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Biomedical subjects

M Browning

Publications and source records attributed to M Browning.

At least 37 records · Page 2Linked to original sources
PubMed1994

Immunoscintigraphy of primary colorectal cancers with indium-111 monoclonal antibody B72.3.

Immunoscintigraphy with CYT-103, an 111indium-labelled immunoconjugate of B72.3, was evaluated in 10 patients before surgery for suspected or biopsy-proven primary colorectal cancer. The imaging results were compared with computed tomography (CT) findings at surgery, histopathology and immunohistochemistry. There were no adverse reactions following the administration of 1.0 mg 111In-CYT-103. Surgical and pathological findings identified 15 sites of disease (10 primary and five metastatic) and all but one lesion (severe dysplasia) were malignant. CT detected nine of 14 sites of malignancy compared to 12 as identified by immunoscintigraphy. It failed to detect two primary lesions and one case of peritoneal metastasis, all of which were imaged by CYT-103. Both imaging modalities failed to detect two of three cases with lymph node metastases and the dysplastic lesion (true negatives). The results indicate that 111In-CYT-103 imaging exhibits high sensitivity and specificity in the detection of primary and secondary lesions in patients with colorectal cancer.

Adenocarcinoma↗
PubMed1994

Fatal encephalitis caused by Ochroconis gallopavum in a domestic cat (Felis domesticus).

Ochroconis gallopavum was identified as the causal agent of fatal encephalitis in a young, short-hair, domestic cat. The cat initially developed an ulcerated mass on the left side of the tongue and signs of pain in the abdomen. The tongue lesion was surgically removed and exploratory abdominal surgery revealed abnormalities suggestive of pancreatitis and peritonitis. During the month after surgery, the cat's health declined, manifested by sluggishness, loss of appetite and abnormal behaviour. Following a final rapid deterioration, the cat became non-responsive and was euthanized. Histologic examination of the brain, lung and mediastinal lymph node lesions revealed large numbers of pigmented, septate, branched, hyphal elements with swollen intercalary and terminal vesicles, and short chains of moniliform hyphal cells. Cultures of the mediastinal lymph nodes yielded a dematiaceous, thermotolerant fungus that was identified as O. gallopavum. This report describes the first well-documented infection in a cat caused by O. gallopavum.

Animals↗
PubMed1993

Cocaine inhibits hippocampal long-term potentiation.

Long-term potentiation (LTP) is a form of synaptic plasticity that may underlie learning and memory. The experiments reported here demonstrate that cocaine blocks the induction of LTP at the excitatory synapses in the CA1 region of the hippocampus, but does not appear to do so by blocking NMDA receptors or channels. Once LTP had been established, however, cocaine had no effect on the potentiated response. Cocaine was also able to block LTP initiated by superfusing slices with 25 mM TEA. The ability to block LTP was shared by the local anesthetics lidocaine and procaine, but not by tetrodotoxin, suggesting that the blockade of sodium channels alone did not disrupt LTP. Biochemical experiments demonstrated that cocaine can inhibit phosphorylation of purified Synapsin I by Ca2+/calmodulin-dependent protein kinase II. This effect, presumably mediated by effects on calmodulin, is a previously unreported action of cocaine, and suggests that cocaine at high dose levels might disrupt types of learning that are mediated by an LTP-like mechanism.

Animals↗
PubMed1992

Development of synapsin I and synapsin II in intraocular hippocampal transplants.

Previous studies have indicated that the appearance of synaptic vesicle-associated proteins known as the synapsins is one indicator of synapse formation. In this study, the levels and morphological distribution of synapsin I and synapsin IIa and IIb were studied in intraocular hippocampal transplants and in situ in the intact hippocampus. No detectable levels of either synapsin I or synapsin II were found in the fetal brain. The in situ levels of the synapsins exhibited parallel increases rapidly after birth, reaching peak levels at 8 weeks, after which a slight decline was noted in synapsin I and synapsin IIb. In hippocampal transplants, a comparable increase in the synapsins was seen during the first 8 weeks in oculo. It is likely that the synapse formation in the hippocampal transplants represents synapses from neurons within the transplant, as well as from various peripheral ganglia that send collaterals into the graft. Peripheral and central synapses express different synapsin I: synapsin IIa and IIb ratios. When the ratios of the synapsin proteins in hippocampal transplants were examined ratios essentially identical to those seen in the normal hippocampus were found, despite the numerous peripheral neurites innervating the grafts. Immunohistochemical studies supported the immunoblot data, showing no detectable immunofluorescence with synapsin antibodies in fetal or newborn hippocampal formation. The density of immunoreactive profiles increased substantially both in transplants and in the hippocampal formation in situ during the first 2 postnatal months. In conclusion, the present data demonstrate that hippocampal transplants in oculo can develop significant levels of the synapsins and that there is no time lag in development in these levels compared to the hippocampal formation in situ.

