutant cerebellum. Mapping the distribution of Purkinje cells is facilitated by a monoclonal antibody which selectively stains neurons of this class in the cerebellum. Although some Purkinje cells form a normal monolayer, most lie in heterotopic positions within or below the granule cell layer. The major contingent is segregated in subcortical masses in the depths of the cerebellum. Fiber bundles continuous with the cerebellar peduncles run in septa between the subcortical Purkinje cell masses. The distribution of Purkinje cell masses as well as the roof nuclei and areas of normal cortex and fiber bundles are identical from animal to animal. These consistent architectonic variations serve to partition the reeler cerebellum into 7 sagittally oriented compartments: one medial, two intermediate, two lateral and two additional lateral lobular appendages which may correspond to paraflocculus and/or flocculus of the normal cerebellum. The topography of the reeler olivocerebellar, or climbing fiber, system is normal in that the caudal-to-rostral axis of the olivary complex maps onto the medial-to-lateral axis of the contralateral hemicerebellum. The climbing fiber projection in reeler, like that of the normal animal, appears to be organized in parasagittal strips. In the mutant, mossy fibers from the pons and spinal cord project respectively to the lateral and medial cerebellar fields, and overlap in the intermediate compartment. They thus invest different and to a large extent complementary cerebellar territories, which approximate the architectonic divisions. This segregation of the two principal mossy fiber systems is not so marked in the normal cerebellum. In terms of laminar distribution, the pontine projection is distributed principally to the granule cell stratum in the mutant. The reeler spinocerebellar afferents, by contrast, project not only to the granule cell layer but also to the heterotopic Purkinje cells. The present observations suggest that the primary defect in the reeler cerebellum is malposition of Purkinje cells. As appears to be the case during development of the forebrain in reeler, the mutation may affect the terminal phase of migration of Purkinje cells in the cerebellum.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Binding of [3H]forskolin to rat brain membranes.

[12-3H]Forskolin (27 Ci/mmol) has been used to study binding sites in rat brain tissue by using both centrifugation and filtration assays. The binding isotherm measured in the presence of 5 mM MgCl2 by using the centrifugation assay is described best by a two-site model: Kd1 = 15 nM, Bmax1 (maximal binding) = 270 fmol/mg of protein; Kd2 = 1.1 microM; Bmax2 = 4.2 pmol/mg of protein. Only the high-affinity binding sites are detected when the binding is determined by using a filtration assay; Kd = 26 nM, Bmax = 400 fmol/mg of protein. Analogs of forskolin that do not activate adenylate cyclase (EC 4.6.1.1) do not compete effectively for [3H]forskolin binding sites. Analogs of forskolin that are less potent than forskolin in activating adenylate cyclase are also less potent in competing for forskolin binding sites. The presence of 5 mM MgCl2 or MnCl2 was found to enhance binding. In the presence of 1 mM EDTA the amount of high-affinity binding is reduced to 110 fmol/mg of protein with no change in Kd. There is no effect of CaCl2 (20 mM) or NaCl (100 mM) on the binding. No high-affinity binding can be detected in membranes from ram sperm, which contains an adenylate cyclase that is not activated by forskolin. It is proposed that the high-affinity binding sites for forskolin are associated with the activated complex of catalytic subunit and stimulatory guanine nucleotide binding protein.

Adenylyl Cyclases

The Indochinese refugee: an overview.

A review of some of the sociocultural features of Australia's recently arrived 51,000 Indochinese refugees is given. The severe disintegration of Vietnamese society by two decades of warfare would suggest the likelihood of significant psychopathology. This is supported by clinical surveys. The psychological responses to migration and resettlement, including persisting feelings of guilt, bewilderment and pining, are reviewed, with subsequent difficulties in marriage, family, employment and education. Research indicates high continuing levels of psychiatric dysfunction especially among refugees lacking social support or experiencing status dislocation. Suggestions are made for culturally acceptable forms of assessment and therapy.

Adolescent

Speech disability in children: some general considerations.

Difficulties of definition are discussed with reference to overlap between phonological and phonetic disorders. Aspects of delayed speech are described and a brief account is given of deviant speech. Current patterns of management are considered.

Child

Multiple fusiform intracranial aneurysms following curative radiation therapy for suprasellar germinoma. Case report.

A 17-year-old girl died from the rupture of a large fusiform aneurysm of the terminal internal carotid artery. Autopsy revealed three other fusiform aneurysms originating from major cerebral arteries clearly within the ports of previously administered telecobalt radiation therapy. Five years prior to her death, a suprasellar germinoma was partially removed and the area was treated by radiation therapy via three ports. The original arteriograms showed a normal vascular tree. Repeat arteriograms, 3 years and 8 months before her death, demonstrated the aneurysms. The development of aneurysms following radiation damage of the arteries has been reported previously, but not in intracranial vessels.

Adolescent

A comparison of T4 and T7 dermatomal levels of analgesia for caesarean section using the lumbar epidural technique.

We compared analgesia to the T4 dermatomal level with analgesia to the T7 level with and without prophylactic intramuscular administration of ephedrine 25 mg to determine the adequacy and side effects of such analgesia for caesarean section. Unmedicated patients were prehydrated (727 +/- 303 ml of saline solution) and kept in a left lateral tilt position. Sufficient three per cent chloroprocaine was given to obtain analgesia to the T7 (T6-T8) dermatomal level (455 +/- 128 mg) or to the T4 (T3-T5) dermatomal level (758 +/- 168 mg). Patients who received analgesia to the higher level required less narcotic than those who received analgesia to the lower level (21 per cent versus 48 per cent) (p less than 0.05). The incidence of hypotension in patients with analgesia at the T4 level was 21 per cent for those receiving ephedrine and 64 per cent for those who did not receive ephedrine (p less than 0.05). Intramuscular administration of ephedrine 25 mg was not associated with increased plasma levels of norepinephrine, epinephrine or dopamine. There was no difference in Apgar score, behavioural test scores, neonatal acid-base status or oxygenation in children of mothers in the different groups. We conclude that a T4 dermatomal level of analgesia combined with intramuscular administration of ephedrine 25 mg, provides more maternal comfort than a T7 level of analgesia does, with or without ephedrine, and is without significant maternal or foetal side effects.

Acid-Base Equilibrium