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M C Brown

Publications and source records attributed to M C Brown.

At least 127 records · Page 7Linked to original sources
PubMed1990

Elevated soluble CD8 in the synovial fluid from patients with rheumatoid arthritis.

Suppressor/cytotoxic T cells express the surface marker CD8, which can be measured in a soluble form in culture supernatants of activated human lymphocytes. Using a sandwich immunoassay, we assessed the levels of soluble CD8 (sCD8) in serum from patients with rheumatoid arthritis (RA; n = 82), patients with degenerative joint disease (DJD; n = 40), and healthy controls. There were no differences in serum sCD8 levels among these groups. In contrast, the levels of soluble CD8 in the synovial fluid (SF) from patients with RA (n = 53) were significantly increased compared with the levels in 23 samples from patients with DJD (821 +/- 110 U/ml versus 213 +/- 13 U/ml, p less than 0.001). Synovial fluid sCD8 levels in the RA group were strikingly elevated, to a maximum value of 5,026 U/ml. In the majority of RA SF specimens (39 of 53), the values were significantly higher in the SF than the serum. Although the RA group had higher values of sCD8, such values were not significantly correlated with measured laboratory or clinical parameters. Current clinical and laboratory methods of evaluating patients may not be adequate in dealing with the complexity and heterogeneity of RA. Soluble CD8 values may be useful in further grouping patients with this disease.

Antibodies, Monoclonal↗
PubMed1990

Effect of neonatal undernutrition upon cerebroside sulfate degradation in the developing rat brain.

In order to find out if the decreased accumulation of cerebroside sulfates observed in 21-d-old undernourished rats was in part the result of an increased rate of catabolism of these galactolipids, the in vivo degradation of brain cerebroside sulfates was studied in 18-d-old normal and undernourished rats. Two hours after the intracranial injection of the precursor (0 time), the animals were injected intraperitoneally with unlabeled sodium sulfate. Labeled cerebroside sulfates were measured in the brain up to 48 h after the chase. In normal animals, the radioactivity decreased at 24 h and 48 h to 55% and 41%, respectively, of the value obtained at 0 time. In undernourished animals, degradation was negligible, since the radioactivity attained at 0 time remained almost constant up to 48 h. The lack of in vivo degradation of cerebroside sulfates observed in the starved rats cannot be explained by a deficiency of Arylsulfatase A, since the pattern of activity of the enzyme was similar in both groups of animals.

Aging↗
PubMed1990

An antibody to neural cell adhesion molecule impairs motor nerve terminal sprouting in a mouse muscle locally paralysed with botulinum toxin.

We have investigated the possible role of neural cell adhesion molecule, in promoting motor nerve terminal sprouting in the paralysed mouse gluteus maximus muscle, using a rabbit polyclonal antiserum to mouse brain neural cell adhesion molecule (donated by Dr C. Goridis). This antiserum recognizes neural cell adhesion molecule in the basal lamina and extracellular matrix of denervated mouse muscles (1988, Booth C. M. and Brown M. C., Neuroscience 27, 699-709). As a single dose of antibody injected in vivo over the surface of denervated gluteal muscles bound for 12-48 h to over 80% of fibres expressing neural cell-adhesion molecule, once daily injections were used to see if there was any action on terminal sprouting. Injections of antibody were made for four days, starting three days after muscles were paralysed with botulinum toxin. To avoid non-specific complement-mediated attack on neural cell adhesion molecule bearing motor nerve terminals, mice of the DBA/2 strain were used as these lack complement component C5. They were further complement depleted by daily intraperitoneal injections of colloidal inulin. The percentage of end plates bearing terminal sprouts (visualized in whole mounts of the gluteus maximus with zinc iodide-osmium staining) was reduced from a mean of 60.5% +/- 3.2 (n = 11) for mice treated with botulinum toxin alone and 61.5% +/- 1.2 (n = 8) for those treated with non-immune serum, to 37.3% +/- 3.6 (n = 8) in the anti-neural cell adhesion molecule injected series.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The pattern of axonal degeneration in the peripheral nervous system varies with different types of lesion.