Animals↗
PubMed1992

A sensitive assay for detection and measurement of neutralising antibody to human immunodeficiency virus.

An assay based on the inhibition of syncytium formation in C8166 cells was developed to measure low levels of neutralising antibody (NT-AB) to human immunodeficiency virus (HIV) and to detect cross-reactivity between virus strains. The relationship between virus challenge and antibody titre was represented by a tripartite curve which was essentially linear over moderate levels of virus input. Based on these findings, antibody titres were standardised against 100 TCID50 of challenge virus. However, lower virus inocula were found to detect minimum levels of antibody. Reproducibility of antibody titres between tests was high, with variation generally lying within one dilution step. The improved sensitivity of the technique allowed detection of NT-ABs in animals immunised with immune-stimulating complexes (ISCOMS) incorporating HIV antigens. Consistent levels of cross-reactivity between HIV strains was demonstrated, indicating the presence of distinct viral groups, from which dominant isolates may be chosen for use in vaccination studies.

Animals↗
PubMed1992

Incorporation of soluble antigens into ISCOMs: HIV gp120 ISCOMs induce virus neutralizing antibodies.

Through a process of covalent attachment of palmitic acid, we have incorporated recombinant gp120 of HIV strain IIIB into ISCOMs. Rabbits immunized with ISCOMs incorporating 10 micrograms gp120 produced high levels of gp120-specific antibody, comparable to the response to ten times as much antigen in complete Freund's adjuvant. The ISCOM-induced antisera showed virus neutralizing activity against the homologous strain, but failed to neutralize two heterologous strains of HIV-1. The antisera recognized non-conformationally determined epitopes on gp120, and antibody binding to gp120 was affected by glycosylation of the viral glycoprotein.

AIDS Vaccines↗
PubMed1992

Early state organization and follow-up over one year.

Evaluations of state organization at 36 weeks postconceptional age (PCA) were conducted in the special care nursery on 24 low birth weight preterm neonates who were subsequently assessed on three dimensions of outcome at 1 year postterm. Half the subjects (N = 12) had been cared for in an alternative supportive nursery from 32 to 36 weeks PCA; the other half had remained in the regular intermediate care nursery. Although subjects from the alternative nursery demonstrated superior state organization before nursery discharge at 36 weeks PCA (p less than .05), they were not superior on any outcome measures at 1 year postterm. Subjects demonstrating superior state organization within their nursery group were compared with subjects demonstrating inferior state organization within their nursery group. Significant differences in 1-year outcome were found between these two groups of good and poor neonatal state organizers on gross morbidity, on the Bayley motor scale, and on a measure of recovery of state organization observed in the Strange Situation (p less than .05).

Adaptation, Psychological↗
PubMed1991

Perivalvular pseudoaneurysm complicating bacterial endocarditis: MR detection in five cases.

Bacterial endocarditis usually affects the valve leaflets, but erosion into the valve anulus and adjacent myocardium may form a myocardial abscess. Perivalvular abscesses can drain into the ventricles or aorta, forming a life-threatening pseudoaneurysm. We reviewed our experience with cardiac MR imaging of this disorder. Fourteen patients with complicated bacterial endocarditis underwent ECG-gated spin-echo cardiac MR imaging in addition to conventional duplex two-dimensional echocardiography (2-D echo). Angiography was performed in seven patients, six of whom underwent surgery for valve replacement. MR imaging detected the pseudoaneurysms in all five of the surgically proved cases, while 2-D echo detected only three. Clinical follow-up suggested there were no false-negative examinations, but no autopsy data were available for confirmation. Postoperative MR imaging studies were conducted in three patients, revealing two recurrent pseudoaneurysms and one thrombosed aneurysm. Cardiac MR imaging provides useful pre- and postoperative information in patients with perivalvular pseudoaneurysms due to endocarditis.

