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Biomedical subjects

R A Hall

Publications and source records attributed to R A Hall.

At least 91 records · Page 5Linked to original sources
PubMed1994

Arboviruses causing human disease in the Australasian zoogeographic region.

Over 65 arboviruses have been reported from countries in the Australasian zoogeographic region, but only a few have been implicated in human disease. These include the flaviviruses Murray Valley encephalitis (MVE), Kunjin (KUN), Kokobera (KOK), and dengue, particularly types 1 and 2; the alphaviruses Ross River (RR), Barmah Forest (BF), and Sindbis (SIN); and the bunyaviruses, Gan Gan and Trubanaman. In this paper recent epidemiological and clinical results pertaining to these viruses are reviewed, with major emphasis on MVE and RR viruses. The extensive early studies of Australian arboviruses have been reviewed by Doherty [49, 50], and their ecology and vectors more recently by Kay and Standfast [87]. In addition, the biology of MVE and KUN [113] and RR [87, 114] viruses have been the subjects of more detailed reviews. The Australasian zoogeographic region is defined as countries east of the Wallace and Weber lines, two hypothetical lines in the Indo-Australian archipelago where the fauna of the Australasian and Oriental regions meet. Seroepidemiological studies of human arboviral infections have suggested that the Japanese encephalitis flavivirus and the chikungunya alphavirus occur only in the Oriental region, whereas the related MVE and RR viruses, respectively, are restricted to the Australasian region [85, 148]. Serological results from Wallacea, the zone between the Wallace and Weber lines, are not so clear-cut [85]. This review is therefore restricted to countries east of Wallacea, specifically New Guinea and Australia.

Animals↗
PubMed1994

AMPA receptor development in rat telencephalon: [3H]AMPA binding and western blot studies.

Telencephalic membranes from rats of different embryonic (E16, E19) and postnatal (P2, P7, P14, adult) ages were assessed for alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H] AMPA) binding and for immunoreactivity levels of AMPA receptor subunits (GluR1, GluR2/3, and GluR4). In addition, the synaptic markers synaptophysin and NCAM140 (a neural cell adhesion molecule isoform) were examined by immunoblot. The density of [3H]AMPA binding sites increased steadily with advancing age. This increase was due mainly to the development of the large low-affinity component (KD = 400 nM) that dominates the [3H]AMPA binding profile of adult rat brain membranes. As resolved by two-site regression analysis, the high-affinity component (KD = 15 nM) of the [3H]AMPA binding increased by approximately twofold from E16 to adult, whereas the low-affinity component increased by 25-fold. Staining for GluR1 and GluR2/3 increased steadily with increasing age at all time points examined; synaptophysin and NCAM140 exhibited similar ontogenic immunostaining profiles. GluR4 immunoreactivity was first evident at P14 and increased by adulthood.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Cyclothiazide decreases [3H]AMPA binding to rat brain membranes: evidence that AMPA receptor desensitization increases agonist affinity.

The effects of cyclothiazide, a drug which blocks AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor desensitization, were tested on binding of [3H]AMPA to rat brain membranes. Cyclothiazide reduced [3H]AMPA binding by lowering the apparent affinity of the AMPA receptor. The magnitude of the decrease was temperature dependent and greater for membrane-bound than for solubilized receptors. These data provide evidence that desensitization increases the affinity of the AMPA receptor for agonists and indicate that a significant percentage of AMPA receptors in conventional equilibrium binding assays are in a desensitized state.

Animals↗
PubMed1993

Single channel recordings of reconstituted AMPA receptors reveal low and high conductance states.