Degeneration of axons in the mouse sciatic nerve was examined using conventional silver staining and by noting the presence or absence of a compound action potential on stimulating the nerve distal to the point of crush or cut. The presence of myeloperoxidase-positive cells was also examined in frozen sections of the nerve. In all experiments the distal, disconnected segment was studied. Degeneration after crushing with fine watchmakers forceps always began in the most distal part of the nerve and proceeded in a distoproximal direction, from the nerve entry point into a muscle back to the crush site. Myeloperoxidase-positive cells were also recruited into the nerve starting at the distal rather than proximal (the originally injured) end. This result favours the view that degeneration is triggered by lack of trophic support from the cell body rather than entry of deleterious substances at the site of the injury, for the terminals furthest from both the source of supply and the injury are affected first. Degeneration following nerve section was always more rapid than after crushing. The rate of axonal sealing at the injury was, however, no slower than after crushing, so it does not seem likely that greater entry of possible degeneration-triggering material at the injury site is the explanation for this. Crush lesions in which the perineurium was also cut open and the blood supply at the site was damaged, degenerated at the slower rate characteristic of simple crushes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Projections of thin (type-II) and thick (type-I) auditory-nerve fibers into the cochlear nucleus of the mouse.

Injections of horseradish peroxidase into the mouse spiral ganglion were used to label type-I and type-II afferent fibers. Axons presumed to be from type-II spiral ganglion cells because of their small diameter (less than 0.7 microns) and lack of nodes of Ranvier were traced to their terminations in the cochlear nucleus. Thicker fibers presumed to be from type-I ganglion cells were also reconstructed. Type-I and type-II axons labeled by basal turn injections bifurcate together in the dorsal part of the auditory nerve root, forming a branch that ascends into the anteroventral cochlear nucleus and a branch that descends into the posteroventral cochlear nucleus. Type-I fibers formed many collaterals ending in terminal swellings whereas type-II fibers were almost unbranched. Swellings from type-I and type-II fibers were often formed alongside one another. Examples of this proximity include terminal swellings of root collaterals in the auditory nerve root, as well as type-II en passant swellings and type-I terminal swellings throughout the ventral cochlear nucleus. The projections are dissimilar, however, since every type-II fiber projects at least one collateral to the granule-cell lamina. These collaterals usually end in neuropil forming the border between the ventral cochlear nucleus and the granule-cell lamina. In this border region, the type-II terminals overlap with those of branches from thick axons of the olivocochlear (efferent) bundle. Type-II fibers also differ from type-I fibers by only rarely coursing into the dorsal cochlear nucleus and by forming very few terminal swellings. En passant swellings, however, are numerous on type-II fibers, with ellipsoidal-shaped swellings prominent in the nerve root, and angular and complex-shaped swellings common nearer the terminals. We suggest that the latter swellings are associated with type-II synapses whereas the ellipsoidal swellings represent non-synaptic structures.

Afferent Pathways↗
PubMed1990

Evidence that the Rate of Wallerian Degeneration is Controlled by a Single Autosomal Dominant Gene.

In a substrain of C57BL mice, C57BL/Ola, Wallerian degeneration in the distal segment of the severed sciatic nerve is extremely slow when compared to other mice. Despite this very slow degeneration in the distal segment regeneration of the motor nerves is not impaired. From suitable genetic outcrosses and backcrosses, the authors provide evidence that the rate of Wallerian degeneration in this strain is controlled by a single autosomal gene product. The authors have also shown that the rate of degeneration, in C57BL/Ola mice, is influenced by the environment in which the animals were bred and housed. Wallerian degeneration in the sciatic nerves of mice raised in isolators is slower than in those raised in a conventional animal house. This strain of mouse may prove to be of value in the understanding of nerve degeneration and regeneration.

Journal Article↗
PubMed1990

Evidence that Very Slow Wallerian Degeneration in C57BL/Ola Mice is an Intrinsic Property of the Peripheral Nerve.