Aneurysm, Infected↗
PubMed1991

A new Pick based computer thyroid register based on the national SAFUR requirements for local usage.

Patients with thyroid disease require lifelong surveillance to detect late onset hypothyroidism and to monitor thyroid replacement therapy. This is best achieved by a shared-care computer system. We describe the introduction to Tayside (Ninewells Hospital) of a new computerised thyroid follow-up programme based on the Patient Record System under a Pick operating system, run on a Honeywell-Bull minicomputer. This new programme has allowed the transfer of patients from the previous Aberdeen based SAFUR centralised service to a locally based unit, offering an improved, updated and cost effective method for thyroid disease surveillance. Audit, clinical and financial, may now be more efficiently achieved, allowing local needs to direct the service provision.

Continuity of Patient Care↗
PubMed1990

The soluble viral glycoprotein of vesicular stomatitis virus efficiently sensitizes target cells for lysis by CD4+ T lymphocytes.

The soluble glycoprotein Gs of vesicular stomatitis virus (VSV), at approximately 10(4) molecules per cell, sensitized target cells for lysis by clones of CD4+ cytolytic T lymphocytes (CTL). In addition to lysis, the clones responded by proliferation and interleukin-2 release. Targets sensitized by Gs competed effectively with VSV-infected cells for recognition. Immune cytolysis by these CD4+ CTLs was restricted by class II major histocompatibility complex (MHC) antigens and was specific to VSV. The specific class II MHC antigen which was restricting for each clone remained the same whether the targets were sensitized by infection with VSV or by exogenously added soluble antigen. Sensitization by Gs appeared to require prior processing because the antigen-presenting cells that were fixed prior to exposure to Gs failed to be recognized by the CTL clones. The high efficiency of this uptake and processing was suggested by the inability of Gs at concentrations up to 10(7) per cell to block superinfection by VSV or to effect the RNA-synthetic machinery of uninfected cells. Also, Gs failed to hemolyze sheep erythrocytes when there was hemolysis by virions or an amino-terminal peptide of the VSV glycoprotein. Extrapolation of these results to viral diseases was possible because soluble viral glycoproteins were naturally synthesized during many viral infections and class II MHC antigens were inducible in cells of nonlymphoid origin. Therefore, CD4+ CTLs may be important participants in increasing virus-induced pathology, especially among adjacent uninfected cells.

Animals↗
PubMed1989

Microvesicles of the neurohypophysis are biochemically related to small synaptic vesicles of presynaptic nerve terminals.

Nerve endings of the posterior pituitary are densely populated by dense-core neurosecretory granules which are the storage sites for peptide neurohormones. In addition, they contain numerous clear microvesicles which are the same size as small synaptic vesicles of typical presynaptic nerve terminals. Several of the major proteins of small synaptic vesicles of presynaptic nerve terminals are present at high concentration in the posterior pituitary. We have now investigated the subcellular localization of such proteins. By immunogold electron microscopy carried out on bovine neurohypophysis we have found that three of these proteins, synapsin I, Protein III, and synaptophysin (protein p38) were concentrated on microvesicles but were not detectable in the membranes of neurosecretory granules. In addition, we have studied the distribution of the same proteins and of the synaptic vesicle protein p65 in subcellular fractions of bovine posterior pituitaries obtained by sucrose density centrifugation. We have found that the intrinsic membrane proteins synaptophysin and p65 had an identical distribution and were restricted to low density fractions of the gradient which contained numerous clear microvesicles with a size range the same as that of small synaptic vesicles. The peripheral membrane proteins synapsin I and Protein III exhibited a broader distribution extending into the denser part of the gradient. However, the amount of these proteins clearly declined in the fractions preceding the peak of neurosecretory granules. Our results suggest that microvesicles of the neurohypophysis are biochemically related to small synaptic vesicles of all other nerve terminals and argue against the hypothesis that such vesicles represent an endocytic byproduct of exocytosis of neurosecretory granules.