Glutamate receptors belonging to the AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) subclass were partially purified 30- to 60-fold from forebrain of adult rats and incorporated into planar bimolecular lipid membranes. The channel conductance associated with the reconstituted receptors was activated by kainate and AMPA in a manner that suggests cooperative binding of two to three agonist molecules is required to induce channel opening. This conductance was blocked by the specific antagonist DNQX (6,7-dinitroquinoxaline-2,3-dione). When the partially purified AMPA receptors were reconstituted by the tip-dipping method in asymmetric saline conditions ('outside-out configuration'), the addition of 300 nM AMPA to the pseudo-extracellular solution elicited single channel current fluctuations that were also inhibited by DNQX. Analyses of the currents revealed that the ion channels of reconstituted AMPA receptors have two distinct conductance levels of 12 and 60 pS with the great majority of receptors belonging to the former variety. These results suggest that reconstitution may be useful in identifying factors that regulate the binding and conductance properties of AMPA receptors.

Animals↗
PubMed1993

Diuretic and diet effect on Menière's disease evaluated by the 1985 Committee on Hearing and Equilibrium guidelines.

Fifty-four patients, diagnosed with Menière's disease and treated with diuretics and a low-salt diet, were evaluated retrospectively with the 1985 AAO/HNS Committee on Hearing and Equilibrium (CHE) guidelines for vertigo and hearing changes. The patient data base was also evaluated with other methods that helped determine the effectiveness of the 1985 AAO/HNS CHE guidelines. After 24 months of therapy, vertigo control was complete or substantial in 79% of the patients, limited or insignificant in 19%, and worse in 2% as evaluated by the CHE 1985 guidelines. Hearing improved in 35% of the patients, was unchanged in 29%, was worse in 22%, and could not be classified by CHE guidelines in 14%. Hearing was also evaluated by comparison of individual thresholds before medical therapy, and at 22 and 74 months after the start of medical therapy. We found a stabilization of low- and mid-threshold frequencies, with an average rate of hearing loss approximating 0 dB/yr with 74 months of followup. The results of this preliminary study suggest that diuretics and a low-salt diet may decrease the natural progression of sensorineural hearing loss in patients with Menière's disease. Compared with other methods of data analysis, the 1985 CHE guidelines lacked sensitivity to evaluate the hearing changes observed.

Academies and Institutes↗
PubMed1993

Thiocyanate equally increases affinity for two DL-alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) receptor states.

The effects of potassium thiocyanate on the binding of DL-alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and L-glutamate to the AMPA receptor complex were studied in rat brain membranes. Thiocyanate increased the affinity of AMPA receptors for both AMPA and L-glutamate and decreased the affinity for CNQX. Displacement of [3H]CNQX binding by AMPA revealed that the affinity for AMPA of both the high and the low affinity states of the receptor increased in the presence of thiocyanate, whereas the proportion of the two states was unchanged. In soluble fractions, which exhibit an apparently homogeneous population of the high affinity state of the receptor, the affinity for AMPA was increased by a magnitude similar to that seen for the high affinity state in the membranes. These results indicate that thiocyanate enhances AMPA binding not by converting low affinity receptors into the high affinity state but by equally increasing the affinities of the high and the low affinity states of AMPA receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1993

Hepatic adenoma presenting as a right lower quadrant mass.

Most patients with hepatic cell adenomas present dramatically with an acute abdominal crisis associated with hemorrhage and an upper abdominal mass. We present an unusual case of hepatic cell adenoma presenting as a right lower quadrant mass and review the current literature concerning this tumor.

Abdomen, Acute↗
PubMed1992

Mouse telencephalon exhibits an age-related decrease in glutamate (AMPA) receptors but no change in nerve terminal markers.

The central excitatory amino acid receptor selective for alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) was examined in brain tissue from mice at 3 and 25 months after birth. Antibodies against the rat GluR-A glutamate receptor subunit (selective for kainate and AMPA) labeled a mouse brain component of about M(r) 100,000. Telencephalic tissue from the older group of mice exhibited 31% less immunoreactivity towards this component as compared with that from the young group. Binding of [3H]AMPA also decreased with age in the telencephalon to an extent which was similar to the loss of receptor immunoreactivity. Scatchard analysis revealed that this reduction is due to a decrease in receptor density and not to a change in binding affinity. In contrast, there were only small age-related changes in AMPA receptor immunoreactivity and binding levels in the brain stem and cerebellum. Binding to dopamine, serotonin, or GABA receptors was not significantly reduced in the older mice. Since the nerve terminal markers synaptophysin and the SV2 glycoprotein were not detectably different in the two groups of mice, the age-related reduction in AMPA receptors is not likely to be due to a general decrease in synaptic density. These data suggest that glutamatergic neurotransmission mediated by AMPA-type receptors is selectively impaired with aging in the telencephalon.