We have described a mutant mouse, C57BL/Ola, in which Wallerian degeneration following peripheral nerve transection is very slow. Our previous results suggested that recruited monocytes play a role in rapid Wallerian degeneration. The nature of the mutation in C57BL/Ola mice is not known and we have investigated whether the defect is intrinsic to the nerve or due to a defect in the circulating monocytes. We have made chimaeric mice in which bone marrow from histocompatible mice, with rapidly degenerating nerves and normal monocyte recruitment, was used to reconstitute irradiated C57BL/Ola mice and vice-versa. A substantial degree of donor repopulation of the hosts was confirmed by measures of the levels of glucose-phosphate isomerase alloenzymes in blood and tissue samples from the two different strains. The rate of degeneration of the transected sciatic nerve was found to be host-dependent, providing evidence that the mutation affects cell populations intrinsic to the nerve and not the circulating monocytes. We provide additional evidence that the peripheral nerves of C57BL/Ola mice are different from those of other mice as they degenerate at a slower rate in vitro.

Journal Article↗
PubMed1990

Elevated concentration of soluble interleukin-2 receptors in serum of smokers and patients with lung cancer. Correlation with clinical activity.

Soluble interleukin-2 receptor (sIL-2R) levels in cigarette smokers and in patients with lung cancer were measured using an enzyme immunoassay. The rationale for our study was based on the fact that activation of T-cells is dependent upon the T-cell growth factor, interleukin-2, which may be regulated by its receptor, IL-2R. Measurements of circulating sIL-2R might be useful in the immune assessment of certain conditions. This study assessed elevated concentrations of circulating sIL-2R in smokers and in patients with lung cancer. The data show that healthy smokers, as a group, have an elevated level of sIL-2R compared with that in nonsmokers. Significantly higher than normal levels were found among light, moderate, and heavy smokers. Patients with lung cancer (squamous cell carcinoma [SSC] or adenocarcinoma [AC]) also have abnormally high sIL-2R levels. In the SCC group, the highest level of sIL-2R was among asymptomatic patients with well-differentiated tumors. Similarly, patients with SCC whose tumors were less than 3 cm in diameter had a significantly higher mean level of sIL-2R than did patients whose tumors exceeded 3 cm. The sIL-2R level in the SCC group also correlated with the tumor stage, with the highest level found among Stage I patients. In patients with SCC, but not in those with AC, the sIL-2R level was indicative of the extent of malignancy. These data support the concept that sIL-2R may be important in the pathogenesis of immune alterations associated with smoking and lung cancer.

Adenocarcinoma↗
PubMed1989

Morphology and response properties of single olivocochlear fibers in the guinea pig.

Cochlear efferent and afferent units were recorded from the spiral ganglion in anesthetized guinea pigs. Efferent units were identified by their regular discharge patterns and their long response latencies to tone bursts. In some cases these physiological criteria were confirmed by anatomical tracing of single axons labeled with horseradish peroxidase. Labeled efferent axons traveled in the vestibular nerve root and the intraganglionic spiral bundle, and crossed the tunnel to innervate up to 61 outer hair cells over longitudinal distances of 0.15 to 2.1 mm. Efferent units were subdivided into classes by their excitatory responses to monaural tone bursts. Fifty-seven percent responded only to ipsilateral-ear sound, 28% only to contralateral-ear sound, and 15% to sound in either ear. Tuning curves from efferent units were generally similar in shape to afferent units, often having equally low thresholds and equally high Q10s. Efferent Q10s were somewhat lower from preparations anesthetized with a Urethane/Innovar combination than from preparations anesthetized with a Nembutal/Innovar combination. Efferent units with spontaneous activity were uncommon at the start of the recording sessions but were more frequently encountered later in the experiments. Spontaneous activity could often be suppressed by tonal stimuli, even sometimes to the non-excitatory ear of Ipsi and Contra units.

Acoustic Stimulation↗
PubMed1989

Soluble CD8 during T cell activation.

The CD8 Ag has long been used as a surface marker for the identification of cytotoxic and suppressor cells. Recently CD8-positive cells have been shown to release a soluble form of the CD8 Ag. We have devised a sandwich monoclonal enzyme immunoassay for the quantitation of this released CD8. Soluble CD8 was released in response to lymphocyte activation. In vitro, PHA or anti-CD3 mAb-mediated T cell activation led to release of CD8 into the culture supernatant. In vivo, serum from patients with EBV-induced infectious mononucleosis (IM), a disease associated with intense CD8+ T cell activation, demonstrated elevations in soluble CD8 (7939 U/ml, day 0) compared to serum from normal controls (289 U/ml). Levels of soluble CD8 correlated (r = 0.82, p less than 0.001) with the increased percentage of CD8+/HLA-DR+ (activated CD8+ T cells) observed in acute IM. Sequential analysis of serum during the course of IM shows that soluble CD8 levels parallel the decline in CD8+/HLA-DR+ cells that occurs with the resolution of the disease. These data suggest that released CD8 may be of value in monitoring the involvement of CD8+ T cells in response to a pathologic event. The functional role of the released CD8 molecule will require further investigation.