Animals↗
PubMed1985

Acid-base changes and ventilator mode during maintenance ventilation.

Assist-control ventilation was compared to intermittent mandatory ventilation (IMV) for respiratory support of 35 patients without known respiratory disease, who had undergone coronary bypass surgery. Spontaneous respiratory rates and minute ventilation did not differ significantly between the two groups. Blood gas samples obtained during the assist-control mode had a significantly lower PaCO2 and higher pH than blood gases measured during high-rate IMV. There were six cases of severe alkalemia during assist-control ventilation, all respiratory in origin. These were attributable to the higher respiratory-rate settings and the extra respirator-delivered tidal volumes when spontaneous rates were higher than the set rates. IMV was associated with fewer ventilator-induced acid-base changes.

Acidosis, Respiratory↗
PubMed1983

Renal involvement in systemic amyloidosis.

In a study of 124 patients with systemic amyloidosis, renal involvement was the major presenting feature in 68 per cent of patients with AA and 42 per cent with AL disease. Renal failure contributed to the deaths of 72 per cent and 33 per cent of patients respectively. In 23 renal biopsies from patients with AA disease, quantitative glomerular amyloid infiltration correlated with urinary protein excretion and with serum creatinine. Seven of these patients had repeat biopsies; change in glomerular amyloid correlated with changes in both renal function and proteinuria. Four patients with end-stage renal amyloidosis have been successfully managed on CAPD for 37 patient months.

Adolescent↗
PubMed1981

Evidence that the 40,000 Mr phosphoprotein influenced by high frequency synaptic stimulation is the alpha subunit of pyruvate dehydrogenase.

We have previously shown that brief periods of high frequency synaptic stimulation of the rat hippocampus influence the endogenous phosphorylation of a 40,000 Mr brain protein (Browning et al.). The results of the present study demonstrate that this brain phosphoprotein is enriched in a purified mitochondrial fraction and co-migrates with the alpha-subunit of pyruvate dehydrogenase in sodium dodecyl sulfate polyacrylamide gels. Comparisons of total and partial proteolytic fingerprints indicate that the two proteins are essentially identical. In addition, the phosphorylation of the 40,000 Mr brain protein is sensitive to both dichloroacetate and magnesium as has been reported for pyruvate dehydrogenase. Taken together these data provide persuasive evidence that the brain protein is the alpha-subunit of pyruvate dehydrogenase and thereby raise the possibility that even very short periods of synaptic activity influence an enzyme of particular importance to mitochondrial metabolism in brain.

Animals↗
PubMed1981

Phosphorylation-mediated changes in pyruvate dehydrogenase activity influence pyruvate-supported calcium accumulation by brain mitochondria.

Changes in the activity of pyruvate dehydrogenase [pyruvate:lipoamide oxidoreductase (decarboxylating and acceptor-acetylating), EC 1.2.4.1, PDH], elicited by inhibition of the phosphorylation of its 40,000 Mr alpha-subunit, were compared with changes in pyruvate-supported calcium accumulation by rat brain mitochondria. Dichloroacetate (DCA) produces concentration-dependent inhibition of the phosphorylation of intramitochondrial PDH alpha-subunit, which is accompanied by stimulation of PDH activity and calcium accumulation. DCA did not affect succinate- or ATP-supported mitochondrial calcium accumulation. The concentration of DCA giving half-maximal inhibition of the phosphorylation was almost identical to that giving half-maximal stimulation of PDH activity and calcium accumulation. PDH activity and pyruvate-supported calcium accumulation showed similar dependence on pyruvate concentration with respective apparent affinities for pyruvate of 40 microM and 30 microM, and both activities exhibited positive cooperativity. DCA modified only the maximal activity of PDH or the maximal calcium DCA modified only the maximal activity of PDH or the maximal calcium accumulation without changing either the apparent affinities for pyruvate or calcium or the Hill coefficients. These data provide evidence that calcium accumulation by mitochondria is tightly linked to PDH activity and that changes in the phosphorylation of the PDH alpha-subunit can be reflected in changes in the calcium-buffering ability of mitochondria. This suggests a possible mechanism by which a variety of manipulations, such as repetitive synaptic stimulation, can alter the regulation of internal calcium levels.

Adenosine Triphosphate↗