Aging↗
PubMed1992

Evidence that high- and low-affinity DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) binding sites reflect membrane-dependent states of a single receptor.

Binding of DL-alpha-[3H]amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid ([3H]AMPA) to lysed rat brain membranes in the presence of potassium thiocyanate resulted in curvilinear Scatchard plots that could be resolved by regression analysis into a large low-affinity component and a small high-affinity component. Solubilization with Triton X-100 resulted in solubilized and nonsolubilized fractions that were considerably enriched in the high-affinity component and correspondingly reduced in the low-affinity component. It thus appears that solubilization converts low-affinity AMPA receptors into high-affinity receptors. Also, synaptic plasma membranes were found to be greatly enriched in the low-affinity form and deficient in the high-affinity form of the AMPA receptor. These experiments provide evidence for the hypothesis that the high- and low-affinity components of AMPA binding are interconvertible states of the same receptor rather than separate binding sites and that the conversion of these receptors from their native high-affinity state to the low-affinity state occurs on insertion of the receptors into synapses.

Animals↗
PubMed1992

Functional reconstitution of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors from rat brain.

Glutamate receptors belonging to the subclass specifically activated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) were solubilized from rat forebrain membranes with Triton X-100 and partially purified through a series of three chromatographic steps. Specific [3H]AMPA binding increased 30-60-fold during the isolation procedure. A protein band recognized by antibodies against specific amino acid sequences of the glutamate receptor-A subunit was enriched with each purification step; the molecular mass of this band (105 kDa) corresponded to that of cloned AMPA receptor subunits. Photoaffinity labeling of forebrain membranes with 6-cyano-7-[3H]nitroquinoxaline-2,3-dione, a specific antagonist of the AMPA receptor, labeled a single band that comigrated with the immunolabeled protein. On reconstitution of the partially purified material into bilayer patches, single-channel current fluctuations were elicited by 300 nM AMPA and blocked by 1 microM 6,7-dinitroquinoxaline-2,3-dione.

Animals↗
PubMed1991

Immunoaffinity purification of the NS1 protein of Murray Valley encephalitis virus: selection of the appropriate ligand and optimal conditions for elution.

A novel approach was used to select the most suitable antiviral monoclonal antibody (mAb) and elution conditions for immunoaffinity purification of the NS1 protein of Murray Valley encephalitis virus (MVE). Crude NS1 protein was subjected to a variety of chemical conditions produced by common elution buffers, and tested with a panel of NS1-specific mAbs by ELISA to determine which buffers denatured antigenic epitopes. Buffers that caused least structural damage to NS1 epitopes were tested by ELISA for dissociation of NS1-mAb complexes adsorbed to the solid phase. For each mAb analysed, the conditions required to break the mAb-NS1 complex on the solid phase were similar to those required to release antigen bound to mAb-sepharose beads. From these results we selected an appropriate antibody for affinity purification of the non-structural viral protein NS1 on CNBr-activated sepharose columns. Elution at pH 11.5 yielded good recoveries of highly pure and antigenically intact NS1 dimer. The results demonstrate that the appropriate ligand and optimal elution conditions can be rapidly determined generally by immunoassay in microtitre plates.

Antibodies, Monoclonal↗
PubMed1991

Monoclonal antibodies to Kunjin and Kokobera viruses.

Five monoclonal antibodies (MoAb) were produced to the envelope (E) protein of Kunjin (KUN) virus. Three of these were specific for the KUN/West Nile complex, and two reacted with epitopes that were common to the flavivirus family. These MoAb defined at least four distinct epitopes on the E protein of KUN virus. Eight MoAb were also produced to unidentified proteins of Kokobera (KOK) virus. Seven were specific for KOK, while the remaining antibody cross-reacted with Stratford virus and an unregistered flavivirus CS946. The application of these MoAb to arboviral surveillance is discussed.