Adolescent↗
PubMed1989

Further characterisation of the [35S]-TBPS binding site of the GABA receptor complex in locust (Schistocerca gregaria) ganglia membranes.

1. Using homogenates of supraoesophageal ganglia from locust we observed specific binding of [35S]-TBPS which was linear with protein concentration up to 7 mg/ml, showed a pH optimum at pH 9.0 and was linear with NaCl concentration up to 350 mM. 2. Kinetic analysis of the binding showed positive cooperativity as a result of changes in on and off-rates with occupation of the binding site by the ligand. The apparent KD = 417 nM and Bmax = 1083 fmol/mg of membrane protein were calculated using a computer program for dose-response curve fitting. 3. The binding was enhanced by GABA, pentobarbital and benzodiazepines. Picrotoxinin had no effect on the binding at 0.1 mM. Only the cage convulsants TBPS and IBP were able to displace the binding. 4. Whilst the characteristics of the binding are similar to those reported for house fly thorax and abdomen preparations they are significantly different from those reported for house fly head, cockroach nerve cord and rat brain.

Animals↗
PubMed1989

A critical analysis of serum and urine interleukin-2 receptor assays in renal allograft recipients.

A component of the interleukin 2 receptor (IL-2R) is released in soluble form during T cell activation and can be detected in the blood during acute renal allograft rejection. This study evaluates the diagnostic utility of a sandwich enzyme immunoassay test for serum and urine IL-2R in renal allograft recipients. A rise in serum IL-2R during the week prior to the clinical diagnosis of rejection correlated better with rejection than did isolated serum IL-2R levels or urine values. For the diagnosis of acute rejection, a rise in serum IL-2R (sensitivity 73%, specificity 87%) was comparable in overall test performance to a rise in serum creatinine (sensitivity 70%, specificity 84%). Overall, the two tests had equivalent receiver operating characteristic curves. Because the etiology of false positives in creatinine and IL-2R assays differed (primarily cyclosporine toxicity and infection, respectively), the predictive value of the combined tests was superior to either alone.

Creatinine↗
PubMed1989

Absence of Wallerian Degeneration does not Hinder Regeneration in Peripheral Nerve.

Wallerian degeneration of the distal stump of a severed peripheral nerve involves invasion by myelomonocytic cells, whose presence is necessary for destruction of myelin and for initiating mitosis in Schwann cells (Beuche and Friede, 1984). Degeneration of the distal ends of the axons themselves is assumed to occur by autolytic mechanisms. We describe a strain of mice (C57BL/6/Ola) in which leucocyte invasion is slow and sparse. In these mice, confirming Beuche and Friede, myelin removal is extremely slow. A new finding is that axon degeneration is also very slow. This is a consequence of lack of recruitment of myelomonocytic cells for if such recruitment is prevented in other mouse strains by a monoclonal antibody against the complement type 3 receptor (Rosen and Gordon, 1987) axon degeneration is again slowed. We have also, surprisingly, found that nerve regeneration in the C57BL/6/Ola mice is not impeded by the presence of largely intact axons in the distal stump and absence of recruited cells, myelin debris and the absence of Schwann cell mitosis.

Journal Article↗
PubMed1988

Central trajectories of type II spiral ganglion neurons.

Previous attempts to trace the central pathways of the thin axons from type II spiral ganglion neurons have been hampered by technical difficulties such as fading of the reaction product as distance increases from the injection site (Ryugo et al.: Soc. Neurosci. Abstr. 12:779, '86; Brown: J. Comp. Neurol. 260:591-604, '87). By using small rodents (gerbils and mice), which have short auditory nerves, we have succeeded in filling the entire central axon and terminals of type II neurons after peripheral injections of horseradish peroxidase. The general course of the type II fibers within the auditory nerve and cochlear nucleus is similar to that of type I fibers except that terminals from type II neurons are often found in regions of the cochlear nucleus that have high densities of granule cells.