Animals↗
PubMed1990

Epitope analysis of the envelope and non-structural glycoproteins of Murray Valley encephalitis virus.

Previous studies have shown that antibodies produced against strategic flavivirus epitopes play an important role in recovery and immunity. Definition of the conformation and location of these epitopes and the degree of their conservation among flaviviruses is important to understanding the humoral response to flavivirus infection. In this study we have examined epitopes recognized by 14 monoclonal antibodies (MAbs) produced to the envelope (E) and non-structural (NS1) proteins of Murray Valley encephalitis virus (MVE). These antibodies were analysed for specificity, neutralization, haemagglutination inhibition (HI) and competitive binding. We have identified six distinct epitopes on the E protein which are located in four non-overlapping domains. MAbs to epitopes in one domain neutralized virus, were specific for MVE and Japanese encephalitis virus, and reacted with epitopes resistant to reduction. Two other E domains, one specific to MVE and the other shared by all flaviviruses, also contained neutralization sites and were stabilized by disulphide bonds. The fourth domain on E was conserved among the flaviviruses, sensitive to SDS denaturation and did not induce neutralizing antibody. Studies with MVE NS1 MAbs revealed that they were mostly type-specific, unreactive with conserved epitopes, and unreactive in HI and neutralization tests. The six epitopes identified on NS1 did not overlap and represent antigenic domains either resistant or sensitive to reduction. Immunoblotting of viral proteins in MVE-infected C6/36 cells revealed two distinct forms of NS1 and high Mr proteins of 97K and 108K that represented disulphide-linked heterodimers of E and NS1.

Animals↗
PubMed1989

Lipoprotein subfraction composition in non-insulin-dependent diabetes treated by diet, sulphonylurea, and insulin.

Lipoprotein abnormalities may predispose to an increased risk of coronary heart disease in type II (non-insulin-dependent) diabetes mellitus. To investigate the effects of different treatment modalities, the composition and concentrations of fasting plasma lipoproteins were determined in a cross-sectional study of patients with type II diabetes at diagnosis, treated by diet alone, treated by diet + glibenclamide (2.5 to 15 mg/d for 6 to 48 months), and treated by diet + insulin (25 to 65 U/d for 8 to 144 months). Compared with normal subjects matched for sex, age, body mass index, exercise, alcohol consumption and smoking, type II patients at diagnosis showed increased concentrations of nonesterified and esterified cholesterol, triglyceride, phospholipid, and protein in the very low density lipoprotein (VLDL) fraction. However, the only alteration in VLDL composition was a small decrease in the relative proportion of phospholipid. Apolipoprotein-B and low density lipoprotein (LDL) cholesterol concentrations were also raised in type II patients at diagnosis. Plasma concentrations of high density lipoprotein (HDL) nonesterified and esterified cholesterol, phospholipid, and apo-AI were lower in type II patients at diagnosis. This was largely accounted for by reduced concentrations of these components in the HDL2 subfraction, which retained a normal composition. Type II patients treated by diet alone and diet + glibenclamide exhibited similar abnormalities of plasma lipoprotein concentrations, which are associated with premature coronary disease, to the type II patients at diagnosis. However, in type II patients treated with insulin, plasma lipoprotein concentrations and composition were normal, except LDL cholesterol, which was lower than normal in insulin-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins B↗
PubMed1989

Preoperative crossmatch guidelines for total hip arthroplasty.

The use of crossmatch guidelines has become commonplace as a means of guiding surgeons to efficient preoperative blood ordering. To further refine existing guidelines for a major elective procedure, a number of specific characteristics of 175 patients who underwent 189 total hip arthroplasties were correlated with blood use by univariate and multivariate analyses. The findings of this study demonstrate that for patients with no detectable red cell alloantibody, four units of blood should be crossmatched and reserved preoperatively if the patient is undergoing exchange arthroplasty, or undergoing a transtrochanteric procedure. All other patients with no detectable red cell alloantibody should have two units of blood reserved preoperatively. Proper preoperative crossmatch ordering can result in more labor-efficient and thrifty use of transfusion services, as well as increased effectiveness of autologous predeposit programs.

Analysis of Variance↗
PubMed1989

Apolipoprotein assays: methodological considerations and studies in non-insulin-dependent diabetes treated by diet, glibenclamide and insulin.

The effect of sample pre-treatment as a source of variability of apolipoprotein (apo) AI, AII and B assays was demonstrated with lipid dissociating agents. The average mean percentage change ranged from -58 to +133% compared with untreated samples. The apolipoprotein method selected was validated by comparing their concentrations with their corresponding lipoprotein lipid or protein in normal controls and Type 2 (non-insulin-dependent) diabetic patients. The coefficient of variation was maintained below 3.5% for apo AI, AII, B and HDL2-apo AI. The apolipoprotein concentrations of fasting plasma lipoproteins were determined in a cross-sectional study of non-obese (body-mass index less than or equal to 30) patients with Type 2 diabetes mellitus. Compared with normal subjects matched for sex, age, body-mass index, exercise, alcohol consumption and smoking. Type 2 patients at diagnosis showed reduced apo AI and HDL2-apo AI concentrations, lowered apo AI:B ratio and increased concentrations of apo B. Type 2 patients treated by diet alone (for 6-72 months) and diet plus glibenclamide (2.5-15 mg/day for 6-48 months) exhibited similar abnormalities of plasma apolipoprotein concentration to Type 2 patients at diagnosis. However, in Type 2 patients treated with insulin (25-65 U/day for 8-144 months) concentrations of apo AI and HDL2-apo AI, and the apo AI:B ratio were normal. Apo B concentrations were generally lower compared with all groups of non-insulin treated patients. These abnormalities of apolipoprotein metabolism, which are associated with premature coronary disease, are still evident in patients treated by diet and diet plus glibenclamide, but are not seen in Type 2 patients treated with insulin.

Adult↗
PubMed1989

Lipoprotein subfraction composition in non-obese newly diagnosed non-insulin dependent diabetes after treatment with diet and glibenclamide.

The composition and concentrations of fasting plasma lipoproteins were determined in a prospective study of 11 +/- 2 (mean +/- 1 SD) months in 16 non-obese (body mass index less than or equal to 30) patients with Type 2 (non-insulin dependent) diabetes mellitus at diagnosis, treated by diet alone or diet plus glibenclamide (2.5-7.5 mg/day). Compared with normal subjects matched for sex, age, body mass index, exercise, alcohol consumption and smoking, Type 2 patients at diagnosis showed increased concentrations of non-esterified and esterified cholesterol, triglyceride, phospholipid and protein in the very low density lipoprotein (VLDL) fraction. The apolipoprotein (apo) B concentrations was also raised, but low density lipoprotein (LDL) cholesterol concentrations were not significantly altered in Type 2 patients at diagnosis. Plasma concentrations of high density lipoprotein (HDL) non-esterified and esterified cholesterol, HDL phospholipid and apo AI were lower in Type 2 patients at diagnosis. This was largely accounted for by a reduced number of HDL2 molecules of normal composition. After treatment of Type 2 patients with diet alone, there was a marginal increase in plasma HDL cholesterol and phospholipid, and in plasma HDL2 cholesterol, phospholipid, protein and apo AI concentrations, in association with reductions of VLDL component concentrations, body mass index and glycaemia. Type 2 patients treated with diet plus glibenclamide exhibited similar abnormalities of plasma lipoprotein concentrations before and after treatment, except for a small reduction in VLDL component concentrations and a slight increase in the apo AI:B ratio. Institution of diet alone and diet plus glibenclamide generally failed to restore VLDL, HDL and HDL2 component concentrations and the apo AI:B ratio to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