Animals↗
PubMed1988

Brainstem branches from olivocochlear axons in cats and rodents.

Horseradish peroxidase was used to label axons of olivocochlear (OC) neurons by intracellular injections in cats and extracellular injections in rodents. These axons arise from cell bodies in the superior olivary complex and project to the cochlea. En route to the cochlea, the thick axons (greater than 0.7 micron diam.) of medial olivocochlear (MOC) neurons formed collaterals that terminated in the ventral cochlear nucleus, the interstitial nucleus of the vestibular nerve (in cats), and the inferior vestibular nucleus (in rodents). The thin axons (less than 0.7 micron diam.), presumed to arise from lateral olivocochlear (LOC) neurons, did not branch near the CN. Within the CN, the MOC collaterals tended to ramify in and near regions with high densities of granule cells, regions also associated with the terminals of type II afferent axons (Brown et al.: J. Comp. Neurol. 278:581-590, '88). These results suggest that those fibers associated peripherally with outer hair cells (MOC efferents and type II afferents) are associated centrally with regions containing granule cells, whereas those fibers associated with inner hair cells peripherally (LOC efferents and type I afferents) are not.

Afferent Pathways↗
PubMed1988

Mechanism of interaction between motoneurons and muscles.

Possible ways in which muscle fibres can affect motoneuron properties and motoneurons can affect muscle properties are discussed. A more detailed analysis of the local control by muscle of motor nerve terminal growth is then given. Experimental results from the gluteus maximus muscle of the mouse show that nerve terminal growth occurs very quickly if the muscle under the endplate is killed and that the growth can still be elicited after all communication with the cell body of the motoneuron has been eliminated. These observations show that all the materials needed for axon growth are normally present in axon terminals and that the control of terminal growth by the muscle is exercised at a local level. It is argued that this inhibitory control works by preventing the incorporation of these growth materials rather than by continual degradation of a persistently growing terminal. One reason for taking this view is that recent evidence suggests that the axonal cytoskeleton consists of a largely stationary array of discontinuous neurofilaments and microtubules.

Animals↗
PubMed1988

Localization of neural cell adhesion molecule in denervated muscle to both the plasma membrane and extracellular compartments by immuno-electron microscopy.

The location of neural cell adhesion molecule in mouse skeletal muscle has been investigated using two immuno-electron microscopical techniques. In the first method, 6-micron frozen sections of a normal and a hemi-denervated gluteus muscle were stained by an indirect immunoperoxidase method using a rabbit-derived polyclonal antiserum to neural adhesion molecule as the primary antibody. The stain was visualized with the electron-dense chromogen, diaminobenzidine and the sections fixed, osmicated and processed for electron microscopy whilst still on the slide. Ultrathin sections were cut and viewed in the electron microscope, where the reaction product appeared to be localized in the plasma membrane and on the basal lamina of the muscle fibres. The second method, using a 5-nm immunogold-labelled secondary antibody, confirmed and extended these initial observations. In these experiments, the primary antibody to neural cell adhesion molecule was applied in vivo to hemi-denervated mouse gluteus muscles. The muscles were dissected out 24 h later, divided into denervated and innervated halves and then into junctional and extrajunctional regions. Together with the junctional and extrajunctional regions of normal, control pieces of muscle which had not been incubated with anti-neural cell adhesion molecule, they were lightly fixed, and incubated with the secondary gold-labelled antibody, before further fixation and processing for electron microscopy. Semi-thin, 0.5-micron sections of each were cut and viewed at 20,000 x magnification. Randomly sampled fibres from the extrajunctional regions of the denervated and innervated halves of the hemi-denervated gluteus and the normal, control gluteus were photographed for quantitative analysis. Five micrographs were randomly selected from each group and in these, the numbers, density and position of gold particles were measured using a digitizing tablet. By far the highest number of gold particles was found in the denervated half of the gluteus muscle, there being much less in the innervated half and practically none in the control. The density of gold particles in the denervated muscles was maximal in the plasma membrane-basal lamina complex, but most were located in the extracellular spaces outside this region, where they usually occurred in clusters apparently in association with collagen fibres. We conclude that neural cell adhesion molecule in denervated skeletal muscle is present not only in the plasma membrane but also in the basal lamina and extracellular space.

Animals↗